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Abstract Transcranial brain stimulation is a promising technology for safe modulation of brain function without invasive procedures. Recent advances in transcranial optogenetic techniques with external light sources, using upconversion particles and highly sensitive opsins, have shown promise for precise neuromodulation with improved spatial resolution in deeper brain regions. However, these methods have not yet been used to selectively excite or inhibit specific neural populations in multiple brain regions. In this study, we created a wireless transcranial optogenetic brain modulator that combines highly sensitive opsins and upconversion particles and allows for precise bimodal neuromodulation of multiple brain regions without optical crosstalk. We demonstrate the feasibility of our approach in freely behaving mice. Furthermore, we demonstrate its usefulness in studies of complex behaviors and brain dysfunction by controlling extorting behavior in mice in food competition tests and alleviating the symptoms of Parkinson’s disease. Our approach has potential applications in the study of neural circuits and development of treatments for various brain disorders.

Background To investigate the association of glycemic control and retinal microvascular changes in patients with type 2 diabetes mellitus (T2DM) without diabetic retinopathy (DR). Methods This retrospective, observational, cohort study included patients with T2DM without DR. The patients were categorized into intensive control (IC; mean glycosylated hemoglobin [HbA1c] ≤7.0%) and moderate control (MC; mean HbA1c >7.0%) groups. Optical coherence tomography (OCT) and swept-source OCT angiography (OCTA) image parameters were compared between three groups, including healthy controls. Results In total, 259 eyes of 259 participants (88 IC, 81 MC, and 90 controls) were included. The foveal avascular zone area was significantly larger in the MC group than IC and control groups (all P

Abstract Background Astrocytes, one of the most resilient cells in the brain, transform into reactive astrocytes in response to toxic proteins such as amyloid beta (Aβ) in Alzheimer’s disease (AD). However, reactive astrocyte-mediated non-cell autonomous neuropathological mechanism is not fully understood yet. We aimed our study to find out whether Aβ-induced proteotoxic stress affects the expression of autophagy genes and the modulation of autophagic flux in astrocytes, and if yes, how Aβ-induced autophagy-associated genes are involved Aβ clearance in astrocytes of animal model of AD. Methods Whole RNA sequencing (RNA-seq) was performed to detect gene expression patterns in Aβ-treated human astrocytes in a time-dependent manner. To verify the role of astrocytic autophagy in an AD mouse model, we developed AAVs expressing shRNAs for MAP1LC3B/LC3B (LC3B) and Sequestosome1 (SQSTM1) based on AAV-R-CREon vector, which is a Cre recombinase-dependent gene-silencing system. Also, the effect of astrocyte-specific overexpression of LC3B on the neuropathology in AD (APP/PS1) mice was determined. Neuropathological alterations of AD mice with astrocytic autophagy dysfunction were observed by confocal microscopy and transmission electron microscope (TEM). Behavioral changes of mice were examined through novel object recognition test (NOR) and novel object place recognition test (NOPR). Results Here, we show that astrocytes, unlike neurons, undergo plastic changes in autophagic processes to remove Aβ. Aβ transiently induces expression of LC3B gene and turns on a prolonged transcription of SQSTM1 gene. The Aβ-induced astrocytic autophagy accelerates urea cycle and putrescine degradation pathway. Pharmacological inhibition of autophagy exacerbates mitochondrial dysfunction and oxidative stress in astrocytes. Astrocyte-specific knockdown of LC3B and SQSTM1 significantly increases Aβ plaque formation and GFAP-positive astrocytes in APP/PS1 mice, along with a significant reduction of neuronal marker and cognitive function. In contrast, astrocyte-specific overexpression of LC3B reduced Aβ aggregates in the brain of APP/PS1 mice. An increase of LC3B and SQSTM1 protein is found in astrocytes of the hippocampus in AD patients. Conclusions Taken together, our data indicates that Aβ-induced astrocytic autophagic plasticity is an important cellular event to modulate Aβ clearance and maintain cognitive function in AD mice.

Abstract Despite clinical data stretching over millennia, the neurobiological basis of the effectiveness of acupuncture in treating diseases of the central nervous system has remained elusive. Here, using an established model of acupuncture treatment in Parkinson's disease (PD) model mice, we show that peripheral acupuncture stimulation activates hypothalamic melanin‐concentrating hormone (MCH) neurons via nerve conduction. We further identify two separate neural pathways originating from anatomically and electrophysiologically distinct MCH neuronal subpopulations, projecting to the substantia nigra and hippocampus, respectively. Through chemogenetic manipulation specifically targeting these MCH projections, their respective roles in mediating the acupuncture‐induced motor recovery and memory improvements following PD onset are demonstrated, as well as the underlying mechanisms mediating recovery from dopaminergic neurodegeneration, reactive gliosis, and impaired hippocampal synaptic plasticity. Collectively, these MCH neurons constitute not only a circuit‐based explanation for the therapeutic effectiveness of traditional acupuncture, but also a potential cellular target for treating both motor and non‐motor PD symptoms.

Abstract Background Sentinel lymph node biopsy (SLNB) is recommended for patients with ductal carcinoma in situ (DCIS) undergoing mastectomy, given the concerns regarding upstaging and technical difficulties of post-mastectomy SLNB. However, this may lead to potential overtreatment, considering favorable prognosis and de-escalation trends in DCIS. Data regarding upstaging and axillary lymph node metastasis among these patients remain limited. Methods We retrospectively reviewed patients with DCIS who underwent mastectomy with SLNB or axillary lymph node dissection at Gangnam Severance Hospital between January 2010 and December 2021. To explore the feasibility of omitting SLNB, we assessed the rates of DCIS upgraded to invasive carcinoma and axillary lymph node metastasis. Binary Cox regression analysis was performed to identify clinicopathologic factors associated with upstaging and axillary lymph node metastasis. Results Among 385 patients, 164 (42.6%) experienced an invasive carcinoma upgrade: microinvasion, pT1, and pT2 were confirmed in 53 (13.8%), 97 (25.2%), and 14 (3.6%) patients, respectively. Seventeen (4.4%) patients had axillary lymph node metastasis. Multivariable analysis identified age ≤ 50 years (adjusted odds ratio [OR], 12.73; 95% confidence interval [CI], 1.18–137.51; p = 0.036) and suspicious axillary lymph nodes on radiologic evaluation (adjusted OR, 9.31; 95% CI, 2.06–41.99; p = 0.004) as independent factors associated with axillary lymph node metastasis. Among patients aged > 50 years and/or no suspicious axillary lymph nodes, only 1.7–2.3%) experienced axillary lymph node metastasis. Conclusions Although underestimation of the invasive component was relatively high among patients with DCIS undergoing mastectomy, axillary lymph node metastasis was rare. Our findings suggest that omitting SLNB may be feasible for patients over 50 and/or without suspicious axillary lymph nodes on radiologic evaluation.

