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This study investigates the applicability of the system theory framework (STF) to Korean university students with regard to their career development and counseling. The STF-based career group program content consists of MSCI (My System of Career Influences) and MCC (My Career Chapter), and is conducted over ten sessions for two groups of college students in Korea. Following the program's conclusion, the participants were asked about its usefulness and their experiences participating. An analysis of the survey results revealed the participants to have rated the program as useful. Subsequently, a qualitative analysis was conducted using the Consensual Qualitative Research (CQR) technique, and four domains and ten categories were derived. Further, the significance and the limitations of the research were discussed.

During an investigation of Korean Ascomycetes in 2023, we found two undescribed species from South Korea. We analyzed them using a combined approach, including morphological and phylogenetic analyses of the rDNA regions (internal transcribed spacer and large subunit). The two species were identified to belong to the genus Geoglossum; the species G. simile and a new species named G. subdifforme sp. nov. The phylogenetic tree constructed using the ITS region showed that G. subdifforme is closely related to G. difforme. These species are distinguishable by certain morphological characteristics, particularly the size and septae of ascospores. Morphologically, G. simile is related to G. glabrum, but it is distinguishable by the morphological characteristics of paraphyses as well as ITS sequences. In this study, the descriptions, photographs, and phylogenetic relationships of these Geoglossum species are presented.

Abstract This retrospective study aimed to evaluate the difference in the temporomandibular joint (TMJ) space volume between the deviated (Dev) and non-deviated (NDev) side following transoral vertical ramus osteotomy (TOVRO) in patients with mandibular prognathism combined with asymmetry using reconstructed 3-dimensional images. Sixty joints from 30 patients who underwent TOVRO between January 2018 and December 2021 were included. Computed tomography (CT) or cone-beam CT was performed before surgery (T0), and 6 (T1) and 12 months postoperatively (T2). The volume of the overall joint space (Vjs) and its compartments (i.e., the anterior, posterior, medial, and lateral joint spaces) were calculated at each time point. A linear mixed model and repeated-measures covariance pattern with unstructured covariance were used. Vjs increased at T1 compared to T0 and decreased at T2 compared to T1 (p 0.05). Adjustments for sex and mandibular movements did not affect the results. This study can provide the basis in TMJ spatial change and predicting the prognosis after TOVRO in facial asymmetry.

Background/Aims: We investigated the clinical practice patterns of Korean endoscopists for the endoscopic resection of colorectal polyps. Methods: From September to November 2021, an online survey was conducted regarding the preferred resection methods for colorectal polyps, and responses were compared with the international guidelines. Results: Among 246 respondents, those with

Abstract In breast-conserving surgery (BCS), clear resection margins are crucial to prevent recurrence. Accurate imaging is vital for precise BCS, with MRI being the most accurate. However, MRI has limitations in identifying the exact extent of breast cancer in patients who have undergone neoadjuvant chemotherapy (NACT). A 3D-Printed Breast Surgical Guide (3DP-BSG) can address this issue by effectively pinpointing cancer extent in NACT patients, thus enhancing surgical accuracy. This retrospective single-institution cohort study focused on female patients diagnosed with invasive breast cancer who underwent NACT. Between November 2015 and October 2021, patients received BCS with the aid of a 3DP-BSG. Personalized 3DP-BSG targeted tumors by tracking changes in breast and tumor anatomy on MRI before and after NACT. 203 patients with invasive breast cancer were enrolled in the study. According to exclusion criteria, 197 patients were analyzed. The median follow-up period was 35.3 months (range: 2.2–96.8 months). 3 patients (1.5%) had positive resection margins. During the follow-up period, 17 patients (8.6%) experienced recurrence, with one patient (0.5%) confirmed local recurrences. The application of MRI-based 3DP-BSG is effective in achieving low positive margins and local recurrence in patients undergoing BCS after NACT, offering a promising approach for improving surgical outcomes.

Abstract Background Brain-computer interface (BCI) technology can enhance neural plasticity and motor recovery in persons with stroke. However, the effects of BCI training with motor imagery (MI)-contingent feedback versus MI-independent feedback remain unclear. This study aimed to investigate whether the contingent connection between MI-induced brain activity and feedback influences functional and neural plasticity outcomes. We hypothesized that BCI training, with MI-contingent feedback, would result in greater improvements in upper limb function and neural plasticity compared to BCI training, with MI-independent feedback. Methods This randomized controlled trial included persons with chronic stroke who underwent BCI training involving functional electrical stimulation feedback on the affected wrist extensor. Primary outcomes included the Medical Research Council (MRC) scale score for muscle strength in the wrist extensor (MRC-WE) and active range of motion in wrist extension (AROM-WE). Resting-state electroencephalogram recordings were used to assess neural plasticity. Results Compared to the MI-independent feedback BCI group, the MI-contingent feedback BCI group showed significantly greater improvements in MRC-WE scores (mean difference = 0.52, 95% CI = 0.03–1.00, p = 0.036) and demonstrated increased AROM-WE at 4 weeks post-intervention (p = 0.019). Enhanced functional connectivity in the affected hemisphere was observed in the MI-contingent feedback BCI group, correlating with MRC-WE and Fugl-Meyer assessment-distal scores. Improvements were also observed in the unaffected hemisphere’s functional connectivity. Conclusions BCI training with MI-contingent feedback is more effective than MI-independent feedback in improving AROM-WE, MRC, and neural plasticity in individuals with chronic stroke. BCI technology could be a valuable addition to conventional rehabilitation for stroke survivors, enhancing recovery outcomes. Trial registration CRIS (KCT0009013).

Abstract The mechanistic link between the complex mutational landscape of de novo methyltransferase DNMT3A and the pathology of acute myeloid leukemia (AML) has not been clearly elucidated so far. Motivated by a recent discovery of the significance of DNMT3A-destabilizing mutations (DNMT3A INS) in AML, we here investigate the common characteristics of DNMT3A INS AML methylomes through computational analyses. We present that methylomes of DNMT3A INS AMLs are considerably different from those of DNMT3A R882 AMLs in that they exhibit increased intratumor DNA methylation heterogeneity in bivalent chromatin domains. This epigenetic heterogeneity was associated with the transcriptional variability of developmental and membrane-associated factors shaping stem cell niche, and also was a predictor of the response of AML cells to hypomethylating agents, implying that the survival of AML cells depends on stochastic DNA methylations at bivalent domains. Altogether, our work provides a novel mechanistic model suggesting the genomic origin of the aberrant epigenomic heterogeneity in disease conditions.

