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Organ transplantation, a critical treatment for end-stage organ failure, has witnessed significant advancements due to the integration of improved surgical techniques, immunosuppressive therapies, and donor-recipient matching. This review explores the progress of organ preservation, focusing on the shift from static cold storage (SCS) to advanced machine perfusion techniques such as hypothermic (HMP) and normothermic machine perfusion (NMP). Although SCS has been the standard approach, its limitations in preserving marginal organs and preventing ischemia-reperfusion injury (IRI) have led to the adoption of HMP and NMP. HMP, which is now the gold standard for high-risk donor kidneys, reduces metabolic activity and improves posttransplant outcomes. NMP allows real-time organ viability assessment and reconditioning, especially for liver transplants. Controlled oxygenated rewarming further minimizes IRI by addressing mitochondrial dysfunction. The review also highlights the potential of cryopreservation for long-term organ storage, despite challenges with ice formation. These advances are crucial for expanding the donor pool, improving transplant success rates, and addressing organ shortages. Continued innovation is necessary to meet the growing demands of transplantation and save more lives.

Abstract Background Alzheimer's disease (AD) is a common type of dementia characterized by amyloid-β (Aβ) accumulation, lysosomal dysfunction, and tau hyperphosphorylation, leading to neurite dystrophy and memory loss. This study aimed to investigate whether Rhei Undulati Rhizoma (RUR), which has been reported to have anti-neuroinflammatory effect, attenuates Aβ-induced memory impairment, neuritic dystrophy, and tau hyperphosphorylation, and to reveal its mode of action. Methods Five-month-old 5xFAD mice received RUR (50 mg/kg) orally for 2 months. The Y-maze test was used to assess working memory. After behavioral testing, brain tissue was analyzed using thioflavin S staining, western blotting, and immunofluorescence staining to investigate the mode of action of RUR. To confirm whether RUR directly reduces Aβ aggregation, a thioflavin T assay and dot blot were performed after incubating Aβ with RUR. Results RUR administration attenuated the Aβ-induced memory impairment in 5xFAD mice. Furthermore, decreased accumulation of Aβ was observed in the hippocampus of the RUR-treated 5xFAD group compare to the vehicle-treated 5xFAD group. Moreover, RUR reduced the dystrophic neurites (DNs) that accumulate impaired endolysosomal organelles around Aβ. In particular, RUR treatment downregulated the expression of β-site amyloid precursor protein cleaving enzyme 1 and the hyperphosphorylation of tau within DNs. Additionally, RUR directly suppressed the aggregation of Aβ, and eliminated Aβ oligomers in vitro. Conclusions This study showed that RUR could attenuate Aβ-induced pathology and directly regulate the aggregation of Aβ. These results suggest that RUR could be an efficient material for AD treatment through Aβ regulation. Graphical Abstract

Objective(s): MicroRNAs (miRNAs) are small non-coding RNAs that function in all biological processes. Recent findings suggest that exosomes, which are small vesicles abundantly secreted by various cell types, can transport miRNAs to target cells. Here, we elucidated the effect of miRNA-loaded exosomes on lipopolysaccharide (LPS)-induced inflammation in H9c2 cardiomyocytes.Materials and Methods: Exosomes were isolated from mesenchymal stem cells (MSC) and loaded with miR-412-5p. Additionally, the effect of the miR-412-5p-loaded exosomes on LPS-induced inflammation in H9c2 cardiomyocytes was evaluated by assessing the levels of nitric oxide (NO), reactive oxygen species (ROS), and prostaglandin E2 (PGE2). The expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), inflammatory cytokines, and mitogen-activated protein kinase (MAPK) signaling factors was evaluated using reverse transcription-quantitative PCR and western blotting.Results: miR-412-5p-loaded exosomes inhibited LPS-induced secretion of inflammatory mediators (NO, PGE2, and ROS), pro-inflammatory cytokines (IL-1β and IL-6), and COX-2 and iNOS expression. Additionally, miR-412-5p-loaded exosomes significantly decreased the expression of MAPK signaling molecules, including p-extracellular signal-regulated kinase (ERK), p-p38, and p-Jun kinase (JNK), in H9c2 cardiomyocytes.Conclusion: These findings showed that miR-412-5p-loaded exosomes ameliorated LPS-induced inflammation in H9c2 cardiomyocytes by inhibiting COX-2 and iNOS expression, inflammatory mediators, and pro-inflammatory cytokines via the MAPK pathway. The findings indicate that miR-412-5p-loaded exosomes may be effective for the prevention of myocardial injury.

IntroductionImmune dysfunction is a major cause of neuroinflammation and accelerates the progression of Parkinson’s disease (PD). Numerous studies have shown that stimulation of specific acupuncture points (acupoints) can ameliorate PD symptoms. The purpose of this study was to investigate whether attaching microneedles to acupoints would improve PD pathology by recovering immune dysfunction.MethodsThe PD mouse model was induced by intrastriatal injection of 6-hydroxydopamine (6-OHDA), and microneedle patches (MPs) or sham patches (SPs) were attached to GB20 and GB34, representative acupoints for treating PD for 14 days.ResultsFirst, the behavioral experiment showed that motor disorders induced by 6-OHDA were significantly improved by MP. Simultaneously, 6-OHDA-induced dopaminergic neuronal death and brain neuroinflammation decreased. Conversely, SP had no effect on behavioral disorders, neuronal death, or neuroinflammation. Measurement results from flow cytometry of immune cells in the brain and blood revealed a disruption in the CD4+/CD8+ ratio in the 6-OHDA group, which was significantly restored in the MP group. The brain mRNA expression of cytokines was significantly increased in the 6-OHDA group, which was significantly decreased by MP.DiscussionOverall, our results suggest that the attachment of MPs to GB20 and GB34 is a new method to effectively improve the pathology of PD by restoring peripheral and brain immune function.

Cardiac tamponade (CT) is a rare but potentially lethal complication associated with central venous catheters (CVCs). We present a 6-year-old boy who developed CT after CVC insertion in the right internal jugular vein, with its tip in the inferior vena cava. Initially, he was hospitalized to a tertiary hospital with presumptive diagnoses of pneumonia and left ankle cellulitis. Three days after CVC placement, he developed CT, manifesting as recurrent episodes of hypotension and bradycardia. Once a bedside echocardiography showed CT, pericardiocentesis was performed, resulting in successful resuscitation. Pericardiocentesis revealed a milk-appearing pericardial fluid, indicating chylopericardium. The boy also underwent debridement and joint irrigation of the left ankle, which turned out to be osteomyelitis. Although CVC tips in most reported CVC-related CTs have been commonly located in the right atrium, our case featured a tip located in the inferior vena cava. Additionally, chylopericardium was likely due to the extravasation of total parenteral nutrition fluid, rather than the usual causes, such as recent thoracic surgery. Understanding the mechanisms behind chylopericardium associated with CVCs and timely pericardiocentesis is crucial for improving the outcomes.

