Search

It remains an open question whether second language (L2) learners can process linguistic properties at the syntax-discourse interface. This study examines this issue in the context of the L2 processing of Korean dative sentences under different information structure requirements. Given that discourse constraints associated with information structure tend to manifest more strongly in noncanonical than in canonical structures, we tested whether L2 learners of Korean show sensitivity to such constraints during online processing. In a story-continuation task, both native and nonnative speaker groups showed a strong preference for producing canonical dative patterns, indicating their comparable knowledge of the canonical status of Korean dative sentences. In a self-paced reading task, both groups spent longer reading times when the word order of dative sentences did not follow given-new information structure, but only for the noncanonical and not the canonical structure. These results suggest that L2 processing of dative structures at the syntax-discourse interface relies on the same parsing architecture that guides native-speaker processing.

The social responsibility of college students in the later stages of adolescence for sustainable development is emphasized, and the role of universities has become a crucial task. This study aimed to explore the level of college students' cognition, attitude, and behavior towards sustainable development and the association among them through the moderation effect of informal online learning. The difference verification and structural equation modeling were applied to 559 students who majored in science, and statistical validity was confirmed. Regarding the sustainable development level of college students, there was a significant difference in cognition, attitude, and behavior towards sustainable development between males and females, formal education, and informal online learning. Further, college students' attitudes towards sustainable development played a significant mediating role between cognition and behavior. The study also found a significant moderation effect of informal online learning on students' cognition and attitude toward sustainable development behavior. Accordingly, this study suggests that universities should systematically design educational programs to promote college students' behavioral change toward sustainable development through personal life-oriented learning courses.

Purpose: As university faculty faced new challenges, such as rapid digital social and the coronavirus disease 2019 (COVID-19) response, this study aimed to identify the daily changes in the interaction between the faculty and the organizational environment (colleague, policy and new issue) by exploring their recent dynamic educational efforts and the professional development. Design/methodology/approach: This is a study wherein perceptions of 20 faculty from 15 universities and colleges were collected through in-depth online interviews. The authors analyzed interview data by arranging and visualizing the analyzed data using network clustering. Further, they applied the Latent Dirichlet allocation of the topic modeling to monitor the appropriate number of clusters, ultimately determined as four clusters using partial clustering. Findings: The results showed that university faculty spontaneously tried to solve the problems through informal learning while the commitment to peer learning was deepening, reflecting the collectivist orientation nature of Chinese culture. Besides, the faculty also required support to reflect on their daily efforts for professional development. These results about their various learning routines prove the justification for the faculty's professional development to be discussed from the "learning by doing" perspective of lifelong learning. Originality/value: This study proved the significance of informal learning for university faculty's professional development and the reasonable value of peer learning, and provided insights into how the Chinese context may influence university faculty's informal learning experience.

Abstract Trastuzumab emtansine (T-DM1) is widely utilized as a second-line and subsequent treatment for metastatic HER2+ breast cancer and has shown promise in early breast cancer treatment, particularly in adjuvant settings for residual disease after neoadjuvant chemotherapy. However, concerns have arisen regarding long-term hepatic adverse drug reactions (ADRs) not identified in clinical trials. We investigated potential safety signals of T-DM1 in hepatobiliary disorders and the time-to-onset of ADRs using the FDA Adverse Event Reporting System (FAERS) database. Suspected ADRs were extracted and divided into two groups: T-DM1 (N = 3387) and other drugs (N = 11,833,701). Potential signal for T-DM1 in hepatobiliary disorder were identified (reporting odds ratio [ROR] = 5.66, 95% confidence interval [CI] = 5.11–6.27; information component [IC] = 2.35, 95% Credibility Interval [Crl] = 2.18–2.51). A breast cancer indicated subgroup analysis (2519 T-DM1; 172,329 other drugs) also identified a potential safety signal (ROR = 3.28, 95% CI = 2.92–3.68; IC = 1.53, 95%CrI = 1.35–1.71). The median time-to-onset for T-DM1-associated hepatobiliary disorders was 41 days. For prolonged and chronic hepatobiliary disorders, median times were 322.5 and 301.5 days, respectively. These findings highlight the need for further research to inform clinical decisions on optimal T-DM1 treatment duration, balancing benefits with potential adverse reactions.

Abstract Background The increasing complexity of the healthcare environment and the necessity of multidisciplinary teamwork have highlighted the importance of interprofessional education (IPE). IPE aims to enhance the quality of patient care through collaborative education involving various healthcare professionals, such as doctors, nurses, and pharmacists. This study sought to analyze how game-based IPE activities influence students’ perceptions and reflective thinking. It also aimed to identify the shifts in perception and effectiveness caused by this educational approach. Methods The study is based on a game-based IPE program conducted at University A, involving medical and nursing students in structured learning and team-based activities. Data were collected using essays written by the students after they had participated in IPE activities. Text network analysis was conducted by extracting key terms, performing centrality analysis, and visualizing topic modeling to identify changes in students’ perceptions and reflective thinking. Results Keywords such as “patient,” “thought,” “group,” “doctor,” “nurse,” and “communication” played a crucial role in the network, indicating that students prioritized enhancing their communication and problem-solving skills within the educational environment. The topic modeling results identified three main topics, each demonstrating the positive influence of game-based collaborative activities, interprofessional perspectives, and interdisciplinary educational experiences on students. Topic 3 (interdisciplinary educational experience) acted as a significant mediator connecting Topic 1 (game-based collaborative activity experience) and Topic 2 (interprofessional perspectives). Conclusion This study demonstrates that game-based IPE activities are an effective educational approach for enhancing students’ team building skills, particularly communication and interprofessional perspectives. Based on these findings, future IPE programs should focus on creating collaborative learning environments, strengthening communication skills, and promoting interdisciplinary education. The findings provide essential insights for educational designers and medical educators to enhance the effectiveness of IPE programs. Future research should assess the long-term impacts of game-based IPE on clinical practice, patient outcomes, and participants’ professional development.

Abstract Spaceborne radar remote sensing of the earth system is essential to study natural and man-made changes in the ecosystem, water and energy cycles, weather and air quality, sea level, and surface dynamics. A major challenge with current approaches is the lack of broad spectrum tunability due to narrow band microwave electronics, that limit systems to specific science variable retrievals. This results in a significant limitation in studying dynamic coupled earth system processes such as surface and subsurface hydrology from a single compact instrument, where co-located broad spectrum radar remote sensing is needed to sense multiple variables simultaneously or over a short duration. Rydberg atomic sensors are highly sensitive broad-spectrum quantum detectors that can be dynamically tuned to cover micro-to-millimeter waves with no requirement for RF band-specific electronics. Rydberg atomic sensors can use existing transmitted signals such as from navigation and communication satellites to enable remote sensing. We demonstrate remote sensing of soil moisture, an important earth system variable, via ground-based radar reflectometry with Rydberg atomic systems. To do this, we sensitize the atoms to XM satellite radio signals and use signal correlations to demonstrate use of these satellite signals for remote sensing of soil moisture.

