Activity-dependent endoplasmic reticulum Ca2+ uptake depends on Kv2.1-mediated endoplasmic reticulum/plasma membrane junctions to promote synaptic transmission.

The endoplasmic reticulum (ER) forms a continuous and dynamic network throughout a neuron, extending from dendrites to axon terminals, and axonal ER dysfunction is implicated in several neurological disorders. In addition, tight junctions between the ER and plasma membrane (PM) are formed by several molecules including Kv2 channels, but the cellular functions of many ER-PM junctions remain unknown. Recently, dynamic Ca2+ uptake into the ER during electrical activity was shown to play an essential role in synaptic transmission. Our experiments demonstrate that Kv2.1 channels are necessary for enabling ER Ca2+ uptake during electrical activity, as knockdown (KD) of Kv2.1 rendered both the somatic and axonal ER unable to accumulate Ca2+ during electrical stimulation. Moreover, our experiments demonstrate that the loss of Kv2.1 in the axon impairs synaptic vesicle fusion during stimulation via a mechanism unrelated to voltage. Thus, our data demonstrate that a nonconducting role of Kv2.1 exists through its binding to the ER protein VAMP-associated protein (VAP), which couples ER Ca2+ uptake with electrical activity. Our results further suggest that Kv2.1 has a critical function in neuronal cell biology for Ca2+ handling independent of voltage and reveals a critical pathway for maintaining ER lumen Ca2+ levels and efficient neurotransmitter release. Taken together, these findings reveal an essential nonclassical role for both Kv2.1 and the ER-PM junctions in synaptic transmission.

Fracture Risk Among Stroke Survivors According to Poststroke Disability Status and Stroke Type.

BACKGROUND: Stroke survivors face physical and cognitive challenges, leading to an increased dependency and a higher fall risk. We aimed to investigate the impact of poststroke disability and stroke type on fracture risk at various sites compared with matched controls. METHODS: This retrospective cohort study used data from the Korean National Health Insurance System database (2010-2018), including patients with stroke and 1:1 matched controls. Stroke survivors were grouped based on the presence and severity of their poststroke disability and stroke type. The primary outcome was a newly diagnosed fracture, analyzed by Cox proportional hazard regression analyses adjusting for potential confounders. RESULTS: Among 223 358 stroke survivors (mean age, 64.8±10.9 years; 61.2% men), 16 344 fractures occurred during a mean follow-up of 3.7±2.5 years. In matched controls (n=322 161; mean age, 65.4±11.2 years; 61.3% men), 20 398 fractures were identified. Stroke survivors had increased overall fracture risk compared with matched controls (adjusted hazard ratio [aHR], 1.40 [95% CI, 1.37-1.43]). Specifically, hip fracture risk was even greater in stroke survivors (incidence rate per 1000 person-years, 4.7 [95% CI, 4.5-4.8]; aHR, 2.42 [95% CI, 2.30-2.55]) than controls (incidence rate, 2.2 [95% CI, 2.1-2.3]). The risk of vertebral fractures (aHR, 1.29 [95% CI, 1.25-1.34]) and other fractures (aHR, 1.19 [95% CI, 1.15-1.23]) was also higher than that of the control group. Hip fracture risk was the highest among stroke survivors with severe poststroke disability (aHR, 4.82 [95% CI, 4.28-5.42]), although vertebral or other fracture risk was the highest among those with mild poststroke disability. No significant difference in fracture risk was found between hemorrhagic and ischemic stroke survivors when stratified by disability status. CONCLUSIONS: Our findings showed increased subsequent fracture risk among stroke survivors, particularly those with poststroke disability and for hip fracture. Bone health assessment and treatment should be emphasized as an essential part of stroke management.

Identification and characterization of structural variants related to meat quality in pigs using chromosome-level genome assemblies.

