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Aim: This study aimed to identify the optimal toothpaste for removing coffee-induced stains while also evaluating its impact on tooth enamel through roughness and abraded depth parameters, providing a comprehensive understanding of their effects. Materials and methods: Three whitening toothpastes and 2 conventional toothpastes were prepared for a simulated brushing procedure on coffee-stained bovine enamel tooth specimens. Using a toothbrushing machine, up to 10,000 brushstrokes were completed, while spectrophotometric readings were taken at designated intervals. A mixed-effects model for statistical analysis determined the effects of toothpaste and brushing on colour change, roughness, and abraded depth. Results: Whitening toothpastes significantly deviated from the control (P < .001, P < .001, and P < .003, respectively), whereas the conventional toothpaste did not exhibit a significant contrast (P < .081). Regarding colour restoration following coffee staining, whitening toothpastes showed higher restoration than conventional toothpastes. Surface roughness and abraded depth parameters increased with accumulated brushing. Conclusions: Sodium hexametaphosphate-containing toothpaste demonstrated the highest efficacy in removing coffee-induced stains and restoring tooth colour. Nevertheless, this stronger whitening effect was associated with increased abrasion. While conventional toothpastes exhibited some whitening effects, the most substantial improvement in lightness was consistently observed with whitening toothpastes. Clinical Relevance: Understanding how whitening toothpaste affects enamel integrity is crucial for refining formulations and advancing dental care. This knowledge lays the groundwork for more effective oral care products and improved whitening procedures, ultimately enhancing the overall quality of dental treatments.

Given that the skin is the largest tissue in the human body, performing external barrier functions with innate and adaptive immunity and undergoing substantial changes during aging, it is under investigation as a major target of various bioactive molecules. In the present study, we examined the biological activity of the senolytic piperlongumine by analyzing alterations in mRNA expression of notable skin genes using transformed aneuploid immortal epidermal keratinocytes, HaCaT cells. We observed that piperlongumine increased the mRNA expression of genes playing critical roles in skin barrier function. In addition, piperlongumine increased expression enzymes involved in the synthesis of ceramide, a major component of intercellular lipids. Furthermore, we measured the protein levels of various cytokines secreted by epidermal keratinocytes and found changes in the release of GRO-αβγ, CCL5, and MCP1. Additionally, we observed that piperlongumine treatment modulated the expression of keratinocyte-specific aging markers and influenced telomerase activity. Based on these findings, piperlongumine could regulate the physiological activity of epidermal keratinocytes to induce beneficial effects in human skin by regulating important skin-related genes.

ABSTRACTCa2+ is a key secondary messenger that determines sperm motility patterns. Mammalian sperm undergo capacitation, a process to acquire fertilizing ability, in the female reproductive tract. Capacitated sperm change their flagellar waveform to develop hyperactivated motility, which is crucial for successful sperm navigation to the eggs and fertilization. The sperm-specific channel, CATSPER, and an ATPase transporter, PMCA4, serve as major paths for Ca2+ influx and efflux, respectively, in sperm. The ionic paths coordinate Ca2+ homeostasis in the sperm, and their loss-of-function impairs sperm motility, to cause male infertility. In this review, we summarize the physiological significance of these two Ca2+ gates and suggest their potential applications in novel male contraceptives.

SUMMARY: Purpose: Just culture refers to a culture that encourages members of an organization to exchange important safety information and compensates them when they perform such information exchanges. The establishment of a just culture in hospital organizations might be an important means of enhancing patient safety incident reporting. This study aimed to investigate the impact of just culture on the attitudes and behaviors toward patient safety incident reporting in perioperative nurses. Methods: A nationwide cross-sectional survey was performed using structured questionnaires. The participants were 208 perioperative nurses in tertiary general hospitals in South Korea. Data were collected by self-reported on-line questionnaires, from August to September 2020. Data were analyzed with descriptive statistics, independent t-test, chi-square test, Fisher's exact test, one-way ANOVA, Scheffé test, Pearson's correlation analysis, Spearman rank correlation analysis, hierarchical multiple regression, and hierarchical logistic regression using the SPSS WIN 23.0 program. Results: Hierarchical multiple regression analysis revealed that just culture explained an additional 34.5%p of the attitudes on patient safety incident reporting. Hierarchical logistic regression analysis showed that just culture was a significant predictor of behaviors regarding patient safety incident reporting (odds ratio = 2.25, p = .017). The final regression model accounted for 16.0% of the behaviors regarding patient safety incident reporting. Conclusion: This study empirically shows that just culture impacted the attitudes and behaviors regarding patient safety incident reporting in perioperative nurses. This study provides an evidence about the importance of the just culture in every day nursing practice setting. Personnel and organizational efforts for improving or implementing just culture are required to ensure greater patient safety by enhancing the patient safety incident reporting of perioperative nurses in hospitals.

Abstract To investigate disparities in sensitisation to Staphylococcus aureus enterotoxin A/B (SEA/SEB) and olfactory function in patients with chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), those with CRS without nasal polyps (CRSsNP), and healthy controls who underwent septoplasty only. We retrospectively reviewed the medical records of 388 subjects aged ≥ 8 years, collected between January 2021 and June 2023. We analysed patient demographics, medical history, serum IgE levels against staphylococcal enterotoxins (SEs), and serum total IgE levels against inhalant allergens. We performed olfactory and taste function tests in the participants to evaluate the relationship between olfactory function and SEs. Of 388 patients enrolled, 145 were healthy controls, 111 had CRSsNP, and 133 had CRSwNP. The prevalence of SEA/SEB positivity was significantly higher among the patients with CRSwNP than among those in the CRSsNP and healthy controls. The olfactory test results showed significant differences among the groups; anosmia was observed in 9.7% of healthy controls, 22.7% of patients with CRSsNP, and 45.1% of patients with CRSwNP. Olfactory threshold deterioration was evident in patients with CRS. Distinction and identification were more impaired in patients with CRSwNP than in those of the other groups. Finally, the olfactory function scores decreased as the serum levels of SEs increased. Sinusitis patients seem to suffer from perceiving odours, and patients with CRSwNP have difficulty distinguishing odours. Olfactory function test scores decreased in patients with a history of asthma, and as serum levels of staphylococcus enterotoxin and blood eosinophil percentage increase. Furthermore, our result suggests a potential role for SE sensitisation and eosinophil percentage in deteriorating olfaction, especially in patients with CRSwNP.