BackgroundPeriampullary adenocarcinomas typically exhibit either intestinal or pancreatobiliary (PB) differentiation, and the type of differentiation may be prognostically more important than the anatomic site of origin. This study aimed to evaluate prognostic significance of histological type of periampullary carcinomas.MethodsMicroscopic slides from 110 consecutive pancreatoduodenectomies performed between 2010 and 2020 were reviewed and classified as intestinal or PB type. Clinicopathological factors were compared between PB-(n=93) and intestinal-type (n=17) differentiation.ResultsThe intestinal type included significantly more patients with well-differentiated histology (35.3% vs. 11.8%, p=0.001) and fewer patients with perineural invasion (41.2% vs. 76.4%, p=0.029), advanced T stage (> T3; 41.2% vs.74.2%, p=0.007), and systemic recurrence (71.4% vs. 92.9%, p=0.005) than PB type. The 5-year-overall survival rate of intestinal-type was significantly higher than that of PB-type (58.8% vs. 20.4%, p=0.003). When pancreatic cancer was separately analyzed, the intestinal type showed the best 5-year-overall survival rate, with no significant difference between the PB types excluding PDAC and PDAC (39.4% vs. 19.2%, p=0.148). In multivariate analysis, curative resection (hazard ratio, 0.417; 95% CI, 0.219-0.792, p=0.008) was the only significant prognostic factor.ConclusionAlthough intestinal histologic phenotype was not an independent prognostic factor on multivariate analysis, it showed pathologic features associated with better survival, while the PB type showed more aggressive tumor biology and consequently worse survival. Further studies are needed to demonstrate the prognostic significance of histologic phenotype.

Abstract Dopamine neurons are essential for voluntary movement, reward learning, and motivation, and their dysfunction is closely linked to various psychological and neurodegenerative diseases. Hence, understanding the detailed signaling mechanisms that functionally modulate dopamine neurons is crucial for the development of better therapeutic strategies against dopamine-related disorders. Phospholipase Cγ1 (PLCγ1) is a key enzyme in intracellular signaling that regulates diverse neuronal functions in the brain. It was proposed that PLCγ1 is implicated in the development of dopaminergic neurons, while the physiological function of PLCγ1 remains to be determined. In this study, we investigated the physiological role of PLCγ1, one of the key effector enzymes in intracellular signaling, in regulating dopaminergic function in vivo. We found that cell type-specific deletion of PLCγ1 does not adversely affect the development and cellular morphology of midbrain dopamine neurons but does facilitate dopamine release from dopaminergic axon terminals in the striatum. The enhancement of dopamine release was accompanied by increased colocalization of vesicular monoamine transporter 2 (VMAT2) at dopaminergic axon terminals. Notably, dopamine neuron-specific knockout of PLCγ1 also led to heightened expression and colocalization of synapsin III, which controls the trafficking of synaptic vesicles. Furthermore, the knockdown of VMAT2 and synapsin III in dopamine neurons resulted in a significant attenuation of dopamine release, while this attenuation was less severe in PLCγ1 cKO mice. Our findings suggest that PLCγ1 in dopamine neurons could critically modulate dopamine release at axon terminals by directly or indirectly interacting with synaptic machinery, including VMAT2 and synapsin III.

Background The importance of molecular pathology tests has increased during the last decade, and there is a great need for efficient training of molecular pathology for pathology trainees and as continued medical education. Methods The Molecular Pathology Study Group of the Korean Society of Pathologists appointed a task force composed of experienced molecular pathologists to develop a refined educational curriculum of molecular pathology. A 3-day online educational session was held based on the newly established structure of learning objectives; the audience were asked to score their understanding of 22 selected learning objectives before and after the session to assess the effect of structured education. Results The structured objectives and goals of molecular pathology was established and posted as a web-based interface which can serve as a knowledge bank of molecular pathology. A total of 201 pathologists participated in the educational session. For all 22 learning objectives, the scores of self-reported understanding increased after educational session by 9.9 points on average (range, 6.6 to 17.0). The most effectively improved items were objectives from next-generation sequencing (NGS) section: ‘NGS library preparation and quality control’ (score increased from 51.8 to 68.8), ‘NGS interpretation of variants and reference database’ (score increased from 54.1 to 68.0), and ‘whole genome, whole exome, and targeted gene sequencing’ (score increased from 58.2 to 71.2). Qualitative responses regarding the adequacy of refined educational curriculum were collected, where favorable comments dominated. Conclusions Approach toward the education of molecular pathology was refined, which would greatly benefit the future trainees.

Background Diabetic kidney disease (DKD) is a risk factor for hospitalization for heart failure (HHF). DKD could be classified into four phenotypes by estimated glomerular filtration rate (eGFR, normal vs. low) and proteinuria (PU, negative vs. positive). Also, the phenotype often changes dynamically. This study examined HHF risk according to the DKD phenotype changes across 2-year assessments. Methods The study included 1,343,116 patients with type 2 diabetes mellitus (T2DM) from the Korean National Health Insurance Service database after excluding a very high-risk phenotype (eGFR

T cells regulate adaptive immune responses through complex signaling pathways mediated by T cell receptor (TCR). The functional domains of the TCR are combined with specific antibodies for the development of chimeric antigen receptor (CAR) T cell therapy. In this review, we first overview current understanding on the T cell signaling pathways as well as traditional methods that have been widely used for the T cell study. These methods, however, are still limited to investigating dynamic molecular events with spatiotemporal resolutions. Therefore, genetically encoded biosensors and optogenetic tools have been developed to study dynamic T cell signaling pathways in live cells. We review these cutting-edge technologies that revealed dynamic and complex molecular mechanisms at each stage of T cell signaling pathways. They have been primarily applied to the study of dynamic molecular events in TCR signaling, and they will further aid in understanding the mechanisms of CAR activation and function. Therefore, genetically encoded biosensors and optogenetic tools offer powerful tools for enhancing our understanding of signaling mechanisms in T cells and CAR-T cells.

Abstract Background Nurses’ work engagement has received extensive attention due to its positive impacts on individual and organizational outcomes, including patient safety and quality care in healthcare organizations. Although nurse managers’ leadership and a variety of resources have been identified as important factors of nurses’ work engagement, these relationships have not been well understood in Korean nursing contexts. The purpose of this study was to examine the associations among nurse managers’ leadership, resources, and work engagement among Korean nurses after controlling for nurses’ demographic and work-related characteristics. Methods This is a cross-sectional study using data from the fifth Korean Working Conditions Survey. Using a sample of 477 registered nurses, we employed hierarchical linear regression analyses. Nurse managers’ leadership, job resources (organizational justice and support from peers), professional resources (employee involvement), and personal resources (meaning of work) were examined as potential predictors of nurses’ work engagement. Results We found that nurse managers’ leadership (β = 0.26, 95% confidence interval [CI] = 0.17–0.41) was the strongest predictor of nurses’ work engagement, followed by meaning of work (β = 0.20, 95% CI = 0.07–0.18), organizational justice (β = 0.19, 95% CI = 0.10–0.32), and support from peers (β = 0.14, 95% CI = 0.04–0.23). Employee involvement was not a statistically significant predictor of nurses’ work engagement (β = -0.07, 95% CI = -0.11–0.01). Conclusions Our findings suggest that comprehensive approaches are required to promote nurses’ work engagement. Considering that nurse managers’ leadership was the strongest predictor of nurses’ work engagement, nurse managers should demonstrate supportive leadership behaviors such as acknowledging and praising their unit nurses’ work performance. Furthermore, both individual- and organizational-level strategies are necessary for nurses to be engaged at work.