BACKGROUND: Many studies have been performed to identify various genomic loci and genes associated with the meat quality in pigs. However, the full genetic architecture of the trait still remains unclear in part because of the lack of accurate identification of related structural variations (SVs) which resulted from the shortage of target breeds, the limitations of sequencing data, and the incompleteness of genome assemblies. The recent generation of a new pig breed with superior meat quality, called Nanchukmacdon, and its chromosome-level genome assembly (the NCMD assembly) has provided new opportunities. RESULTS: By applying assembly-based SV calling approaches to various genome assemblies of pigs including Nanchukmacdon, the impact of SVs on meat quality was investigated. Especially, by checking the commonality of SVs with other pig breeds, a total of 13,819 Nanchukmacdon-specific SVs (NSVs) were identified, which have a potential effect on the unique meat quality of Nanchukmacdon. The regulatory potentials of NSVs for the expression of nearby genes were further examined using transcriptome- and epigenome-based analyses in different tissues. CONCLUSIONS: Whole-genome comparisons based on chromosome-level genome assemblies have led to the discovery of SVs affecting meat quality in pigs, and their regulatory potentials were analyzed. The identified NSVs will provide new insights regarding genetic architectures underlying the meat quality in pigs. Finally, this study confirms the utility of chromosome-level genome assemblies and multi-omics analysis to enhance the understanding of unique phenotypes.

Association between physical activity changes and risk of incident ischemic stroke following cancer diagnosis: A nationwide retrospective cohort study.

BACKGROUND: Physical inactivity is prevalent after cancer treatment, which could increase ischemic stroke risk in cancer survivors. This study investigated the association between physical activity change from pre- to post-diagnosis and ischemic stroke risk among cancer survivors. METHODS: Using data from the Korean National Health Insurance Service database, 269,943 cancer survivors (mean [SD] age, 56.3 [12.1] years; 45.7% male) with no history of cardiovascular disease were evaluated based on changes in physical activity from pre- to post-diagnosis. Using the Fine-Gray model, subdistribution hazard ratios (sHRs) and 95% confidence intervals (CIs) for ischemic stroke risk were calculated, considering death as a competing risk. RESULTS: After cancer diagnosis, 62.0% remained inactive, 10.1% remained active, 16.6% became active, and 11.4% became inactive. During a mean (SD) follow-up of 4.1 (2.0) years, being active both pre- and post-diagnosis was associated with a 15% decreased risk of ischemic stroke (sHR, 0.85; 95% CI, 0.75-0.96), compared with those who remained inactive. Cancer survivors who became active and inactive post-diagnosis showed a 16% and 11% lower ischemic stroke risk (sHR, 0.84; 95% CI, 0.75-0.93; sHR, 0.89; 95% CI, 0.79-0.99), respectively, than those who remained inactive. Analysis by the primary cancer site did not substantially differ from the main findings. CONCLUSIONS: Physical activity is associated with reduced ischemic stroke risk among cancer survivors. The potential benefits of physical activity are not limited to individuals who were physically active before cancer diagnosis, thus preventive strategies against ischemic stroke should emphasize physical activity throughout the cancer journey.

Diagnostic Performance of Endoscopic Ultrasound Elastography for Differential Diagnosis of Gallbladder Polyp.

BACKGROUND AND AIMS: It is difficult to differentiate between neoplastic and non-neoplastic gallbladder (GB) polyps before surgery. Endoscopic ultrasound-elastography (EUS-EG) is a non-invasive complementary diagnostic method. The utility of EUS-EG in the differential diagnosis of GB polyps has not been investigated. We aimed to investigate the diagnostic performance of EUS-EG for the differential diagnosis of GB polyps. METHODS: Patients with GB polyps were prospectively enrolled from June 2020 until November 2022. EUS-EG and semi-quantitative evaluation of the strain ratio (SR) were performed for differential diagnosis of GB polyps. Fifty-three eligible patients were divided into two groups based on the final diagnosis after surgery. Patient demographics, EUS characteristics, and SR values were compared. Receiver-operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff SR value that discriminates between neoplastic and non-neoplastic GB polyps. RESULTS: The median SR value for neoplastic polyps (32.93 [interquartile range: 22.37-69.02]) was significantly higher than for non-neoplastic polyps (5.40 [2.36-14.44]; p<0.001). There were significant differences in SR values between non-neoplastic, benign neoplastic (23.38 [13.62-39.04]), and malignant polyps (49.25 [27.90-82.00]). The optimal cut-off SR value to differentiate between neoplastic and non-neoplastic polyps was 18.4. In multivariable logistic regression, SR value >18.4 (odds ratio 33.604, 95% confidence interval 2.588-436.292) was an independent predictor of neoplastic polyps. CONCLUSIONS: EUS-EG and SR values can be used as a supplementary method for evaluating GB polyps.