Abstract Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators in numerous biological processes, including macrophage-mediated inflammatory responses, which play a critical role in the progress of diverse diseases. This study focuses on the regulatory function of lncRNA brain and reproductive organ-expressed protein (BRE) antisense RNA 1 (BRE-AS1) in modulating the inflammatory activation of monocytes/macrophages. Employing the THP-1 cell line as a model, we demonstrate that lipopolysaccharide (LPS) treatment significantly upregulates BRE-AS1 expression. Notably, specific knockdown of BRE-AS1 via siRNA transfection enhances LPS-induced expression of interleukin (IL)-6 and IL-1β, while not affecting tumor necrosis factor (TNF)-α levels. This selective augmentation of pro-inflammatory cytokine production coincides with increased phosphorylation of Janus kinase (JAK)2 and signal transducer and activator of transcription (STAT)3. Furthermore, BRE-AS1 suppression results in the downregulation of suppressor of cytokine signaling (SOCS)3, an established inhibitor of the JAK2/STAT3 pathway. Bioinformatics analysis identified binding sites for miR-30b-5p on both BRE-AS1 and SOCS3 mRNA. Intervention with a miR-30b-5p inhibitor and a synthetic RNA fragment that represents the miR-30b-5p binding site on BRE-AS1 attenuates the pro-inflammatory effects of BRE-AS1 knockdown. Conversely, a miR-30b-5p mimic replicated the BRE-AS1 attenuation outcomes. Our findings elucidate the role of lncRNA BRE-AS1 in modulating inflammatory activation in THP-1 cells via the miR-30b-5p/SOCS3/JAK2/STAT3 signaling pathway, proposing that manipulation of macrophage BRE-AS1 activity may offer a novel therapeutic avenue in diseases characterized by macrophage-driven pathogenesis.

Various kinetic parameters of serum CA-125 have been reported to have better correlation with outcomes for patients treated with neoadjuvant chemotherapy (NAC). This study aimed to compare the available kinetic parameters of serum CA-125 in an external cohort of advanced-stage ovarian cancer. Using the cancer registry databases from the Yonsei Cancer Hospital, we retrospectively reviewed 210 patients with advanced-stage ovarian cancer, treated with NAC followed by interval debulking surgery. We compared area under the receiver-operating characteristics curves (AUCs), false negative rate, and negative predictive value (NPV) using 10 different models for optimal cytoreduction and platinum resistance. In addition, we compared incremental AUC for progression-free survival (PFS) and overall survival (OS). No gross residual tumor was observed in 37.0% and residual tumors 0.6 for predicting optimal cytoreduction. After adjusting for age, BMI, disease stage, and histologic subtypes, all models had an AUC >0.70 for predicting platinum resistance. However, no model had a high enough NPV (highest value = 82.0%) to avoid chemotherapy futility. For survival outcomes, no model had an incremental AUC >0.70 for predicting either PFS or OS. None of the proposed serum CA-125 kinetic parameters showed high accuracy in predicting optimal cytoreduction, platinum resistance, or survival in patients receiving NAC. For advanced-stage ovarian cancer treated with NAC, there is a need to discover reliable biomarkers to better stratify patient response groups for optimal treatment decision-making.

Anthracnose crown rot (ACR), caused by Colletotrichum fructicola, is a serious disease of strawberry in Korea. The primary inoculums of ACR were symptomless strawberry plants, plant debris, and other host plants. To effectively control anthracnose in symptomless transplanted strawberries, it is necessary to use diseasefree plants, detect the disease early, and apply a fungicide. Therefore, in 2010 and 2011, we evaluated the efficacy of pre-plant fungicide dips by using strawberry transplants infected by C. fructicola for the control of anthracnose. Dipping plants in prochloraz-Mn for 10 min before planting was most effective for controlling anthracnose in symptomless strawberry plants and resulted in more than 76% control efficacy. Azoxystrobin showed a control efficacy of over 40%, but plants treated with pyraclostrobin, mancozeb and iminoctadine tris showed high disease severity. The control efficacy of the dip treatment with prochloraz-Mn did not differ with temperature and time. Treatment with prochloraz-Mn for more than an hour caused growth suppression in strawberry plants. Therefore, the development of anthracnose can be effectively reduced by dipping strawberry plants for 10 min in prochloraz-Mn before planting.

The frozen elephant trunk (FET) technique can be applied to extensive aortic pathology, including lesions in the aortic arch and proximal descending thoracic aorta. FET is useful for tear-oriented surgery in dissections, managing malperfusion syndrome, and promoting positive aortic remodeling. Despite these benefits, complications such as distal stent-induced new entry and spinal cord ischemia can pose serious problems with the FET technique. To prevent these complications, careful sizing and planning of the FET are crucial. Additionally, since the FET technique involves total arch replacement, meticulous surgical skills are essential, particularly for young surgeons. In this article, we propose several techniques to simplify surgical procedures, which may lead to better outcomes for patients with extensive aortic pathology. In the era of precision medicine, the next-generation FET device could facilitate the treatment of complex aortic diseases through a patient- tailored approach.