Abstract Since the etiology of diabetic chronic kidney disease (CKD) is multifactorial, studies on DNA methylation for kidney function deterioration have rarely been performed despite the need for an epigenetic approach. Therefore, this study aimed to identify epigenetic markers associated with CKD progression based on the decline in the estimated glomerular filtration rate in diabetic CKD in Korea. An epigenome-wide association study was performed using whole blood samples from 180 CKD recruited from the KNOW-CKD cohort. Pyrosequencing was also performed on 133 CKD participants as an external replication analysis. Functional analyses, including the analysis of disease-gene networks, reactome pathways, and protein–protein interaction networks, were conducted to identify the biological mechanisms of CpG sites. A phenome-wide association study was performed to determine the associations between CpG sites and other phenotypes. Two epigenetic markers, cg10297223 on AGTR1 and cg02990553 on KRT28 indicated a potential association with diabetic CKD progression. Based on the functional analyses, other phenotypes (blood pressure and cardiac arrhythmia for AGTR1) and biological pathways (keratinization and cornified envelope for KRT28) related to CKD were also identified. This study suggests a potential association between the cg10297223 and cg02990553 and the progression of diabetic CKD in Koreans. Nevertheless, further validation is needed through additional studies.

We identified a new human voltage-gated potassium channel blocker, NnK-1, in the jellyfish Nemopilema nomurai based on its genomic information. The gene sequence encoding NnK-1 contains 5408 base pairs, with five introns and six exons. The coding sequence of the NnK-1 precursor is 894 nucleotides long and encodes 297 amino acids containing five presumptive ShK-like peptides. An electrophysiological assay demonstrated that the fifth peptide, NnK-1, which was chemically synthesized, is an effective blocker of hKv1.3, hKv1.4, and hKv1.5. Multiple-sequence alignment with cnidarian Shk-like peptides, which have Kv1.3-blocking activity, revealed that three residues (3Asp, 25Lys, and 34Thr) of NnK-1, together with six cysteine residues, were conserved. Therefore, we hypothesized that these three residues are crucial for the binding of the toxin to voltage-gated potassium channels. This notion was confirmed by an electrophysiological assay with a synthetic peptide (NnK-1 mu) where these three peptides were substituted with 3Glu, 25Arg, and 34Met. In conclusion, we successfully identified and characterized a new voltage-gated potassium channel blocker in jellyfish that interacts with three different voltage-gated potassium channels. A peptide that interacts with multiple voltage-gated potassium channels has many therapeutic applications in various physiological and pathophysiological contexts.

Summary: Dopamine synapses play a crucial role in volitional movement and reward-related behaviors, while dysfunction of dopamine synapses causes various psychiatric and neurological disorders. Despite this significance, the true biological nature of dopamine synapses remains poorly understood. Here, we show that dopamine transmission is strongly correlated with GABA co-transmission across the brain and dopamine synapses are structured and function like GABAergic synapses with marked regional heterogeneity. In addition, GABAergic-like dopamine synapses are clustered on the dendrites, and GABA transmission at dopamine synapses has distinct physiological properties. Interestingly, the knockdown of neuroligin-2, a key postsynaptic protein at GABAergic synapses, unexpectedly does not weaken GABA co-transmission but instead facilitates it at dopamine synapses in the striatal neurons. More importantly, the attenuation of GABA co-transmission precedes deficits in dopaminergic transmission in animal models of Parkinson’s disease. Our findings reveal the spatial and functional nature of GABAergic-like dopamine synapses in health and disease.

Abstract Background Diabetes mellitus is a major risk factor for heart failure. A recent consensus statement recommended annual cardiac biomarker testing (e.g. natriuretic peptide or high-sensitivity cardiac troponin) for all patients with diabetes. We aimed to identify patients at a higher risk of hospitalization for heart failure among patients with type 2 diabetes to prioritize those who would require screening. Methods Overall, 1,189,113 patients who underwent two medical health checkup cycles (2009–2012 and 2011–2014) and had stable diabetic kidney disease (DKD) phenotype in the Korean National Health Insurance Service database were included in this study. After excluding those with concurrent proteinuria (PU) and reduced estimated glomerular filtration rate, three groups (no-DKD, PU+DKD, and PU−DKD) were identified. A fatty liver index of ≥ 60 was defined as metabolic dysfunction–associated fatty liver disease (MAFLD). Patients were followed up until December 2018 or until outcomes developed. The Cox proportional hazard model was used to compare the risk of hospitalization for heart failure across groups. Results During an average of 6.6 years of follow-up, 5781 patients developed hospitalization for heart failure. After adjusting for covariates, the risk of hospitalization for heart failure was highest in the PU+DKD group [HR 3.12, 95% CI (2.75–3.55)], followed by the PU−DKD group [HR 1.85, 95% CI (1.73–1.99)] using the no-DKD group as the reference category. The risk of hospitalization for heart failure was comparable regardless of MAFLD status in patients who already had DKD. However, in the no-DKD group, the risk of hospitalization for heart failure was 1.4 times higher in patients with MAFLD than in those without [HR 1.41, 95% CI (1.31–1.52)]. Conclusions In lines with the international consensus statement, we suggest that annual cardiac biomarker testing should be conducted at least in patients with DKD and/or MAFLD.

SUMMARY: Purpose: Although previous research showed the importance of safety culture on health care workers' speaking up behaviors, it is not clear how particular safety culture domains are associated with the speaking up behaviors of hospital staff. Also, researchers have suggested that health care workers’ speaking up behaviors vary by profession, but there has been limited research into such differences. Thus, this study examined differences in perceptions of patient safety culture and the promotive and prohibitive speaking up behaviors of health care workers by profession and investigated the relationships between patient safety culture and the two types of speaking up behaviors. Methods: A descriptive correlational study was conducted using secondary data collected through an online survey of health care workers at a private, nonprofit, tertiary-level teaching hospital in South Korea. The sample (N = 831) consisted of nurses (54.0%), physicians (13.0%), and other licensed and unlicensed hospital personnel (33.0%). Analyses of variance were conducted to examine differences in study variables by profession. Hierarchical regression analyses were conducted to evaluate the effects of the seven patient safety culture factors on promotive and prohibitive voice after controlling for tenure and profession. Results: Perceptions of safety culture and promotive voice behaviors were higher for physicians compared with nurses. Communication openness, reporting patient adverse events, and unit supervisors' and hospital managements’ support for patient safety were significant predictors of both types of voice behaviors. Conclusion: Hospital administrators and unit managers should create a supportive environment where staff feel free to voice their concerns and suggestions. They should also pay attention to the varying perspectives held by different groups of hospital workers and their different voice behaviors. Knowing which dimensions of patient safety culture are most strongly related to health care workers’ voice behaviors can guide patient safety improvement activities in health care organizations.