Background This study examines integrating physical and mental healthcare for disadvantaged persons with type 2 diabetes mellitus and mild-to-moderate depression in the community, using a mobile application within a public-private-academic partnership. Methods The Korean Diabetes Association has developed a mobile application combining behavioral activation for psychological well-being and diabetes self-management, with conventional medical therapy. Participants were randomly assigned to receive the application with usual care or only usual care. Primary outcomes measured changes in psychological status and diabetes self-management through questionnaires at week 12 from the baseline. Secondary outcomes assessed glycemic and lipid control, with psychological assessments at week 16. Results Thirty-nine of 73 participants completed the study (20 and 19 in the intervention and control groups, respectively) and were included in the analysis. At week 12, the intervention group showed significant reductions in depression severity and perceived stress compared to the control group. Additionally, they reported increased perceived social support and demonstrated improved diabetes self-care behavior. These positive effects persisted through week 16, with the added benefit of reduced anxiety. While fasting glucose levels in the intervention group tended to improve, no other significant differences were observed in laboratory assessments between the groups. Conclusion This study provides compelling evidence for the potential efficacy of a mobile application that integrates physical and mental health components to address depressive symptoms and enhance diabetes self-management in disadvantaged individuals with type 2 diabetes mellitus and depression. Further research involving larger and more diverse populations is warranted to validate these findings and solidify their implications.

Breast lymphomas are rare, malignant breast neoplasms with a heterogeneous pattern of clinical symptoms. Burkitt’s lymphoma is a rare, highly aggressive, and rapidly growing B-cell non-Hodgkin lymphoma. We report about a 27-year-old woman diagnosed as having secondary breast Burkitt’s lymphoma, probably originating from the stomach, with multiple distant metastases. Breast ultrasonography revealed multiple, variable sized, heterogeneous masses with posterior acoustic enhancement and echogenic rims. These imaging findings may sometimes overlap with those of other breast malignancies. However, unlike other breast malignancies, lymphoma can be diagnosed by biopsy and does not require surgical excision. To avoid unnecessary treatment, radiologists and clinicians should be aware of the characteristic imaging features of breast lymphomas.

Abstract Genomic analysis of structural variants(SVs) in breast cancer (BC) patients has been conducted, but the relationship between genomic alterations and BC prognosis remains unclear. We performed RNA sequencing of 297 early BC fresh-frozen tissues. We identified SVs using three tools (STAR.Arriba, STAR.fusion, and STAR.SEQR) with the COSMIC and Mitelman databases as guide references. We found a median of five to eight fusions per sample. In BC intrinsic subtypes, normal subtype had the fewest fusions (median: 1, interquartile range [IQR]: 0, 3) followed by luminal A (median: 5.5, IQR: 2.75, 10.25), luminal B (median: 9, IQR: 6, 16.5), HER2-enriched (median: 9, IQR: 6, 16.5) and basal (median 10, IQR: 6, 15.5) subtypes (p

Wire and arc additive manufacturing (WAAM) technique has introduced a novel approach for producing complex Ti–6Al–4V parts with metric dimensions. However, the produced part leads to the development of a strong texture and anisotropic mechanical properties due to the formation of large columnar β grains. To resolve this issue, the plastic deformation of each deposited track through hammer peening was developed as a means to refine these large β grains. In this study, we have investigated an innovative approach to further enhance the efficiency of β grain refinement by minimizing the arc heat input associated with previous deposited layer, which is achieved by employing a C-type filler wire. Our findings reveal a notable enhancement in grain refinement efficiency through the utilization of a C-type filler wire with peening process, as compared to available conventional commercial round shape filler wire. Specifically, the employment of the C-type filler wire results in a reduced melt pool penetration depth of WAAM Ti–6Al–4V (3.3 mm), compared to the commercially available round shape (R-Type) filler wire (4.48 mm). Within the plastically deformed region by peening, fine and randomly oriented β grains are observed, extending to a depth of deformation reaching 844 ± 32.65 μm. Peening WAAM Ti–6Al–4V with the C-type filler wire leads to the development of isotropic mechanical properties in both horizontal and vertical directions, offering high strength due to the presence of small equiaxed β grains and thin α laths (0.56 ± 0.18 μm), in contrast to the use of conventional commercial round shape filler wire.

Abstract Breast cancer is the most commonly diagnosed cancer among women worldwide. Breast cancer patients experience significant distress relating to their diagnosis and treatment. Managing this distress is critical for improving the lifespan and quality of life of breast cancer survivors. This study aimed to assess the level of distress in breast cancer survivors and analyze the variables that significantly affect distress using machine learning techniques. A survey was conducted with 641 adult breast cancer patients using the National Comprehensive Cancer Network Distress Thermometer tool. Participants identified various factors that caused distress. Five machine learning models were used to predict the classification of patients into mild and severe distress groups. The survey results indicated that 57.7% of the participants experienced severe distress. The top-three best-performing models indicated that depression, dealing with a partner, housing, work/school, and fatigue are the primary indicators. Among the emotional problems, depression, fear, worry, loss of interest in regular activities, and nervousness were determined as significant predictive factors. Therefore, machine learning models can be effectively applied to determine various factors influencing distress in breast cancer patients who have completed primary treatment, thereby identifying breast cancer patients who are vulnerable to distress in clinical settings.

ABSTRACTTumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has chemotherapeutic potential as a regulator of an extrinsic apoptotic ligand, but its effect as a drug is limited by innate and acquired resistance. Recent findings suggest that an intermediate drug tolerance could mediate acquired resistance, which has made the main obstacle for limited utility of TRAIL as an anti-cancer therapeutics. We propose miRNA-dependent epigenetic modification drives the drug tolerant state in TRAIL-induced drug tolerant (TDT). Transcriptomic analysis revealed miR-29 target gene activation in TDT cells, showing oncogenic signature in lung cancer. Also, the restored TRAIL-sensitivity was associated with miR-29ac and 140-5p expressions, which is known as tumor suppressor by suppressing oncogenic protein RSK2 (p90 ribosomal S6 kinase), further confirmed in patient samples. Moreover, we extended this finding into 119 lung cancer cell lines from public data set, suggesting a significant correlation between TRAIL-sensitivity and RSK2 mRNA expression. Finally, we found that increased RSK2 mRNA is responsible for NF-κB activation, which we previously showed as a key determinant in both innate and acquired TRAIL-resistance. Our findings support further investigation of miR-29ac and -140-5p inhibition to maintain TRAIL-sensitivity and improve the durability of response to TRAIL in lung cancer.

Abstract Introduction Deucravacitinib demonstrated superior efficacy to apremilast in patients with moderate to severe plaque psoriasis in the POETYK PSO-1 and PSO-2 clinical trials. In the study reported here, we aimed to determine the overall 52-week cumulative clinical benefit of treatment initiated with deucravacitinib versus apremilast and to compare the 52-week cumulative benefit of initiating and staying on deucravacitinib versus initiating apremilast and continuing or switching to deucravacitinib at week 24 of treatment. Methods This post hoc analysis of POETYK PSO-1 data (ClinicalTrials.gov identifier: NCT03624127) determined the cumulative clinical benefit of deucravacitinib 6 mg once daily and apremilast 30 mg twice daily in adults with moderate to severe plaque psoriasis. Patients treated with apremilast who did not achieve a 50% reduction in the Psoriasis Area and Severity Index (PASI 50) at week 24 were switched to deucravacitinib. The cumulative clinical benefit of deucravacitinib versus apremilast over 52 weeks was based on cumulative measures of ≥ 75% improvement from baseline in PASI score (PASI 75) and the proportion of patients with a static Physician Global Assessment score of 0 or 1 (sPGA 0/1). Ratios of area under the curve estimates between treatments were calculated and compared based on analysis of covariance regression models. Results Patients initiating deucravacitinib (N = 332) had a greater cumulative benefit as measured by the PASI 75 and sPGA 0/1 than those initiating apremilast (N = 168). Over 52 weeks, those initiating deucravacitinib experienced 50% more benefit as measured by PASI 75 and 58% more benefit as measured by sPGA 0/1 than those initiating apremilast. Results were consistent with the primary analysis when patients were classified by prior systemic and prior biologic therapy exposure. Conclusion Results from this analysis corroborate the primary efficacy analysis supporting the use of deucravacitinib compared with apremilast for moderate to severe plaque psoriasis, regardless of prior systemic or biologic use.