Abstract Excessive clotting or abnormal platelet accumulation can lead to serious cardiovascular disorders such as atherosclerosis, stroke, and thrombosis. Therefore, it is imperative to identify compounds capable of controlling or impeding platelet aggregation to prevent the onset of cardiovascular diseases. Arteanoflavone, a compound extracted from Artemisia iwayomogi, has not garnered scientific recognition for its potential health benefits, recent studies have substantiated its anti-inflammatory, antioxidant, and anti-allergic properties. However, the precise mechanisms by which arteanoflavone influences platelet aggregation and blood clot formation have not been conclusively established. This research investigates arteanoflavone’s role in these processes, particularly in platelets induced by collagen. The study reveals a significant increase in the production of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) correlating with the administered dosage of arteanoflavone. Concurrently, a noticeable escalation is observed in substrates of cAMP-dependent kinase and cGMP-dependent kinase, specifically VASP and inositol 1,4,5-trisphosphate receptor (IP3R). Arteanoflavone demonstrates its ability to limit Ca2+ movement in the dense tubular system through IP3R phosphorylation. Moreover, phosphorylated VASP inhibits the binding of fibrinogen to αIIb/β3, thus suppressing platelet activity. Arteanoflavone also stimulates the phosphorylation of PI3K/Akt, a protein linked to platelet granule release, and MAPK (ERK, JNK, and p38) protein, associated with both platelet granule release and TXA2 production. Lastly, arteanoflavone impedes collagen-induced platelet aggregation and blood clot formation by inhibiting fibrin production in thrombin-induced platelets. Hence, it is suggested that arteanoflavone could be valuable as an agent that effectively deters platelet inhibition and blood clot formation through antiplatelet mechanisms.

Edible insects are a promising source of bioactive compounds with diverse health benefits. This study investigated the immunomodulatory properties of polysaccharides isolated from Protaetia brevitarsis seulensis larvae (PBSL). Polysaccharides were fractionated using a molecular weight cutoff membrane, and among these fractions, the higher molecular weight fraction (H-PBSL, 666.84 kDa) demonstrated significant immunomodulatory activity. Methylation and NMR structural analyses revealed H-PBSL to be an acidic heteroglycan with a complex structure, consisting of a backbone of repeating (1→4)-linked α-glucan units highly branched at O-6 positions with T-α-Glcp, T-α-GlcpA, and T-β-Galp. The immunomodulatory effects of H-PBSL were evaluated using RAW264.7 macrophage cells. H-PBSL treatment enhanced phagocytic activity and increased the expression of immune modulators and macrophage activation surface molecules. In addition, H-PBSL activated the NF-κB signaling pathway, evidenced by increased phosphorylation of IκB and NF-κB, and translocation of NF-κB from cytosol to nucleus. Moreover, inhibition of Toll-like receptor 4 (TLR4) reduced H-PBSL-induced nitric oxide synthesis, indicating TLR4′s pivotal role in H-PBSL-mediated macrophage activation. These findings highlight the potential of H-PBSL as a novel immunomodulatory agent derived from an edible insect, with possible applications in functional foods and nutraceuticals.

Bacteria associated with plants play crucial roles in promoting plant growth and health by aiding in nutrient acquisition, including phosphorus. This study presents the isolation and genomic characterization of a potentially new bacterial strain, Lelliottia sp. JS-SCA-14, which exhibits significant plant growth-promoting effects through phosphorus solubilization. A comparative phylogenomic analysis of the complete genome of strain JS-SCA-14 and its closely related strains revealed a unique genomic profile, suggesting it could be a novel species. Genomic identity calculations indicated that JS-SCA-14 significantly deviates from strains belonging to closely related genera, such as Buttiauxella, Citrobacter, Enterobacter, Leclercia, and Lelliottia. A biochemical assay comparing JS-SCA-14 and a closely related strain, Lelliottia jeotgali PFL01T, showed differing patterns in carbon source utilization and enzyme activities. To assess the plant growth-promoting capabilities of strain JS-SCA-14, tests were conducted to evaluate its siderophore-producing and phosphate-solubilizing abilities. Seed germination assays demonstrated an improvement in germination, seedling length, and vigor compared to untreated controls. Notably, the phosphate-dissolving strain JS-SCA-14 led to a significant increase of 34.4% in fresh weight and 35.4% in dry weight of tomato plants compared to the negative control. These findings underscore the significant potential of strain JS-SCA-14 in solubilizing phosphate, thereby enhancing phosphorus availability in the rhizosphere and promoting plant growth and development. This study contributes to our understanding of plant-microbe interactions and suggests the potential application of strain JS-SCA-14 as a bioinoculant for sustainable agriculture and plant nutrient management strategies.

Due to their worldwide distribution and persistence, mercury (Hg), and nano- and microplastics (NMPs) pose major threats to global ocean ecosystems. Hg and NMPs co-exist in the ocean and can interact with each other. However, information on the toxicity of this interaction to marine biota remains limited. Thus, we investigated the toxicological interaction between HgCl2 (Hg) and NMPs by studying the influence of different sizes of polystyrene beads (0.05-, 0.5-, and 6-μm) on Hg accumulation in the brackish water flea Diaphanosoma celebensis. The Hg adsorption capacity of NPs (0.05-μm) was higher than that of MPs (0.5- and 6-μm). Only the group co-exposed to both Hg and NPs showed increased Hg content in D. celebensis. Multixenobiotic resistance (MXR) activity and transcriptional modulation of transporter genes (ABCBs and ABCCs) were decreased by NMP exposure, particularly by NPs, suggesting MXR disruption by NPs. However, only the activity of multidrug resistance-associated proteins (MRPs; ABCCs) increased with Hg exposure and decreased upon NP+Hg co-exposure, indicating an important role of ABCC in Hg efflux. Furthermore, in vivo toxicity tests showed a synergistic toxic interaction between Hg and NPs on the reproduction of D. celebensis. Our findings suggest that NPs have the potential to enhance the toxicity of Hg, increasing Hg accumulation not only by serving Hg as a carrier but also by disrupting MXR.

