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The treatment of patients with triple negative breast cancer (TNBC) relies on cytotoxic therapy. Currently, atezolizumab and chemotherapy can be combined in patients with TNBC. However, this approach is not effective for all patients with low reactivity to atezolizumab. As there is a lack of alternative treatment options, new anti-cancer drugs are urgently needed to enhance atezolizumab reactivity against TNBC. Recent strategies have focused on regulating the expression of programmed death-ligand 1 (PD-L1) or enhancing immune response activation by combining anti-cancer drugs with immune checkpoint inhibitors (ICIs). Cannabidiol (CBD), a cannabinoid component derived from the cannabis plant, has been reported to have anti-cancer therapeutic potential because of its capacity to induce apoptotic cell death in tumor cells while avoiding cytotoxicity in normal cells. Previous studies have demonstrated the effects of CBD on apoptosis in various cancer cell types. However, the potential role of CBD as an immune modulator in the regulation of PD-L1 expression and anti-cancer immune responses remains to be explored. In this study, we found that CBD stimulated PD-L1 expression in TNBC cells, which significantly induced the CBD-mediated cGAS-STING pathway activation. Taken together, we demonstrated that the combination of CBD and anti-PD-L1 antibody enhances the anti-cancer immune response in vitro and in vivo experiments. Our findings identified the mechanism of PD-L1 regulation by CBD in TNBC cells and suggested that CBD could be a potential candidate for the development of new combinatorial strategies with ICIs in TNBC patients.

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Diagnosis of bruxism is challenging because not all contractions of the masticatory muscles can be classified as bruxism. Conventional methods for sleep bruxism detection vary in effectiveness. Some provide objective data through EMG, ECG, or EEG; others, such as dental implants, are less accessible for daily practice. These methods have targeted the masseter as the key muscle for bruxism detection. However, it is important to consider that the temporalis muscle is also active during bruxism among masticatory muscles. Moreover, studies have predominantly examined sleep bruxism in the supine position, but other anatomical positions are also associated with sleep. In this research, we have collected EMG data to detect the maximum voluntary contraction of the temporalis and masseter muscles in three primary anatomical positions associated with sleep, i.e., supine and left and right lateral recumbent positions. A total of 10 time domain features were extracted, and six machine learning classifiers were compared, with random forest outperforming others. The models achieved better accuracies in the detection of sleep bruxism with the temporalis muscle. An accuracy of 93.33% was specifically found for the left lateral recumbent position among the specified anatomical positions. These results indicate a promising direction of machine learning in clinical applications, facilitating enhanced diagnosis and management of sleep bruxism.

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Poly(ADP-ribose) polymerase (PARP) inhibitors are targeted therapies that accumulate DNA damage by interfering with DNA repair mechanisms and are approved for treating several cancers with BRCA1/2 mutations. In this study, we utilized CRISPR-dCas9 interference screening to identify genes regulating sensitivity to PARP inhibitors in breast cancer cell lines. Our findings indicated that the interferon (IFN) signaling gene IRF9 was critically involved in modulating sensitivity to these inhibitors. We revealed that the loss of IRF9 leads to increased resistance to the PARP inhibitor in MDA-MB-468 cells, and a similar desensitization was observed in another breast cancer cell line, MDA-MB-231. Further analysis indicated that while the basal expression of IRF9 did not correlate with the response to the PARP inhibitor olaparib, its transcriptional induction was significantly associated with increased sensitivity to the DNA-damaging agent cisplatin in the NCI-60 cell line panel. This finding suggests a mechanistic link between IRF9 induction and cellular responses to DNA damage. Additionally, data from the METABRIC patient tissue study revealed a complex network of IFN-responsive gene expressions postchemotherapy, with seven upregulated genes, including IRF9, and three downregulated genes. These findings underscore the intricate role of IFN signaling in the cellular response to chemotherapy. Collectively, our CRISPR screening data and subsequent bioinformatic analyses suggest that IRF9 is a novel biomarker for sensitivity to DNA-damaging agents, such as olaparib and platinum-based chemotherapeutic agents. Our findings for IRF9 not only enhance our understanding of the genetic basis of drug sensitivity, but also elucidate the role of IRF9 as a critical effector within IFN signaling pathways, potentially influencing the association between the host immune system and chemotherapeutic efficacy.