Abstract This paper aims to elucidate the variations in wage inequality within the service industry across different nations. Scholars have emphasised the pivotal role of policies designed to balance flexibility and job security in the service sector, crucial for fostering its growth while mitigating wage disparities. We argue that the balance between flexibility and security of service sector employment is most likely to emerge under centre party governments in high-magnitude electoral systems. Centre parties, owing to their political detachment from organised labour and industry, encounter fewer obstacles in representing the unorganised interests of service sector workers. Furthermore, high-district magnitude systems incentivise centre parties to build comprehensive coalitions that address the diverse concerns of service sector workers. Our empirical analysis, spanning 14 OECD countries from 1995 to 2007, demonstrates that service sector wage inequality diminishes as district magnitude and the cabinet share of centre parties increase.

Abstract Epithelial-to-mesenchymal transition (EMT) is one of the main causes of peritoneal fibrosis. However, the pathophysiological mechanisms of EMT, specifically its relationship with autophagy, are still unknown. This study aimed to evaluate the role of autophagy in transforming growth factor-beta 1 (TGF-β1)-induced EMT in human peritoneal mesothelial cells (HPMCs). Primary cultured HPMCs were treated with TGF-β1 (2 and 5 ng/mL) and changes in autophagy markers and the relationship between autophagy and EMT were evaluated. We also identified changes in EMT- and autophagy-related signaling pathways after autophagy and NADPH oxidase 4 (NOX4) inhibition. TGF-β1 increased the generation of NOX4 and reactive oxygen species (ROS) in HPMCs, resulting in mitochondrial damage. Treatment with GKT137831 (20 μM), a NOX1/4 inhibitor, reduced ROS in the mitochondria of HPMC cells and reduced TGF-β1-induced mitochondrial damage. Additionally, the indirect inhibition of autophagy by GKT137831 (20 μM) downregulated TGF-β1-induced EMT, whereas direct inhibition of autophagy using 3-methyladenine (3-MA) (2 mM) or autophagy-related gene 5 (ATG5) gene silencing decreased the TGF-β1-induced EMT in HPMCs. The suppressor of mothers against decapentaplegic 2/3 (Smad2/3), autophagy-related phosphoinositide 3-kinase (PI3K) class III, and protein kinase B (Akt) pathways, and mitogen-activated protein kinase (MAPK) signaling pathways, such as extracellular signal-regulated kinase (ERK) and P38, were involved in TGF-β1-induced EMT. Autophagy and NOX4 inhibition suppressed the activation of these signaling pathways. Direct inhibition of autophagy and its indirect inhibition through the reduction of mitochondrial damage by upstream NOX4 inhibition reduced EMT in HPMCs. These results suggest that autophagy could serve as a therapeutic target for the prevention of peritoneal fibrosis in patients undergoing peritoneal dialysis.

Abstract Background HER2-positive, estrogen receptor-positive breast cancer (HER2+, ER+ BC) is a distinct disease subtype associated with inferior response to chemotherapy plus HER2-targeted therapy compared with HER2+, ER-negative BC. Bi-directional crosstalk leads to cooperation of the HER2 and ER pathways that may drive treatment resistance; thus, simultaneous co-targeting may optimize treatment impact and survival outcomes in patients with HER2+, ER+ BC. First-line (1L) treatment for patients with HER2+ metastatic BC (mBC) is pertuzumab, trastuzumab, and taxane chemotherapy. In clinical practice, dual HER2 blockade plus a fixed number of chemotherapy cycles are given as induction therapy to maximize tumor response, with subsequent HER2-targeted maintenance treatment given as a more tolerable regimen for long-term disease control. For patients whose tumors co-express ER, maintenance endocrine therapy (ET) can be added, but uptake varies due to lack of data from randomized clinical trials investigating the superiority of maintenance ET plus dual HER2 blockade versus dual HER2 blockade alone. Giredestrant, a novel oral selective ER antagonist and degrader, shows promising clinical activity and manageable safety across phase I–II trials of patients with ER+, HER2-negative BC, with therapeutic potential in those with HER2 co-expression. Methods This phase III, randomized, open-label, two-arm study aims to recruit 812 patients with HER2+, ER+ locally advanced (LA)/mBC into the induction phase (fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection [PH FDC SC] plus a taxane) to enable 730 patients to be randomized 1:1 to the maintenance phase (giredestrant plus PH FDC SC or PH FDC SC [plus optional ET]), stratified by disease site (visceral versus non-visceral), type of LA/metastatic presentation (de novo versus recurrent), best overall response to induction therapy (partial/complete response versus stable disease), and intent to give ET (yes versus no). The primary endpoint is investigator-assessed progression-free survival. Secondary endpoints include overall survival, objective response rate, clinical benefit rate, duration of response, safety, and patient-reported outcomes. Discussion heredERA BC will address whether giredestrant plus dual HER2 blockade is superior to dual HER2 blockade alone, to inform the use of this combination in clinical practice for maintenance 1L treatment of patients with HER2+, ER+ LA/mBC. Trial registration ClinicalTrials.gov, NCT05296798; registered on March 25, 2022. Protocol version 3.0 (November 18, 2022). Sponsor: F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124 4070, Basel, Switzerland.

Abstract Mature osteoclasts degrade bone matrix by exocytosis of active proteases from secretory lysosomes through a ruffled border. However, the molecular mechanisms underlying lysosomal trafficking and secretion in osteoclasts remain largely unknown. Here, we show with GeneChip analysis that RUN and FYVE domain-containing protein 4 (RUFY4) is strongly upregulated during osteoclastogenesis. Mice lacking Rufy4 exhibited a high trabecular bone mass phenotype with abnormalities in osteoclast function in vivo. Furthermore, deleting Rufy4 did not affect osteoclast differentiation, but inhibited bone-resorbing activity due to disruption in the acidic maturation of secondary lysosomes, their trafficking to the membrane, and their secretion of cathepsin K into the extracellular space. Mechanistically, RUFY4 promotes late endosome-lysosome fusion by acting as an adaptor protein between Rab7 on late endosomes and LAMP2 on primary lysosomes. Consequently, Rufy4-deficient mice were highly protected from lipopolysaccharide- and ovariectomy-induced bone loss. Thus, RUFY4 plays as a new regulator in osteoclast activity by mediating endo-lysosomal trafficking and have a potential to be specific target for therapies against bone-loss diseases such as osteoporosis.