Histological stains, such as hematoxylin and eosin, tend to fade over time, compromising subsequent analysis accuracy. Traditional methods of restoring stain color in faded samples involve physical re-staining, which is time-consuming and expensive and may damage tissue samples. In addition, digital post-processing techniques, such as color normalization, face limitations when dealing with highly faded slides. To address this, we propose the non-invasive phase-to-color “virtual re-staining” framework. This approach utilizes a trained generative adversarial network with label-free quantitative phase imaging, capturing the intrinsic physiochemical properties of histological samples. It employs multi-channel Fourier ptychographic microscopy to generate pixel-wise paired phase and color images in a high-throughput manner. To streamline data generation, near-infrared illumination is used to mitigate the impact of absorption variations in faded and stained samples, eliminating the need for repetitive data acquisition and potential physical alterations in samples. Our trained network yields comparable or better results to other digitally staining methods, successfully demonstrating the re-staining of approximately decade-old faded slides archived in hospital storage.

Objective The study compared the morphometric changes of the cervical spinal cord using dynamic magnetic resonance imaging (MRI) in patients with cervical spondylotic myelopathy (CSM) and assessed the correlation with kinematic changes, cord cross-sectional area (CSA), and high signal intensity (SI) on T2-weighted imaging (T2WI). Methods Patients with CSM were evaluated through dynamic MRI for sagittal and axial CSA changes of the cervical cord, cerebrospinal fluid (CSF) reserve ratio, degree of cord impingement, cord compression rate, range of motion (ROM), and severity of SI on T2WI. The degree of cord impingement was evaluated using the Muhle grading system. Clinical outcomes were assessed using Japanese Orthopaedic Association scoring and Nurick grade. Results The study included 191 patients (113 males) with a mean age of 55.34 ± 12.09 years. The lowest sagittal CSF reserve ratio and cord occupation rate were observed during extension. Cord impingement and SI change were more prevalent in extension-positioned MRI. There was no difference between ROM on dynamic radiographs and dynamic MRI. Preoperative cervical ROM was greater in patients with intensely high SI change. Conclusion Dynamic MRI is useful for evaluating neck movement. Patients with high SI had greater ROM before surgery but worse outcomes after. Neck extension exacerbated cervical stenosis and cord compression compared to flexion, and cervical spinal motion contributed to the severity of CSM. Cervical spinal motion should be carefully evaluated, particularly in hyperextension, to prevent worsening of CSM.

Objectives This study aimed to compare positive airway pressure (PAP) therapy compliance between patients with comorbid insomnia and sleep apnea (COMISA) and those with obstructive sleep apnea (OSA) alone. It also assessed the influence of insomnia clinic visits on PAP compliance. Methods Patients diagnosed with OSA and initiated on PAP therapy between January 2012 and December 2021 were included. The COMISA group (n=43) comprised patients with insomnia, while the control group (n=86) consisted of OSA patients without insomnia, matched 1:2 based on age and sex. COMISA patients were further categorized into group A (n=20), with at least two insomnia clinic visits, and group B (n=23) with one or no visits. PAP compliance in each group was evaluated at 3 and 9 months. Results No significant differences were observed in PAP compliance between the COMISA patients and OSA patients without insomnia. Within the COMISA group, the impact of insomnia clinic visits on PAP compliance was not significant. No significant difference was observed in daily PAP usage between the two groups at 3 months (265.5±145.9 minutes in group A vs. 236.3±152.3 minutes in group B, P=0.760) or 9 months (213.4±155.3 minutes in group A vs. 166.3±158.3 minutes in group B, P=0.538). The percentages of PAP users and nights with PAP use exceeding 4 hours also showed no significant differences at either time point. Conclusion This study demonstrated no significant disparity in PAP compliance between the COMISA and OSA groups at either 3 or 9 months. Furthermore, insomnia clinic visits did not significantly impact PAP compliance in COMISA patients during 3- and 9-month intervals.

Abstract Alcohol consumption, a pervasive societal issue, poses considerable health risks and socioeconomic consequences. Alcohol-induced hepatic disorders, such as fatty liver disease, alcoholic hepatitis, chronic hepatitis, liver fibrosis, and cirrhosis, underscore the need for comprehensive research. Existing challenges in mimicking chronic alcohol exposure in cellular systems, attributed to ethanol evaporation, necessitate innovative approaches. In this study, we developed a simple, reusable, and controllable device for examining the physiological reactions of hepatocytes to long-term alcohol exposure. Our approach involved a novel device designed to continuously release ethanol into the culture medium, maintaining a consistent ethanol concentration over several days. We evaluated device performance by examining gene expression patterns and cytokine secretion alterations during long-term exposure to ethanol. These patterns were correlated with those observed in patients with alcoholic hepatitis. Our results suggest that our ethanol-releasing device can be used as a valuable tool to study the mechanisms of chronic alcohol-mediated hepatic diseases at the cellular level. Our device offers a practical solution for studying chronic alcohol exposure, providing a reliable platform for cellular research. This innovative tool holds promise for advancing our understanding of the molecular processes involved in chronic alcohol-mediated hepatic diseases. Future research avenues should explore broader applications and potential implications for predicting and treating alcohol-related illnesses.