Abstract Polarization-sensitive optical coherence tomography (PS-OCT) measures the polarization state of backscattered light from tissues and provides valuable insights into the birefringence properties of biological tissues. Contrastive unpaired translation (CUT) was used in this study to generate a synthetic PS-OCT image from a single OCT image. The challenges related to extensive data requirements relying on labeled datasets using only pixel-wise correlations that make it difficult to efficiently regenerate the periodic patterns observed in PS-OCT images were addressed. The CUT model captures birefringence patterns by leveraging patch-wise correlations from unpaired data, which allows learning of the underlying structural features of biological tissues responsible for birefringence. To demonstrate the performance of the proposed approach, three generative models (Pix2pix, CycleGAN, and CUT) were compared on an in vivo dataset of injured mouse tendons over a six-week healing period. CUT outperformed Pix2pix and CycleGAN by producing high-fidelity synthetic PS-OCT images that closely matched the original PS-OCT images. Pearson correlation and two-way ANOVA tests confirmed the superior performance of CUT (p-value

Multi-gene assays have been widely used to predict the recurrence risk for hormone receptor (HR)-positive breast cancer patients. However, these assays lack explanatory power regarding the underlying mechanisms of the recurrence risk. To address this limitation, we proposed a novel multi-layered knowledge graph neural network for the multi-gene assays. Our model elucidated the regulatory pathways of assay genes and utilized an attention-based graph neural network to predict recurrence risk while interpreting transcriptional subpathways relevant to risk prediction. Evaluation on three multi-gene assays—Oncotype DX, Prosigna, and EndoPredict—using SCAN-B dataset demonstrated the efficacy of our method. Through interpretation of attention weights, we found that all three assays are mainly regulated by signaling pathways driving cancer proliferation especially RTK-ERK-ETS-mediated cell proliferation for breast cancer recurrence. In addition, our analysis highlighted that the important regulatory subpathways remain consistent across different knowledgebases used for constructing the multi-level knowledge graph. Furthermore, through attention analysis, we demonstrated the biological significance and clinical relevance of these subpathways in predicting patient outcomes. The source code is available at http://biohealth.snu.ac.kr/software/ExplainableMLKGNN.

Parkinson’s disease (PD) often results in hippocampal dysfunction, which leads to cognitive and emotional challenges and synaptic irregularities. This study attempted to assess behavioral anomalies and identify differentially expressed genes (DEGs) within the hippocampus of a hemiparkinsonian rat model to potentially uncover novel genetic candidates linked to hippocampal dysfunction. Striatal 6-hydroxydopamine (6-OHDA) infusions were performed unilaterally in the brains of adult SD rats, while dopaminergic impairments were verified in rats with 6-OHDA-lesioned striata. RNA sequencing and gene expression analysis unveiled 1018 DEGs in the ipsilateral rat hippocampus following 6-OHDA infusion: 631 genes exhibited upregulation, while 387 genes were downregulated (with FDR-adjusted p-value 1.5). Gene ontology analysis of DEGs indicated that alterations in the hippocampi of 6-OHDA-lesioned rats were primarily associated with synaptic signaling, axon development, behavior, postsynaptic membrane, synaptic membrane, neurotransmitter receptor activity, and peptide receptor activity. The Kyoto Encyclopedia of Genes and Genomes analysis of DEGs demonstrated significant enrichment of the neuroactive ligand–receptor interaction, calcium signaling pathway, cAMP signaling pathway, axon guidance, and notch signaling pathway in rat hippocampi that had been subjected to striatal 6-OHDA infusion. STRING analysis confirmed a notable upregulation of eight hub genes (Notch3, Gng4, Itga3, Grin2d, Hgf, Fgf11, Htr3a, and Col6a2), along with a significant downregulation of two hub genes (Itga11 and Plp1), as validated by reverse transcription-quantitative polymerase chain reaction. This study provides a comprehensive transcriptomic profile of the hippocampi in a hemiparkinsonian rat model, thereby offering insights into the signaling pathways underlying hippocampal dysfunction.

Developing new strawberry varieties with high level of disease resistance and superior fruit quality is critical for strawberry production. Despite the complexity of the octoploid strawberry genome, recent advances in genomics and DNA sequencing technologies have allowed us to identify causal sequence variants associated with specific phenotypes. These have enabled the development of new and improved DNA markers for integration in marker-assisted breeding (MAB) efforts. The use of MAB has significantly improved the efficiency of stacking loci responsible for disease resistance and fruit quality characteristics. The “Strawberry DNA Testing Handbook” is currently accessible in the Genome Database for Rosaceae and has been an essential resource for the national and international strawberry research community. Based on the information provided in the handbook, the UF strawberry breeding program implemented seedling selection from 2021 to 2023, retaining 25.3%, 19.2%, and 37.9% of seedlings for further evaluation in each respective year. In this report, we provide updates on DNA markers associated with disease resistance and fruit quality traits. Additionally, we demonstrate the practical implementation of these markers in high-throughput marker-assisted selection and their potential to enhance strawberry breeding.

Abstract Background Early diagnosis of Nonalcoholic steatohepatitis (NASH) is crucial to prevent its progression to hepatocellular carcinoma, but its gold standard diagnosis still requires invasive biopsy. Here, a new marker-based noninvasive chemical biopsy approach is introduced that uses urine-secreted tyrosine metabolites. Methods We first identified NASH-specific decrease in TAT expression, the first enzyme in the tyrosine degradation pathway (TDP), by employing exometabolome-transcriptome correlations, single-cell RNA -seq, and tissue staining on human NASH patient samples. A selective extrahepatic monitoring of the TAT activity was established by the chemical biopsy exploiting the enzyme’s metabolic conversion of D2-tyrosine into D2-4HPP. The approach was applied to a NASH mouse model using the methionine-choline deficient diet, where urine D2-4HPP level was measured with a specific LC-MS detection, following oral administration of D2-tyrosine. Results The noninvasive urine chemical biopsy approach could effectively differentiate NASH from normal mice (normal = 14, NASH = 15, p = 0.0054), correlated with the NASH pathology and TAT level decrease observed with immunostaining on the liver tissue. In addition, we showed that the diagnostic differentiation could be enhanced by measuring the downstream metabolites of TDP. The specificity of the TAT and the related TDP enzymes in NASH were also addressed in other settings employing high fat high fructose mouse NASH model and human obesity vs. NASH cohort. Conclusions Overall, we propose TAT and TDP as pathology-relevant markers for NASH and present the urine chemical biopsy as a noninvasive modality to evaluate the NASH-specific changes in urine that may help the NASH diagnosis.

This report presents the case of a 39-year-old male with left temporomandibular joint movement disorder and left facial sensory abnormalities after a trigeminal nerve tumor removal. Integrative Korean medicine treatments, including acupuncture, electroacupuncture, pharmacoacupuncture, Chuna manual therapy, wet-cupping, and herbal medicine administration, were performed on the patient. Post treatments, the patient’s visual analog scale score for pain decreased, the Jaw Functional Limitation Scale-8 scores improved, and significant improvements in chewing and yawning were noted. The patient’s maximum unassisted opening increased to 50 mm, as confirmed using temporomandibular joint radiography. However, further research is required to evaluate the individual effects of the integrative Korean medicine treatments and their overall effectiveness.