Abstract Background Obesity is associated with airway hyperresponsiveness and lung fibrosis, which may reduce the effectiveness of standard asthma treatment in individuals suffering from both conditions. Statins and proprotein convertase subtilisin/kexin-9 inhibitors not only reduce serum cholesterol, free fatty acids but also diminish renin-angiotensin system activity and exhibit anti-inflammatory effects. These mechanisms may play a role in mitigating lung pathologies associated with obesity. Methods Male C57BL/6 mice were induced to develop obesity through high-fat diet for 16 weeks. Conditional TGF-β1 transgenic mice were fed a normal diet. These mice were given either atorvastatin or proprotein convertase subtilisin/kexin-9 inhibitor (alirocumab), and the impact on airway hyperresponsiveness and lung pathologies was assessed. Results High-fat diet-induced obesity enhanced airway hyperresponsiveness, lung fibrosis, macrophages in bronchoalveolar lavage fluid, and pro-inflammatory mediators in the lung. These lipid-lowering agents attenuated airway hyperresponsiveness, macrophages in BALF, lung fibrosis, serum leptin, free fatty acids, TGF-β1, IL-1β, IL-6, and IL-17a in the lung. Furthermore, the increased RAS, NLRP3 inflammasome, and cholecystokinin in lung tissue of obese mice were reduced with statin or alirocumab. These agents also suppressed the pro-inflammatory immune responses and lung fibrosis in TGF-β1 over-expressed transgenic mice with normal diet. Conclusions Lipid-lowering treatment has the potential to alleviate obesity-induced airway hyperresponsiveness and lung fibrosis by inhibiting the NLRP3 inflammasome, RAS and cholecystokinin activity. Graphical abstract

Abstract Background Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for detection of minimal residual disease (MRD), monitoring treatment response, and early detection of recurrence in cancer patients. In this study, we explored the utility of ctDNA‐based MRD detection to predict recurrence in a real‐world cohort of primarily early‐stage non‐small cell lung cancer (NSCLC) patients treated with curative intent. Methods Longitudinal plasma samples were collected post curative‐intent treatment from 36 patients with stage I–IV NSCLC. A personalized, tumor‐informed assay was used to detect and quantify ctDNA in plasma samples. Results Of the 24 patients with plasma samples available during the MRD window (within 6 months of curative surgery and before adjuvant therapy), ctDNA was detectable in two patients. Patients with ctDNA‐positivity during the MRD window were 15 times more likely to recur compared to ctDNA‐negative patients (HR: 15.0, 95% CI: 1.0–253.0, p = 0.010). At any time post‐curative intent treatment, ctDNA‐positivity was associated with significantly poorer recurrence‐free survival compared to persistently ctDNA‐negative patients (p

Abstract Dopamine plays important roles in cognitive function and inflammation and therefore is involved in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Drugs that increase or maintain dopamine levels in the brain could be a therapeutic strategy for AD. However, the effects of dopamine and its precursor levodopa (L-DOPA) on Aβ/tau pathology in vivo and the underlying molecular mechanisms have not been studied in detail. Here, we investigated whether L-DOPA treatment alters neuroinflammation, Aβ pathology, and tau phosphorylation in 5xFAD mice, a model of AD. We found that L-DOPA administration significantly reduced microgliosis and astrogliosis in 5xFAD mice. In addition, L-DOPA treatment significantly decreased Aβ plaque number by upregulating NEP and ADAM17 levels in 5xFAD mice. However, L-DOPA-treated 5xFAD mice did not exhibit changes in tau hyperphosphorylation or tau kinase levels. These data suggest that L-DOPA alleviates neuroinflammatory responses and Aβ pathology but not tau pathology in this mouse model of AD.

Background: Sleep accounts for approximately one-third of a person’s lifetime. It is a relaxing activity that relieves mental and physical fatigue. Pillows of different sizes, shapes, and materials have been designed to improve sleep quality by achieving an optimal sleep posture. Objects: This study aimed to determine which pillow provides the most comfortable and supports the head and neck during sleep, which may enhance sleep quality. Methods: Twenty-eight healthy adults (19 males and 9 females) with an average age of 29 years participated in this cross-sectional study. This experiment was conducted while the participants laid down for 5 minutes in four different pillow conditions: (1) no pillow (NP), (2) neck support foam pillow (NSFP), (3) standard microfiber filled pillow (SFP), and (4) hybrid foam pillow (HFP). The head-neck peak pressure, cranio-vertebral angle in supine (CVAs), cranio-horizontal angle in supine (CHAs), chin-sternum distance (CSD), and muscle tone of sternocleidomastoid were analyzed using one-way repeated measures analysis of variance (ANOVA). The significance level was set at p < 0.05. Results: The head-neck peak pressure was the highest in the NSFP condition, followed by the NP, SFP, and HFP conditions. The CVAs, CHAs, and CSD of the SFP were lower than those of the other pillows. Muscle tone was the highest in the NP condition, followed by the of NSFP, HFP, and SFP conditions. The participants subjective comfort level in both the supine and side-lying postures was highest in the HFP condition, followed by the SFP and NSFP conditions. Conclusion: This study can be used to establish the importance of pillow selection for highquality sleep. The results of this study, suggest that a hybrid pillow with a good supportive core and appropriate fluffiness can maintain comfort and correct cervical spine alignment during sleep.

Purpose Electroencephalography (EEG) is useful for clarifying the association between cortical activity and cognitive processes in children. We investigated whether EEG abnormalities were correlated with developmental delay/intellectual disability (DD/ID) in the absence of clinical seizures. Methods We retrospectively identified 166 children with DD/ID who underwent EEG at Pusan National University Hospital between January 2011 and December 2021. We compared clinical characteristics and test results between those with normal and those with abnormal EEGs. Additionally, we analyzed EEG abnormalities in relation to neurodevelopmental disorders, specifically autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Results Of the 166 patients, 39 (23.5%) displayed abnormal EEGs, while 127 (76.5%) had normal EEGs. Of the former, 25 (64.1%) patients exhibited epileptiform discharges, including 22 (56.3%) with focal and three (7.7%) with generalized discharges. Focal discharges most frequently affected the central area (35.9%). Twenty patients (51.3%) exhibited rhythmic slowing patterns. Epilepsy diagnoses were significantly more common among patients with abnormal EEGs (n=8, 20.5%) than among those with normal EEGs (n=9, 7.1%) (P

Abstract Background Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease that sometimes recurs in patients after kidney transplantation (KT) and increases the risk of graft loss. Proteinuria is a common early sign of recurrent FSGS, but an abrupt decrease in urine volume is rare. Herein, we report a patient with early recurrence of FSGS with anuria following KT. Case presentation A 55-year-old man with end-stage kidney disease caused by primary FSGS experienced anuria on postoperative day 2 following deceased donor KT. Laboratory results revealed that serum tacrolimus trough levels were consistently elevated at the time of anuria. At first, we considered acute calcineurin inhibitor (CNI) nephrotoxicity based on graft biopsy on light microscopy, laboratory findings, and clinical courses. However, the allograft function did not recover even after discontinuation of CNI, and recurrent FSGS was diagnosed 2 weeks later on electron microscopy. A total of 13 sessions of plasmapheresis and two administrations of rituximab (375 mg/m2) were required to treat recurrent FSGS. The patient achieved a partial response, and the spot urine protein-to-creatinine ratio decreased from 15.5 g/g creatinine to 5.2 g/g creatinine. At 5 months following KT, the serum creatinine level was stable at 1.15 mg/dL. Conclusions These findings highlight that anuria can occur in cases of early recurrence of FSGS combined with acute CNI nephrotoxicity.