Abstract The COHORT trial was conducted to compare the efficacy of androgen deprivation therapy (ADT) alone versus combined with radiation therapy (ADT + RT) for clinically node-positive prostate cancer. We reported adverse events and quality of life between the two treatment groups. Fifty-nine patients were randomized to receive ADT alone or ADT + RT and analyzed as per-protocol. Patients allocated to the ADT alone arm received ADT for at least 2 years. Patients in the ADT + RT arm received additional pelvic RT. Higher rates of grade ≥ 2 acute genitourinary (0% vs. 7.1%) and late gastrointestinal adverse events (0% vs. 14.3%) were reported in the ADT + RT arm compared with the ADT alone. However, grade ≥ 2 late genitourinary toxicity was more common in the ADT alone than the ADT + RT arm (9.7% vs. 3.6%). No grade ≥ 3 adverse events were reported. There was no statistically significant difference in EPIC scores between two treatment arms. However, the urinary and bowel domains tended to decrease and recover in the ADT + RT arm. In conclusion, ADT + RT demonstrated higher rates of adverse events compared to ADT alone. However, the addition of RT did not significantly impact the quality of life.

Abstract In order to ensure prolonged pharmacokinetic profile along with local tolerability at the injection site, tricaprylin‐based drug crystalline suspension (TS) was designed and its local distribution, pharmacokinetics, and inflammatory response, were evaluated with conventional aqueous suspension (AS). As model drug particles, entecavir 3‐palmitate (EV‐P), an ester lipidic prodrug for entecavir (EV), was employed. The EV‐P‐loaded TS was prepared by ultra‐sonication method. Prepared TS and conventional AS exhibited comparable morphology (rod or rectangular), median diameter (2.7 and 2.6 μm), crystallinity (melting point of 160–165°C), and in vitro dissolution profile. However, in vivo performances of drug microparticles were markedly different, depending on delivery vehicle. At AS‐injected site, drug aggregates of up to 500 μm were formed upon intramuscular injection, and were surrounded with inflammatory cells and fibroblastic bands. In contrast, no distinct particle aggregation and adjacent granulation was observed at TS‐injected site, with >4 weeks remaining of the oily vehicle in micro‐computed tomographic observation. Surprisingly, TS exhibited markedly alleviated local inflammation compared to AS, endowing markedly lessened necrosis, fibrosis thickness, inflammatory area, and macrophage infiltration. The higher initial systemic exposure was observed with TS compared to AS, but TS provided prolonged delivery of EV for 3 weeks. Therefore, we suggest that the novel TS system can be a promising tool in designing parenteral long‐acting delivery, with improved local tolerability.

Mitochondria are essential organelles for cell survival that manage the cellular energy supply by producing ATP. Mitochondrial dysfunction is associated with various human diseases, including metabolic syndromes, aging, and neurodegenerative diseases. Among the diseases related to mitochondrial dysfunction, Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic neuronal loss and neuroinflammation. Recently, it was reported that mitochondrial transfer between cells occurred naturally and that exogenous mitochondrial transplantation was beneficial for treating mitochondrial dysfunction. The current study aimed to investigate the therapeutic effect of mitochondrial transfer on PD in vitro and in vivo. The results showed that PN-101 mitochondria isolated from human mesenchymal stem cells exhibited a neuroprotective effect against 1-methyl-4-phenylpyridinium, 6-hydroxydopamine and rotenone in dopaminergic cells and ameliorated dopaminergic neuronal loss in the brains of C57BL/6J mice injected 30 ​mg/kg of methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally. In addition, PN-101 exhibited anti-inflammatory effects by reducing the expression of pro-inflammatory cytokines in microglial cells and suppressing microglial activation in the striatum. Furthermore, intravenous mitochondrial treatment was associated with behavioral improvements during the pole test and rotarod test in the MPTP-induced PD mice. These dual effects of neuroprotection and anti-neuroinflammation support the potential for mitochondrial transplantation as a novel therapeutic strategy for PD.

Abstract Background We aimed to identify the ideal chest compression site for cardiopulmonary resuscitation (CPR) in patients with a single ventricle with dextrocardia corrected by Fontan surgery. Methods The most recent stored chest computed tomography images of all patients with a single ventricle who underwent Fontan surgery were retrospectively analysed. We reported that the ideal chest compression site is the largest part of the compressed single ventricle. To identify the ideal chest compression site, we measured the distance from the midline of the sternum to the point of the maximum sagittal area of the single ventricle as a deviation and calculated the area fraction of the compressed structures. Results 58 patients (67.2% male) were analysed. The mean right deviation from the midline of the sternum to the ideal compression site was similar to the mean sternum width (32.85 ± 15.61 vs. 31.05 ± 6.75 mm). When chest compression was performed at the ideal site, the area fraction of the single ventricle significantly increased by 7%, which was greater than that of conventional compression (0.15 ± 0.10 vs. 0.22 ± 0.11, P

Purpose This study was performed to identify risk factors associated with post-tonsillectomy hemorrhage (PTH)-related hospitalization in pediatric patients visiting an emergency department (ED). Methods We retrospectively reviewed the medical records of patients who underwent tonsillectomy at a single children’s hospital ED from January 2009 through December 2020. Data were collected on patient demographics, chief complaints, surgical methods, postoperative days, initial vital signs, and laboratory findings. The study population was divided into hospitalized and discharged groups. Results Among a total of 2,716 patients reviewed, 67 met the inclusion criteria. The hospitalized group showed a lower median systolic blood pressure (108.0 [interquartile range, 82.0-134.0] vs. 118.5 [89.8-147.2] mmHg; P = 0.021) and a faster median respiratory rate (23.0 [18.0-28.0] vs. 20.0 [17.0-23.0] breaths/minute; P = 0.019), compared with the discharged group. Multivariable logistic regression identified systolic blood pressure under 100 mmHg (odds ratio, 5.21; 95% confidence interval, 1.17-37.60) and respiratory rate over 24 breaths/minute (7.31; 1.07-145.79) as the factors associated with PTH-related hospitalization. Conclusion When pediatric patients visit EDs for PTH, close monitoring or hospitalization may be needed in those with low systolic blood pressure or rapid respiratory rate.