Abstract Oncolytic viruses (OV) are designed to selectively infect and kill cancer cells, while simultaneously eliciting antitumour immunity. The mechanism is expected to originate from infected cancer cells. However, recent reports of tumour regression unaccompanied by cancer cell infection suggest a more complex mechanism of action. Here, we engineered vesicular stomatitis virus (VSV)ΔM51-sensitive and VSVΔM51-resistant tumour lines to elucidate the role of OV-infected cancer and non-cancer cells. We found that, while cancer cell infections elicit oncolysis and antitumour immunity as expected, infection of non-cancer cells alone can also contribute to tumour regression. This effect is partly attributed to the systemic production of cytokines that promote dendritic cell (DC) activation, migration and antigen cross-presentation, leading to magnified antitumour CD8+ T cell activation and tumour regression. Such OV-induced antitumour immunity is complementary to PD-1 blockade. Overall, our results reveal mechanistic insights into OV-induced antitumour immunity that can be leveraged to improve OV-based therapeutics.

The intestine and liver share a unique regenerative property that sets them apart from other mammalian visceral organs. The intestinal epithelium exhibits rapid renewal, making it one of the fastest renewing tissues in humans. Under physiological conditions, intestinal stem cells within each intestinal crypt continuously differentiate into the different types of intestinal epithelial cells to maintain intestinal homeostasis. However, when exposed to tissue damage or stressful conditions such as inflammation, intestinal epithelial cells in the gastrointestinal tract exhibit plasticity, allowing fully differentiated cells to regain their stem cell properties. Likewise, hepatic epithelial cells possess a remarkable regenerative capacity to restore lost liver mass through proliferation-mediated liver regeneration. When the proliferation-mediated regenerative capacity is impaired, hepatocytes and biliary epithelial cells (BECs) can undergo plasticity-mediated regeneration and replenish each other. The transition of mammalian liver progenitor cells to hepatocytes/BECs can be observed under tightly controlled experimental conditions such as severe hepatocyte injury accompanied by the loss of regenerative capacity. In this review, we will discuss the mechanism by which cellular plasticity contributes to the regeneration process and the potential therapeutic implications of understanding and harnessing cellular plasticity in the gut and liver.

Abstract Introduction Real-world data are needed to understand the effectiveness of new therapeutic options for low-density lipoprotein cholesterol (LDL-C) reduction in Asia–Pacific clinical practice. Description of evolocumab use among adults with establisHed Atherosclerotic cardiovascuLar diseasE or hypercholesterolemia in ASia–Pacific region (HALES) was performed to better understand characteristics of and clinical decision-making for adults with established atherosclerotic cardiovascular disease/hypercholesterolemia after local evolocumab approval. Methods The HALES observational study, conducted at 33 sites (Hong Kong, Thailand, South Korea, Singapore, Taiwan, and Australia) comprised (1) chart review of patients who received evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i), and (2) physician/patient survey and one-time data collection of patients with high cardiovascular risk initiating evolocumab or initiating/continuing non-PCSK9i lipid-lowering therapy. Patients could only enroll in (1) or (2). Results Chart review included 724 very high-risk patients initiating evolocumab from regulatory approval to 2021. From median baseline LDL-C of 3.2 mmol/L (123.7 mg/dL), patients had a median percent change in LDL-C of − 60.8% at 1–6 months. Goal achievement increased from 7.9% to 69.8% for

Background/purpose: In clinical settings, there may be a need for a guide device that is simple and enhances the positioning accuracy of prosthetics. This study aimed to compare the accuracy of implant positioning using two methods: implant placement with a simple guide device (SGD) and freehand surgery. Materials and methods: A total of 103 patients were randomly assigned to the control or study group. In the control group, implant placement was performed using the freehand technique. In the study group, implant placement was conducted with an SGD. Implant positioning accuracy was assessed by measuring how much the central position, fixture angulation, and fixture position differed from the ideal implant position based on periapical radiographs and cone-beam computed tomography images. In patients with double implants, parallelism between the two fixtures was also measured. Results: There were 124 subjects, with 84 having single implants (42 in the control group and 42 in the study group) and 40 having double implants (20 in the control group and 20 in the study group). Utilization of the SGD for both single and double implant placement improved the accuracy of the central position, fixture angulation, and fixture position (P

Abstract Low muscle mass is a risk factor for mortality in patients with chronic kidney disease (CKD). However, it is not clear to what extent low muscle mass contributes to this risk, either independently or in combination with metabolic abnormalities and frailty. This study used data from the National Health and Nutrition Examination Survey 1999–2006 and 2011–2018. Low muscle mass was defined as Appendicular Skeletal Mass Index

Abstract Recent studies showed that the likelihood of drug approval can be predicted with clinical data and structure information of drug using computational approaches. Predicting the likelihood of drug approval can be innovative and of high impact. However, models that leverage clinical data are applicable only in clinical stages, which is not very practical. Prioritizing drug candidates and early-stage decision-making in the de novo drug development process is crucial in pharmaceutical research to optimize resource allocation. For early-stage decision-making, we need a computational model that uses only chemical structures. This seemingly impossible task may utilize the predictive power with multi-modal features including clinical data. In this work, we introduce ChemAP (Chemical structure-based drug Approval Predictor), a novel deep learning scheme for drug approval prediction in the early-stage drug discovery phase. ChemAP aims to enhance the possibility of early-stage decision-making by enriching semantic knowledge to fill in the gap between multi-modal and single-modal chemical spaces through knowledge distillation techniques. This approach facilitates the effective construction of chemical space solely from chemical structure data, guided by multi-modal knowledge related to efficacy, such as clinical trials and patents of drugs. In this study, ChemAP achieved state-of-the-art performance, outperforming both traditional machine learning and deep learning models in drug approval prediction, with AUROC and AUPRC scores of 0.782 and 0.842 respectively on the drug approval benchmark dataset. Additionally, we demonstrated its generalizability by outperforming baseline models on a recent external dataset, which included drugs from the 2023 FDA-approved list and the 2024 clinical trial failure drug list, achieving AUROC and AUPRC scores of 0.694 and 0.851. These results demonstrate that ChemAP is an effective method in predicting drug approval only with chemical structure information of drug so that decision-making can be done at the early stages of drug development process. To the best of our knowledge, our work is the first of its kind to show that prediction of drug approval is possible only with structure information of drug by defining the chemical space of approved and unapproved drugs using deep learning technology.