Abstract Background Despite evidence linking a safety culture with patient safety, the processes by which aspect of safety culture influences patient safety are not yet well understood. Thus, this study aimed to test a theoretical model of the relationships between three enabling factors (supervisor/clinical leader support for patient safety, hospital management support for patient safety, and psychological safety), and four enacting factors of patient safety culture (handoffs and information exchange, teamwork, error reporting intention, and withholding voice) with nurse assessments of patient safety. Methods A cross-sectional, descriptive correlational study design was used. Between May and June 2020, 526 nurses who provided direct care to patients in medical surgical units in three Korean hospitals completed an online survey that included four standardized scales or subscales. Structural equation modelling was used to test the hypothesized model. Results Among the three enabling factors, psychological safety was associated with all four enacting factors, and all enacting factors were associated with overall patient safety. Hospital management support was associated with all enacting factors except teamwork, but supervisor/clinical leader support was associated with only handoffs and information exchange, and withholding voice. Thus, teamwork was influenced only by psychological safety. Findings demonstrate overall support for the theoretical model of safety culture wherein enabling factors influence enacting factors which, in turn, lead to patient safety outcomes, but emphasize the critical nature of psychological safety among nursing staff. Conclusion This study provides further insight into the importance of support from hospital management and unit supervisors/clinical leaders for patient safety to motivate and enable hospital nurses to enact behaviours necessary for patient safety. However, such support must also take the form of enhancing psychological safety for nursing staff.

Edge computing is becoming increasingly popular in artificial intelligence (AI) application development due to the benefits of local execution. One widely used approach to overcome hardware limitations in edge computing is heterogeneous computing, which combines a general-purpose processor with a domain-specific AI processor. However, this approach can be inefficient due to the communication overhead resulting from the complex communication protocol. To avoid communication overhead, the concept of an application-specific instruction set processor based on customizable instruction set architecture (ISA) has emerged. By integrating the AI processor into the processor core, on-chip communication replaces the complex communication protocol. Further, custom instruction set extension (ISE) reduces the number of instructions needed to execute AI applications. In this paper, we propose a uniprocessor system architecture for lightweight AI systems. First, we define the custom ISE to integrate the AI processor and GPP into a single processor, minimizing communication overhead. Next, we designed the processor based on the integrated core architecture, including the base core and the AI core, and implemented the processor on an FPGA. Finally, we evaluated the proposed architecture through simulation and implementation of the processor. The results show that the designed processor consumed 6.62% more lookup tables and 74% fewer flip-flops while achieving up to 193.88 times enhanced throughput performance and 52.75 times the energy efficiency compared to the previous system.

Abstract Background The limitation of activity due to dyspnea in chronic obstructive pulmonary disease (COPD) patients is affected by diaphragmatic dysfunction and reduced lung function. This study aimed to analyze the association between diaphragm function variables and forced expiratory volume in the first second (FEV1) and to estimate the clinical significance of diaphragm function in the correlation between COPD severity and lung function. Methods This prospective, single-center, cross-sectional observational study enrolled 60 COPD patients in a respiratory outpatient clinic. Data for baseline characteristics and the dyspnea scale were collected. Participants underwent a pulmonary function test (PFT), a 6-minute walk test (6MWT), and diaphragm function by ultrasonography. Results The right excursion at forced breathing showed the most significant correlation with FEV1 (r = 0.370, p = 0.004). The cutoff value was 6.7 cm of the right diaphragmatic excursion at forced breathing to identify the FEV1 above 50% group. In the group with a right diaphragmatic excursion at forced breathing 0.05). In the group with ≥ 6.7 cm, mMRC and the total distance of 6MWT showed a significant difference between FEV1 under and above 50% (p = 0.014, 456.7 ± 69.7 m vs. 513.9 ± 60.3 m, p = 0.018, respectively). Conclusion The right diaphragmatic forced excursion was closely related to FEV1, and analysis according to the right diaphragmatic forced excursion-based cut-off value showed a significant difference between both groups. When the diaphragm function was maintained, there was a lot of difference in the 6MWT’s factors according to the FEV1 value. Our data suggest that diaphragmatic function should be performed when interpreting PFT.

Abstract Background Few studies have examined the relationship between patient safety climate and two forms of patient safety behavior (i.e., safety compliance and safety participation) among nurses. Better understanding of factors contributing to nurses’ safety behaviors could enhance patient safety. Therefore, this study aimed to examine the effect of patient safety climate on nurses’ patient safety behavior and to explore whether patient safety knowledge and motivation mediate this relationship. Methods This correlational, cross-sectional study used survey data from 1,053 staff nurses working at a general hospital located in a metropolitan area of South Korea. Structural equation modeling was employed to test a hypothesized multiple mediation model that was guided by Griffin and Neal’s model of safety performance. Results The results indicated that patient safety climate was directly related to both patient safety compliance behavior (β = 0.27, p

This scientific investigation emphasizes the essential integration of nature’s influence in crafting multifunctional surfaces with bio-inspired designs for enhanced functionality and environmental advantages. The study introduces an innovative approach, merging color decoration, humidity sensing, and antiviral properties into a unified surface using chitosan, an organo-biological polymer, to create cost-effective multilayered films through sol-gel deposition and UV photoinduced deposition of metal nanoparticles. The resulting chitosan films showcase diverse structural colors and demonstrate significant antiviral efficiency, with a 50% and 85% virus inhibition rate within a rapid 20 min reaction, validated through fluorescence cell expression and real-time qPCR (polymerase chain reaction) assays. Silver-deposited chitosan films further enhance antiviral activity, achieving remarkable 91% and 95% inhibition in independent assays. These films exhibit humidity-responsive color modifications across a 25–90% relative humidity range, enabling real-time monitoring validated through simulation studies. The proposed three-in-one functional surface can have versatile applications in surface decoration, medicine, air conditioning, and the food industry. It can serve as a real-time humidity sensor for indoor and outdoor surfaces, find use in biomedical devices for continuous humidity monitoring, and offer antiviral protection for frequently handled devices and tools. The customizable colors enhance visual appeal, making it a comprehensive solution for diverse applications.

Vascular diseases are the leading causes of death worldwide, and they are attributable to multiple pathologies, such as atherosclerosis, diabetes, and chronic obstructive pulmonary disease. Exposure to various environmental contaminants is associated with the development of various diseases, including vascular diseases. Among environmental contaminants, micro- and nanoplastics have gained attention as global environmental risk factors that threaten human health. Recently, extensive research has been conducted on the effects of micro- and nanoplastics on various human diseases, including vascular diseases. In this review, we highlight the effects of micro- and nanoplastics on vascular diseases.

Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA–target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC–MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.