AbstractJeju-Joritdae (Sasa quelpaertensis Nakai) is a broad-leaved bamboo grass endemic to Mount Halla, Jeju Island, South Korea. In this study, we report the complete chloroplast genome sequence of S. quelpaertensis. Its chloroplast genome is 139,730 bp in size and consists of a large single-copy (LSC, 83,351 bp) region, one small single-copy (SSC, 12,788 bp) region, and two inverted repeats (IRs, 21,796 bp each). The chloroplast genome of S. quelpaertensis encodes 131 genes, including 86 protein-coding, 37 tRNA, and 8 rRNA genes. The overall GC content of the S. quelpaertensis chloroplast genome is 38.86%. Phylogenetic analysis using the chloroplast genome sequence showed that S. quelpaertensis is closely related to Sasa veitchii and Sasella kogasensis. These findings provide valuable genomic resources for future studies of the Sasa genus in South Korea and other countries encompassing its distribution area.

Abstract Topological phase transitions, influenced by magnetic fields, dopants, pressure, and temperature, create Berry curvature in band structures, challenging to detect due to resolution and scattering issues in spectroscopy and transport. Here, we propose nonlinear electrical transport phenomena as fingerprints of a topological phase transition in ZrTe5 under magnetic fields. Both a nonlinear longitudinal conductivity Δσ L in a magnetic-field-aligned electric field and a third-order nonlinear Hall (transverse) conductivity Δσ xy in a magnetic-field-perpendicular electric field arise below a characteristic temperature T *. The sensitivity of nonlinear transport to the band topology allows the detection of a subtle change in the band topology hidden in linear transport coefficients. Extending the previous scaling theory between linear transport coefficients (σ xx and σ xy ), we also propose scaling relations for both linear (σ xx and σ xy ) and nonlinear (Δσ L and Δσ xy ) transport coefficients. These scaling relations will help understand the interplay between the mechanisms of nonlinear transport coefficients and the influence of Berry curvature.

Cancer is well recognized as a leading cause of mortality. Although surgery tends to be the primary treatment option for many solid cancers, cancer surgery is still a risk factor for metastatic diseases and recurrence. For this reason, a variety of medications has been adopted for the postsurgical care of patients with cancer. However, conventional medicines have shown major challenges such as drug resistance, a high level of drug toxicity, and different drug responses, due to tumor heterogeneity. Nanotechnology-based therapeutic formulations could effectively overcome the challenges faced by conventional treatment methods. In particular, the combined use of nanomedicine with natural phytochemicals can enhance tumor targeting and increase the efficacy of anticancer agents with better solubility and bioavailability and reduced side effects. However, there is limited evidence in relation to the application of phytochemicals in cancer treatment, particularly focusing on nanotechnology. Therefore, in this review, first, we introduce the drug carriers used in advanced nanotechnology and their strengths and limitations. Second, we provide an update on well-studied nanotechnology-based anticancer therapies related to the carcinogenesis process, including signaling pathways related to transforming growth factor-β (TGF-β), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K), Wnt, poly(ADP-ribose) polymerase (PARP), Notch, and Hedgehog (HH). Third, we introduce approved nanomedicines currently available for anticancer therapy. Fourth, we discuss the potential roles of natural phytochemicals as anticancer drugs. Fifth, we also discuss the synergistic effect of nanocarriers and phytochemicals in anticancer therapy.

Laundry detergent pod (LDP) exposure has been reported to be fatal in children younger than 2 years, leading to respiratory or central nervous system depression. While gastrointestinal irritation is the most common symptom, there are reported cases of severe acidosis with respiratory depression or pneumonia, resulting in mortality. To our best knowledge, there is no report on a case of LDP exposure presenting with acute respiratory distress syndrome requiring extracorporeal membrane oxygenation support. Here, we present a case of a child with severe acute respiratory distress syndrome following LDP exposure, who was successfully treated with veno-pulmonary extracorporeal membrane oxygenation and steroids.

Abstract Background Abdominal pain, which is a common cause of children presenting to the paediatric emergency department (PED), is often evaluated by ultrasonography (US). However, uncertainty in US reports may necessitate additional imaging. Objective In this study, we evaluated factors contributing to uncertainty in paediatric abdominal US reports in the PED. Materials and methods This retrospective cohort study included children younger than 18 years of age who underwent abdominal US in the PED of the study hospital between January 2017 and December 2019. After exclusion, the researchers manually reviewed and classified all US reports as ‘certain’ or ‘uncertain’. Univariate and multivariate logistic regression analyses were performed to identify the factors contributing to uncertain reports. Results In total, 1006 patients were included in the final analysis., 796 patients were tagged as having certain reports, and 210 as having uncertain reports. Children with uncertain reports had a significantly higher rate of undergoing an additional computed tomography (CT) scan (31.0% vs. 2.5%, p

We investigated the magnetocaloric and electrical transport properties of the Eu8CuNi2.5Si42.5 clathrate compound, synthesized by an arc melting and annealing method. X-ray photoemission spectroscopy revealed a mixed valence state of Eu2+ and Eu3+. The low-field and low-temperature magnetic measurements indicated a multiple magnetic transition, from ferromagnetic near 35 K to antiferromagnetic at 25 K. Increasing the magnetic field led to the broadening of antiferromagnetic peaks and a final ferromagnetic state under high magnetic fields, indicative of spin reorientation. The transition from a ferromagnetic to an antiferromagnetic state was further corroborated by specific heat measurements. We noted spontaneous magnetization at low temperatures via magnetic hysteresis and Arrott plot analysis. The coexistence of an antiferromagnetic ground state (attributed to the Eu2+ ions) and ferromagnetic clusters (associated with the Ni2+ ions) was supported by spontaneous magnetization at low temperatures in the antiferromagnetic state. The magnetocaloric analyses revealed a high spin entropy change over a broad temperature range for Eu8CuNi2.5Si42.5, which implies its potential as a robust low-temperature magnetocaloric material, distinguished by its high refrigerant capacity.

This study reports the synthesis of type-I Ba8CuNi2.5Ga10Si33.5 clathrate as a single crystal by the flux method and physical properties investigations such as structural, chemical, magnetic, and thermal properties. Structural refinements indicate Ba atoms are situated at 2a and 6d positions with mixed occupancy across framework sites. Raman spectroscopy assessed host-guest interactions, while the compound's morphology and composition were investigated by the scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS) analyses. Magnetic properties revealed ferromagnetic interactions characterized by a positive Weiss constant and weak ferromagnetic hysteresis. The compound's metallic nature is evidenced by increased resistivity with temperature. The Sommerfeld coefficient, estimated at 12.59 mJ mol−1 K−2 from heat capacity data, alongside a pronounced peak around 15 K in the Cp/T3 vs T plot, suggests an Einstein contribution in heat capacity.