Abstract Endoscopic middle meatal antrostomy (MMA) is commonly used for maxillary sinus (MS) fungal ball removal. For challenging cases involving anterior or inferior recess, an additional inferior meatal approach (IMA) might be needed. We analyzed the differences in MS dimensions on CT scans according to the surgical approach to suggest preoperative variables that could facilitate an additional IMA. CT scans of 281 adult patients who underwent ESS for the MS fungal ball (139 MMA, 62 MMA & IMA) were evaluated for comparative analysis of 8 MS measurements based on the surgical approach. Complete removal was achieved in all cases. Age and sex didn't differ significantly (p > 0.05). The maximum distances between the anterior–posterior walls, the inferior ostium border to the lateral recess, and the ostium to the inferior wall of the MS were statistically greater in the MMA & IMA group compared to the MMA group (p = 0.003, p = 0.005, and p = 0.010, respectively), especially among females. This study underscores the clinical importance of specific measurements—anterior to posterior wall, medial wall to lateral recess, and ostium to inferior wall of the maxillary sinus—for guiding optimal surgical approaches in MS lesions.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients’ values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

We investigated the effect of Cr thin film deposition on the thermal stability and corrosion resistance of hot-dip aluminized steel. A high-quality Cr thin film was deposited on the surface of the Al-9 wt. % Si-coated steel sheets by physical vapor deposition. When the Al-Si coated steel sheets were exposed to a high temperature of 500℃, Fe from the steel substrate diffused into the Al-Si coating layer resulting in discoloration. However, the highly heat-resistant Cr thin film deposited on the Al-Si coating prevented diffusion and surface exposure of Fe, improving the heat and corrosion resistances of the Al-Si alloy coated steel sheet.

Abstract The extent of surgical resection is an important prognostic factor in the treatment of patients with glioblastoma. Optical coherence tomography (OCT) imaging is one of the adjunctive methods available to achieve the maximal surgical resection. In this study, the tumor margins were visualized with the OCT image obtained from a murine glioma model. A commercialized human glioblastoma cell line (U-87) was employed to develop the orthotopic murine glioma model. A swept-source OCT (SS-OCT) system of 1300 nm was used for three-dimensional imaging. Based on the OCT intensity signal, which was obtained via accumulation of each A-scan data, an en-face optical attenuation coefficient (OAC) map was drawn. Due to the limited working distance of the focused beam, OAC values decrease with depth, and using the OAC difference in the superficial area was chosen to outline the tumor boundary, presenting a challenge in analyzing the tumor margin along the depth direction. To overcome this and enable three-dimensional tumor margin detection, we converted the en-face OAC map into an en-face difference map with x- and y-directions and computed the normalized absolute difference (NAD) at each depth to construct a volumetric NAD map, which was compared with the corresponding H&E-stained image. The proposed method successfully revealed the tumor margin along the peripheral boundaries as well as the margin depth. We believe this method can serve as a useful adjunct in glioma surgery, with further studies necessary for real-world practical applications.

BackgroundPirfenidone is an antifibrotic medication approved for idiopathic pulmonary fibrosis (IPF). Fybro®, a generic version of pirfenidone developed in South Korea, gained approval and is available in 200 mg and in higher-dose formulations of 400 and 600 mg. This real-world prospective cohort study investigated the safety and effectiveness of Fybro®.MethodsA nationwide observational study was conducted in patients with IPF. Patients were followed up for 6 months, with a subset of patients being followed up for 12 months. Data on lung function and adverse events were collected. Patient adherence to fewer-pill (400 and/or 600 mg tablets) and multiple-pill (200 mg tablets) regimens were compared.ResultsOf the 359 enrolled patients, 352 received pirfenidone (Fybro®) at least once and were included in the analysis. The mean age was 69.0 years and 82.4% of patients were male. The median treatment duration was 186.0 days. A total of 253 patients (71.9%) experienced adverse events, with decreased appetite being the most common (16.5%). The adjusted decline rates in lung function were −1.5% and −2.2% predicted per year for forced vital capacity and diffusing capacity, respectively. No significant differences were observed based on the pirfenidone dose. For a daily intake of 1,200 or 1800 mg of pirfenidone, a significantly longer duration of drug administration was observed with the fewer-pill regimen than with multiple-pill regimen.ConclusionThe safety and effectiveness of Fybro® observed in this real-world cohort study are consistent with previous studies. Using higher-strength tablets to reduce pill burden may improve medication adherence.

Shape-memory polyurethanes (SMPUs) are promising materials that change shape in response to external heat. These polymers have a dual-segment structure: a hard segment for netpoint and a soft segment for molecular switch. Understanding the molecular behavior of each segment and microphase-separated morphology is crucial for comprehending the shape-memory mechanism. This study aimed to understand the shape-memory behavior by observing the phase separation of SMPU using mesoscale models based on dissipative particle dynamics (DPD) simulations. The SMPU copolymer was modeled using 4,4′-diphenylmethane diisocyanate (MDI, hard segment) and poly(ethylene oxide) (PEO, soft segment). By calculating segment solubility and repulsion parameters, we found that the hard-segment domain changes from isolated form to a lamellar and interconnected structure and eventually to a continuous form as its content increases. Combining these insights with shape-memory performance models can enhance our understanding of better SMPU design and contribute significantly to the optimization of smart stimuli-responsive materials.