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This study conducted real-time monitoring of size-resolved particle concentrations ranging from 9 nm to 10 µm simultaneously at four sites on the park ground and the roof of a five-story apartment buildings in the upwind and downwind areas of the Olympic Expressway next to apartment complex areas of Seoul, Korea. Using a positive matrix factorization model for source apportionment, eight factors were resolved at each monitoring site: four exhaust emissions of vehicles, one non-exhaust emission of vehicle, two regional sources, and one unknown source. After categorizing monitoring data into three cases by wind conditions, impact and contribution of each vehicle-related source on the local road to the roadside pollution was quantified and characterized by subtracting the urban background concentrations. Throughout the measurement period, the contribution of vehicle-related sources to the particle number concentration at each monitoring site ranged from 61 % to 69 %, while that to the particle mass concentration ranged from 39 % to 87 %. During periods of steady traffic flow and wind blowing from the road to three downwind sites at speeds exceeding >0.5 m/s during working hours, the particle number concentrations at the downwind sites were 2.2-2.5 times higher than the average levels. Among vehicle-related sources, gasoline vehicles with multiple injections or high-emitting diesel vehicles showed the highest contribution to particle number concentrations at all sites. As wind speed increased, the number concentrations of particles from vehicle exhaust and non-exhaust emissions decreased and increased, respectively, probably due to enhanced dilution and transport, respectively. In addition, particle number concentrations showed a parabolic curve-like trend with traffic volumes increasing to approximately 10,000 vehicles/h, and then decreasing for both vehicle exhaust and non-exhaust emissions. These results can be utilized in numerical modeling studies and in establishing traffic-related environmental policies to reduce seasonal and temporal particle exposure near the roadsides.

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Production of medium chain length polyhydroxyalkanoate (mcl-PHA) was attempted using Pseudomonas gessardii NIBRBAC000509957, which was isolated from Sunchang, Jeollabuk-do, Republic of Korea (35°24'27.7"N, 127°09'13.0"E) and effectively utilized acetate and formate as carbon sources. We first evaluated the utilization of acetate as a carbon source, revealing optimal growth at 5 g/L acetate. Then, formate was supplied to the acetate minimal medium as a carbon source to enhance cell growth. After overexpressing the acetate and formate assimilation pathway enzymes, this strain grew at a significantly higher rate in the medium. As this strain naturally produces PHA, it was further engineered metabolically to enhance mcl-PHA production. The engineered strain produced 0.40 g/L of mcl-PHA with a biomass content of 30.43% in fed-batch fermentation. Overall, this strain can be further developed to convert acetate and formate into valuable products.

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Objectives: This study aimed to identify the effectiveness of treatment programs for children with reading (RD) or mathematics disorders (MD). Structured treatment programs were developed to improve phonological awareness and number sense among children and adolescents with RD or MD, respectively, and the effectiveness of the learning disorder treatment programs were evaluated. Methods: We used standardized, objective diagnostic, and evaluation tools not only to recruit participants with RD, MD, or comorbid attention deficit and hyperactivity disorder, but also to assess the effectiveness of the treatments regarding both improved core neurocognitive deficits of RD or MD and academic achievement. Forty children with RD or MD received one-on-one treatments from therapists. Results: In the RD group, treatment effects were observed in all subtests. In the word and paragraph reading tests, the accuracy rates and fluency improved. The results of the phonological working memory test, word-sound correspondence test, and rapid automatic naming tests also improved. In the MD group, the accuracy rate and fluency on the arithmetic test improved. An increase in the accuracy rate in the size and distance comparison tests and a decrease in the error rate in the estimation test were also observed. However, there were no improvements in reaction time in these subtests. Conclusion: Learning disorder treatment programs that focus on improving phonological awareness or number sense in children with RD or MD improved achievement, phonological awareness, and number sense.