The present study aimed to investigate the effect of 6-shogaol (6S) treatment on brain senescence. Mice were naturally aged until 25-month-old and treated with 10 mg/kg of 6S for a month. Behavioral tests were performed to measure locomotion and cognitive function. Neuronal damage, synaptic plasticity, neuroinflammation, neurogenesis and p75 neurotrophin receptor (p75NTR) expression were examined by immunohistochemistry or immunofluorescence. 6S treatment improved locomotion during open field test in the aged mice and spontaneous alternation in Y-maze. These data are in line with that 6S administration improved dopaminergic neuronal loss and dopamine signaling and attenuated hippocampal synaptic plasticity in the aged brain. Additionally, 6S treatment reduced striatal and hippocampal microgliosis and astrocytosis but promoted neurogenesis in subventricular zone. Furthermore, 6S treatment reversed the p75NTR expression in the senescent brain. The current findings suggest that 6S can be a functional food for successful aging through brain rejuvenation at the molecular level.

Purpose: To quantify interobserver variation (IOV) in target volume and organs-at-risk (OAR) contouring across 31 institutions in breast cancer cases and to explore the clinical utility of deep learning (DL)-based auto-contouring in reducing potential IOV. Methods and materials: In phase 1, two breast cancer cases were randomly selected and distributed to multiple institutions for contouring six clinical target volumes (CTVs) and eight OAR. In Phase 2, auto-contour sets were generated using a previously published DL Breast segmentation model and were made available for all participants. The difference in IOV of submitted contours in phases 1 and 2 was investigated quantitatively using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). The qualitative analysis involved using contour heat maps to visualize the extent and location of these variations and the required modification. Results: Over 800 pairwise comparisons were analysed for each structure in each case. Quantitative phase 2 metrics showed significant improvement in the mean DSC (from 0.69 to 0.77) and HD (from 34.9 to 17.9 mm). Quantitative analysis showed increased interobserver agreement in phase 2, specifically for CTV structures (5–19 %), leading to fewer manual adjustments. Underlying IOV differences causes were reported using a questionnaire and hierarchical clustering analysis based on the volume of CTVs. Conclusion: DL-based auto-contours improved the contour agreement for OARs and CTVs significantly, both qualitatively and quantitatively, suggesting its potential role in minimizing radiation therapy protocol deviation.

Abstract Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

With the age of exposure to illegal substances decreasing and abuse of drugs such as methamphetamine increasing, substance abuse is no longer limited to adults. We report a Korean case of a 17-year-old girl with acute methamphetamine poisoning. The girl visited the emergency department for vomiting and loss of consciousness, with needle marks found on both arms. QT prolongation was confirmed on the initial electrocardiogram, so that we suspected drug addiction and proceeded with toxicologic tests. A lethal dose of methamphetamine was confirmed. We discontinued QT prolonging drugs, and closely monitored the girl in the pediatric emergency intensive care unit until the QT prolongation was resolved. This case highlights the recognition of pediatric methamphetamine poisoning in emergency departments.

Abstract Background The Korean Radiation Oncology Group (KROG) 19 − 09 prospective cohort study aims to determine the effect of regional nodal irradiation on regional recurrence rates in ypN0 breast cancer patients. Dosimetric variations between radiotherapy (RT) plans of participating institutions may affect the clinical outcome of the study. We performed this study to assess inter-institutional dosimetric variations by dummy run. Methods Twelve participating institutions created RT plans for four clinical scenarios using computed tomography images of two dummy cases. Based on a reference structure set, we analyzed dose-volume histograms after collecting the RT plans. Results We found variations in dose distribution between institutions, especially in the regional nodal areas. Whole breast and regional nodal irradiation (WBI + RNI) plans had lower inter-institutional agreement and similarity for 95% isodose lines than WBI plans. Fleiss’s kappa values, which were used to measure inter-institutional agreement for the 95% isodose lines, were 0.830 and 0.767 for the large and medium breast WBI plans, respectively, and 0.731 and 0.679 for the large and medium breast WBI + RNI plans, respectively. There were outliers in minimum dose delivered to 95% of the structure (D95%) of axillary level 1 among WBI plans and in D95% of the interpectoral region and axillary level 4 among WBI + RNI plans. Conclusion We found inter-institutional and inter-case variations in radiation dose delivered to target volumes and organs at risk. As KROG 19 − 09 is a prospective cohort study, we accepted the dosimetric variation among the different institutions. Actual patient RT plan data should be collected to achieve reliable KROG 19 − 09 study results.

IntroductionParkinson’s disease (PD) is a representative neurodegenerative disease, and its diagnosis relies on the evaluation of clinical manifestations or brain neuroimaging in the absence of a crucial noninvasive biomarker. Here, we used non-targeted metabolomics profiling to identify metabolic alterations in the colon and plasma samples of Proteus mirabilis (P. mirabilis)-treated mice, which is a possible animal model for investigating the microbiota-gut-brain axis.MethodsWe performed gas chromatography–mass spectrometry to analyze the samples and detected metabolites that could reflect P. mirabilis-induced disease progression and pathology.Results and discussionPattern, correlation and pathway enrichment analyses showed significant alterations in sugar metabolism such as galactose metabolism and fructose and mannose metabolism, which are closely associated with energy metabolism and lipid metabolism. This study indicates possible metabolic factors for P. mirabilis-induced pathological progression and provides evidence of metabolic alterations associated with P. mirabilis-mediated pathology of brain neurodegeneration.

Background/Aims: Flagellin, which is abundant in gram-negative bacteria, including Pseudomonas, is reported to influence on inflammatory responses in various lung diseases. However, its effect on airway epithelial cells in contribution to asthma pathogenesis is not elucidated yet. We aimed to investigate the effect of TLR5 ligand flagellin on the transcriptomic profile of primary human epithelial cells and to determine the markers of airway inflammation. Methods: Normal human bronchial epithelial (NHBE) cells were grown and differentiated in air-liquid interface (ALI) culture for 14–16 days. The cells were treated with flagellin in vitro at 10 and 100 ng/ml for 3 and 24 h. The conditioned media and cells were harvested to validate inflammatory markers involved in airway inflammation using ELISA, Western blot, and quantitative PCR methods. RNA-sequencing was performed to investigate the transcriptional response to flagellin in ALI-NHBE cells. Results: Altered transcriptional responses to flagellin in differentiated bronchial epithelial cells were determined, including genes encoding chemokines, matrix metalloproteinases, and antimicrobial biomolecules. Pathway analysis of the transcriptionally responsive genes revealed enrichment of signaling pathways. Flagellin induced the mRNA expressions of proinflammatory cytokines and chemokines, and secretion of GM-CSF, CXCL5, CCL5 and CXCL10. Flagellin enhanced the protein expression of MMP-13 in TGF-β1 and TGF-β2 pretreated cell lysates and Wnt/β-catenin signaling. Conclusions: These findings suggest that flagellin could be a potent inducer of inflammatory markers that may contribute to airway inflammation and remodeling.