Background Although cardiovascular outcome trials using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) showed a reduction in risk of 3-point major adverse cardiovascular events (MACE), they did not demonstrate beneficial effects on stroke risk. Additionally, meta-analysis showed SGLT-2i potentially had an adverse effect on stroke risk. Contrarily, pioglitazone, a type of thiazolidinedione (TZD), has been shown to reduce recurrent stroke risk. Thus, we aimed to compare the effect of SGLT-2i and TZD on the risk of stroke in type 2 diabetes mellitus (T2DM) patients. Methods Using the Korean National Health Insurance Service data, we compared a 1:1 propensity score-matched cohort of patients who used SGLT-2i or TZD from January 2014 to December 2018. The primary outcome was stroke. The secondary outcomes were myocardial infarction (MI), cardiovascular death, 3-point MACE, and heart failure (HF). Results After propensity-matching, each group included 56,794 patients. Baseline characteristics were well balanced. During the follow-up, 862 patients were newly hospitalized for stroke. The incidence rate of stroke was 4.11 and 4.22 per 1,000 person-years for the TZD and SGLT-2i groups respectively. The hazard ratio (HR) of stroke was 1.054 (95% confidence interval [CI], 0.904 to 1.229) in the SGLT-2i group compared to the TZD group. There was no difference in the risk of MI, cardiovascular death, 3-point MACE between groups. Hospitalization for HF was significantly decreased in SGLT-2i-treated patients (HR, 0.645; 95% CI, 0.466 to 0.893). Results were consistent regardless of prior cardiovascular disease. Conclusion In this real-world data, the risk of stroke was comparable in T2DM patients treated with SGLT-2i or TZD.

Second-look ultrasonography (US) is a targeted breast US examination that evaluates suspicious lesions detected on magnetic resonance imaging (MRI). It is a useful tool for determining the probability of malignancy and facilitating US-guided biopsy. Lesions detected on MRI and US should be correlated accurately, which is challenging in some cases. This article documents second-look US and MRI findings that are correlated with the pathology, and suggests helpful approaches for correlating between the two modalities.

Abstract Aim This study identified and evaluated tested patient safety educational interventions. This study also described the content, curricular structures and teaching strategies of the educational interventions and determined the methods used for evaluating patient safety learning outcomes. Design The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines directed this review. Methods Searches for articles describing and evaluating patient safety educational interventions were conducted using four scholarly databases. Study quality was assessed using the McMaster Critical Review Form. Results Seven studies met the inclusion criteria. Educational interventions were either presented as stand‐alone courses or as lessons embedded in an existing course. All studies employed a mixture of various teaching modalities and several evaluation methods and outcomes. Mixed results were observed in terms of the effects of educational interventions. Future researchers should continue to develop patient safety curricula and examine their effect on student competencies with stronger methodological rigour.

BackgroundIt is unclear whether upfront surgery or neoadjuvant chemotherapy is appropriate for first treatment in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with 1–2 suspicious axillary lymph node (ALN) metastases on preoperative breast magnetic resonance imaging (MRI).MethodWe identified 282 patients with HR+HER2- breast cancer and 1–2 suspicious ALN metastases on baseline breast MRI (147 received upfront surgery; 135 received neoadjuvant chemotherapy). We evaluated the predictive clinicopathological factors for pN2-3 in the adjuvant setting and axillary pathologic complete response (pCR) in the neoadjuvant setting.ResultsLymphovascular invasion (LVI)-positive and clinical tumors >3 cm were significantly associated with pN2-3 in patients who received upfront surgery. The pN2-3 rate was 9.3% in patients with a clinical tumor ≤ 3 cm and LVI-negative versus 34.7% in the others (p < 0.001). The pN2-3 rate in patients with a clinical tumor ≤ 3 cm and LVI-negative and in the others were 9.3% versus 34.7% in all patients (p < 0.001), 10.7% versus 40.0% (p = 0.033) in patients aged < 50 years, and 8.5% versus 31.0% in patients aged ≥ 50 years (p < 0.001), respectively. In the neoadjuvant setting, patients with tumor-infiltrating lymphocytes (TILs) ≥ 20% had a higher axillary pCR than those with TILs < 20% (46.7% vs. 15.3%, p < 0.001). A similar significant finding was also observed in patients < 50 years.ConclusionsUpfront surgery may be preferable for patients aged ≥ 50 years with a clinical tumor < 3 cm and LVI-negative, while neoadjuvant chemotherapy may be preferable for those aged < 50 years with TILs ≥ 20%.

An acellular dermal matrix (ADM) is a type of allograft that can be made from human, bovine, or porcine dermis and is used to support or reconstruct soft tissue. During breast reconstructive surgeries, ADMs are widely used to partially cover breast implants following a mastectomy to correct for insufficient subcutaneous tissue. Recently, ADMs have been used as a filling material for volume replacement in oncoplastic breast conserving surgery. In this report, we present the case of a female, middle-aged patient who underwent breast conserving surgery with volume replacement using an ADM.

Fibrosing mediastinitis is a rare benign disorder characterized by the proliferation of dense fibrous tissue within the mediastinum. It typically manifests as localized or infiltrative soft-tissue masses in the middle mediastinum or hilar area, which cause compression and encasement of adjacent mediastinal structures, such as the vessels or airway. Here, we report a rare case of fibrosing mediastinitis in a 13-year-old girl that presented as a middle mediastinal mass lesion on CT scan with obliterating left lower lobar bronchus. The patient’s symptoms and follow-up chest CT showed significant improvement following systemic corticosteroid treatment. As fibrosing mediastinitis can improve with systemic steroid therapy, radiologists must be aware of its radiologic findings when discriminating between infiltrating soft tissue lesions in the mediastinum.

Background Triple-negative breast cancer (TNBC) has a relatively poor prognosis. Research has identified potential metabolic targets, including fatty acid metabolism, in TNBC. The absence of effective target therapies for TNBC led to exploration of the role of fatty acid synthetase (FASN) as a potential target for TNBC therapy. Here, we analyzed the expression of FASN, a representative lipid metabolism–related protein, and investigated the association between FASN expression and Ki-67 and the programmed death ligand 1 (PD-L1) biomarkers in TNBC. Methods Immunohistochemical expression of FASN was analyzed in 166 patients with TNBC. For analytical purposes, patients with 0–1+ FASN staining were grouped as low-grade FASN and patients with 2–3+ FASN staining as high-grade FASN. Results FASN expression was observed in 47.1% of TNBC patients. Low and high expression of FASN was identified in 75.9% and 24.1%, respectively, and no statistically significant difference was found in T category, N category, American Joint Committee on Cancer stage, or recurrence rate between the low and high-FASN expression groups. Ki-67 proliferation level was significantly different between the low and high-FASN expression groups. FASN expression was significantly related to Ki-67 as the level increased. There was no significant difference in PD-L1 positivity between the low- and high-FASN expression groups. Conclusions We identified FASN expression in 166 TNBC patients. The Ki-67 proliferation index was positively correlated with FASN level, indicating higher proliferation activity as FASN increases. However, there was no statistical association with PD-L1 SP142, the currently FDA-approved assay, or FASN expression level.