Background: Several biologics have been developed and used to treat severe asthma. However, commercialized biologics have limitations in treating T2-low asthma because their main target is the T2 inflammation marker. Therefore, there is an unmet need for treating T2-low severe asthma. Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is an auxiliary protein in the mammalian multi-aminoacyl-tRNA synthetase complex. AIMP1 also acts as a cytokine and induces the secretion of proinflammatory cytokines. Since anti-AIMP1 has been shown to reduce interleukin (IL)-6, tumor necrosis factor-α, and IL-17A levels in a mouse model, it could be effective in the treatment of T2-low severe asthma. Methods: Wild-type BALB/c mice were sensitized and challenged with intranasal inoculation of a crude HDM extract. Atliximab, a chimeric AIMP1 antibody, was administered once (20 μg, 40 μg, 100 μg) on Day 14. We evaluated airway hyperresponsiveness (AHR), performed cellular analyses of the bronchoalveolar lavage fluid (BALF), measured inflammatory cytokine levels, and examined peribronchial histological features. Results: Atliximab reduced AIMP1 levels in asthmatic mice in a dose-dependent manner. AHR and Inflammatory cells such as neutrophils and eosinophils in the BALF decreased in asthmatic mice treated with atliximab. The levels of IL-6, IL-13, and transforming growth factor-β (TGF-β) in the lung tissue decreased in asthmatic mice treated with a high dose of atliximab (100 μg). Atliximab also reduced goblet cell hyperplasia and peribronchial fibrosis. Conclusions: Atliximab improved asthmatic airway inflammation including neutrophilic inflammation in HDM-induced asthma mice. These data suggest that anti-AIMP1 plays an important role in the treatment of severe T2-low asthma.

Background: Korean red ginseng extract (KRGE) (Family: Araliaceae) is one of the most widely used traditional herbs in Asia. Multiple studies have shown that KRGE has anti-inflammation, anti-fatigue, anti-obesity, anti-oxidant, and anti-cancer effects. Methods: Sprague-Dawley rats were divided into five groups for PTU-induced hypothyroidism and six groups for LT4-induced hyperthyroidism. At the experiment's conclusion, rats were sacrificed, and blood, thyroid gland, and liver samples were collected. Body weight was recorded weekly, and serum hormone levels were assessed using enzyme-linked immunoassay. Thyroid gland and liver tissues were stained with hematoxylin and eosin. KRGE was prepared in 0.5% CMC and stored at 4 °C before administration. Results: In the LT4-induced hyperthyroidism model, KRGE prevented decreases in body weight, thyroid gland weight, liver weight, serum glucose, and thyroid hormone levels compared to the PTU group. It also reduced increases in T3, T4, and serum aspartate aminotransferase levels after LT4 treatment. Additionally, KRGE improved thyroid gland and liver histopathology, effects not observed in the PTU-induced hypothyroidism model. Conclusion: All things considered, our research points to KRGE's potential protective role in rat hyperthyroidism caused by LT4 by lowering thyroid hormone production.

Objective: Currently, little is known about the mechanism(s) regulating global and specific protein translation during metabolic dysfunction-associated steatohepatitis (MASH; previously known as non-alcoholic steatohepatitis, NASH). Methods: Unbiased label-free quantitative proteome, puromycin-labelling and polysome profiling were used to understand protein translation activity in vitro and in vivo. Results: We observed a global decrease in protein translation during lipotoxicity in human primary hepatocytes, mouse hepatic AML12 cells, and livers from a dietary mouse model of MASH. Interestingly, proteomic analysis showed that Rplp1, which regulates ribosome and translation pathways, was one of the most downregulated proteins. Moreover, decreased Esrra expression and binding to the Rplp1 promoter, diminished Rplp1 gene expression during lipotoxicity. This, in turn, reduced global protein translation and Esrra/Rplp1-dependent translation of lysosome (Lamp2, Ctsd) and autophagy (sqstm1, Map1lc3b) proteins. Of note, Esrra did not increase its binding to these gene promoters or their gene transcription, confirming its regulation of their translation during lipotoxicity. Notably, hepatic Esrra-Rplp1-dependent translation of lysosomal and autophagy proteins also was impaired in MASH patients and liver-specific Esrra knockout mice. Remarkably, alternate day fasting induced Esrra-Rplp1-dependent expression of lysosomal proteins, restored autophagy, and reduced lipotoxicity, inflammation, and fibrosis in hepatic cell culture and in vivo models of MASH. Conclusions: Esrra regulation of Rplp1-mediated translation of lysosome/autolysosome proteins was downregulated during MASH. Alternate day fasting activated this novel pathway and improved MASH, suggesting that Esrra and Rplp1 may serve as therapeutic targets for MASH. Our findings also provided the first example of a nuclear hormone receptor, Esrra, to not only regulate transcription but also protein translation, via induction of Rplp1.

Our study was to explore the effects of subchronic particulate matter (PM) exposure on lung injury induced by polyhexamethylene guanidine phosphate (PHMG-p) in a rat model. Specifically, we investigated pulmonary inflammation, fibrosis, and tumor formation using chest computed tomography (CT), and histopathologic examination. PHMG-p was administered intratracheally to 20 male rats. After an initial week of PHMG-p treatment, the experimental group (PM group) received intratracheal administration of PM suspension, while the control group received normal saline. This regimen was continued for 10 weeks to induce subchronic PM exposure. Chest CT scans were conducted on all rats, followed by the extraction of both lungs for histopathological analysis. All CT images underwent comprehensive quantitative and qualitative analyses. Pulmonary inflammation was markedly intensified in rats subjected to subchronic PM exposure in the PM group compared to those in the control. Similarly, lung fibrosis was more severe in the PM group as observed on both chest CT and histopathologic examination. Quantitative chest CT analysis revealed that the mean lesion volume was significantly greater in the PM group than in the control group. Although the incidence of bronchiolo-alveolar hyperplasia was higher in the PM group compared to the control group, this difference was not statistically significant. In summary, subchronic PM exposure exacerbated pulmonary inflammation and fibrosis underlying lung injury induced by PHMG-p.

IntroductionPrevious studies on adolescent smoking cessation behavior based on the transtheoretical model have primarily focused on the development of cessation programs. Attempting to quit smoking is a prerequisite for executing smoking cessation. Appropriate methods must be selected based on the characteristics and intentions of individuals to increase smokers’ satisfaction and success rates in quitting. Therefore, this study aimed to identify changing processes influencing the stages of change associated with successful smoking cessation among adolescents and examined the related factors. This descriptive study explored a transtheoretical model of different stages of changes in smoking cessation behavior among adolescent smokers.MethodsThe participants included 237 middle and high school students in South Korea. We examined the differences in stages of changes in smoking cessation behaviors based on general characteristics, smoking-related characteristics, smoking cessation change processes (cognitive and behavioral), smoking decisional balance (pros and cons of smoking), and self-efficacy.ResultsThe probability of reaching the preparation stage of smoking cessation was significantly lower among participants who did not know their father’s educational level than among those who knew their father’s educational level. Conversely, this probability was significantly higher among participants whose mothers had a college or higher education level and those who did not know their mother’s educational level than in those whose mothers had a high school or lower education level.ConclusionThese findings indicated that parental education is a significant predictor of the preparation stage of smoking cessation, highlighting the importance of the family environment in facilitating smoking cessation among adolescents. Accordingly, communication and support at home could help reinforce adolescents’ determination to quit smoking and make relevant plans. Thus, smoking cessation support should stress the need to enhance communication at home.