Thin-film high-entropy alloy (HEA) superconductors have recently attracted a lot of attention, but their critical current density and potential usefulness in engineering applications has remained unclear. Here, the authors fabricate HEA films with remarkably high critical current density and resistance to radiation damage.

Objective: The effectiveness of adjuvant treatments for resected gallbladder carcinoma (GBC) has remained unclear due to lack of randomized controlled trials; thus, the aim of present study was to evaluate the role of adjuvant treatments, including chemoradiotherapy (CRT) and/or chemotherapy (CTx), in patients with resected GBC. Methods: A total of 733 GBC patients who received curative-intent surgical resection were identified in a multi-institutional database. Of 733 patients, 372 (50.8%) did not receive adjuvant treatment, whereas 215 (29.3%) and 146 (19.9%) received adjuvant CTx and CRT, respectively. The locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), and overall survival (OS) of the adjuvant treatment groups were compared according to tumor stage (stage II vs. stage III–IV). Results: In stage II disease (n = 381), the 5-year LRFS, RFS, and OS were not significantly different among the no-adjuvant therapy, CTx, and CRT groups, and positive resection margin, presence of perineural invasion, and Nx classification were consistently associated with worse LRFS, RFS, and OS in the multivariate analysis (P < 0.05). For stage III–IV (n = 352), the CRT group had significantly higher 5-year LRFS, RFS, and OS than the no-adjuvant therapy and CTx groups (67.8%, 45.2%, and 56.9%; 37.9%, 28.8%, and 35.4%; and 45.0%, 30.0%, and 45.7%, respectively) (P < 0.05). Conclusions: CRT has value as adjuvant treatment for resected GBC with stage III–IV disease. Further study is needed for stage II disease with high-risk features.

The lawn grass Zoysia japonica is widely cultivated for its ornamental and recreational value. However, its green period is subject to shortening, which significantly decreases the economic value of Z. japonica, especially for large cultivations. Leaf senescence is a crucial biological and developmental process that significantly influences the lifespan of plants. Moreover, manipulation of this process can improve the economic value of Z. japonica by extending its greening period. In this study, we conducted a comparative transcriptomic analysis using high-throughput RNA sequencing (RNA-seq) to investigate early senescence responses triggered by age, dark, and salt. Gene set enrichment analysis results indicated that while distinct biological processes were involved in each type of senescence response, common processes were also enriched across all senescence responses. The identification and validation of differentially expressed genes (DEGs) via RNA-seq and quantitative real-time PCR provided up- and down-regulated senescence markers for each senescence and putative senescence regulators that trigger common senescence pathways. Our findings revealed that the NAC, WRKY, bHLH, and ARF transcription factor (TF) groups are major senescence-associated TF families that may be required for the transcriptional regulation of DEGs during leaf senescence. In addition, we experimentally validated the senescence regulatory function of seven TFs including ZjNAP, ZjWRKY75, ZjARF2, ZjNAC1, ZjNAC083, ZjARF1, and ZjPIL5 using a protoplast-based senescence assay. This study provides new insight into the molecular mechanisms underlying Z. japonica leaf senescence and identifies potential genetic resources for enhancing its economic value by prolonging its green period.

Clear cell hidradenoma (CCH) is a rare tumor of the sweat glands of eccrine or apocrine differentiation. It can occur anywhere in the body, but common sites of involvement are the head, face, trunk, and extremities. Although several reports have described sonographic findings of CCH, only one study on the axilla mentioned its strain elastographic findings. Here, we present a case of CCH in the right calf with its sonographic and strain elastographic findings in a tumor that looked like an epidermoid tumor.

Abstract Parkinson’s disease (PD) is a movement disorder caused by progressive degeneration of the midbrain dopaminergic (mDA) neurons in the substantia nigra pars compacta (SNc). Despite intense research efforts over the past decades, the etiology of PD remains largely unknown. Here, we discovered the involvement of trophoblast glycoprotein (Tpbg) in the development of PD-like phenotypes in mice. Tpbg expression was detected in the ventral midbrain during embryonic development and in mDA neurons in adulthood. Genetic ablation of Tpbg resulted in mild degeneration of mDA neurons in aged mice (12–14 months) with behavioral deficits reminiscent of PD symptoms. Through in silico analysis, we predicted potential TPBG-interacting partners whose functions were relevant to PD pathogenesis; this result was substantiated by transcriptomic analysis of the SNc of aged Tpbg knockout mice. These findings suggest that Tpbg is a new candidate gene associated with PD and provide a new insight into PD pathogenesis.

Multiple heteroatom-doped graphene is of great interest for developing an efficient electrocatalyst for oxygen reduction reaction (ORR). To maximize the electrocatalytic performance of doped graphene, the competitive doping mechanism caused by the different atomic sizes of dopants should be developed. Herein, three different heteroatoms (e.g., N, P and B) are competitively introduced into reduced graphene oxide (RGO) using both single- and two-step processes. The total quantity of heteroatoms for ternary RGO synthesized using the two-step process is lower than that when using the single-step process. Higher ORR electrocatalytic activity for the two-step-synthesized RGO compared to the single-step-synthesized RGO can be explained by: (a) a high amount of P atoms; (b) the fact that B doping itself decreases the less electrocatalytic N moieties such as pyrrole and pyridine and increases the high electrocatalytic moieties such as quaternary N; (c) a high amount of B atoms itself within the RGO act as an electrocatalytic active center for O2 adsorption; and (d) a small amount of substitutional B might increase the electrical conductivity of RGO. Our findings provide new insights into the design of heteroatom-doped carbon materials with excellent electrocatalytic performance.

Purpose: Emerging data suggest that higher radiation doses in post-mastectomy radiotherapy may be associated with an increased risk of reconstruction complications. This study aimed to validate previous findings regarding the impact of radiation dose on complications among women with breast cancer using a multi-center dataset. Methods: Fifteen institutions participated, and women with breast cancer who received radiotherapy after either autologous or prosthetic breast reconstruction were included. The primary endpoint was major post-radiation therapy complications requiring re-operation for explantation, flap failure, or bleeding control. Results: In total, 314 patients were included. Radiotherapy was performed using both conventional fractionation and hypofractionation in various schedules. The range of the radiation therapy dose in Equivalent Dose in 2 Gy fractions (EQD2; α/β = 3.5) varied from 43.4 to 71.0 Gy (median dose: 48.6 Gy). Boost radiation therapy was administered to 49 patients. Major post-radiation therapy complications were observed in 24 (7.6%) patients. In multivariate analysis, an increasing EQD2 per Gy (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.26–1.98; p