Abstract Background Fabry disease is an X-linked lysosomal storage disease caused by the impairment of α-galactosidase A. The complex intronic haplotype (CIH) variants, located in promoter and intronic regulatory lesions, has been found in patients with classical forms of Fabry disease. We present a case of Fabry disease in female monozygotic twins exhibiting the CIH mutation and classical manifestations. Case presentation A 61-year-old woman with a history of stroke, carotid artery occlusion, hypertrophic cardiomyopathy, and chronic kidney disease was referred to the nephrology clinic for management of her chronic kidney disease. Her monozygotic twin sister also presented with hypertrophic cardiomyopathy, atrial flutter, carotid stenosis, and proteinuria. Clinical symptoms and a comprehensive family history strongly suggested the presence of Fabry disease. Genetic analysis revealed the presence of 5 variants within a complex intronic haplotype (CIH): c.−10 C > T, c.369 + 990 C > A, c.370 − 81_370–77delCAGCC, c.640–16 A > G, and c.1000–22 C > T. We conducted a review of the patient’s previous kidney biopsy findings, which demonstrated the presence of lamellated inclusion bodies in electron microscopy. Remarkably, both the monozygotic twin sister and her son exhibited the same genetic mutation. Enzyme replacement therapy was initiated for the patient. Her kidney function decreased throughout a thorough 2-year follow-up period, while there was a slight decrease in the left ventricular mass index. Conclusions This is the first reported case of female monozygotic twins with the CIH variants representing cardiac, cerebrovascular, and renal manifestations suggestive of Fabry disease.

Abstract Background Endovascular therapy (EVT) is the treatment of choice for acute ischemic stroke (AIS) with large vessel occlusion. However, in many patients, successful EVT recanalization does not correspond to a clinical improvement, called futile recanalization (FR). We aimed to identify stroke risk factors and patient characteristics associated with FR in AIS with large core infarct (LCI). Methods A total of 137 patients with AIS with LCI treated by EVT at a single stroke center were retrospectively included from January 2016 to June 2023. LCI was defined by Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECT)

Abstract Background Periodontitis, a prevalent chronic inflammatory disease, offers insights into the broader landscape of chronic inflammatory conditions. The progression and treatment outcomes of periodontitis are closely related to the oral microbiota’s composition. Adjunctive systemic Amoxicillin 500 mg and Metronidazole 400 mg, often prescribed thrice daily for 7 days to enhance periodontal therapy’s efficacy, have lasting effects on the oral microbiome. However, the precise mechanism through which the oral microbiome influences clinical outcomes in periodontitis patients remains debated. This investigation explores the pivotal role of the oral microbiome's composition in mediating the outcomes of adjunctive systemic antibiotic treatment. Methods Subgingival plaque samples from 10 periodontally healthy and 163 periodontitis patients from a randomized clinical trial on periodontal therapy were analyzed. Patients received either adjunctive amoxicillin/metronidazole or a placebo after mechanical periodontal treatment. Microbial samples were collected at various intervals up to 26 months post-therapy. Using topic models, we identified microbial communities associated with normobiotic and dysbiotic states, validated with 86 external and 40 internal samples. Logistic regression models evaluated the association between these microbial communities and clinical periodontitis parameters. A Directed Acyclic Graph (DAG) determined the mediating role of oral microbiota in the causal path of antibiotic treatment effects on clinical outcomes. Results We identified clear distinctions between dysbiotic and normobiotic microbial communities, differentiating healthy from periodontitis subjects. Dysbiotic states consistently associated with below median %Pocket Probing Depth ≥ 5 mm (OR = 1.26, 95% CI [1.14–1.42]) and %Bleeding on Probing (OR = 1.09, 95% CI [1.00–1.18]). Factors like microbial response to treatment, smoking, and age were predictors of clinical attachment loss progression, whereas sex and antibiotic treatment were not. Further, we showed that the oral microbial treatment response plays a crucial role in the causal effect of antibiotic treatment on clinical treatment outcomes. Conclusions The shift towards a normobiotic subgingival microbiome, primarily induced by adjunctive antibiotics, underscores the potential for microbiome-targeted interventions to enhance therapeutic efficacy in chronic inflammatory conditions. This study reaffirms the importance of understanding the oral microbiome's role in periodontal health and paves the way for future research exploring personalized treatment strategies based on individual microbiome profiles. Video Abstract

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 It has been reported that a scenario-based cognitive behavioral therapy mobile app including Todac Todac was effective in improving depression in the general public. However, no study has been conducted on whether Todac Todac is effective in dialysis patients. Therefore, this study was intended to determine whether the use of this app was effective in improving depression in dialysis patients. Sixty-five end-stage kidney disease patients receiving dialysis at Soonchunhyang University Cheonan Hospital were randomly assigned to the Todac Todac app program (experimental group) or an E-moods daily mood chart app program (control group) for 3 weeks. The degree of depression was measured before and after using the app.After the end of the 3-week program, a small but significant improvement was observed in the Trait anxiety (p

Abstract Genetic parasites, including viruses and transposons, exploit components from the host for their own replication. However, little is known about virus-transposon interactions within host cells. Here, we discover a strategy where human cytomegalovirus (HCMV) hijacks L1 retrotransposon encoded protein during its replication cycle. HCMV infection upregulates L1 expression by enhancing both the expression of L1-activating transcription factors, YY1 and RUNX3, and the chromatin accessibility of L1 promoter regions. Increased L1 expression, in turn, promotes HCMV replicative fitness. Affinity proteomics reveals UL44, HCMV DNA polymerase subunit, as the most abundant viral binding protein of the L1 ribonucleoprotein (RNP) complex. UL44 directly interacts with L1 ORF2p, inducing DNA damage responses in replicating HCMV compartments. While increased L1-induced mutagenesis is not observed in HCMV for genetic adaptation, the interplay between UL44 and ORF2p accelerates viral DNA replication by alleviating replication stress. Our findings shed light on how HCMV exploits host retrotransposons for enhanced viral fitness.

Abstract T cell immunoglobulin and mucin-containing molecule 3 (TIM-3) exhibits unique, cell type- and context-dependent characteristics and functions. Here, we report that TIM-3 on myeloid cells plays essential roles in modulating lung inflammation. We found that myeloid cell-specific TIM-3 knock-in (FSF-TIM3/LysM-Cre+) mice have lower body weight and shorter lifespan than WT mice. Intriguingly, the lungs of FSF-TIM3/LysM-Cre+ mice display excessive inflammation and features of disease-associated pathology. We further revealed that galectin-3 levels are notably elevated in TIM-3-overexpressing lung-derived myeloid cells. Furthermore, both TIM-3 blockade and GB1107, a galectin-3 inhibitor, ameliorated lung inflammation in FSF-TIM3/LysM-Cre+/− mice. Using an LPS-induced lung inflammation model with myeloid cell-specific TIM-3 knock-out mice, we demonstrated the association of TIM-3 with both lung inflammation and galectin-3. Collectively, our findings suggest that myeloid TIM-3 is an important regulator in the lungs and that modulation of TIM-3 and galectin-3 could offer therapeutic benefits for inflammation-associated lung diseases.