Background Diabetic kidney disease (DKD) is associated with an elevated risk of fractures. However, little is known about the association between proteinuric or non-proteinuric DKD and the risk of hip fracture. Thus, we investigated the incidence of hip fractures among Korean adults with type 2 diabetes mellitus (T2DM) stratified by DKD phenotype. Methods In this retrospective cohort study using the Korean National Health Insurance Service database, patients with T2DM who received at least one general health checkup between 2009 and 2012 were followed until the date of hip fracture, death, or December 31, 2018. We classified the DKD phenotype by proteinuria and estimated glomerular filtration rate (eGFR), as follows: no DKD (PU−GFR−), proteinuric DKD with normal eGFR (PU+GFR−), non-proteinuric DKD with reduced eGFR (PU−GFR+), and proteinuric DKD with reduced eGFR (PU+GFR+) Results The cumulative incidence of hip fractures was highest in the PU+GFR+ group, followed by the PU−GFR+ group and the PU+GFR− group. After adjustment for confounding factors, the hazard ratio (HR) for hip fracture was still highest in the PU+GFR+ group. However, the PU+GFR− group had a higher HR for hip fracture than the PU−GFR+ group (PU+GFR+: HR, 1.69; 95% confidence interval [CI], 1.57 to 1.81; PU+GFR−: HR, 1.37; 95% CI, 1.30 to 1.46; PU−GFR+: HR, 1.20; 95% CI, 1.16 to 1.24 using the PU−GFR− group as the reference category). Conclusion The present study demonstrated that DKD was significantly associated with a higher risk of hip fracture, with proteinuria as a major determinant.

Background With the introduction of Xpert MTB/RIF assay (Xpert), its incorporation into tuberculosis (TB) diagnostic algorithm has become an important issue. The aim of this study was to evaluate the performance of the Xpert assay in comparison with a commercial polymerase chain reaction (PCR) assay. Methods Medical records of patients having results of both Xpert and AdvanSure TB/NTM real-time PCR (AdvanSure) assays using the same bronchial washing specimens were retrospectively reviewed. Results Of the 1,297 patients included in this study, 205 (15.8%) were diagnosed with pulmonary TB. Using mycobacterial culture as the reference method, sensitivity of the Xpert assay using smear-positive specimens was 97.5%, which was comparable to that of the AdvanSure assay (96.3%, p=0.193). However, the sensitivity of the Xpert assay using smear-negative specimens was 70.6%, which was significantly higher than that of the AdvanSure assay (52.9%, p=0.018). Usng phenotypic drug susceptibility testing as the reference method, sensitivity and specificity for detecting rifampicin resistance were 100% and 99.1%, respectively. Moreover, a median turnaround time of the Xpert assay was 1 day, which was significantly shorter than 3 days of the AdvanSure assay (p

Background & Aims: Sphingosine 1-phosphate receptors (S1PRs) are a group of G-protein–coupled receptors that confer a broad range of functional effects in chronic inflammatory and metabolic diseases. S1PRs also may mediate the development of nonalcoholic steatohepatitis (NASH), but the specific subtypes involved and the mechanism of action are unclear. Methods: We investigated which type of S1PR isoforms is activated in various murine models of NASH. The mechanism of action of S1PR4 was examined in hepatic macrophages isolated from high-fat, high-cholesterol diet (HFHCD)-fed mice. We developed a selective S1PR4 functional antagonist by screening the fingolimod (2-amino-2-[2-(4- n -octylphenyl)ethyl]-1,3- propanediol hydrochloride)-like sphingolipid-focused library. Results: The livers of various mouse models of NASH as well as hepatic macrophages showed high expression of S1pr4. Moreover, in a cohort of NASH patients, expression of S1PR4 was 6-fold higher than those of healthy controls. S1pr4+/- mice were protected from HFHCD-induced NASH and hepatic fibrosis without changes in steatosis. S1pr4 depletion in hepatic macrophages inhibited lipopolysaccharide-mediated Ca++ release and deactivated the Nod-like receptor pyrin domain-containning protein 3 (NLRP3) inflammasome. S1P increased the expression of S1pr4 in hepatic macrophages and activated NLRP3 inflammasome through inositol trisphosphate/inositol trisphosphate–receptor–dependent [Ca++] signaling. To further clarify the biological function of S1PR4, we developed SLB736, a novel selective functional antagonist of SIPR4. Similar to S1pr4+/- mice, administration of SLB736 to HFHCD-fed mice prevented the development of NASH and hepatic fibrosis, but not steatosis, by deactivating the NLRP3 inflammasome. Conclusions: S1PR4 may be a new therapeutic target for NASH that mediates the activation of NLRP3 inflammasome in hepatic macrophages.

Background : The increasing prevalence of type 2 diabetes mellitus (T2DM) has led to a significant health burden. Technological advancements have highlighted the benefits of digital therapeutics for chronic diseases. In this study, we aimed to investigate the effects of a mobile application on weight reduction in patients with T2DM. Methods : A total of 48 patients with T2DM was included in this single-center, randomized, controlled trial. In addition to conventional treatment, participants in the intervention group used a mobile application-based self-management system for diet, exercise, and medication adherence. The primary outcome of this study was weight change after 3 months of intervention, and secondary outcomes were metabolic parameters. Results : After 12 weeks, no significant differences in body weight change were observed between the intervention and control groups (P=0.229). However, a significant difference was found in waist circumference (WC) between the two groups, wherein the control group showed an increase in WC (from 95.00±8.89 cm to 95.76±9.72 cm), while the intervention group showed a reduction (from 91.93±6.25 cm to 90.75±6.01 cm) with a significant time by group interaction (P=0.016). Additionally, participants with good compliance exhibited a more evident reduction in WC (P=0.037). However, no significant differences were found in other metabolic parameters between the two groups. Conclusion : Lifestyle modification using short-term mobile applications effectively reduced WC, especially in patients with good adherence to the application. However, weight reduction was not achieved.

Background/Aims: Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database. Methods: Data from the Surveillance, Epidemiology and End Results : (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated. Results: Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively. Conclusions: The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.

Currently, the trend of elderly people living alone is rising due to rapid aging and shifts in family structures. Accordingly, the efficient implementation and management of monitoring systems tailored for elderly people living alone have become paramount. Monitoring systems are generally implemented based on multiple sensors, and the collected data are processed on a server to provide monitoring services to users. Due to the use of multiple sensors and a reliance on servers, there are limitations to economical maintenance and a risk of highly personal information being leaked. In this paper, we propose an intelligent monitoring system with privacy preservation based on edge AI. The proposed system achieves cost competitiveness and ensures high security by blocking communication between the camera module and the server with an edge AI module. Additionally, applying edge computing technology allows for the efficient processing of data traffic. The edge AI module was designed with Verilog HDL and was implemented on a field-programmable gate array (FPGA). Through experiments conducted on 6144 frames, we achieved 95.34% accuracy. Synthesis results in a 180 nm CMOS technology indicated a gate count of 1516 K and a power consumption of 344.44 mW.

Pancreatic collision tumors are rare neoplasm, and cases consisting of ductal adenocarcinoma with a neuroendocrine tumor, intraductal papillary mucinous neoplasm with a neuroendocrine tumor, and solid pseudopapillary neoplasm with a neuroendocrine tumor have been reported. We report a case of a rapidly growing pancreatic collision tumor consisting of desmoidtype fibromatosis and mucinous cystic neoplasm in a 30-year-old pregnant female. To the best of our knowledge, this is the first reported case of a pancreatic collision tumor consisting of desmoid- type fibromatosis and mucinous cystic neoplasm.