We previously reported CD63-BCAR4 fusion as a novel oncogene that significantly enhanced cell migration and metastasis in lung cancer. To identify effective inhibitors of metastatic activity induced by BCAR4 fusion, we screened a drug library of 381 FDA-approved compounds. The effect of drugs on cell migration was evaluated by monitoring wound healing. Drugs that decreased the cellular mobility of fusion-overexpressing cells compared with that of control cells were selected as candidates. Library screening revealed that erlotinib, canertinib, and lapatinib demonstrated inhibitory effects on cell migration. Activation of the EGFR signaling pathway was detected after ectopic expression of CD63-BCAR4 in normal bronchial epithelial cells, as observed by the increased phosphorylation of tyrosine residues in the EGFR protein. We also confirmed increased levels of the phosphorylated EGFR protein in resected tumors from mice injected with CD63-BCAR4 overexpressing cells. Tyrosine kinase inhibitors (TKIs) of the EGFR family significantly inhibit the migration of BCAR4 fusion-overexpressing cells and induce apoptosis at high concentrations. Among the EGFR family TKIs, canertinib, a dual EGFR/HER2 inhibitor, showed the best inhibitory effect on the migration and viability of BCAR4 fusion-overexpressing cells. We examined the effect of canertinib in vivo using a mouse xenograft model. Oral administration of canertinib to xenografted mice reduced tumor growth induced by the CD63-BCAR4 fusion gene. In addition, canertinib treatment restored E-cadherin expression and reduced the expression of epithelial–mesenchymal transition regulatory factors such as Slug and Snail. Taken together, these results suggest that EGFR/HER2 inhibitors are potential therapeutic options for BCAR4 fusion-harboring lung cancer patients, even in the absence of EGFR mutations.

Traditional cancer treatments have posed numerous obstacles, including toxicity, multiple drug resistance, and financial cost. On the contrary, bioactive phytochemicals used in complementary alternative medicine have recently increased attention due to their potential to modulate a wide range of molecular mechanisms with a less toxic effect. Therefore, we investigated the potential regulatory mechanisms of andrographolide to treat colorectal cancer (CRC) using a network pharmacology approach. Target genes of andrographolide were retrieved from public databases (PharmMapper, Swiss target prediction, Targetnet, STITCH, and SuperPred), while targets related to CRC were retrieved from disease databases (Genecards and DisGeNet) and expression datasets (GSE32323 and GSE8671) were retrieved from gene expression omnibus (GEO). Protein-protein interaction networks (PPI) were generated using STRING and Cytoscape, and hub genes were identified by topology analysis and MCODE. Annotation of target proteins was performed using Gene Ontology (GO) database DAVID and signaling pathway enrichment analysis using the Kyoto Encyclopedia and Genome Database (KEGG). Survival and molecular docking analysis for the hub genes revealed three genes (PDGFRA, PTGS2, and MMP9) were involved in the overall survival of CRC patients, and the top three genes with the lowest binding energy include PDGFRA, MET, and MAPK1. MET gene upregulation and PDGFRA and PTGS2 gene downregulation are associated with the survival of CRC patients, as revealed by box plots and correlation analysis. In conclusion, this study has provided the first scientific evidence to support the use of andrographolide to inhibit cellular proliferation, migration, and growth, and induce apoptosis by targeting the hub genes (PDGFRA, PTGS2, MMP9, MAPK1, and MET) involved in CRC migration and invasion.

Purpose: This study was aimed to assess the outcome of radiotherapy and determine prognostic factors for survival in breast cancer patients with clinically overt metastasis to the internal mammary lymph node (IMN+). Methods: We retrospectively reviewed the medical records of 193 patients with IMN + breast cancer who received neoadjuvant chemotherapy (NAC), breast surgery without internal mammary lymph node (IMN) dissection, and postoperative radiotherapy at 9 hospitals between 2009 and 2013. Breast-conserving surgery or mastectomy was performed after taxane-based NAC. Radiotherapy was administered to the whole breast/chest wall and regional nodes. IMN-covering radiotherapy was performed in 92.2% of patients with median dose of 58.4 Gy (range, 44.9–69.1 Gy). The overall survival (OS), disease-free survival (DFS), and IMN failure-free survival (IMNFFS) were analyzed. Results: After median follow-up of 71 months, 9 patients (4.7%) developed IMN failure and simultaneous distant metastasis. The 5-year DFS, OS, and IMNFFS was 68.6%, 81.8%, and 95.3%, respectively. Non-triple-negative breast cancer, Ki-67 ≤ 10%, pathological complete response (CR) in tumor and axillary node, and radiologic CR of IMN after NAC were significant factors for predicting higher DFS; however, IMN radiation dose was not significant determinants for DFS. The 5-year DFS of patients with IMN-dose ≤ 50.0 Gy and those with >50.0 Gy was 86.7% and 76.7%, respectively (p = 0.41). Conclusions: A multimodality strategy including NAC, breast surgery, and IMN-covering radiotherapy was effective for patients with overt IMN + breast cancer. Even without an IMN dissection, most patients were IMN failure-free with an IMN-focusing radiotherapy.

Objectives : Manufacturing－based production facilities are required to install dust collection devices for air pollution prevention facilities. In particular, manufacturing-based companies need low-power hazardous gas treatment devices. However, due to the slowing economic growth, the cost of replacing new hazardous gas treatment devices is increasing, and new products in the form of parts that can be attached to scrubbers that are already installed are urgently needed. Methods : To deal with residual gas from organic and inorganic compounds used in semiconductor manufacturing processes, the concentration of air pollutants emitted through the process of removing harmful substances from the primary scrubber and re-treatment of gases emitted from the secondary scrubber is further lowered. Results and Discussion : In this study, a cooling block device which is a hazardous gas treatment part is developed to solve the limitation of scrubber processing capacity from overcapacity harmful gases such as strong toxicity, corrosivity, combustion, and environmental pollution in semiconductor manufacturing process. Conclusions : In the design factors and performance survey of cooling module using thermoelectric element, it was calculated that the cooling capacity of the peltier thermoelectric element with a margin of 9,300 W was required. Based on these results, the absolute humidity decreased by 5.8 g/kg and the temperature decreased by 9.5 degrees, showing the possibility of solving the problem of the decrease in the effectiveness of hazardous gas treatment of secondary scrubber due to increased moisture.