IntroductionSweetpotato faces breeding challenges due to physiological and genomic issues. Gamma radiation is a novel approach for inducing genetic variation in crops. We analyzed the transcriptomic changes in gamma ray-induced sweetpotato mutants with altered stem development compared with those in the wild-type 'Tongchaeru’ cultivar.MethodsRNA sequencing analyses were performed to identify changes in the expression of genes related to stem development.ResultsTranscriptomic analysis identified 8,931 upregulated and 6,901 downregulated genes, including the upregulation of the auxin-responsive SMALL AUXIN UP RNA (SAUR) and three PHYTOCHROME INTERACTING FACTOR 4 (PIF4) genes. PIF4 is crucial for regulating the expression of early auxin-responsive SAUR genes and stem growth in Arabidopsis thaliana. In the mutant, several genes related to stem elongation, including PIF4 and those involved in various signaling pathways such as auxin and gibberellin, were upregulated.DiscussionOur results suggest that gamma ray-induced mutations influence auxin-dependent stem development by modulating a complex regulatory network involving the expression of PIF4 and SAUR genes, and other signaling pathways such as gibberellin and ethylene signaling genes. This study enhances our understanding of the regulatory mechanisms underlying stem growth in sweetpotato, providing valuable insights for genomics-assisted breeding efforts.

Background Chimeric antigen receptor T-cell (CAR-T) therapy has achieved remarkable remission in patients with B-cell malignancies. However, its efficacy in treating solid tumors remains limited. Here, we investigated a combination therapy approach using an engineered long-acting interleukin (IL)-7 (rhIL-7-hyFc or NT-I7) and CAR-T cells targeting three antigens, glypican-2 (GPC2), glypican-3 (GPC3), and mesothelin (MSLN), against multiple solid tumor types including liver cancer, neuroblastoma, ovarian cancer, and pancreatic cancer in mice.Methods CAR-T cells targeting GPC2, GPC3, and MSLN were used in combination with NT-I7 to assess the anticancer activity. Xenograft tumor models, including the liver cancer orthotopic model, were established using NOD scid gamma mice engrafted with cell lines derived from hepatocellular carcinoma, neuroblastoma, ovarian cancer, and pancreatic cancer. The mice were monitored by bioluminescence in vivo tumor imaging and tumor volume measurement using a caliper. Immunophenotyping of CAR-T cells on NT-I7 stimulation was evaluated for memory markers, exhaust markers, and T-cell signaling molecules by flow cytometry and western blotting.Results Compared with the IL-2 combination, preclinical evaluation of NT-I7 exhibited regression of solid tumors via enhanced occupancy of CD4+ CAR-T, improved T-cell expansion, reduced exhaustion markers (programmed cell death protein 1 or PD-1 and lymphocyte-activation gene 3 or LAG-3) expression, and increased generation of stem cell-like memory CAR-T cells. The STAT5 pathway was demonstrated to be downstream of NT-I7 signaling, mediated by increased expression of the IL-7 receptor expression in CAR-T cells. Furthermore, CAR-T cells improved efficacy against tumors with low antigen density when combined with NT-I7 in mice, presenting an avenue for patients with heterogeneous antigenic profiles.Conclusion This study provides a rationale for NT-I7 plus CAR-T cell combination therapy for solid tumors in humans.

Objectives: This research delves into the application of texture analysis in spine computed tomography (CT) scans and its correlation with bone mineral density (BMD), as determined by dual-energy X-ray absorptiometry (DXA). It specifically addresses the discordance between the 2 measurements, suggesting that certain spinal-specific factors may contribute to this discrepancy. Methods: The study involved 405 cases from a single institution collected between May 6, 2012 and June 30, 2021. Each case underwent a spinal CT scan and a DXA scan. BMD values at the lumbar region (T12 to S1) and total hip were recorded. Texture features from axial cuts of T12 to S1 vertebrae were extracted using gray-level co-occurrence matrices, and a regression model was constructed to predict the BMD values. Results: The correlation between CT texture analysis results and BMD from DXA was moderate, with a correlation coefficient ranging between 0.4 and 0.5. This discordance was examined in light of factors unique to the spine region, such as abdominal obesity, aortic calcification, and lumbar degenerative changes, which could potentially affect BMD measurements. Conclusions: Emerging from this study is a novel insight into the discordance between spinal CT texture analysis and DXA-derived BMD measurements, highlighting the unique influence of spinal attributes. This revelation calls into question the exclusive reliance on DXA scans for BMD assessment, particularly in scenarios where DXA scanning may not be feasible or accurate.

Abstract COVID-19 caused by SARS-CoV-2 spread rapidly around the world, endangering the health of people globally. The SARS-CoV-2 spike protein initiates entry into target cells by binding to human angiotensin-converting enzyme 2 (ACE2). In this study, we developed DNA aptamers that specifically bind to the SARS-CoV-2 spike protein, thereby inhibiting its binding to ACE2. DNA aptamers are small nucleic acid fragments with random structures that selectively bind to various target molecules. We identified nine aptamers targeting the SARS-CoV-2 spike protein using the systematic evolution of ligands by exponential enrichment (SELEX) method and selected three optimal aptamers by comparing their binding affinities. Additionally, we confirmed that the DNA aptamers suppressed pro-inflammatory cytokines induced by the SARS-CoV-2 spike protein in ACE2-overexpressing HEK293 cells. Overall, the DNA aptamer developed in this study has the potential to bind to the SARS-CoV-2 spike protein and inhibit or block its interaction with ACE2. Thus, our DNA aptamers can be used as new biological tools for the prevention and diagnosis of SARS-CoV-2 infection.