Glycaemic Status and Risk of Abdominal Aortic Aneurysm: A Nationwide Cohort Study of Four Million Adults using Korean National Health Screening Data.

OBJECTIVE: This retrospective cohort study aimed to confirm the previously reported inverse association between diabetes mellitus (DM) and abdominal aortic aneurysm (AAA) using large population based data. It also investigated the associations between AAA and impaired fasting glucose (IFG) and new onset DM (not yet treated). METHODS: A representative dataset was obtained from the Korean National Health Insurance Service. Participants who were aged ≥ 50 years and received a national health examination in 2009 were included and followed until 31 December 2019. Glycaemic status was defined based on fasting plasma glucose level and the relevant diagnostic codes. AAA was ascertained using medical facility use records with relevant diagnostic codes or aneurysm repair surgery. A Cox proportional hazards model was used to examine the association between glycaemic status and AAA, with adjustment for confounders. Additionally, the interactions between glycaemic status and subgroups based on baseline characteristics were examined. RESULTS: The study population comprised 4 162 640 participants. Participants with IFG or DM were significantly more likely to be male, older, and have comorbidities compared with normoglycaemic participants at baseline. The incidence of AAA was lower in participants with IFG or DM compared with normoglycaemic participants. The AAA risk was lower in patients with DM than in patients with IFG, and decreased linearly according to glycaemic status: the adjusted hazard ratio was 0.88 (95% confidence interval [CI] 0.85 - 0.91) for IFG, 0.72 (95% CI 0.67 - 0.78) for newly diagnosed DM, 0.65 (95% CI 0.61 - 0.69) for DM duration < 5 years, and 0.47 (95% CI 0.44 - 0.51) for DM duration ≥ 5 years compared with the normoglycaemia group. Both IFG and DM were related to reduced AAA risk in all subgroups, suggesting an independent association. CONCLUSION: Both IFG and DM, even when not treated with antihyperglycaemic medication, were associated with a lower incidence of AAA. The AAA risk decreased linearly according to DM duration.

Association of body adiposity with left ventricular concentric remodeling and diastolic dysfunction.

BACKGROUND: Obesity is a significant risk factor for heart failure with preserved ejection fraction (HFpEF). In this study, we explore the relationships between body mass index (BMI) and adipose tissue compartments such as visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and epicardial adipose tissue (EAT), with respect to left ventricular (LV) structure and function in subjects with preserved LV systolic function. METHODS: Between January and December 2020, this retrospective study included 749 participants who exhibited preserved LV systolic function and underwent transthoracic echocardiography along with abdominal computed tomography. LV structural and functional variables as well as EAT, VAT, and SAT thickness were evaluated using echocardiography and computed tomography. RESULTS: SAT decreased, while VAT and EAT progressively increased with age. There were significant correlations between BMI and various adipose tissues, with the strongest correlation observed with SAT (r = .491, p < .001) compared to VAT (r = .371, p < .001) or EAT (r = .135, p < .001). However, EAT demonstrated the most substantial association with decreased LV end-diastolic dimension, LV end-systolic dimension, and septal mitral annular velocity and increased relative wall thickness (all p < .05), while VAT and SAT did not show significant associations with LV remodeling and functional parameters after adjusting for clinical variables. CONCLUSION: EAT is the most critical adipose tissue influencing LV geometric and functional changes, compared with VAT or SAT. Thick EAT is associated small LV chamber size, concentric remodeling, and relaxation abnormalities.

Comparative Evaluation of Visual Outcomes in Combined Cataract and Vitrectomy for Idiopathic Epiretinal Membrane with an Advanced or Conventional Intraocular Lens.