Background Glucagon-like peptide-1 (GLP-1) analogues regulate glucose homeostasis and have anti-inflammatory properties, but cause gastrointestinal side effects. The fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism that has poor pharmacokinetic properties, including a short half-life. To overcome these limitations, we investigated the effect of a low-dose combination of a GLP-1 analogue and FGF21 on atherosclerosis-related molecular pathways. Methods C57BL/6J mice were fed a high-fat diet for 30 weeks followed by an atherogenic diet for 10 weeks and were divided into four groups: control (saline), liraglutide (0.3 mg/kg/day), FGF21 (5 mg/kg/day), and low-dose combination treatment with liraglutide (0.1 mg/kg/day) and FGF21 (2.5 mg/kg/day) (n=6/group) for 6 weeks. The effects of each treatment on various atherogenesis-related pathways were assessed. Results Liraglutide, FGF21, and their low-dose combination significantly reduced atheromatous plaque in aorta, decreased weight, glucose, and leptin levels, and increased adiponectin levels. The combination treatment upregulated the hepatic uncoupling protein-1 (UCP1) and Akt1 mRNAs compared with controls. Matric mentalloproteinase-9 (MMP-9), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were downregulated and phosphorylated Akt (p-Akt) and phosphorylated extracellular signal-regulated kinase (p-ERK) were upregulated in liver of the liraglutide-alone and combination-treatment groups. The combination therapy also significantly decreased the proliferation of vascular smooth muscle cells. Caspase-3 was increased, whereas MMP-9, ICAM-1, p-Akt, and p-ERK1/2 were downregulated in the liraglutide-alone and combination-treatment groups. Conclusion Administration of a low-dose GLP-1 analogue and FGF21 combination exerts beneficial effects on critical pathways related to atherosclerosis, suggesting the synergism of the two compounds.

In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.

SGLT2 inhibitors, a class of type 2 diabetes medication, reduce cardiovascular events in patients beyond expectation from blood sugar control. Here the authors report a randomized controlled trial showing that SGLT2 inhibitors reduce inflammasome activation in peripheral macrophages, which may contribute to the cardiovascular protection.

A ketogenic diet (KD) is known to have beneficial health effects. Various types of KD interventions have been applied to manage metabolic syndrome based on modification of diet parameters such as duration of intervention, macronutrient components, and total calories. Nevertheless, the beneficial health impact of isocaloric KD is largely unknown, especially in healthy subjects. The present study investigated the acute effects of a 3-day isocaloric KD. In this non-randomized intervention study, we recruited 15 healthy volunteers aged 24-38 years (7 men and 8 women) and placed them on an isocaloric KD restricting intake of carbohydrates but not energy (75% fat, 20% protein, 5% carbohydrate) for 3 days. Biochemical profiles and laboratory measurements were performed. Peripheral blood monocular cells were cultured, and measured cell stimulated cytokines. After short-term isocaloric KD, subjects lost body weight and serum free fatty acid levels were increased. These results accompanied elevated serum β-hydroxybutyrate (BHB) concentration and fibroblast growth factor 21 (FGF21) levels and improved insulin sensitivity. Regarding the direct effect of BHB on inflammasome activation, interleukin-1β (IL-1β) and tumor necrosis factor-α secretion in response to adenosine triphosphate or palmitate stimulation in human macrophages decreased significantly after isocaloric KD. In ex-vivo experiments with macrophages, both FGF21 and BHB further reduced IL-1β secretion compared to either BHB or FGF21 alone. The inhibitory effect of FGF21 on IL-1β secretion was blunted with bafilomycin treatment, which blocked autophagy flux. In conclusion, isocaloric KD for 3 days is a promising approach to improve metabolic and inflammatory status.Clinical Trial Registrationclinicaltrials.gov (NCT02964572).

Leaf senescence is the final stage of leaf development preceding death, which involves a significant cellular metabolic transition from anabolism to catabolism. Several processes during leaf senescence require coordinated regulation by senescence regulatory genes. In this study, we developed a rapid and systematic cellular approach to dissect the functional roles of genes in senescence regulation through their transient expression in Arabidopsis protoplasts. We established and validated this system by monitoring the differential expression of a luciferase-based reporter that was driven by promoters of SEN4 and SAG12, early and late senescence-responsive genes, depending on effectors of known positive and negative senescence regulators. Overexpression of positive senescence regulators, including ORE1, RPK1, and RAV1, increased the expression of both SEN4- and SAG12-LUC while ORE7, a negative senescence regulator decreased their expression. Consistently with overexpression, knockdown of target genes using amiRNAs resulted in opposite SAG12-LUC expression patterns. The timing and patterns of reporter responses induced by senescence regulators provided molecular evidence for their distinct kinetic involvement in leaf senescence regulation. Remarkably, ORE1 and RPK1 are involved in cell death responses, with more prominent and earlier involvement of ORE1 than RPK1. Consistent with the results in protoplasts, further time series of reactive oxygen species (ROS) and cell death assays using different tobacco transient systems reveal that ORE1 causes acute cell death and RPK1 mediates superoxide-dependent intermediate cell death signaling during leaf senescence. Overall, our results indicated that the luciferase-based reporter system in protoplasts is a reliable experimental system that can be effectively used to examine the regulatory roles of Arabidopsis senescence-associated genes.

Abstract Pulmonary pleomorphic carcinoma (PPC) is a rare type of non‐small cell lung cancer (NSCLC) with a more aggressive clinical course and a worse outcome than other types of NSCLC. Pembrolizumab, a monoclonal antibody targeting programmed cell death‐1 (PD‐1), has been approved as the first‐line treatment for advanced NSCLC with robust PD‐L1 expression in at least 50% of tumour cells, without epidermal growth factor receptor gene (EGFR) mutations or anaplastic lymphoma kinase gene (ALK) rearrangement. Here, we report the case of an 81‐year‐old man with multiple comorbidities who was diagnosed with PPC and showed a robust response to pembrolizumab followed by radiation therapy without adverse effects. In the absence of randomized clinical trials for PPCs, our case report demonstrates the potential application of pembrolizumab and radiation therapy for the treatment of PPCs.