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Purpose: Recent advances in the treatment of breast cancer have led to the improvement of breast cancer patient's survival. With the prolonged survival of these patients, pregnancy became an important issue, especially in young cancer patient aged 35 years or under. Increased hormone levels during pregnancy, however, raise concerns about elevating the risk of cancer recurrence. The aim of this study was to validate the notion of increased risk associated with pregnancy after breast cancer treatment in young patients. Methods: From January 2009 to December 2020, newly diagnosed breast cancer patients 35 years old or under who underwent optimal surgery in Korea University Guro Hospital were enrolled in this study. Patients were categorized into 3 groups: nulliparous, pregnancy prior to treatment of breast cancer, and patients with pregnancy after breast cancer treatment. Their overall survival and disease-free survival were evaluated. Results: A total of 107 patients were enrolled in this study. Thirteen patients (12.1%) conceived and successfully delivered. The mean follow-up period after surgery was 58.9 (± 33.5) months. There was no significant difference in overall survival (P = 0.608) and disease-free survival (P = 0.591) among different groups. Conclusion: In young patients, pregnancy after treatment for breast cancer did not affect their overall survival or diseasefree survival as compared to nullipara or previously delivered groups. Therefore, pregnancy counseling should not be prevented in young breast cancer patients 35 years old or under.

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The increasing number of IoT devices has led to more electronic waste production, which harms the environment and human health. Self-powered sensor systems are a solution, but they often use toxic materials. We propose using biocompatible peanut skin as the active material for a self-powered humidity sensor (PSP-SPHS) through integration with a peanut-skin-based triboelectric nanogenerator (PSP-TENG). The PSP-TENG was characterized electrically and showed promising results, including an open circuit voltage (162 V), short circuit current (0.2 µA), and instantaneous power (2.2 mW) at a loading resistance of 20 MΩ. Peanut skin is a great choice for the sensor due to its porous surface, large surface area, eco-friendliness, and affordability. PSP-TENG was further used as a power source for the PSP-humidity sensor. PSP-SPHS worked as a humidity-dependent resistor, whose resistance decreased with increasing relative humidity (%RH), which further resulted in decreasing voltage across the humidity sensor. This proposed PSP-SPHS exhibited a good sensitivity (0.8 V/RH%), fast response/recovery time (4/10 s), along with excellent stability and repeatability, making it a potential candidate for self-powered humidity sensor technology.

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In this paper, we propose an improved clustering algorithm for wireless sensor networks (WSNs) that aims to increase network lifetime and efficiency. We introduce an enhanced fuzzy spider monkey optimization technique and a hidden Markov model-based clustering algorithm for selecting cluster heads. Our approach considers factors such as network cluster head energy, cluster head density, and cluster head position. We also enhance the energy-efficient routing strategy for connecting cluster heads to the base station. Additionally, we introduce a polling control method to improve network performance while maintaining energy efficiency during steady transmission periods. Simulation results demonstrate a 1.2% improvement in network performance using our proposed model.

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Employing a combination of Polyethylene terephthalate (PET) thermoforming and 3D-printed cylindrical patterns, we carefully engineer a linear resistive temperature sensor. This intricate process involves initial PET thermoforming, yielding a hollow cylindrical chamber. This chamber is then precisely infused with a composite fluid of graphite and water glue. Ensuring electrical connectivity, both ends are affixed with metal wires and securely sealed using a hot gun. This cost-effective, versatile sensor adeptly gauges temperature shifts by assessing composite fluid resistance alterations. Its PET outer surface grants immunity to water and solubility concerns, enabling application in aquatic and aerial settings without extra encapsulation. Rigorous testing reveals the sensor's linearity and stability within a 10 °C to 60 °C range, whether submerged or airborne. Beyond 65 °C, plastic deformation arises. To mitigate hysteresis, a 58 °C operational limit is recommended. Examining fluidic composite width and length effects, we ascertain a 12 Ω/°C sensitivity for these linear sensors, a hallmark of their precision. Impressive response and recovery times of 4 and 8 s, respectively, highlight their efficiency. These findings endorse thermoforming's potential for fabricating advanced temperature sensors. This cost-effective approach's adaptability underscores its viability for diverse applications.