INTRODUCTION: The aim of this study was to investigate the efficacy of new monofocal intraocular lens (IOL) in comparison with conventional monofocal IOL in patients undergoing combined cataract and vitrectomy surgery for epiretinal membrane (ERM). METHODS: This prospective non-randomized comparative study included 65 eyes of 65 patients who underwent combined cataract and vitrectomy for ERM with implantation of advanced monofocal IOL (Eyhance ICB00, 33 patients) and standard monofocal IOL (Tecnis ZCB00, 32 patients). Monocular visual acuities were measured 6 months post-operatively, including corrected and uncorrected distance visual acuity (CDVA, UCDVA), uncorrected intermediate visual acuity (UCIVA), and uncorrected near visual acuity (UCNVA). Furthermore, contrast sensitivity and metamorphopsia were measured. RESULTS: There was no significant difference between two groups regarding operation time, post-operative CDVA, UCDVA, UCNVA, and spherical equivalent (p > 0.05). Monocular UCIVA was significantly higher in the Eyhance IOL group than in the Tecnis IOL group (p = 0.005). The photopic and mesopic contrast sensitivities were comparable between each group for any spatial frequency (p > 0.05). The correlation coefficients from correlations between retinal wrinkling ratio and M score did not differ significantly between groups (p = 0.877), and the degree of metamorphopsia was not significantly related to the type of IOL (p = 0.969). CONCLUSIONS: In combined cataract and vitrectomy for ERM, Eyhance IOL provided significant better visual performance at intermediate distance than standard monofocal IOL without compromising operation time, distance vision, contrast sensitivity, and evaluating metamorphopsia. Eyhance IOL can be a useful option for both surgeons and patients.

Metabolic dysfunction-associated steatotic liver disease and risk of esophageal cancer in patients with diabetes mellitus: a nationwide cohort study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with type 2 diabetes and a developing several cancers including esophageal cancer (EC). However, the association between MASLD and EC in diabetic patients has not been investigated. Therefore, we aimed to investigate the relation between MASLD and developing EC in diabetic patients. This was a population-based retrospective cohort study of data from the Korean National Health Insurance Service (NHIS). A total of 1,904,468 subjects diagnosed with diabetes who underwent NHIS-provided health checkups from 2009 to 2012 were included. We constructed a Cox proportional hazard model for the association of fatty liver index (FLI) and the risk of EC stratified by potential confounders. Over a mean follow-up duration of 6.9 years, the incidence of EC was higher in the high (≥60) FLI group compared to the low (<30) FLI group (14.4 vs. 13.7 event per 100,000 person-years). The risk of EC correlated with the degree of FLI, particularly in older (P = 0.002), female (P = 0.033), non-smoking (P = 0.002), and non-drinking patients (P = 0.025). Among obese patients, the risk of EC was not associated with FLI; however, the risk of EC was higher in the high FLI group in non-obese patients. Lean MASLD patients had the highest risk of EC (adjusted hazard ratio 1.78; 95% confidence interval, 1.5-2.13). MASLD was associated with an increased risk of EC in diabetic patients, and lean MASLD has the highest risk. Further studies are required to determine the causal relationship between MASLD and EC.

Survival benefit of adjuvant treatment for ampullary cancer with lymph nodal involvement: A systematic review and meta-analysis.

BACKGROUND: The efficacy of adjuvant treatment (AT) in ampullary cancer (AmC) remains controversial. This systematic review and meta-analysis aimed to evaluate the role of AT for AmC. DATA SOURCES: A comprehensive systematic search was performed in PubMed, EMBASE, Cochrane Library, and Web of Science databases. Studies comparing overall survival (OS) and recurrence-free survival (RFS) of patients who underwent AT or not following AmC resection were included. RESULTS: A total of 3971 patients in 21 studies were analyzed. Overall pooled data showed no significant difference in effect on the OS by AT [hazard ratio (HR) = 0.998, 95% confidence interval (CI): 0.768-1.297]. No significant difference in recurrence between the AT and non-AT (nAT) groups was noted (HR = 1.158, 95% CI: 0.764-1.755). In subgroup analysis, patients who received AT showed favorable outcomes in the OS compared with those who received nAT in nodal-positive AmC (HR = 0.627, 95% CI: 0.451-0.870). Neither AT consisted of adjuvant chemotherapy with radiotherapy (HR = 0.804, 95% CI: 0.563-1.149) nor AT with adjuvant chemotherapy (HR = 0.883, 95% CI: 0.642-1.214) showed any significant effect on the OS. CONCLUSIONS: The effect of AT in AmC on survival and recurrence did not show a significant benefit. Furthermore, effectiveness according to AT strategies did not show enhancement in survival. AT had an advantage in survival compared with nAT strategy in nodal-positive AmC. In cases of AmC with positive lymph nodal involvement, AT may be warranted regardless of detailed strategies.