Abstract Diffusion-weighted imaging (DWI) is proven useful to differentiate benign and malignant soft tissue tumors (STTs). Radiomics utilizing a vast array of extracted imaging features has a potential to uncover disease characteristics. We aim to assess radiomics using DWI can outperform the conventional DWI for STT differentiation. In 151 patients with 80 benign and 71 malignant tumors, ADCmean and ADCmin were measured on solid portion within the mass by two different readers. For radiomics approach, tumors were segmented and 100 original radiomic features were extracted on ADC map. Eight radiomics models were built with training set (n = 105), using combinations of 2 different algorithms—multivariate logistic regression (MLR) and random forest (RF)—and 4 different inputs: radiomics features (R), R + ADCmin (I), R + ADCmean (E), R + ADCmin and ADCmean (A). All models were validated with test set (n = 46), and AUCs of ADCmean, ADCmin, MLR-R, RF-R, MLR-I, RF-I, MLR-E, RF-E, MLR-A and RF-A models were 0.729, 0.753 0.698, 0.700, 0.773, 0.807, 0.762, 0.744, 0.773 and 0.807, respectively, without statistically significant difference. In conclusion, radiomics approach did not add diagnostic value to conventional ADC measurement for differentiating benign and malignant STTs.

AimsHypoglycemic encephalopathy (HE) can cause long-lasting mental changes, disability, and even death. We aimed to investigate prognostic factors for HE and to determine when the treatment of HE becomes futile.MethodsWe retrospectively evaluated the data of patients admitted for prolonged HE at Dongguk University Ilsan Hospital between December 2005 and July 2021. We assessed the Glasgow Outcome Scale (GOS) to assess functional outcome.ResultsForty-four patients were enrolled in the study. Thirty-two of these showed the improvement on GOS after treatment. Patients with improved consciousness had a shorter duration of hypoglycemia (1.6±1.4 vs. 7.8±15.0 hours, p = 0.04) and a lower incidence of brain lesions than those without improvements in consciousness (76.0% vs. 25.0%, p < 0.01). Patients whose lesions were detected in initial MRIs were 1.3 times less likely to recover consciousness after HE (odds ratios, 1.28; 95% CI, 1.09-1.52; p < 0.01). None of the patients recovered consciousness after 320 h. Maximum time spent to recover was 194 in patients without brain lesions and 319 in those with lesions.ConclusionsHypoglycemic brain injury detected in initial MRIs predicted poorer HE prognosis. Nevertheless, treatment should be provided for at least for 14 days after admission.

Abstract Background Sodium-glucose cotransporter 2 inhibitor (SGLT2i) should be considered for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) having estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR) > 30 mg/g. However, SGLT2i is currently underprescribed among eligible, at-risk patients for CKD progression. We analyzed prescription patterns and barriers to initiating SGLT2i in patients with T2D and CKD in real practice. Methods A total of 3,703 consecutive outpatients with T2D from four teaching hospitals during six months (2019 ~ 2020) were reviewed. Five eGFR categories (G1, ≥ 90; G2, 60–89; G3ab, 30–59; G4-5, < 30 mL/min/1.73 m2) and three UACR categories (A1, < 30; A2, 30–300; A3, > 300 mg/g) were used to define CKD status. Results Overall, 25.8 % patients received SGLT2i in the following eGFR and albuminuria categories: G1 (A1, 31 %; A2, 48 %; A3, 45 %); G2 (A1, 18 %; A2, 24 %; A3, 30%); and G3 (A1, 9 %; A2, 7 %; A3, 13 %). Total prevalence estimate of CKD was 33.8 % (n = 1,253), of whom 25.6 % patients received SGLT2i. We defined eGFR ≥ 45 mL/min/1.73 m2 and UACR ≥ 30 mg/g as high-risk CKD group eligible for SGLT2i (n = 905), of whom 32.9 % patients were treated with an SGLT2i. In this high-risk group, SGLT2i initiation showed negative correlations with age ≥ 65 years and recent hospitalization. Conversely, HbA1c level, body mass index (BMI), presence of diabetic retinopathy, and previous heart failure events were positively correlated with SGLT2i initiation. Conclusions Only 32.9 % of T2D with CKD eligible for SGLT2i is currently treated with SGLT2i in real-world clinical practice. The older patient group and clinical inertia are the main barriers to initiate SGLT2i for eligible patients. Clinicians should change the glucocentric approach and focus on reducing renal events in T2D.

Gene therapy is an innovative approach in the field of regenerative medicine. This therapy entails the transfer of genetic material into a patient’s cells to treat diseases. In particular, gene therapy for neurological diseases has recently achieved significant progress, with numerous studies investigating the use of adeno-associated viruses for the targeted delivery of therapeutic genetic fragments. This approach has potential applications for treating incurable diseases, including paralysis and motor impairment caused by spinal cord injury and Parkinson’s disease, and it is characterized by dopaminergic neuron degeneration. Recently, several studies have explored the potential of direct lineage reprogramming (DLR) for treating incurable diseases, and highlighted the advantages of DLR over conventional stem cell therapy. However, application of DLR technology in clinical practice is hindered by its low efficiency compared with cell therapy using stem cell differentiation. To overcome this limitation, researchers have explored various strategies such as the efficiency of DLR. In this study, we focused on innovative strategies, including the use of a nanoporous particle-based gene delivery system to improve the reprogramming efficiency of DLR-induced neurons. We believe that discussing these approaches can facilitate the development of more effective gene therapies for neurological disorders.

Salivary gland tumors are histologically diverse, and each entity has distinctive histopathological and molecular features. We report two cases of salivary gland tumors with unique histological and molecular findings, which have not been documented previously. The tumors were located in the base of the tongue in both patients. Most tumor cells were arranged in cords and nests, giving a trabecular-like appearance. Focally, glandular structures with intraluminal mucin and perivascular pseudorosette-like configurations were identified. Tumor cells had eosinophilic to clear cytoplasm, and showed mild nuclear atypia. They were positive for pancytokeratin and negative for S-100, p63, c-KIT, androgen receptor, and neuroendocrine markers. Multiple foci of capsular or lymphovascular invasion were identified, but the Ki-67 labeling index was low (< 5%). Fluorescence in situ hybridization revealed concurrent alterations of MAML2 and EWSR1 gene. Further investigations with a larger number of cases with similar histological and molecular features will accurately classify this tumor.

Background Although studies have shown that obesity is associated with aeroallergen sensitization (atopy), controversy still exists. We aimed to investigate the association between metabolic status, obesity, and atopy stratified by sex and menopausal status. Methods A total of 1,700 adults from the 2010 Korean National Health and Nutrition Examination Survey were classified into metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) by body mass index and insulin resistance. Atopy was defined as a positive response to at least one aeroallergen. Multiple regression analysis was used to evaluate the risk of immunoglobulin E (IgE) elevation or atopy in relation to the degree of metabolic abnormality and obesity. Results In premenopausal women, total IgE was positively correlated with obesity and insulin resistance. MUNO participants had a higher risk of having elevated total IgE compared to MHNO participants (odds ratio [OR], 2.271; 95% confidence interval [CI], 1.201 to 4.294), while MHO participants did not show a significant difference (OR, 1.435; 95% CI, 0.656 to 3.137) in premenopausal women. MUNO, but not MHO was also associated with atopy (OR, 2.157; 95% CI, 1.284 to 3.625). In men and postmenopausal women, there was no significant difference between metabolic status, obesity, and atopy among groups. Conclusion Increased insulin resistance is associated with total IgE and atopy in premenopausal women but not in postmenopausal women or men.