Abstract Background High-risk stage III colon cancer has a considerably poorer prognosis than stage II and low-risk stage III colon cancers. Nevertheless, most guidelines recommend similar adjuvant treatment approaches for all these stages despite the dearth of research focusing on high-risk stage III colon cancer and the potential for improved prognosis with intensive adjuvant treatment. Given the the proven efficacy of triplet chemotherapy in metastatic colorectal cancer treatment, the goal of this study is to evaluate the oncologic efficacy and safety of mFOLFIRINOX in comparison to those of the current standard of care, mFOLFOX 6, as an adjuvant treatment for patients diagnosed with high-risk stage III colon cancer after radical resection. Methods This multicenter, randomized (1:1), open-label, phase II trial will assess and compare the effectiveness and toxicity of mFOLFIRINOX and mFOLFOX 6 in patients with high-risk stage III colon cancer after radical resection. The goal of the trial is to enroll 312 eligible patients, from 11 institutes, aged between 20 and 70 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, or between 70 and 75 with an ECOG performance status of 0. Patients will be randomized into two arms - Arm A, the experimental arm, and Arm B, the reference arm - and will receive 12 cycles of mFOLFIRINOX and mFOLFOX 6 every 2 weeks, respectively. The primary endpoint of this study is the 3-year disease-free survival, and secondary endpoints include the 3-year overall survival and treatment toxicity. Discussion The Frost trial would help determine the oncologic efficacy and safety of adjuvant triplet chemotherapy for high-risk stage III colon cancers and ultimately improve prognoses. Trial registration ClinicalTrials.gov NCT05179889, registered on 17 December 2021.

Abstract The current study investigated the hemispheric dynamics underlying semantic and syntactic priming in lexical decision tasks. Utilizing primed-lateralized paradigms, we observed a distinct pattern of semantic priming contingent on the priming hemisphere. The right hemisphere (RH) exhibited robust semantic priming irrespective of syntactic congruency between prime and target, underscoring its proclivity for semantic processing. Conversely, the left hemisphere (LH) demonstrated slower response times for semantically congruent yet syntactically incongruent word pairs, highlighting its syntactic processing specialization. Additionally, nonword data revealed a hemispheric divergence in syntactic processing, with the LH showing significant intrahemispheric syntactic priming. These findings illuminate the intrinsic hemispheric specializations for semantic and syntactic processing, offering empirical support for serial processing models. The study advances our understanding of the complex interplay between semantic and syntactic factors in hemispheric interactions.

Purpose The ability to concentrate urine becomes an important index in determining nocturnal enuresis (NE) treatment. The aim of our study was to investigate first-morning urine osmolality (Uosm) changes at the end of treatment compared to before treatment in children with NE. Methods A total of 71 children with NE were divided into two groups according to the level of first-morning Uosm before treatment: high group (≥800 mOsm/kg) and low group (

Abstract Current soft neural probes are still operated by bulky, rigid electronics mounted to a body, which deteriorate the integrity of the device to biological systems and restrict the free behavior of a subject. We report a soft, conformable neural interface system that can monitor the single-unit activities of neurons with long-term stability. The system implements soft neural probes in the brain, and their subsidiary electronics which are directly printed on the cranial surface. The high-resolution printing of liquid metals forms soft neural probes with a cellular-scale diameter and adaptable lengths. Also, the printing of liquid metal-based circuits and interconnections along the curvature of the cranium enables the conformal integration of electronics to the body, and the cranial circuit delivers neural signals to a smartphone wirelessly. In the in-vivo studies using mice, the system demonstrates long-term recording (33 weeks) of neural activities in arbitrary brain regions. In T-maze behavioral tests, the system shows the behavior-induced activation of neurons in multiple brain regions.

Abstract Elasto-inertial microfluidic separation offers many advantages including high throughput and separation resolution. Even though the separation efficiency highly depends on precise control of the flow conditions, no concrete guidelines have been reported yet in elasto-inertial microfluidics. Here, we propose a dimensionless analysis for precise estimation of the microsphere behaviors across the interface of Newtonian and viscoelastic fluids. Reynolds number, modified Weissenberg number, and modified elastic number are used to investigate the balance between inertial and elastic lift forces. Based on the findings, we introduce a new dimensionless number defined as the width of the Newtonian fluid stream divided by microsphere diameter. The proposed dimensionless analysis allows us to predict whether the microspheres migrate across the co-flow interface. The theoretical estimation is found to be in good agreement with the experimental results using 2.1- and 3.2-μm-diameter polystyrene microspheres in a co-flow of water and polyethylene oxide solution. Based on the theoretical estimation, we also realize submicron separation of the microspheres with 2.1 and 2.5 μm in diameter at high throughput, high purity (>95%), and high recovery rate (>97%). The applicability of the proposed method was validated by separation of platelets from similar-sized Escherichia coli (E.coli).

Abstract Most microfluidic separation techniques rely largely on object size as a separation marker. The ability to separate micro-objects based on their shape is crucial in various biomedical and chemical assays. Here, we develop an on-demand, label-free acoustofluidic method to separate prolate ellipsoids from spherical microparticles based on traveling surface acoustic wave-induced acoustic radiation force and torque. The freely rotating non-spherical micro-objects were aligned under the progressive acoustic field by the counterrotating radiation torque, and the major axis of the prolate ellipsoids was parallel to the progressive wave propagation. The specific alignment of the ellipsoidal particles resulted in a reduction in the cross-sectional area perpendicular to the wave propagation. As a consequence, the acoustic backscattering decreased, resulting in a decreased magnitude of the radiation force. Through the variation in radiation force, which depended on the micro-object morphology enabled the acoustofluidic shape-based separation. We conducted numerical simulations for the wave scattering of spherical and prolate objects to elucidate the working mechanism underlying the proposed method. A series of experiments with polystyrene microspheres, prolate ellipsoids, and peanut-shaped microparticles were performed for validation. Through quantitative analysis of the separation efficiency, we confirmed the high purity and high recovery rate of the proposed acoustofluidic shape-based separation of micro-objects. As a bioparticle, we utilize Thalassiosira eccentrica to perform shape-based separation, as the species has a variety of potential applications in drug delivery, biosensing, nanofabrication, bioencapsulation and immunoisolation.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia with a very poor prognosis. Accurate diagnosis of IPF is essential for good outcomes but remains a major medical challenge due to variability in clinical presentation and the shortcomings of existing diagnostic tests. Medical history collection is the first and most important step in the IPF diagnosis process; the clinical probability of IPF is high if the suspected patient is 60 years or older, male, and has a history of cigarette smoking. Systemic assessment for connective tissue disease is essential in the initial evaluation of patients with suspected IPF to identify potential causes of interstitial lung disease (ILD). Radiologic examination using high-resolution computed tomography plays a pivotal role in the evaluation of patients with ILD, and prone and expiratory computed tomography images can be considered. If additional tests such as surgical lung biopsy or transbronchial lung cryobiopsy are needed, transbronchial lung cryobiopsy should be considered as an alternative to surgical lung biopsy in medical centers with experience performing this procedure. Diagnosis through multidisciplinary discussion (MDD) is strongly recommended as MDD has become the cornerstone for diagnosis of IPF, and the scope of MDD has expanded to monitoring of disease progression and suggestion of appropriate treatment options.