Development and effectiveness of a metaverse reality-based family-centered handoff education program in nursing students.

PURPOSE: Effective patient handoffs are vital in pediatric populations. This study aimed to develop and identify the impact of a metaverse-based handoff program using ZEPETO on nursing students' handoff competence, handoff self-efficacy, learning realism, and satisfaction. DESIGN AND METHODS: This study used a non-randomized, pre-post nonequivalent group design to develop, implement, and verify a metaverse-based handoff simulation program in a nursing school in South Korea. We assigned 69 senior nursing students from a university to an experimental group or a control group. We developed a metaverse-based, handoff simulation program of family-centered care by building a pediatric intensive care unit (PICU) using ZEPETO. The program included an online lecture, a metaverse rounding discussion, and a metaverse-based handoff simulation of postoperative care for infants with congenital heart disease. We measured handoff competence, handoff self-efficacy, learning realism, and learning satisfaction pre- and post-program. RESULT(S): The experimental group showed significantly higher handoff self-efficacy than the control group (t = 3.17, p = 0.002). No significant differences were found in handoff competency, learning realism, or learning satisfaction between the groups. CONCLUSION(S): This study confirmed that a family-centered care-based handoff metaverse simulation program based on the experiential learning theory enhanced nursing students' handoff self-efficacy. The program equipped students to conduct safe and effective handoffs in real-world clinical settings by providing an immersive learning experience and emphasizing patient-centered communication. PRACTICAL IMPLICATIONS: Based on these results, family-centered, handoff education programs are recommended to be developed that focus on learning realism and learning satisfaction to enhance nursing students' handoff competence.

Identification of Viruses Infecting Phalaenopsis Orchids Using Nanopore Sequencing and Development of an RT-RPA-CRISPR/Cas12a for Rapid Visual Detection of Nerine Latent Virus.

Phalaenopsis orchids are one of the most popular ornamental plants. More than thirty orchid viruses have been reported, and virus-infected Phalaenopsis orchids significantly lose their commercial value. Therefore, the development of improved viral disease detection methods could be useful for quality control in orchid cultivation. In this study, we first utilized the MinION, a portable sequencing device based on Oxford Nanopore Technologies (ONT) to rapidly detect plant viruses in Phalaenopsis orchids. Nanopore sequencing revealed the presence of three plant viruses in Phalaenopsis orchids: odontoglossum ringspot virus, cymbidium mosaic virus, and nerine latent virus (NeLV). Furthermore, for the first time, we detected NeLV infection in Phalaenopsis orchids using nanopore sequencing and developed the reverse transcription-recombinase polymerase amplification (RT-RPA)-CRISPR/Cas12a method for rapid, instrument-flexible, and accurate diagnosis. The developed RT-RPA-CRISPR/Cas12a technique can confirm NeLV infection in less than 20 min and exhibits no cross-reactivity with other viruses. To determine the sensitivity of RT-RPA-CRISPR/Cas12a for NeLV, we compared it with RT-PCR using serially diluted transcripts and found a detection limit of 10 zg/µL, which is approximately 1000-fold more sensitive. Taken together, the ONT platform offers an efficient strategy for monitoring plant viral pathogens, and the RT-RPA-CRISPR/Cas12a method has great potential as a useful tool for the rapid and sensitive diagnosis of NeLV.

Chronic alcohol use primes bronchial cells for altered inflammatory response and barrier dysfunction during SARS-CoV-2 infection.