Abstract With the progression of acute cholecystitis, antimicrobial therapy becomes important for infection control. Current antibiotic recommendations were mostly based on reports of patients with acute cholangitis whose bile specimens were sampled from the biliary tract. However, as most infections of acute cholecystitis are limited to the gallbladder, direct sampling from the site increases the probability of identifying the causative pathogen. We investigated 321 positive bile cultures from 931 patients with acute cholecystitis who underwent laparoscopic cholecystectomy between January 2003 and December 2017. The frequency of enterococci declined (P = 0.041), whereas that of Enterobacteriales (P = 0.005), particularly Escherichia (P = 0.008), increased over time. The incidence of ciprofloxacin-resistant Enterobacteriales showed a significant increasing trend (P = 0.031). Vancomycin-resistant E.faecium, carbapenem-resistant Enterobacteriales, and extended-spectrum beta-lactamase-producing Enterobacteriales were recently observed. In grade I and II acute cholecystitis, there were no significant differences in perioperative outcomes in patients with and without early appropriate antimicrobial therapy. In conclusion, the changing incidence of frequently isolated microorganisms and their antibiotic resistance over time would be considered before selecting antibiotics for the treatment of acute cholecystitis. Surgery might be a crucial component of infection control in grade I and II acute cholecystitis.

Pancreatic metastasis from malignant phyllodes tumor (PT) of the breast is rare, and only a few cases have been reported in the literature. Here, we report a case of pancreatic metastasis from malignant PT of the breast in a 48-year-old woman. She had had three episodes of recurrence of malignant PT in her right breast. She presented with epigastric pain for 2 months. Computed tomography and magnetic resonance imaging revealed a 6 cm-sized, well-defined, heterogeneous mass with peripheral enhancement in the body of the pancreas. Endoscopic ultrasonography-guided fine-needle aspiration was performed, and the pathologic report suggested spindle cell mesenchymal neoplasm. Subsequently, surgical excision was performed, and the mass was confirmed as a metastatic malignant PT. The imaging findings are discussed and the literature is briefly reviewed in this report.

Abstract Background To date, there has been no universal and validated tool for measuring safety culture in Korea. The Hospital Survey on Patient Safety Culture (HSOPSC), version 2.0 was released by the Agency for Healthcare Research and Quality in 2019, but it had not yet been translated and assessed for use in Korea. The aim of this study was to assess the content validity and other psychometric properties of the Korean-language version of the HSOPSC 2.0. Methods Instrument adaptation was performed using a committee-based translation, cognitive interviews, and expert panel reviews. Confirmatory factor analysis was conducted on data obtained through an online survey from 526 registered nurses who worked on medical-surgical units in three teaching hospitals in South Korea. Results One item was dropped during the translation and adaption phase of the study as being a poor fit for the Korean healthcare context, resulting in excellent content validity. Confirmatory factor analysis supported the factorial structure of the K-HSOPSC 2.0. Correlations with an overall measure of patient safety provided further evidence of construct validity. Additionally, in comparing the results of this current study to those from U.S. research using the HSOPSC 2.0, it was found that Korean nurses assigned less positive scores to all dimensions of patient safety culture. Conclusion Our findings provide evidence of the content validity, reliability, and construct validity of the K-HOSPSC 2.0 for measuring patient safety culture in South Korean hospitals. Hospital administrators can use this tool to assess safety culture and identify areas for improvement to enhance patient safety and quality of care.

Ewing sarcomas constitute a group of small, round, blue cell tumors of the bone and soft tissue. Extraskeletal Ewing sarcoma (EES) is a rare malignant neoplasm that arises from soft tissues, and it usually affects children and young adults. EES of the thoracopulmonary region commonly presents with a palpable mass or pain. Although rarely reported, EES affecting the anterior chest wall may present as a breast mass. We report a case of EES arising from the chest wall and manifesting as a palpable breast mass in a 22-year-old woman. The large mass was initially misdiagnosed as a breast origin mass on ultrasonography, but subsequent CT and MRI showed that the mass originated from the chest wall. Radiologists should be aware of the imaging findings of EES, and they should understand that chest wall lesions may be clinically confused as breast lesions.

Blood liquid biopsy has emerged as a way of overcoming the clinical limitations of repeat biopsy by testing for the presence of acquired resistance mutations to therapeutic agents. Despite its merits of repeatability and non-invasiveness, this method is currently only used as a supplemental test due to a relatively low sensitivity rate of 50%–60%, and cannot replace tissue biopsy. The circulating tumor DNAs used in blood liquid biopsies are passive products of fragmented DNA with a short half-life released following tumor cell death; the low sensitivity seen with liquid blood biopsy results from this instability, which makes increasing the sensitivity of this test fundamentally difficult. Extracellular vesicles (EVs) are ideal carriers of cancer biomarkers, as cancer cells secret an abundance of EVs, and the contents of tumor cell-originated EVs reflect the molecular and genetic composition of parental cells. In addition, EV-derived DNAs (EV DNAs) consist of large-sized genomic DNAs and tumor-specific oncogenic mutant DNAs. For these reasons, liquid biopsy using EV DNA has the potential to overcome issues arising from tissue shortages associated with small biopsies, which are often seen in lung cancer patients, and the biopsy product can be used in other diagnostic methods, such as epidermal growth factor receptor (EGFR) mutation testing and next-generation sequencing (NGS). A higher sensitivity can be achieved when EV DNAs obtained from bronchoalveolar lavage fluid (BALF) are used rather than those from blood. BALF, when obtained close to the tumor site, is a promising liquid biopsy tool, as it enables the gathering of both cellular and non-cellular fractions of the tumor microenvironment, and provides increased diagnostic sensitivity when compared to blood.

Synovial sarcoma is a malignant soft tissue tumor that usually involves the extremities, particularly near the knees; a synovial sarcoma originating in the chest wall is extremely rare. We describe a 26-year-old woman diagnosed with a synovial sarcoma originating in the chest wall, based on CT and MRI findings. Contrast-enhanced CT images revealed a small, well-defined enhancing mass with calcification, in the subpleural area. This lesion was initially diagnosed as a benign tumor; however, the patient developed sudden severe pain with spontaneous bleeding and hemothorax, suggesting the possibility of malignancy. MRI revealed a multilobulated mass with a fluid-fluid level, which characterizes a synovial sarcoma.

A wide range of breast lesions can arise during pregnancy and lactation, from benign or Epub ahead of print inflammatory diseases to malignant tumors. Hormone-influenced physiological changes of the breast make the radiological evaluation of breast lesions challenging. Knowledge of the imaging features of normal physiological changes and common breast lesions during this period can help radiologists accurately diagnose and appropriately manage conditions. As such, this pictorial essay illustrates normal physiological changes related to pregnancy and lactation, as well as common benign and malignant breast lesions encountered during those periods.