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Introduction: Single-port access (SPA) laparoscopy requires only one incision, unlike conventional laparoscopy. However, its umbilical incision is larger than that of conventional laparoscopy and can be vulnerable to postoperative pain. This study aimed to evaluate whether simultaneous use of a continuous wound infiltration (CWI) system and intravenous patient-controlled analgesia (IV PCA) effectively decreases surgical site pain in patients who underwent SPA laparoscopy due to gynecologic adnexal disease. Methods: A total of 371 patients who underwent SPA laparoscopy and who received IV PCA or CWI was retrospectively reviewed (combined group [CWI + IV PCA, n = 159] vs. PCA group [IV PCA only, n = 212]). To evaluate postoperative pain management, the numeric rating scale (NRS) pain score after surgery, total amount of fentanyl administered via IV PCA, and additional pain killer consumption were collected. Results: The NRS scores at 12 h (1.90 ± 1.11 vs. 2.70 ± 1.08, p < 0.001) and 24 h (1.82 ± 0.82 vs. 2.11 ± 1.44, p = 0.026) after surgery were significantly lower in the combined group than in the PCA group. The total amount of PCA fentanyl was significantly smaller in the combined group than in the PCA group (p < 0.001). The total quantity of rescue analgesics was smaller in the combined group than in the PCA group (p < 0.05). Conclusion: Combined use of the CWI system and IV PCA is an effective postoperative pain management strategy in patient who underwent SPA laparoscopy for adnexal disease.

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We investigated the role of TONSL, a mediator of homologous recombination repair (HRR), in stalled replication fork double-strand breaks (DSBs) in cancer. Publicly available clinical data (tumors from the ovary, breast, stomach and lung) were analyzed through KM Plotter, cBioPortal and Qomics. Cancer stem cell (CSC)-enriched cultures and bulk/general mixed cell cultures (BCCs) with RNAi were employed to determine the effect of TONSL loss in cancer cell lines from the ovary, breast, stomach, lung, colon and brain. Limited dilution assays and ALDH assays were used to quantify the loss of CSCs. Western blotting and cell-based homologous recombination assays were used to identify DNA damage derived from TONSL loss. TONSL was expressed at higher levels in cancer tissues than in normal tissues, and higher expression was an unfavorable prognostic marker for lung, stomach, breast and ovarian cancers. Higher expression of TONSL is partly associated with the coamplification of TONSL and MYC, suggesting its oncogenic role. The suppression of TONSL using RNAi revealed that it is required in the survival of CSCs in cancer cells, while BCCs could frequently survive without TONSL. TONSL dependency occurs through accumulated DNA damage-induced senescence and apoptosis in TONSL-suppressed CSCs. The expression of several other major mediators of HRR was also associated with worse prognosis, whereas the expression of error-prone nonhomologous end joining molecules was associated with better survival in lung adenocarcinoma. Collectively, these results suggest that TONSL-mediated HRR at the replication fork is critical for CSC survival; targeting TONSL may lead to the effective eradication of CSCs.

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In urban areas, particulate matter emitted from vehicles directly affects the health of citizens near roads. Thus, in this study, particle size distribution was measured by the horizontal and vertical distances along a highway road with heavy traffic to characterize the dispersion phenomena of particulate matter emitted from vehicles. In addition, the contribution of pollution sources was analyzed using a source-receptor model. A concentration gradient was observed in which the concentration decreased with the increase in the distance from the road when the wind blew from the road to the monitoring locations. The concentration was slightly higher within 50 m of the road when the wind blows parallel to the road, and similar concentrations were found at the other monitoring locations further away from the roads. In particular, the higher the turbulence intensity of the wind, the lower is the concentration gradient coefficient because of the more enhanced mixing and dispersion. A positive matrix factorization (PMF) model with the measured particle size distribution data in the range of 9-300 nm resulted in a contribution of about 70 % (number) and 20 % (mass) to particle concentrations because of six types of vehicles including LPG, two gasoline vehicles (GDI, MPI), and three diesel vehicles with 3rd, 4th, and 5th emission classes. It showed a decrease in the vehicular contribution as the distance from the road increased. Particle number concentrations decreased with increasing altitude up to 30 m above the ground. The results of this study can be useful in deriving generalized gradient equations of particle concentrations exposed by distance and wind direction at the roadside using traffic and meteorological conditions and for establishing environmental policies, such as roadside exposure assessment, in the future. A CAPSULE ABSTRACT: Dispersion of particles emitted from vehicles on a busy highway was characterized by roadside measurements of horizontal and vertical profiles of particle size distributions measured at four locations. The source profiles and contributions were estimated by major sources using a source-receptor model such as PMF.