Hemophilia B is a congenital bleeding disorder caused by factor IX (FIX) deficiency. Generation of recombinant FIX (rFIX) is required for detecting a Hemophilia B indicator, anti-FIX antibody. In this study, we described a method for producing recombinant FIX (rFIX) using Escherichia coli. We constructed a FIX-expressing plasmid without a fusion tag protein-encoding gene and produced rFIX as a soluble form within five days. Dose-dependent curve was obtained from ELISA using anti-FIX antibody, indicating that the rFIX can be used as an antigen to detect anti-FIX antibody with high affinity and sensitivity.

Background We aimed to identify the risk of incident depression according to cumulative exposure to a low-household income status in individuals with type 2 diabetes mellitus (T2DM). Methods For this retrospective longitudinal population-based cohort study, we used Korean National Health Insurance Service data from 2002 to 2018. Risk of depression was assessed according to cumulative exposure to low-household income status (defined as Medical Aid registration) during the previous 5 years among adults (aged ≥20 years) with T2DM and without baseline depression who underwent health examinations from 2009 to 2012 (n=2,027,317). Results During an average 6.23 years of follow-up, 401,175 incident depression cases occurred. Advance in cumulative number of years registered for medical aid during the previous 5 years from baseline was associated with an increased risk of depression in a dose-dependent manner (hazard ratio [HR], 1.44 [95% confidence interval (CI), 1.38 to 1.50]; HR, 1.40 [95% CI, 1.35 to 1.46]; HR, 1.42, [95% CI, 1.37 to 1.48]; HR, 1.46, [95% CI, 1.40 to 1.53]; HR, 1.69, [95% CI, 1.63 to 1.74] in groups with 1 to 5 exposed years, respectively). Insulin users exposed for 5 years to a low-household income state had the highest risk of depression among groups categorized by insulin use and duration of low-household income status. Conclusion Cumulative duration of low-household income status, defined as medical aid registration, was associated with an increased risk of depression in a dose-response manner in individuals with T2DM.

Abstract Polyhexamethylene guanidine phosphate (PHMG-p) is a major component in humidifier disinfectants, which cause life-threatening lung injuries. However, to our knowledge, no published studies have investigated associations between PHMG-p dose and lung damage severity with long-term follow-up. Therefore, we evaluated longitudinal dose-dependent changes in lung injuries using repeated chest computed tomography (CT). Rats were exposed to low (0.2 mg/kg, n = 10), intermediate (1.0 mg/kg, n = 10), and high (5.0 mg/kg, n = 10) doses of PHMG-p. All rats underwent repeated CT scans after 10 and 40 weeks following the first exposure. All CT images were quantitatively analyzed using commercial software. Inflammation/fibrosis and tumor counts underwent histopathological evaluation. In both radiological and histopathologic results, the lung damage severity increased as the PHMG-p dose increased. Moreover, the number, size, and malignancy of the lung tumors increased as the dose increased. Bronchiolar–alveolar hyperplasia developed in all groups. During follow-up, there was intergroup variation in bronchiolar–alveolar hyperplasia progression, although bronchiolar–alveolar adenomas or carcinomas usually increase in size over time. Thirty-three carcinomas were detected in the high-dose group in two rats. Overall, lung damage from PHMG-p and the number and malignancy of lung tumors were shown to be dose-dependent in a rat model using repeated chest CT scans during a long-term follow-up.

Abstract Intracranial arterial dolichoectasia (IADE) is associated with the interaction of hypertension and inflammation, and microcurrent can be effective in hypertension. Therefore, this study aimed to investigate the therapeutic effect of microcurrent electrical stimulation in a mouse IADE model. This study randomly categorized 20 mice into five groups: group 1-C (healthy control), group 2-D (IADE model), group 3-M + D (microcurrent administration before nephrectomy and until brain surgery), group 4-D + M (microcurrent administration for 4 weeks following brain surgery), and group 5-M (microcurrent administration for 4 weeks). Cerebral artery diameter and thickness and cerebral arterial wall extracellular matrix components were assessed. Among the five groups, group 2-D showed significantly higher cerebral arterial wall diameter (117.79 ± 17.05 µm) and proportion of collagen (42.46 ± 14.12%) and significantly lower arterial wall thickness (9.31 ± 2.26 µm) and proportion of smooth muscle cell (SMC) and elastin in the cerebral arterial wall (SMC: 38.05 ± 10.32%, elastin: 11.11 ± 6.97%). Additionally, group 4-D + M exhibited a non-significantly lower diameter (100.28 ± 25.99 µm) and higher thickness (12.82 ± 5.17 µm). Group 5-M demonstrated no evidence of toxicity in the liver and brain. The pilot study revealed that microcurrent is effective in preventing IADE development, although these beneficial effects warrant further investigation.

Background: Recently, plant-derived exosome-like nanoparticles (PDENs) have been isolated, and active research was focusing on understanding their properties and functions. In this study, the characteristics and molecular properties of ginseng root-derived exosome-like nanoparticles (GrDENs) were examined in terms of skin protection. Methods: HPLC-MS protocols were used to analyze the ginsenoside contents in GrDENs. To investigate the beneficial effect of GrDENs on skin, HaCaT cells were pre-treated with GrDENs (0–2 × 109 particles/mL), and followed by UVB irradiation or H2O2 exposure. In addition, the antioxidant activity of GrDENs was measured using a fluorescence microscope or flow cytometry. Finally, molecular mechanisms were examined with immunoblotting analysis. Results: GrDENs contained detectable levels of ginsenosides (Re, Rg1, Rb1, Rf, Rg2 (S), Gyp17, Rd, C-Mc1, C–O, and F2). In UVB-irradiated HaCaT cells, GrDENs protected cells from death and reduced ROS production. GrDENs downregulated the mRNA expression of proapoptotic genes, including BAX, caspase-1, -3, -6, -7, and -8 and the ratio of cleaved caspase-8, -9, and -3 in a dose-dependent manner. In addition, GrDENs reduced the mRNA levels of aging-related genes (MMP2 and 3), proinflammatory genes (COX-2 and IL-6), and cellular senescence biomarker p21, possibly by suppressing activator protein-1 signaling. Conclusions: This study demonstrates the protective effects of GrDENs against skin damage caused by UV and oxidative stress, providing new insights into beneficial uses of ginseng. In particular, our results suggest GrDENs as a potential active ingredient in cosmeceuticals to promote skin health.