Abstract The neuropathology of mood disorders, including the diagnostic transition from major depressive disorder (MDD) to bipolar disorder (BD), is poorly understood. This study investigated resting-state electroencephalography (EEG) activity in patients with MDD and those whose diagnosis changed from MDD to BD. Among sixty-eight enrolled patients with MDD, the diagnosis of 17 patients converted to BD during the study period. We applied machine learning techniques to differentiate the two groups using sensor- and source-level EEG features. At the sensor level, patients with BD showed higher theta band power at the AF3 channel and low-alpha band power at the FC5 channel compared to patients with MDD. At the source level, patients with BD showed higher theta band activity in the right anterior cingulate and low-alpha band activity in the left parahippocampal gyrus. These four EEG features were selected for discriminating between BD and MDD with the best classification performance showing an accuracy of 80.88%, a sensitivity of 76.47%, and a specificity of 82.35%. Our findings revealed distinct theta and low-alpha band activities in patients with BD and MDD. These differences could potentially serve as candidate neuromarkers for the diagnosis and diagnostic transition between the two distinct mood disorders.

Abstract This article seeks to argue that although AI language has developed to the level where it can answer human questions, AI language cannot yet contain the truth. In the AI era, humans who speak their minds will no longer express their thoughts directly in words and will depend more on AI’s artificial language. However, it is only a question for now whether AI will be able to substitute for human speech and whether such a fact will contribute to the expansion of human thinking and the state of being. Accordingly, in this paper, we try to identify the limitations of artificial intelligence language by precisely clarifying the meaning of human language and discourse. Foucault and Heidegger’s discussion of discourse deals with issues of language, subject, existence, and authentic discourse. We use their discussions as a tool to illuminate our own perspectives. Therefore, we will re-analyze the language produced in the AI environment in relation to the issue of truth.

Abstract Accurate assessment of pediatric vital signs is critical for detecting abnormalities and guiding medical interventions, but interpretation is challenging due to age-dependent physiological variations. Therefore, this study aimed to develop age-specific centile curves for blood pressure, heart rate, and respiratory rate in pediatric patients and create a user-friendly web-based application for easy access to these data. We conducted a retrospective cross-sectional observational study analyzing 3,779,482 records from the National Emergency Department Information System of Korea, focusing on patients under 15 years old admitted between January 2016 and December 2017. After applying exclusion criteria to minimize the impact of patients’ symptoms on vital signs, 1,369,608 records were used for final analysis. The box–cox power exponential distribution and Lambda–Mu–Sigma (LMS) method were used to generate blood pressure centile charts, while heart rate and respiratory rate values were drawn from previously collected LMS values. We developed comprehensive age-specific centile curves for systolic, diastolic, and mean blood pressure, heart rate, and respiratory rate. These were integrated into a web-based application ( http://centile.research.or.kr ), allowing users to input patient data and promptly obtain centile and z-score information for vital signs. Our study provides an accessible system for pediatric vital sign evaluation, addressing previous limitations and offering a practical solution for clinical assessment. Future research should validate these centile curves in diverse populations.

Abstract The misuse and overtreatment of antibiotics in hospitalized patients with community-acquired pneumonia (CAP) can cause multi-drug resistance and worsen clinical outcomes. We aimed to analyze the trends and appropriateness of antibiotic changes in hospitalized patients with CAP and their impact on clinical outcomes. This retrospective study enrolled patients with CAP, aged > 18 years, admitted from January 2017 to December 2021 at Seoul National University Bundang Hospital, South Korea. We examined the pathogens identified, antibiotics prescribed, and the appropriateness of antibiotic changes as reviewed by infectious disease specialists. Antibiotic appropriateness was assessed based on adherence to the 2019 ATS/IDSA guidelines and the 2018 Korean national guidelines for CAP, targeting appropriate pathogens, proper route, dosage, and duration of therapy. Outcomes measured included time to clinical stability (TCS), length of hospital stay, duration of antibiotic treatment, and in-hospital mortality. The study included 436 patients with a mean age of 72.11 years, of whom 35.1% were male. The average duration of antibiotic treatment was 13.5 days. More than 55% of patients experienced at least one antibiotic change, and 21.7% had consecutive changes. Throughout their hospital stay, 273 patients (62.6%) received appropriate antibiotic treatment, while 163 patients (37.4%) received at least one inappropriate antibiotic prescription. Those who received at least one inappropriate prescription experienced longer antibiotic treatment durations and extended hospital stays, despite having similar TCS. In conclusion, inappropriate antibiotic prescribing in hospitalized patients with CAP is associated with prolonged antibiotic treatment and increased length of stay. Emphasizing the appropriate initial antibiotic selection may help mitigate these negative effects.

The development of soluble boron-free (SBF) operation in the innovative Small Modular Reactor (i-SMR) requires effective strategies for managing excess reactivity over extended operational cycles. This paper introduces a practical approach to reactor core design for SBF operation in i-SMR, emphasizing the use of gadolinia burnable absorbers (BA). The study investigates the feasibility of Highly Intensive and Discrete Gadolinia/Alumina Burnable Absorber (HIGA) rods for controlling excess reactivity sustainably. Through comprehensive analysis and simulations, the reactivity behavior with varying quantities of HIGA rods is examined, leading to the development of optimized fuel assembly designs. Furthermore, the integration of HIGA rods with integral gadolinia BA rods is discussed to enhance reactivity control and operational flexibility further. This approach utilizes the spatial self-shielding effect of gadolinia for extended reactivity management, crucial for stable and efficient reactor performance. The paper thoroughly addresses core design considerations, including fuel assembly configurations and control rod patterns, to ensure safety and performance in initial and reload cycles. This research advances the development of SBF operation in i-SMR by offering practical reactivity management solutions.

Abstract Aims Frailty is an obstacle to performing cardiopulmonary exercise test (CPET) in patients with chronic heart failure (CHF). We evaluated the usefulness of oxygen uptake efficiency slope (OUES) using a 6 min walk test (6MWT) with portable gas analysis compared with CPET‐derived parameters in patients with CHF. Methods and results Patients with CHF who underwent both the 6MWT with portable gas analysis and CPET between December 2016 and May 2020 were retrospectively investigated. The 6MWT‐derived and echocardiographic parameters were compared with the OUES and peak oxygen consumption (VO2) from the CPET. Forty patients were analysed; 50% were male with a mean age of 55.45 ± 14.70 years. Twenty‐six patients (65%) had New York Heart Association Functional Classification II or III dyspnoea. Twenty‐five patients (62.5%) had heart failure (HF) with preserved ejection fraction (EF) (left ventricular EF > 50%), and nine patients (22.5%) had HF with reduced EF (EF

Abstract Background The indications, benefits, and outcomes of percutaneous transluminal renal artery intervention (PTRI) remain controversial. The study purpose was to evaluate the long-term outcomes of PTRI in clinical practice. Methods A retrospective review of 217 subjects (254 renal arteries; mean age, 59.8 years) who underwent PTRI based on medical database. Results The most common cause of renal artery stenosis was atherosclerosis in 217 (85.4%), followed by Takayasu arteritis (TA) in 23 (9.1%), fibromuscular dysplasia in five (2.0%) and others in nine (3.5%). Mean follow-up duration was 5.7 ± 3.7 years. The first restenosis rate was 7.5% (n = 19; highest in TA: n = 9, 47.4%) and second restenosis occurred in six arteries (five TAs, one fibromuscular dysplasia). Follow-up blood pressure improved from 142.0/83.5 to 122.8/73.5 mmHg (P