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The main challenge in preparing a flexible mold stamp using roll-to-roll nanoimprint lithography is to simultaneously increase the imprintable area with a minimized perceptible seam. However, the current methods for stitching multiple small molds to fabricate large-area molds and functional surfaces typically rely on the alignment mark, which inevitably produces a clear alignment mark and stitched seam. In this study, we propose a mark-less alignment by the pattern itself method inspired by moiré technique, which uses the Fourier spectral analysis of moiré patterns formed by superposed identical patterns for alignment. This method is capable of fabricating scalable functional surfaces and imprint molds with quasi-seamless and alignment mark-free patterning. By harnessing the rotational invariance property in the Fourier transform, our approach is confirmed to be a simple and efficient method for extracting the rotational and translational offsets in overlapped periodic or nonperiodic patterns with a minimized stitched region, thereby allowing for the large-area and quasi-seamless fabrication of imprinting molds and functional surfaces, such as liquid-repellent film and micro-optical sheets, that surpass the conventional alignment and stitching limits and potentially expand their application in producing large-area metasurfaces.

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Pulmonary emphysema is a destructive inflammatory disease primarily caused by cigarette smoking (CS). Recovery from CS-induced injury requires proper stem cell (SC) activities with a tightly controlled balance of proliferation and differentiation. Here we show that acute alveolar injury induced by two representative tobacco carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene (N/B), increased IGF2 expression in alveolar type 2 (AT2) cells to promote their SC function and facilitate alveolar regeneration. Autocrine IGF2 signaling upregulated Wnt genes, particularly Wnt3, to stimulate AT2 proliferation and alveolar barrier regeneration after N/B-induced acute injury. In contrast, repetitive N/B exposure provoked sustained IGF2-Wnt signaling through DNMT3A-mediated epigenetic control of IGF2 expression, causing a proliferation/differentiation imbalance in AT2s and development of emphysema and cancer. Hypermethylation of the IGF2 promoter and overexpression of DNMT3A, IGF2, and the Wnt target gene AXIN2 were seen in the lungs of patients with CS-associated emphysema and cancer. Pharmacologic or genetic approaches targeting IGF2-Wnt signaling or DNMT prevented the development of N/B-induced pulmonary diseases. These findings support dual roles of AT2 cells, which can either stimulate alveolar repair or promote emphysema and cancer depending on IGF2 expression levels. SIGNIFICANCE: IGF2-Wnt signaling plays a key role in AT2-mediated alveolar repair after cigarette smoking-induced injury but also drives pathogenesis of pulmonary emphysema and cancer when hyperactivated.

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Sarcoidosis is a granulomatous disease with the potential of multiple organ system involvement and its etiology remains unknown. Cardiac involvement is associated with worse clinical outcome, and has been reported to be 20-30% in white and as high as 58% in Japanese populations with sarcoidosis. Clinical manifestations of cardiac sarcoidosis highly depend on the extent and location of granulomatous inflammation. The most frequent presentations include heart block, tachyarrhythmia, or heart failure. Endomyocardial biopsy is the most specific diagnostic test, but has poor sensitivity due to often patchy involvement. The diagnosis of cardiac sarcoidosis remains challenging due to nonspecific imaging findings. Both 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and cardiac magnetic resonance imaging can be used to evaluate cardiac sarcoidosis, but evaluate different stages of the disease process. FDG-PET detects metabolically active inflammatory cells while cardiac magnetic resonance imaging with late gadolinium enhancement reveals areas of myocardial necrosis and fibrosis. Aggressive therapy of symptomatic cardiac sarcoidosis is often sought due to the high risk of sudden death and/or progression to heart failure. Prednisone 20-40 mg a day is the recommended initial treatment. In refractory or severe cases, higher doses of prednisone, 1-1.5 mg/kg/d (or its equivalent) and addition of a steroid-sparing agent have been utilized. Methotrexate is added most commonly. Long-term improvement has been reported with the use of a combination of weekly methotrexate and prednisone versus prednisone alone. After initiation of treatment, a cardiac FDG-PET scan may be performed 2-3 months later to assess treatment response.