Alcohol use disorder (AUD) is a significant public health concern and people with AUD are more likely to develop severe acute respiratory distress syndrome (ARDS) in response to respiratory infections. To examine whether AUD was a risk factor for more severe outcome in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we examined early responses to infection using cultured differentiated bronchial epithelial cells derived from brushings obtained from people with AUD or without AUD. RNA-seq analysis of uninfected cells determined that AUD cells were enriched for expression of epidermal genes as compared with non-AUD cells. Bronchial epithelial cells from patients with AUD showed a significant decrease in barrier function 72 h postinfection, as determined by transepithelial electrical resistance. In contrast, barrier function of non-AUD cells was enhanced 72 h after SARS-CoV-2 infection. AUD cells showed claudin-7 that did not colocalize with zonula occludens-1 (ZO-1), indicative of disorganized tight junctions. However, both AUD and non-AUD cells showed decreased ß-catenin expression following SARS-CoV-2 infection. To determine the impact of AUD on the inflammatory response to SARS-CoV-2 infection, cytokine secretion was measured by multiplex analysis. SARS-CoV-2-infected AUD bronchial cells had enhanced secretion of multiple proinflammatory cytokines including TNFα, IL-1ß, and IFNγ as opposed to non-AUD cells. In contrast, secretion of the barrier-protective cytokines epidermal growth factor (EGF) and granulocyte macrophage-colony stimulating factor (GM-CSF) was enhanced for non-AUD bronchial cells. Taken together, these data support the hypothesis that AUD is a risk factor for COVID-19, where alcohol primes airway epithelial cells for increased inflammation and increased barrier dysfunction and increased inflammation in response to infection by SARS-CoV-2.NEW & NOTEWORTHY Alcohol use disorder (AUD) is a significant risk factor for severe acute respiratory distress syndrome. We found that AUD causes a phenotypic shift in gene expression in human bronchial epithelial cells, enhancing expression of epidermal genes. AUD cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had higher levels of proinflammatory cytokine secretion and barrier dysfunction not present in infected non-AUD cells, consistent with increased early COVID-19 severity due to AUD.

Risk of CKD Following Detection of Microscopic Hematuria: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Microscopic hematuria is an uncertain risk factor for chronic kidney disease (CKD). We investigated the association between persistent or single episodes of microscopic hematuria and the development of incident CKD, overall and separately among men and women. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A total of 232,220 Korean adults without CKD at baseline who underwent repeated regular health examinations at Kangbuk Samsung Health Study formed the study cohort. EXPOSURE: Microscopic hematuria was defined by≥5 red blood cells per high-power field. Participants were categorized into 1 of 4 groups according to the presence of hematuria at 2 consecutive examinations: (1) no hematuria at both examinations (reference group); (2) hematuria followed by no hematuria (regressed hematuria group); (3) no hematuria followed by hematuria (developed hematuria group); and (4) hematuria at both examinations (persistent hematuria group). OUTCOME: CKD was defined as an estimated glomerular filtration rate<60mL/min/1.73m2 or proteinuria (1+or more on dipstick examination). ANALYTICAL APPROACH: Semiparametric proportional hazards models were used to estimate hazard ratios. RESULTS: During a 4.8-year median follow-up period, 2,392 participants developed CKD. Multivariable-adjusted hazard ratios for incident CKD, comparing the regressed, developed, and persistent hematuria groups to the no-hematuria group were 1.85 (95% CI, 1.35-2.53), 3.18 (95% CI, 2.54-3.98), and 5.23 (95% CI, 4.15-6.59), respectively. The association between persistent hematuria and incident CKD was stronger in men than women (P for interaction<0.001), although a statistically significant association was observed in both sexes. LIMITATIONS: Lack of albuminuria and inability to consider specific glomerular diseases. CONCLUSIONS: Men and women with microscopic hematuria, especially persistent hematuria, may be at increased risk of CKD.

Diagnostic performance of endoscopic ultrasound elastography for differential diagnosis of solid pancreatic lesions: A propensity score-matched analysis.