Background Mechanical power (MP) has been reported to be associated with clinical outcomes. Because the original MP equation is derived from paralyzed patients under volume-controlled ventilation, its application in practice could be limited in patients receiving pressure-controlled ventilation (PCV). Recently, a simplified equation for patients under PCV was developed. We investigated the association between MP and intensive care unit (ICU) mortality. Methods We conducted a retrospective analysis of Korean data from the Fourth International Study of Mechanical Ventilation. We extracted data of patients under PCV on day 1 and calculated MP using the following simplified equation: MPPCV = 0.098 ∙ respiratory rate ∙ tidal volume ∙ (ΔPinsp + positive end-expiratory pressure), where ΔPinsp is the change in airway pressure during inspiration. Patients were divided into survivors and non-survivors and then compared. Multivariable logistic regression was performed to determine association between MPPCV and ICU mortality. The interaction of MPPCV and use of neuromuscular blocking agent (NMBA) was also analyzed. Results A total of 125 patients was eligible for final analysis, of whom 38 died in the ICU. MPPCV was higher in non-survivors (17.6 vs. 26.3 J/min, P

Dual immunoglobulin domain-containing cell adhesion molecule (DICAM) is a type I transmembrane protein that presents in various cells including renal tubular cells. This study evaluated the expression and protective role of DICAM in renal tubular cell injury. HK-2 cells were incubated and treated with lipopolysaccharide (LPS, 30 μg/mL) or hydrogen peroxide (H2O2, 100 μM) for 24 h. To investigate the effect of the gene silencing of DICAM, small interfering RNA of DICAM was used. Additionally, to explain its role in cellular response to injury, DICAM was overexpressed using an adenoviral vector. DICAM protein expression levels significantly increased following treatment with LPS or H2O2 in HK-2 cells. In response to oxidative stress, DICAM showed an earlier increase (2–4 h following treatment) than neutrophil gelatinase-associated lipocalin (NGAL) (24 h following treatment). DICAM gene silencing increased the protein expression of inflammation-related markers, including IL-1β, TNF-α, NOX4, integrin β1, and integrin β3, in H2O2-induced HK-2 cell injury. Likewise, in the LPS-induced HK-2 cell injury, DICAM knockdown led to a decrease in occludin levels and an increase in integrin β3, IL-1β, and IL-6 levels. Furthermore, DICAM overexpression followed by LPS-induced HK-2 cell injury resulted in an increase in occludin levels and a decrease in integrin β1, integrin β3, TNF-α, IL-1β, and IL-6 levels, suggesting an alleviating effect on inflammatory responses. DICAM was elevated in the early stage of regular tubular cell injury and may protect against renal tubular injury through its anti-inflammatory properties. DICAM has a potential as an early diagnostic marker and therapeutic target for renal cell injury.

Abstract Over the past decade, numerous studies have highlighted the importance of acid sphingomyelinase (ASM) in disease treatment in humans. This enzyme functions primarily to generate ceramide, maintain the cellular membrane, and regulate cellular function. However, in the blood and brain of patients with neurological disorders, including major depression, ischemic stroke, amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer’s disease (AD), elevated ASM levels significantly suggest disease onset or progression. In these diseases, increased ASM is profoundly involved in neuronal death, abnormal autophagy, neuroinflammation, blood–brain barrier disruption, hippocampal neurogenesis loss, and immune cell dysfunction. Moreover, genetic and pharmacological inhibition of ASM can prevent or ameliorate various diseases. The therapeutic effects of ASM inhibition have prompted the urgent need to develop ASM inhibitors, and several ASM inhibitors have been identified. In this review, we summarize the current knowledge on the critical roles and mechanisms of ASM in brain cells and blood that are associated with different neuropathological features, especially those observed in AD. Furthermore, we elucidate the potential possibility and limitations of existing ASM-targeting drugs according to experimental studies in neurological disorder mouse models.

Abstract To identify risk factors and biomarker for early recurrence in patients diagnosed with pancreatic cancer who undergo curative resection. Early recurrence after curative resection of pancreatic cancer is an obstacle to long-term survival. We retrospectively reviewed 162 patients diagnosed with pancreatic cancer who underwent curative resection. Early recurrence was defined as recurrence within 12 months of surgery. We selected S100A2 as a biomarker and investigated its expression using immunohistochemistry. Of the total, 79.6% (n = 129) of patients received adjuvant chemotherapy after surgery and 117 (72.2%) experienced recurrence, of which 73 (45.1%) experience early recurrence. In multivariate analysis, age 5) was significantly lower in the early recurrence group (41.5% vs. 63.3%, P = 0.020). The cumulative incidence rate of early recurrence was higher in patients with an S100A2 H-score

Summary: Purpose: This study explored the work adjustment trajectory and its predictors and characteristics among newly registered nurses. Methods: A total of 245 newly registered nurses working in a university hospital provided general baseline characteristics and completed a work adjustment questionnaire along with self-report measures of clinical competency, psychological capital, preceptor exchange, social support, and role conflict when they started working independently (baseline) and at 7 and 12 months after employment. Data were collected from July 2020 to August 2022. The collected data were subjected to a group-based trajectory model, χ2 test, F test, one-way ANOVA, and multiple logistic regression using SAS 9.4, and SPSS 25.0. Results: Group-based trajectory modeling classified three newly registered nurse groups: nurses with a high work adjustment level in all subscales from the beginning of employment (early adjustment group, 16.1%), nurses with a moderate level of adjustment from beginning to end (standard adjustment group, 60.6%), and nurses with a low level of work adjustment from early to mid-term, rising later (delayed adjustment group, 23.3%). Higher hope, optimism, and emotional support predicted early and standard adjustments. Conclusions: Based on the trajectory characteristics, newly registered nurses need to improve their work adjustment. The early and standard adjustment groups should continuously monitor their levels of work adjustment while monitoring their hopes, optimism, and emotional support. In particular, the delayed adjustment group required customized educational programs and strengthened peer support.

Abstract The polymeric gel electrolytes are attractive owing to their higher ionic conductivities than those of dry polymer electrolytes and lowered water activity for enlarged potential window. However, the ionic conductivity and mechanical strength of the Na‐ion conducting polymeric gel electrolytes are limited by below 20 mS cm−1 and 2.2 MPa. Herein, we demonstrate Na‐ion conducting and flexible polymeric hydrogel electrolytes of the chemically coupled poly(diallyldimethylammonium chloride)‐dextrin‐N,N′‐methylene‐bis‐acrylamide film immersed in NaClO4 solution (ex‐DDA‐Dex + NaClO4) for flexible sodium‐ion hybrid capacitors (f‐NIHC). In particular, the anion exchange reaction and synergistic interaction of ex‐DDA‐Dex with the optimum ClO4− enable to greatly improve the ionic conductivity up to 27.63 mS cm−1 at 25°C and electrochemical stability window up to 2.6 V, whereas the double networking structure leads to achieve both the mechanical strength (7.48 MPa) and softness of hydrogel electrolytes. Therefore, the f‐NIHCs with the ex‐DDA‐Dex + NaClO4 achieved high specific and high‐rate capacities of 192.04 F g−1 at 500 mA g−1 and 116.06 F g−1 at 10 000 mA g−1, respectively, delivering a large energy density of 120.03 W h kg−1 at 906 W kg−1 and long cyclability of 70% over 500 cycles as well as demonstrating functional operation under mechanical stresses.

Bone damage is one of the main causes of disability in humans, and tissue engineering technology by applying biomaterial-based scaffold has been developed as an effective solution. This can be achieved using various natural and synthetic polymers combined with carbon-based and metal-oxide materials. Therefore, this study aimed to develop bone scaffold using collagen, alginate, and poly(vinyl alcohol), with the addition of multi-walled carbon nanotube, reduced graphene oxide, titanium dioxide, and zinc oxide materials. Scaffold was fabricated with the freeze-drying method and characterized physicochemically by observing the morphology through scanning electron microscopy (SEM), identification of functional groups by Fourier transform infrared spectroscopy (FTIR), compressive mechanical properties, porosity, and degradation rate. The results showed that each group of scaffold had a compact structure, with a small pore size and less than 50% porosity. The functional groups of each material were detected, and the compressive strength matched the trabecular bone, approximately 6 MPa. However, the scaffold lacked appropriate porosity and a fast degradation rate exceeding 35% in 7 days.