Abstract Background The impact of rosuvastatin versus atorvastatin on new-onset diabetes mellitus (NODM) among patients treated with high-intensity statin therapy for coronary artery disease (CAD) remains to be clarified. This study aimed to evaluate the risk of NODM in patients with CAD treated with rosuvastatin compared to atorvastatin in the randomized LODESTAR trial. Methods In the LODESTAR trial, patients with CAD were randomly assigned to receive either rosuvastatin or atorvastatin using a 2-by-2 factorial randomization. In this post-hoc analysis, the 3-year incidence of NODM was compared between rosuvastatin and atorvastatin treatment in the as-treated population with high-intensity statin therapy as the principal population of interest. Results Among 2932 patients without diabetes mellitus at baseline, 2377 were included in the as-treated population analysis. In the as-treated population with high-intensity statin therapy, the incidence of NODM was not significantly different between the rosuvastatin and atorvastatin groups (11.4% [106/948] versus 8.8% [73/856], hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 0.98 to 1.77, P = 0.071). When the risk of NODM with rosuvastatin versus atorvastatin was assessed according to the achieved low-density lipoprotein cholesterol (LDL-C) level, the risk of NODM began to increase at a LDL-C level below 70 mg/dL. The incidence of NODM was significantly greater in the rosuvastatin group than it was in the atorvastatin group when the achieved LDL-C level was

Abstract Background Lake Bonney, which is divided into a west lobe (WLB) and an east lobe (ELB), is a perennially ice-covered lake located in the McMurdo Dry Valleys of Antarctica. Despite previous reports on the microbial community dynamics of ice-covered lakes in this region, there is a paucity of information on the relationship between microbial genomic diversity and associated nutrient cycling. Here, we applied gene- and genome-centric approaches to investigate the microbial ecology and reconstruct microbial metabolic potential along the depth gradient in Lake Bonney. Results Lake Bonney is strongly chemically stratified with three distinct redox zones, yielding different microbial niches. Our genome enabled approach revealed that in the sunlit and relatively freshwater epilimnion, oxygenic photosynthetic production by the cyanobacterium Pseudanabaena and a diversity of protists and microalgae may provide new organic carbon to the environment. CO-oxidizing bacteria, such as Acidimicrobiales, Nanopelagicales, and Burkholderiaceae were also prominent in the epilimnion and their ability to oxidize carbon monoxide to carbon dioxide may serve as a supplementary energy conservation strategy. In the more saline metalimnion of ELB, an accumulation of inorganic nitrogen and phosphorus supports photosynthesis despite relatively low light levels. Conversely, in WLB the release of organic rich subglacial discharge from Taylor Glacier into WLB would be implicated in the possible high abundance of heterotrophs supported by increased potential for glycolysis, beta-oxidation, and glycoside hydrolase and may contribute to the growth of iron reducers in the dark and extremely saline hypolimnion of WLB. The suboxic and subzero temperature zones beneath the metalimnia in both lobes supported microorganisms capable of utilizing reduced nitrogens and sulfurs as electron donors. Heterotrophs, including nitrate reducing sulfur oxidizing bacteria, such as Acidimicrobiales (MAG72) and Salinisphaeraceae (MAG109), and denitrifying bacteria, such as Gracilimonas (MAG7), Acidimicrobiales (MAG72) and Salinisphaeraceae (MAG109), dominated the hypolimnion of WLB, whereas the environmental harshness of the hypolimnion of ELB was supported by the relatively low in metabolic potential, as well as the abundance of halophile Halomonas and endospore-forming Virgibacillus. Conclusions The vertical distribution of microbially driven C, N and S cycling genes/pathways in Lake Bonney reveals the importance of geochemical gradients to microbial diversity and biogeochemical cycles with the vertical water column.

Abstract Hepatocellular carcinoma (HCC) is known to be lethal disease. However, its prognosis remains poor, primarily because the precise oncogenic mechanisms underlying HCC progression remain elusive, thus hampering effective treatment. Here, we aimed to identify the potential oncogenes in HCC and elucidate the underlying mechanisms of their action. To identify potential candidate genes, an integrative analysis of eight publicly available genomic datasets was performed, and the functional implications of the identified genes were assessed in vitro and in vivo. Sortilin 1 (SORT1) was identified as a potential candidate oncogene in HCC, and its overexpression in HCC cells was confirmed by analyzing spatial transcriptomic and single-cell data. Silencing SORT1 in Huh-7 and Hep3B cells significantly reduced HCC progression in vitro and in vivo. Functional analyses of oncogenic pathways revealed that SORT1 expression regulated the Notch signaling pathway activation and CD133 expression. Furthermore, analysis of epigenetic regulation of the candidate gene and its clinical implications using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA LIHC) and our HCC cohort (AJOU_HCC cohort) data demonstrated an inverse correlation between the methylation status of the SORT1 promoter region, specifically at the cg16988986 site, and SORT1 mRNA expression, indicating the epigenetic regulation of SORT1 in HCC. In addition, the distinct methylation status of cg16988986 was significantly associated with patient survival. In conclusion, SORT1 plays a pivotal role in HCC by activating the Notch signaling pathway and increasing CD133 expression. These findings suggest SORT1 as a promising therapeutic target for HCC.

IntroductionDrug-induced liver injury (DILI) has been investigated at the patient level. Analysis of gene perturbation at the cellular level can help better characterize biological mechanisms of hepatotoxicity. Despite accumulating drug-induced transcriptome data such as LINCS, analyzing such transcriptome data upon drug treatment is a challenging task because the perturbation of expression is dose and time dependent. In addition, the mechanisms of drug toxicity are known only as literature information, not in a computable form.MethodsTo address these challenges, we propose a Multi-Dimensional Transcriptomic Ruler (MDTR) that quantifies the degree of DILI at the transcriptome level. To translate transcriptome data to toxicity-related mechanisms, MDTR incorporates KEGG pathways as representatives of mechanisms, mapping transcriptome data to biological pathways and subsequently aggregating them for each of the five hepatotoxicity mechanisms. Given that a single mechanism involves multiple pathways, MDTR measures pathway-level perturbation by constructing a radial basis kernel-based toxicity space and measuring the Mahalanobis distance in the transcriptomic kernel space. Representing each mechanism as a dimension, MDTR is visualized in a radar chart, enabling an effective visual presentation of hepatotoxicity at transcriptomic level.Results and DiscussionIn experiments with the LINCS dataset, we show that MDTR outperforms existing methods for measuring the distance of transcriptome data when describing for dose-dependent drug perturbations. In addition, MDTR shows interpretability at the level of DILI mechanisms in terms of the distance, i.e., in a metric space. Furthermore, we provided a user-friendly and freely accessible website (http://biohealth.snu.ac.kr/software/MDTR), enabling users to easily measure DILI in drug-induced transcriptome data.