BACKGROUND: Endoscopic ultrasound-elastography (EUS-EG) is a non-invasive complementary diagnostic method for differential diagnosis of solid pancreatic lesions (SPL). However, the optimal strain ratio (SR) value and diagnostic performance of EUS-EG have not yet been determined in pancreatic neuroendocrine neoplasm (PNEN), mass-forming pancreatitis (MFP), and pancreatic ductal adenocarcinoma (PDAC). We aimed to determine the optimal SR value in EUS-EG for differential diagnosis of SPLs. METHODS: Patients who underwent EUS-EG for SPL evaluation between July 2016 and June 2019 were retrospectively investigated. Patients were divided into three groups based on the final diagnosis (PNEN, MFP, or PDAC). Patient demographics, characteristics of SPL, and EUS-EG were compared. RESULTS: The mean (± standard deviation) SR value for each group were 11.85 ± 7.56 (PNEN, n = 10), 11.45 ± 5.97 (MFP, n = 37), and 22.50 ± 13.19 (PDAC, n = 87). Multinomial logistic regression analysis revealed that an increase of SR value was significantly associated with PDAC (PNEN versus PDAC, p = 0.0216; MFP versus PDAC, p = 0.0006). The optimal cut-off value for differential diagnosis was confirmed as 17.14 after propensity score matching. CONCLUSIONS: We provided the optimal cut-off SR values for differential diagnosis between MFP and PDAC. EUS-EG can be used as a supplementary diagnostic method in the diagnosis of SPLs. (Clinical trial registration number: https://cris.nih.go.kr/cris: KCT0002082).

Trace assay of insulin in a pharmacy drug with a paste electrode.

This paper describes the development of a voltammetric assay of insulin using a DNA immobilized onto a carbon nanotube paste electrode (CNPE), the peak potential of which was 0.2 V, vs. Ag/AgCl on the CNPE. The cyclic voltammetry (CV) and square-wave (SW) stripping voltammetry parameters of the optimized conditions were determined. Low analytical working ranges of 10-80 ugL-1 CV and 0.01-0.1 ngL-1 SW were attained. The precision of the insulin concentration of 0.01 ugL-1 was 0.14 (n = 15) RSD using the optimum conditions, in which the detection limit was 0.004 ngL-1 (6.9 × 10-12 M) (S/N = 3) using only an accumulation time of 400 s. The developed method was applied to determine insulin in a pharmacy drug from analytical-grade chemicals (from Aldrich).

Prolonged patency of fully covered self-expandable metal stents with an externally anchored plastic stent in distal malignant biliary obstruction.

BACKGROUND : Fully covered self-expandable metal stents (FCSEMSs) are widely used for endoscopic treatment of distal malignant biliary obstruction (dMBO). We aimed to assess the efficacy of anchoring an external plastic stent to an FCSEMS in dMBO. METHODS : A multicenter retrospective cohort study was performed in patients with dMBO to compare stent patency between FCSEMSs and FCSEMSs with an externally anchored plastic stent (EPS). For external anchoring, a 7-Fr double-pigtail plastic stent (DPPS) was placed first in the bile duct, then an FCSEMS was deployed side-by-side. RESULTS : Among a total of 185 patients, 65 had an FCSEMS alone and 120 had an FCSEMS with an EPS. The median stent patency was significantly longer in the FCSEMS with an EPS group than in the FCSEMS only group (342 vs. 240 days; P = 0.04). The rate of stent migration was significantly lower in the FCSEMS with an EPS group than in the FCSEMS only group (10.8 % vs. 27.7 %; P = 0.01). There were no significant differences in the rates of stent occlusion and adverse events between the two groups. CONCLUSIONS : A novel and simple technique of anchoring an external plastic stent may decrease the risk of FCSEMS migration and prolong stent patency, without significantly increasing the adverse events rate in dMBO.

Different neuroprognostication thresholds of neuron-specific enolase in shockable and non-shockable out-of-hospital cardiac arrest: a prospective multicenter observational study in Korea (the KORHN-PRO registry).