Background Long-term oxygen therapy (LTOT) improves the survival of patients with hypoxemia due to chronic respiratory diseases. The clinical outcomes of LTOT are strongly associated with patient adherence. To improve the adherence of patients, physicians have focused on the efficacy of LTOT. However, poor adherence may stem from patients’ perceptions of LTOT. Herein we evaluated patients’ perceptions of LTOT affecting adherence. Methods We conducted a cross-sectional survey study using descriptive, open, and closed-ended questionnaire. Patients using oxygen therapy (OT) or requiring it but avoiding OT responded to the questionnaires at three university hospitals. Results Seventy-nine patients responded to the questionnaires. The number of patients using home and portable OT was 69 (93%) and 37 (46.3%), respectively. Patients with good adherence were 22 (30.1%). Among patients with good adherence, 90.9% used oxygen according to physicians’ prescriptions whereas only 37.3% of those with poor adherence followed physicians’ prescriptions (p

Background/Objectives: Neuroinflammation is associated with the progression of various brain diseases, and the management of neuroinflammation-induced neural damage is a crucial aspect of treating neurological disorders. This study investigated the anti-inflammatory efficacy of photobiomodulation therapy (PBMT) using 660 nm phototherapy in a rat model with lipopolysaccharide (LPS)-induced neuroinflammation. Methods: We induced inflammation in rat brains via intraperitoneal injection of LPS and subjected the treatment group to 660 nm phototherapy to examine its protective effect against hippocampal damage based on pathological, histological, and immunohistochemical tissue analyses. Results: The 660 nm treated rats showed a significant decrease in hippocampal structural damage and cell death compared to the LPS-treated group. We observed reduced expression of the inflammation markers GFAP, TNF-α, and IL-1β in the hippocampus of the treatment group, and an increase in SIRT1 expression across all hippocampal regions. Conclusions: This study presents a promising method for controlling neuroinflammation and providing neuroprotection and inflammation relief. PBMT represents a non-invasive therapeutic approach with minimal side effects ensured through the proper control of light irradiation.

This study proposes a two-degree-of-freedom PID controller design and tuning method based on a simple pole placement approach to enhance servo and regulatory performance while ensuring the stability of diesel engines. In the modeling of the control target, the actuator is analytically modeled. In contrast, the type of model for the diesel engine is derived analytically, and its parameter estimation uses operational data from naval ships. The proposed controller consists of a PID controller to improve regulatory performance and a set-point filter to enhance servo response. PID controller parameters consist of the parameters of the controlled plant model and a single tuning variable. At the same time, the set-point filter comprises the controller parameters and a single weighting factor. To ensure the robust stability of the controller, the controller parameters are tuned based on the maximum sensitivity. To verify the effectiveness of this study, simulations for the speed control of a diesel engine with inherent nonlinearity were conducted under three scenarios. Performance was quantitatively analyzed using the integral of time-weighted absolute error, 2% settling time, 2% recovery time, specified maximum sensitivity, and maximum peak response value, and was compared with Skogestad’s IMC and Lee’s IMC. Based on evaluation indices, the proposed controller demonstrated superior performance in both servo and regulatory responses compared to the two existing control techniques while ensuring stability.

The need for antibiotics in commercial laying hens is increasing owing to intensive farming systems. Amoxicillin trihydrate (AMX), an aminopenicillin β-lactam antibiotic, exerts broad bactericidal activity. However, its short half-life necessitates frequent administration to ensure efficacy, thus limiting its use. Herein, we investigated the effect of concurrent administration of bromhexine hydrochloride (BRM), a mucolytic agent, on AMX pharmacokinetics, performing a comparative pharmacokinetic analysis of AMX administration alone and in combination with BRM. AMX (50 mg/kg) was administered by oral gavage once daily for three days alone or in combination with 10 mg/kg BRM. Plasma and egg samples were collected to evaluate pharmacokinetic profiles and egg residues. The area under the curve and maximum plasma concentration values were significantly higher in the AMX + BRM group than the AMX only group. However, there were no significant differences in AMX half-life in the elimination phase (T1/2), elimination rate constant (kel), or apparent clearance (CL/F) values. In the egg residue study, the withdrawal period for AMX was 5 days in both groups, with no significant difference when using the maximum residue limit (MRL) of 10 μg/kg. The concentration of BRM in the eggs remained at 100 μg/kg up to the fourth day following drug administration. Conclusion: These results confirmed that BRM co-administration increased systemic exposure to AMX, with a negligible residual impact of amoxicillin in eggs.