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The screening of siRNAs targeting 390 human G protein-coupled receptors (GPCRs) was multiplexed in combination with cisplatin against lung cancer cells. While the cell viability measure hardly captured the anticancer effect of siGPCRs, the direct cell count revealed the anticancer potential of diverse GPCRs (46 hits with > twofold growth inhibition, p-value < 0.01). In combined treatment with cisplatin, siRNAs against five genes (ADRA2A, F2RL3, NPSR1, NPY and TACR3) enhanced the anti-proliferation efficacy on cancer cells and reduced the self-recovery ability of surviving cells after the removal of the combined treatment. Further on-target validation confirmed that the knockdown of TACR3 expression exhibited anticancer efficacy under both single and combined treatment with cisplatin. Q-omics ( http://qomics.io ) analysis showed that high expression of TACR3 was unfavorable for patient survival, particularly with mutations in GPCR signaling pathways. The present screening data provide a useful resource for GPCR targets and biomarkers for improving the efficacy of cisplatin treatment.

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A memristor is a fundamental electronic device that operates like a biological synapse and is considered as the solution of classical von Neumann computers. Here, a fully printed and flexible memristor is fabricated by depositing a thin film of metal-non-metal (chromium-nitrogen)-doped titanium dioxide (TiO2). The resulting device exhibited enhanced performance with self-rectifying and forming free bipolar switching behavior. Doping was performed to bring stability in the performance of the memristor by controlling the defects and impurity levels. The forming free memristor exhibited characteristic behavior of bipolar resistive switching with a high on/off ratio (2.5 × 103), high endurance (500 cycles), long retention time (5 × 103 s) and low operating voltage (±1 V). Doping the thin film of TiO2 with metal-non-metal had a significant effect on the switching properties and conduction mechanism as it directly affected the energy bandgap by lowering it from 3.2 eV to 2.76 eV. Doping enhanced the mobility of charge carriers and eased the process of filament formation by suppressing its randomness between electrodes under the applied electric field. Furthermore, metal-non-metal-doped TiO2 thin film exhibited less switching current and improved non-linearity by controlling the surface defects.

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Background and Objectives: Prion diseases are fatal neurodegenerative disorders caused by the abnormal proteinase K-resistant prion protein (PrPSc). Since variant Creutzfeldt-Jakob disease (CJD) was first reported in the United Kingdom (UK) in 1996, the occurrence of variant CJD has been reported in over 10 countries. To date, variant CJD has not been reported in Korea. However, the E211K somatic mutation in the prion protein gene (PRNP), which is related to bovine spongiform encephalopathy (BSE), was reported in Korean Holstein cattle, and atypical BSE, which is supposed to be sporadic BSE, has been occurring in many countries, including Japan and the USA. These results suggest that BSE may occur naturally in Korea. Thus, we performed a preemptive PrPSc test in appendix specimens to diagnose variant CJD in a Korean population. Materials and Methods: In the present study, we investigated CJD-related mutations and polymorphisms of the PRNP gene and carried out an examination on PrPSc in appendix specimens of Korean patients after appendectomy. Results: In all Korean appendix specimens tested, PrPSc bands were not detected. Conclusion: To the best of our knowledge, this was the first evaluation of PrPSc in Korean appendix specimens.

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Purpose: Phyllodes tumors (PTs) of the breast are rare fibroepithelial neoplasms, and factors associated with the recurrence of PTs are poorly understood. This study sought to identify clinicopathological factors associated with the recurrence of PTs. Method: From January 2009 to December 2019, we identified 100 patients who underwent definitive surgery for PT. Clinicopathological risk factors associated with the recurrence of PT were assessed. Results: The median age of the patients was 44 y (range, 19-62 y), and the median tumor size was 4 cm (0.8-30 cm). At a median follow-up of 26.7 mo (0-103 mo), 22 of the 100 patients experienced local recurrence. In the univariate and multivariate analyses, body mass index ≥ 23 kg/m2 (P = 0.042 in the univariate analysis; P = 0.039 in the multivariate analysis), tumor size ≥ 5 cm (P = 0.006 in the univariate analysis; P = 0.036 in the multivariate analysis), and the presence of stromal overgrowth (P = 0.032 in the univariate analysis; P = 0.040 in the multivariate analysis) were associated with an increased risk of local recurrence. Resection margins and grade were not associated with local recurrence. Conclusion: Normal- or underweight patients and those with larger tumor sizes were more prone to local recurrence. Further larger, multicenter studies with a long-term follow-up are required.

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