BACKGROUND: Serum neuron-specific enolase (NSE) is the only recommended biomarker for multimodal prognostication in postcardiac arrest patients, but low sensitivity of absolute NSE threshold limits its utility. This study aimed to evaluate the prognostic performance of serum NSE for poor neurologic outcome in out-of-hospital cardiac arrest (OHCA) survivors based on their initial rhythm and to determine the NSE cutoff values with false positive rate (FPR) < 1% for each group. METHODS: This study included OHCA survivors who received targeted temperature management (TTM) and had serum NSE levels measured at 48 h after return of spontaneous circulation in the Korean Hypothermia Network, a prospective multicenter registry from 22 university-affiliated teaching hospitals in South Korea between October 2015 and December 2018. The primary outcome was poor outcome at 6 month, defined as a cerebral performance category of 3-5. RESULTS: Of 623 patients who underwent TTM with NSE measured 48 h after the return of spontaneous circulation, 245 had an initial shockable rhythm. Median NSE level was significantly higher in the non-shockable group than in the shockable group (104.6 [40.6-228.4] vs. 25.9 [16.7-53.4] ng/mL, P < 0.001). Prognostic performance of NSE assessed by area under the receiver operating characteristic curve to predict poor outcome was significantly higher in the non-shockable group than in the shockable group (0.92 vs 0.86). NSE cutoff values with an FPR < 1% in the non-shockable and shockable groups were 69.3 (sensitivity of 42.1%) and 102.7 ng/mL (sensitivity of 76%), respectively. CONCLUSION: NSE prognostic performance and its cutoff values with FPR < 1% for predicting poor outcome in OHCA survivors who underwent TTM differed between shockable and non-shockable rhythms, suggesting postcardiac arrest survivor heterogeneity. Trial registration KORHN-PRO, NCT02827422. Registered 11 September 2016-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02827422.

Strong, Chemically Stable, and Enzymatically On-Demand Detachable Hydrogel Adhesion Using Protein Crosslink.

Achieving strong adhesion between hydrogels and diverse materials is greatly significant for emerging technologies yet remains challenging. Existing methods using non-covalent bonds have limited pH and ion stability, while those using covalent bonds typically lack on-demand detachment capability, limiting their applications. In this study, a general strategy of covalent bond-based and detachable adhesion by incorporating amine-rich proteins in various hydrogels and inducing the interfacial crosslinking of the hydrogels using a protein-crosslinking agent is demonstrated. The protein crosslink offers topological adhesion and can reach a strong adhesion energy of ≈750 J m-2 . The chemistry of the adhesion is characterized and that the inclusion of proteins inside the hydrogels does not alter the hydrogels' properties is shown. The adhesion remains intact after treating the adhered hydrogels with various pH solutions and ions, even at an elevated temperature. The detachment is triggered by treating proteinase solution at the bonding front, causing the digestion of proteins, thus breaking up the interfacial crosslink network. In addition, that this approach can be used to adhere hydrogels to diverse dry surfaces, including glass, elastomers and plastics, is shown. The stable chemistry of protein crosslinks opens the door for various applications in a wide range of chemical environments.

Efficacy and predictive factors of endoscopic ultrasound-guided ethanol ablation in benign solid pancreatic tumors.

BACKGROUNDS AND OBJECTIVES: Endoscopic ultrasound-guided ethanol ablation (EUS-EA) has recently been introduced for the management of solid pancreatic tumors, including pancreatic neuroendocrine tumors (PNETs) and solid pseudopapillary tumors (SPTs). The study aims to evaluate the efficacy and predictive factors for response of EUS-EA in solid pancreatic tumors. METHODS: Between October 2015 and July 2021, 72 patients who underwent EUS-EA for solid pancreatic tumors were included. The study outcomes were to evaluate the efficacy of EUS-EA with complete remission (CR) and objective response, and their predictive factors. RESULTS: During follow-up, 47 patients were diagnosed with PNETs and 25 with SPTs. Eight cases reached CR and 48 reached objective response. When compared with SPTs, PNETs showed similar duration to reach CR (median not reached; p = 0.319), but shorter duration to reach objective response (PNETs: median 20.6 months, 95%CI 10.26-30.88; SPTs: median 47.7 months, 95%CI 18.14-77.20; p = 0.018). Ethanol dosage > 0.35 ml/cm3 shortened the duration to reach CR (median not reached; p = 0.026) and objective response (median 42.5 months, 95%CI 25.34-59.66 vs. 19.6 months, 95%CI 10.17-29.09; p = 0.006). CR had no significant predictive factors, but PNETs showed significant predictive factors for objective response (HR 3.34, 95%CI 1.07-10.43; p = 0.038). Twenty-seven patients experienced adverse events, and there were two severe cases. CONCLUSION: EUS-EA for pancreatic solid lesions seems feasible as a local treatment for patients who refuse or are unfit for surgery. Additionally, PNETs seem to be the better candidate for EUS-EA.