Carbonic anhydrases (CAs) are ubiquitous enzymes that catalyze reversibly both the hydration and dehydration reactions of CO2 and HCO3-, respectively. Higher plants contain many different isoforms of CAs that can be classified into α-, β- and γ-type subfamilies. β-type CAs play a key role in the CO2-concentrating mechanism, thereby contributing to efficient photosynthesis in the C4 plants in addition to many other biochemical reactions in plant metabolism. Here, we characterized at the molecular, cellular and biochemical levels two β-type CAs in Bienertia sinuspersici, a plant that operates a C4 carbon concentrating mechanism within individual cells without the Kranz anatomy. These two β-type CAs (BsCAβs), named BsCAβ1 and BsCAβ2, in Bienertia were strongly induced along with maturation of leaves. Both BsCAβ1 and BsCAβ2 existed as a dimeric form in vivo but showed differential localization. BsCAβ2 was localized exclusively to the plasma membrane in Bienertia and when expressed heterologously in the C3 Arabidopsis. In contrast, BsCAβ1 largely localized to the cytosol together with a portion to the plasma membrane (PM) in both plants. BsCAβ2 had two cysteine residues at the N-terminal region for palmitoylation and their substitution with serine residues led to a change in the localization from the plasma membrane (PM) to the cytosol. Thus, we propose that BsCAβ2 localizes to the PM using a lipid moiety added posttranslationally plays a role in conversion of cytosolic CO2 into HCO3- as part of the CO2-concentrating mechanism, thereby contributing to the single-cell C4 photosynthesis in Bienertia.

BackgroundGlobally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative bacteriological test result. There is limited information on the factors that determine clinicians' decisions to initiate TB treatment when initial bacteriological test results are negative.Methods and findingsWe performed a systematic review and individual patient data meta-analysis using studies conducted between January 2010 and December 2022 (PROSPERO: CRD42022287613). We included trials or cohort studies that enrolled individuals evaluated for TB in routine settings. In these studies, participants were evaluated based on clinical examination and routinely used diagnostics and were followed for ≥1 week after the initial test result. We used hierarchical Bayesian logistic regression to identify factors associated with treatment initiation following a negative result on an initial bacteriological test (e.g., sputum smear microscopy (SSM), Xpert MTB/RIF). Multiple factors were positively associated with treatment initiation: male sex [adjusted odds ratio (aOR) 1.61 (1.31, 1.95)], history of prior TB [aOR 1.36 (1.06, 1.73)], reported cough [aOR 4.62 (3.42, 6.27)], reported night sweats [aOR 1.50 (1.21, 1.90)], and having HIV infection but not on ART [aOR 1.68 (1.23, 2.32)]. Treatment initiation was substantially less likely for individuals testing negative with Xpert [aOR 0.77 (0.62, 0.96)] compared to smear microscopy and declined in more recent years. We were not able assess why clinicians made treatment decisions, as these data were not available.ConclusionsMultiple factors influenced decisions to initiate TB treatment despite negative test results. Clinicians were substantially less likely to treat in the absence of a positive test result when using more sensitive, PCR-based diagnostics.

Asian sand dust (ASD), a seasonal dust storm originating from the deserts of China and Mongolia, affects Korea and Japan during the spring, carrying soil particles and a variety of biochemical components. Exposure to ASD has been associated with the onset and exacerbation of respiratory disorders, although the underlying mechanisms remain unclear. This study investigates ASD-induced pulmonary toxicity and its mechanistic pathways, focusing on the role of thioredoxin-interacting protein (TXNIP). Using TXNIP knock-out (KO) mice and adeno-associated virus (AAV)-mediated TXNIP overexpression transgenic mice, we explored how TXNIP modulates ASD-induced pulmonary inflammation. Mice were exposed to ASD via intranasal administration on days 1, 3, and 5 to induce inflammation. ASD exposure led to significant pulmonary inflammation, evidenced by increased inflammatory cell counts and elevated cytokine levels in bronchoalveolar lavage fluid, as well as heightened protein expression of the TXNIP/NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. TXNIP KO mice exhibited attenuated airway inflammation and downregulation of the NLRP3 inflammasome compared to wild-type controls, while AAV-mediated TXNIP overexpression mice showed exacerbated inflammatory responses, including elevated NLRP3 inflammasome expression, compared to AAV-GFP controls. These findings suggest that TXNIP is a key regulator of ASD-induced pulmonary inflammation.

Although HIV-1 integration sites favor active transcription units in the human genome, high-resolution analysis of individual HIV-1 integration sites has shown that the virus can integrate into a variety of host genomic locations, including non-genic regions. The invisible infection by HIV-1 integrating into non-genic regions, challenging the traditional understanding of HIV-1 integration site selection, is more problematic because they are selected for preservation in the host genome during prolonged antiretroviral therapies. Here, we showed that HIV-1 integrates its viral genome into the vicinity of R-loops, a genomic structure composed of DNA-RNA hybrids. VSV-G-pseudotyped HIV-1 infection initiates the formation of R-loops in both genic and non-genic regions of the host genome and preferentially integrates into R-loop-rich regions. Using a HeLa cell model that can independently control transcriptional activity and R-loop formation, we demonstrated that the exogenous formation of R-loops directs HIV-1 integration-targeting sites. We also found that HIV-1 integrase proteins physically bind to the host genomic R-loops. These findings provide novel insights into the mechanisms underlying retroviral integration and the new strategies for antiretroviral therapy against HIV-1 latent infection.

AbstractBackground The lack of association between serum testosterone levels and symptoms suggestive of hypogonadism is a significant barrier in the determination of late-onset hypogonadism (LOH) in men. This study explored whether testosterone levels increase after morning awakening, likewise the cortisol awakening response (CAR) in the hypothalamic–pituitary–adrenal (HPA) axis, and whether testosterone levels during the post-awakening period are associated with age and symptoms suggestive of late-onset hypogonadism (LOH) in men.Methods Testosterone and cortisol levels were determined in saliva samples collected immediately upon awakening and 30 and 60 min after awakening, and scores of the Aging Males’ Symptoms (AMS) questionnaire were obtained from 225 healthy adult men.Results A typical CAR (an increase in cortisol level ≥ 2.5 nmol/L above individual baseline) was observed in 155 participants (the subgroup exhibiting typical CAR). In the subgroup exhibiting CAR, testosterone levels sharply increased during the post-awakening period, showing a significant negative correlation with age, total AMS score, and the scores of 11 items on the somatic, psychological, and sexual AMS subscales. Of these items, three sexual items (AMS items #15–17) were correlated with age. Meanwhile, there was no notable increase in testosterone levels and no significant correlation of testosterone levels with age and AMS score in the subgroup exhibiting no typical CAR (n = 70).Conclusions The results indicate that the hypothalamus-pituitary-gonad (HPG) axis responds to morning awakening, and determining testosterone levels during the post-awakening period in men with typical CAR may be useful for assessing HPG axis function and LOH.