This paper gives an extensive analysis on the characterization of xenon isotopic ratios for various nuclear reactors and nuclear explosions through neutronic depletion codes. The results of the characterization can be used for discriminating the sources of the xenon isotopes’ release among the nuclear explosions and nuclear reactors. The considered sources of the xenon radionuclides do not only include PWR, CANDU, and nuclear explosions using uranium and plutonium bombs, but also IRT-200 and 5MWe Yongbyon (MAGNOX reactor) research reactors operated in North Korea. A new data base (DB) on xenon isotopic activity ratios was produced using the results of the characterization, which can be used in discrimination of the sources of xenon isotopes. The results of the study show that 5MWe Yongbyon reactor has quite different characteristics in 135Xe/133Xe ratio from the PWRs and the nuclear reactors have different characteristics in 135Xe/133Xe ratios from the nuclear explosions.

Recent threats to deep learning-based biometric authentication systems stem from adversarial attacks exploiting vulnerabilities in deep learning models. While existing studies extensively analyze the risk of such attacks, they primarily focus on isolated modules (e.g., liveness detectors or identity matchers) or specific adversarial attack types (e.g., evasion and poisoning attacks). In this paper, we introduce a novel approach that comprehensively assesses the risk of adversarial attacks by simulating multiple scenarios within biometric authentication systems. We identify the surfaces susceptible to adversarial attacks within these systems and devise scenarios that reflect the dependencies between modules. Moreover, we establish evaluation metrics to comprehensively assess the risk involved. Through a case study conducted on a real-world face recognition system, we successfully demonstrate the effectiveness of our approach. Our approach facilitates the systematic evaluation of the security of target biometric authentication systems against adversarial attacks. Ultimately, it enables the establishment of robust and proactive defense mechanisms.

Abstract Background Canine mammary gland cancer (CMGC) is a common neoplasm in intact bitches. However, the benefit of adjuvant chemotherapy is unclear. The aim of this study was to investigate the anti-proliferative effects of paclitaxel on CMGC in in-vitro and in-vivo settings. Results Paclitaxel dose-dependently inhibited viability and induced G2/M phase cell cycle arrest and apoptosis in both primary and metastatic CMGC cell lines (CIPp and CIPm). In animal experiments, the average tumour volume decreased significantly in proportion to the administered oral paclitaxel dose. By examining tumour tissue using a TUNEL assay and immunohistochemical staining with anti-CD31 as a marker of endothelial differentiation, respectively, it was confirmed that oral paclitaxel induced apoptosis and exerted an anti-angiogenetic effect in tumour tissues. Further, downregulation of cyclin D1 in tumour tissues suggested that oral paclitaxel induced cell cycle arrest in tumour tissues in-vivo. Conclusions Our results suggest that paclitaxel may have anti-cancer effects on CMGC through cell cycle arrest, induction of apoptosis, and anti-angiogenesis. This study could provide a novel approach to treat CMGC.

Abstract Smart farms and precision agriculture require automatic monitoring and supply of water and nutrients for crops, but sensors to monitor plant available nutrients in soil are not available. Soil electrical conductivity (EC) is related to nutrients in soil solution, which can be affected by soil organic matter, soil texture, temperature, and water content. Therefore, the objective of this study is to evaluate factors influencing soil EC sensor values by monitoring EC under different soil organic matter and water contents. Ten soil samples with various sand and clay contents, EC, pH, and organic matter contents were selected and saturated with water. Volumetric water content and EC of the soil were monitored while drying the soil. Humic acid and manure were added to soils in order to evaluate the effect of organic matter on soil EC. Soil EC values linearly increased with increasing water content at 10–25% which is favorable water content for plant growth. The EC increased when organic matter was added to soils, which was related to ions released from the organic matter. Soil EC calibration factor for soil water content increased when EC of the soil was high and organic matter was added. The sensor EC values in sandy loam and loam soils was related to the ion contents in pore water, and exchangeable ions in soil, respectively. Sensor EC values were highly correlated with organic matter and K contents in soil and can be used as an indicator for plant available nutrients in soil. Therefore, the sensor EC at optimal soil water content for plant growth can be used to monitor changes in plant available nutrients in soil.

Abstract Background After the revision of the Korean Pharmaceutical Affairs Act, the certification of specialized pharmacists is scheduled to be legally recognized in 2023. Considering that the specialized pharmacist certification was developed based on the working model of hospital clinical pharmacists, it is necessary to establish standards for clinical pharmacists in hospitals and to calculate appropriate manpower. Through this study, we aim to establish practical standards for clinical pharmacists and propose a method for calculating staffing levels based on an investigation of actual workloads. Methods This survey-based study consisted of two phases. In the first phase, a literature review was conducted to establish standards for clinical pharmacy services, and tasks in relevant literature were classified to identify clinical pharmacy service tasks that are applicable to the practice of Korean hospitals. Additionally, a preliminary survey was conducted to investigate the essential tasks. In the second phase of the investigation, a multicenter survey was conducted targeting pharmacists in facilities with more than 1,000 beds to explore their perceptions and actual workloads related to tasks. Results According to the standards for clinical pharmacists in Korea, clinical pharmacy services consist of a total of 23 tasks, of which 16 have been identified as essential tasks. Essential tasks accounted for 93% of the total tasks in clinical pharmacy services. The average full-time equivalent (FTE) through workload calculation was 2.5 ± 1.9 for each field, while the FTE allocated to actual practice was 2.1 ± 1.6. The distribution of each type of clinical pharmacy service was as follows: 77% for medication therapy management, 13% for medication education, 8% for multidisciplinary team activities, and 3% for medication use evaluation. Conclusion This study identified essential tasks common to clinical pharmacy services across different healthcare institutions. However, the FTE of clinical pharmacists in actual practice was insufficient compared to the required amount. In order to establish and expand clinical pharmacy services in a hospital, it is necessary to ensure an adequate workforce for essential tasks.

Abstract Background Recent studies using single-cell transcriptomic analysis have reported several distinct clusters of neoplastic epithelial cells and cancer-associated fibroblasts in the pancreatic cancer tumor microenvironment. However, their molecular characteristics and biological significance have not been clearly elucidated due to intra- and inter-tumoral heterogeneity. Methods We performed single-cell RNA sequencing using enriched non-immune cell populations from 17 pancreatic tumor tissues (16 pancreatic cancer and one high-grade dysplasia) and generated paired spatial transcriptomic data from seven patient samples. Results We identified five distinct functional subclusters of pancreatic cancer cells and six distinct cancer-associated fibroblast subclusters. We deeply profiled their characteristics, and we found that these subclusters successfully deconvoluted most of the features suggested in bulk transcriptome analysis of pancreatic cancer. Among those subclusters, we identified a novel cancer cell subcluster, Ep_VGLL1, showing intermediate characteristics between the extremities of basal-like and classical dichotomy, despite its prognostic value. Molecular features of Ep_VGLL1 suggest its transitional properties between basal-like and classical subtypes, which is supported by spatial transcriptomic data. Conclusions This integrative analysis not only provides a comprehensive landscape of pancreatic cancer and fibroblast population, but also suggests a novel insight to the dynamic states of pancreatic cancer cells and unveils potential therapeutic targets. Graphical Abstract