Background: The appearance of the scalp and hair is very important aesthetically regardless of age or sex. Although there are many drugs and treatment methods for scalp problems and hair loss, the treatment response is still insufficient. Aims and Objectives: To evaluate the efficacy of low-level light therapy in a helmet-like device. Materials and Methods: This study was designed as a 24-week trial with 50 participants. All participants used a helmet-shaped device emitting 630–690, 820–880, and 910–970 nm light wavelengths, for 20 minutes, daily for 24 weeks. A phototrichogram for hair density and thickness, Global Aesthetic Improvement Scale score, erythema index, and sebum secretions of the scalp were evaluated at baseline and at 12 and 24 weeks. Results: After 24 weeks of treatment, hair density and hair thickness were found to have significantly increased (P

N6-adenosine methylation (m6A) is a prevalent form of RNA modification found in the expressed transcripts of many eukaryotic organisms. Moreover, m6A methylation is a dynamic and reversible process that requires the functioning of various proteins and their complexes that are evolutionarily conserved between species and include methylases, demethylases, and m6A-binding proteins. Over the past decade, the m6A methylation process in plants has been extensively studied and the understanding thereof has drastically increased, although the regulatory function of some components relies on information derived from animal systems. Notably, m6A has been found to be involved in a variety of factors in RNA processing, such as RNA stability, alternative polyadenylation, and miRNA regulation. The circadian clock in plants is a molecular timekeeping system that regulates the daily and rhythmic activity of many cellular and physiological processes in response to environmental changes such as the day-night cycle. The circadian clock regulates the rhythmic expression of genes through post-transcriptional regulation of mRNA. Recently, m6A methylation has emerged as an additional layer of post-transcriptional regulation that is necessary for the proper functioning of the plant circadian clock. In this review, we have compiled and summarized recent insights into the molecular mechanisms behind m6A modification and its various roles in the regulation of RNA. We discuss the potential role of m6A modification in regulating the plant circadian clock and outline potential future directions for the study of mRNA methylation in plants. A deeper understanding of the mechanism of m6A RNA regulation and its role in plant circadian clocks will contribute to a greater understanding of the plant circadian clock.

Introduction: We sought to determine whether the delta neutrophil index (DNI), a marker that is reported to be used to predict the diagnosis, prognosis, and disease severity of bacteremia and sepsis, is useful in differentiating bacterial infection without bacteremia (BIWB) from viral infections (VI) in pediatric febrile patients in the emergency department (ED). Method: We conducted a retrospective analysis of febrile patients’ medical records from the pediatric ED of the teaching hospital. The patients with BIWB and those with VI were identified with a review of medical records. The primary outcome was the diagnostic performance of DNI in differentiating BIWB from VI. The secondary outcome was a comparison of the diagnostic performances of DNI, CRP, WBC, and neutrophil count between the two groups. Results: A total of 151 (26.3%) patients were in the BIWB group, and 423 (73.7%) were in the VI group. There was no significant difference in DNI between the two groups (3.51 ± 6.90 vs. 3.07 ± 5.82, mean ± SD, BIWB vs. VI). However, CRP levels were significantly higher in the BIWB group than in the VI group (4.56 ± 5.45 vs. 1.39 ± 2.12, mean ± SD, BIWB vs. VI, p < 0.05). The AUROCs of DNI, WBC count, neutrophil levels, RDW, and CRP levels were 0.5016, 0.5531, 0.5631, 0.5131, and 0.7389, respectively, and only CRP levels were helpful in differentiating BIWB from VI. Conclusion: In the absence of bacteremia, DNI would not be helpful in differentiating BIWB from VI in pediatric febrile patients.

Neuroinflammation causes various neurological disorders, including depression and neurodegenerative diseases. Therefore, regulation of neuroinflammation is a promising therapeutic strategy for inflammation-related neurological disorders. This study aimed to investigate whether yomogin, isolated from Artemisia iwayomogi, has anti-neuroinflammatory effects. First, we evaluated the effects of yomogin by assessing pro-inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. The results showed that yomogin inhibited the increase in neuroinflammatory factors, including nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, interleukin-6, and tumor necrosis factor-α, and suppressed phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase and p38, which participate in the mitogen-activated protein kinase (MAPK) pathway. To confirm these effects in vivo, we measured the activation of astrocyte and microglia in LPS-injected mouse brains. Results showed that yomogin treatment decreased astrocyte and microglia activations. Collectively, these results suggest that yomogin suppresses neuroinflammation by regulating the MAPK pathway and it could be a potential candidate for inflammation-mediated neurological diseases.

Objectives: To assess the clinical outcomes of prostate cancer patients treated with salvage radiotherapy (SRT) for locoregional clinical recurrence (CR) after radical prostatectomy (RP). Methods: Records of 60 patients with macroscopic locoregional recurrence after prostatectomy and referrals for SRT were retrospectively investigated in the multi-institutional database. The median radiation dose was 70.2 Gy. Biochemical failure was defined as the prostate-specific antigen (PSA) ≥ nadir + 2 or initiation of androgen deprivation therapy (ADT) for increased PSA. Results: Median recurrent tumor size was 1.1 cm and pre-radiotherapy PSA level was 0.4 ng/ml. At a median follow-up of 83.1-month after SRT, 7-year biochemical failure-free survival (BCFFS), locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), and overall survival (OS) were 67.0%, 89.7%, 83.6%, and 91.2%, respectively. Higher Gleason's scores were associated with unfavorable BCFFS, DMFS, and OS. Pre-SRT PSA ≥0.5 ng/ml predicted worse BCFFS, LRFFS, and DMFS. In multivariate analyses, a Gleason's score of 8 to 10 was associated with decreased BCFFS (hazard ratio [HR] 3.12, 95% confidence interval [CI] 1.11-8.74, P = .031) and OS (HR 17.72, 95% CI 1.75-179.64, P = .015), and combined ADT decreased the risks of distant metastasis (HR 0.18, 95% CI 0.04-0.92, P = .039). Two patients (3.3%) experienced late grade 3 urinary toxicity. Conclusions: SRT for locoregional CR after RP achieved favorable outcomes with acceptable long-term toxicities. Higher Gleason's scores and pre-radiotherapy PSA level were unfavorable prognostic variables. Combined ADT may decrease the risks of metastases.

Purpose: We conducted this study to investigate the prognosis and failure pattern after breast-conserving treatment (BCT) in patients with occult breast cancer (OBC) with negative breast magnetic resonance imaging (MRI) (MRI-OBC). Materials and methods: Survival rates and failure patterns in 66 patients who received axillary lymph node dissection (ALND) and BCT for MRI-OBC between 2001 and 2013 at seven hospitals were analyzed. OBC was defined as adenocarcinoma in the axillary lymph node (ALN) +/− supraclavicular (SCN) or internal mammary lymph node (IMN) with a negative breast MRI. Results: Fifty-four patients had only ALN metastasis (ALN only), and 12 patients had ALN metastasis along with SCN or IMN metastasis (ALN + SCN/IMN). Median follow-up was 82 months. The 5-year overall, disease-free, and breast cancer-free survival rates were 93.4%, 92.1%, and 96.8%, respectively. Nine patients experienced recurrence: breast (n = 4), regional lymph nodes (RLN, n = 1), distant metastases (DM, n = 2), breast/RLN (n = 1), and breast/RLN/DM (n = 1). Five-year disease-free survival was significantly higher in ALN only patients compared to ALN + SCN/IMN patients (96.1% vs. 75.0%; p = 0.02). Conclusions: Patients with MRI-OBC were successfully treated with BCT. There was a small risk of ipsilateral breast cancer recurrence. Failure patterns depended on the extent of initial disease.