Music therapy stakeholders may benefit from a more comprehensive understanding about international students and their process for becoming music therapists in the U.S. The purposes of this paper are to: (a) articulate the international student process from home country to credentialed music therapist in the U.S., (b) outline common concerns and difficulties of international students studying in the U.S., and (c) share best practices obtained from the research literature to support international students through the process from student to professional. The process for international music therapy students from home country to professional includes pre-departure tasks related to information, finances, and student visas; mid-coursework requirements related to clinical practice, curricular degree, and full-time status; and post-coursework aspects of curricular practical training, board certification, optional practical training, and applying for a work visa. Common challenges of international music therapy students include culture shock and racism, academic challenges, financial and psychological issues, and developing music skills and repertoire. Best practices identified from the literature encourage international students to improve language competence, utilize campus support, develop social networks, and increase culture competence. The authors discuss implications for music therapy education and training, provide suggestions for students, and share recommendations for key stakeholders.

Background/Aims: Appropriate tissue tension and clear visibility of the dissection area using traction are essential for effective and safe endoscopic submucosal dissection (ESD). In this study, we developed a retractable robot-assisted traction device and evaluated its performance in colorectal ESD. Methods: An experienced endoscopist performed ESD 18 times on an ex vivo porcine colon using the robot and 18 times using the conventional method. The outcome measures were procedure time, dissection speed, procedure-related adverse events, and blind dissection rate. Results: Thirty-six colonic lesions were resected from ex vivo porcine colon samples. The total procedure time was significantly shorter in robot-assisted ESD (RESD) than in conventional ESD (CESD) (20.1±4.1 minutes vs 34.3±8.3 minutes, p

This study reviews the recent progress of artificial intelligence for colonoscopy from detection to diagnosis. The source of data was 27 original studies in PubMed. The search terms were “colonoscopy” (title) and “deep learning” (abstract). The eligibility criteria were: (1) the dependent variable of gastrointestinal disease; (2) the interventions of deep learning for classification, detection and/or segmentation for colonoscopy; (3) the outcomes of accuracy, sensitivity, specificity, area under the curve (AUC), precision, F1, intersection of union (IOU), Dice and/or inference frames per second (FPS); (3) the publication year of 2021 or later; (4) the publication language of English. Based on the results of this study, different deep learning methods would be appropriate for different tasks for colonoscopy, e.g., Efficientnet with neural architecture search (AUC 99.8%) in the case of classification, You Only Look Once with the instance tracking head (F1 96.3%) in the case of detection, and Unet with dense-dilation-residual blocks (Dice 97.3%) in the case of segmentation. Their performance measures reported varied within 74.0–95.0% for accuracy, 60.0–93.0% for sensitivity, 60.0–100.0% for specificity, 71.0–99.8% for the AUC, 70.1–93.3% for precision, 81.0–96.3% for F1, 57.2–89.5% for the IOU, 75.1–97.3% for Dice and 66–182 for FPS. In conclusion, artificial intelligence provides an effective, non-invasive decision support system for colonoscopy from detection to diagnosis.

Background/Aims Atezolizumab plus bevacizumab (ATE+BEV) therapy has become the recommended first-line therapy for patients with unresectable hepatocellular carcinoma (HCC) because of favorable treatment responses. However, there is a lack of data on sequential regimens after ATE+BEV treatment failure. We aimed to investigate the clinical outcomes of patients with advanced HCC who received subsequent systemic therapy for disease progression after ATE+BEV. Methods This multicenter, retrospective study included patients who started second-line systemic treatment with sorafenib or lenvatinib after HCC progressed on ATE+BEV between August 2019 and December 2022. Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1.). Clinical features of the two groups were balanced through propensity score (PS) matching. Results This study enrolled 126 patients, 40 (31.7%) in the lenvatinib group, and 86 (68.3%) in the sorafenib group. The median age was 63 years, and males were predominant (88.1%). In PS-matched cohorts (36 patients in each group), the objective response rate was similar between the lenvatinib- and sorafenib-treated groups (5.6% vs. 8.3%; P=0.643), but the disease control rate was superior in the lenvatinib group (66.7% vs. 22.2%; P

Background/Aims Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Despite identification of several biomarkers for HCC diagnosis, challenges such as low sensitivity and intratumoral heterogeneity have impeded early detection, highlighting the need for etiology-specific blood biomarkers. Methods We generated whole-transcriptome sequencing (WTS) and targeted proteome data from buffy coat and plasma samples from HCC patients. By integrating etiological information on viral infection, we investigated the etiology-specific gene expression landscape at the blood level. Validation of differentially expressed genes (DEGs) was performed using publicly available RNA-seq datasets and qRT‒PCR with AUC analyses. Results Differential expression analyses with multiomics data revealed distinct gene expression profiles between HBV-associated HCC and nonviral HCC, indicating the presence of etiology-specific blood biomarkers. The identified DEGs were validated across multiple independent datasets, underscoring their utility as biomarkers. Additionally, single-cell RNA-seq analysis of HCC confirmed differences in DEG expression across distinct immune cell types. Conclusions Our buffy coat WTS data and plasma proteome data may serve as reliable sources for identifying etiology-specific blood biomarkers of HCC and might contribute to discovery of therapeutic targets for HCC across different etiologies.

Abstract Background The calcar of the proximal humerus is a fundamental structure for medial humeral column support. This study aimed to assess the outcome of osteosynthesis across cases of unstable proximal humerus fractures (PHFs) with medial calcar comminution, following treatment with a PHILOS locking plate and medial support screw (MSS). Methods Between January 2010 and December 2018, we retrospectively analyzed the outcomes of 121 cases of osteosynthesis for PHFs with medial column disruption. For the medial support, at least one oblique screw was inserted within 5 mm of the subchondral bone in the inferomedial quadrant of the humeral head. All patients were categorized into two groups: 26 patients in the single MSS group, and 95 in the multiple MSS group. Follow-up after at least an year involved clinical and radiographic outcome evaluations, and correspondingly measuring the Constant-Murley score, University of California, Los Angeles (UCLA) shoulder scale, pain visual analogue scale (VAS), major complications, neck-shaft angle (NSA), humeral head height (HHH), and the eventual time to bone union. Risk factors for the major complications were assessed by multivariate logistic regression analyses. Results The cohort’s mean age was 64.4 ± 15.4 years, and the mean follow-up duration was 19.5 ± 7.6 months. At the final follow-up, between the single MSS and multiple MSS groups, no significant differences in the Constant-Murley score (p = 0.367), UCLA score (p = 0.558), VAS (p = 0.571), time to bone union (p = 0.621), NSA loss (p = 0.424), and HHH loss (p = 0.364) were observed. The incidence of complications (p = 0.446) based on the number of MSS were not significantly different. The initial insufficient reduction after surgery (of NSA