OBJECTIVES: Only a few studies have solely investigated the health impacts of electronic cigarettes on diabetes while considering the impact of conventional cigarettes. Therefore, this study aimed to examine the effect of electronic cigarette smoking on diabetes in Korean dual smokers, electronic cigarette smokers, conventional cigarette smokers, and non-smokers. METHODS: Data were obtained from the 2021 and 2022 Korean Community Health Surveys of 460,603 Korean adults. The main independent variable was smoking behavior. Participants were categorized according to their smoking behavior, as dual smokers, electronic cigarette smokers, conventional cigarette smokers, and non-smokers. The dependent variable, the presence of diabetes, was defined by a doctor’s diagnosis. Multiple logistic regression analysis was performed to examine the association between smoking behavior and diabetes. Subgroup analyses were also performed to investigate the associations among different socioeconomic groups. RESULTS: Conventional cigarette smokers had a higher risk of diabetes than did non-smokers (adjusted odds ratio [aOR], 1.22; 95% confidence interval [CI], 1.19 to 1.26). More importantly, those who only vaped electronic cigarettes were at high risk of diabetes (aOR, 1.15; 95% CI, 1.01 to 1.31). Lastly, dual smokers had the highest aOR for diabetes among other smoking behavior groups (aOR, 1.39; 95% CI, 1.22 to 1.58). Dual smoking was associated with the highest risk of diabetes in most subgroups. CONCLUSIONS This study suggests that conventional cigarette use and smoking electronic cigarettes negatively impact diabetes, and using both types leads to worse health outcomes. Therefore, cessation of all types of smoking is necessary for a healthy life.

Many packages for a meta-analysis of genome-wide association studies (GWAS) have beendeveloped to discover genetic variants. Although variations across studies must be considered, there are not many currently-accessible packages that estimate between-study heterogeneity. Thus, we propose a python based application called Beta-Meta which can easilyprocess a meta-analysis by automatically selecting between a fixed effects and a randomeffects model based on heterogeneity. Beta-Meta implements flexible input data manipulation to allow multiple meta-analyses of different genotype-phenotype associations in asingle process. It provides a step-by-step meta-analysis of GWAS for each association inthe following order: heterogeneity test, two different calculations of an effect size and ap-value based on heterogeneity, and the Benjamini-Hochberg p-value adjustment. Thesemethods enable users to validate the results of individual studies with greater statisticalpower and better estimation precision. We elaborate on these and illustrate them with examples from several studies of infertility-related disorders.

It has been reported that activation of metabotropic glutamate receptor 1 (mGluR1) can mediate endocannabinoid-induced short-term depression of synaptic transmission in cerebellar parallel fiber (PF)-Purkinje cell (PC) synapse. mGluR1 has signaling pathways involved in intracellular calcium increase which may contribute to endocannabinoid release. Two major mGluR1-evoked calcium signaling pathways are known: (1) slow-kinetic inward current carried by transient receptor potential canonical (TRPC) channel which is permeable to Ca2+; (2) IP3-induced calcium release from intracellular calcium store. However, it is unclear how much each calcium source contributes to endocannabinoid signaling. Here, we investigated whether calcium influx through mGluR1-evoked TRPC channel contributes to endocannabinoid signaling in cerebellar Purkinje cells. At first, we applied SKF96365 to inhibit TRPC, which blocked endocannabinoid-induced short-term depression completely. However, an alternative TRP channel inhibitor, BTP2 did not affect endocannabinoid-induced short-term depression although it blocked mGluR1-evoked TRPC currents. Endocannabinoid signaling occurred normally even though the TRPC current was mostly blocked by BTP2. Our data imply that TRPC current does not play an important role in endocannabinoid signaling. We also suggest precaution in applying SKF96365 to inhibit TRP channels and propose BTP2 as an alternative TRPC inhibitor.
Calcium ; Calcium Signaling ; Cerebellum ; Depression ; Endocannabinoids ; Imidazoles ; Purkinje Cells ; Receptors, Metabotropic Glutamate ; Synapses ; Synaptic Transmission

Purpose: EGFR-mutation (EGFR-mt) is a major oncogenic driver mutation in lung adenocarcinoma (ADC) and is more oftenobserved in Asian population. In lung ADC, some radiomics parameters of FDG PET have been reported to be associated withEGFR-mt. Here, the associations between EGFR-mt and PET parameters, particularly asphericity (ASP), were evaluated inAsian population. Methods: Lung ADC patients who underwent curative surgical resection as the first treatment were retrospectively enrolled.EGFR mutation was defined as exon 19 deletion and exon 21 point mutation and was evaluated using surgical specimens. OnFDG PET, image parameters of maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesionglycolysis (TLG), and ASP were obtained. The parameters were compared between EGFR-mt and wild type (EGFR-wt) groups,and the relationships between these PET parameters and EGFR-mt were evaluated. Results: A total of 64 patients (median age 66 years, M:F = 34:30) were included in the analysis, and 29 (45%) patients showedEGFR-mt. In EGFR-mt group, all the image parameters of SUVmax, MTV, TLG, and ASP were significantly lower than inEGFR-wt group (all adjusted P< 0.050). In univariable logistic regression, SUVmax (P= 0.003) and ASP (P= 0.010) weresignificant determinants for EGFR-mt, whereasMTV was not (P= 0.690). Multivariate analysis revealed that SUVmax and ASPare independent determinants for EGFR-mt, regardless of inclusion of MTV in the analysis (P< 0.05). Conclusion In Asian NSCLC/ADC patients, SUVmax, MTV, and ASP on FDG PET are significantly related to EGFR mutationstatus. Particularly, low SUVmax and ASP are independent determinants for EGFR-mt.

Purpose: The precise quantification of dopamine transporter (DAT) density on N-(3-[18F]Fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane positron emission tomography ([18F]FP-CIT PET) imaging is crucial to measure the degree of striatal DAT loss in patients with parkinsonism. The quantitative analysis requires a spatial normalization process based on a template brain. Since the spatial normalization method based on a delayed-phase PET has limited performance, we suggest an early-phase PET-based method and compared its accuracy, referring to the MRI-based approach as a gold standard. Methods: A total of 39 referred patients from the movement disorder clinic who underwent dual-phase [18F]FP-CIT PET and took MRI within 1 year were retrospectively analyzed. The three spatial normalization methods were applied for quantification of [18F]FP-CIT PET-MRI-based anatomical normalization, PET template-based method based on delayed PET, and that based on early PET. The striatal binding ratios (BRs) were compared, and voxelwise paired t tests were implemented between different methods. Results: The early image-based normalization showed concordant patterns of putaminal [18F]FP-CIT binding with an MRI-based method. The BRs of the putamen from the MRI-based approach showed higher agreement with early image- than delayed image-based method as presented by Bland-Altman plots and intraclass correlation coefficients (early image-based, 0.980; delayed image-based, 0.895). The voxelwise test exhibited a smaller volume of significantly different counts in putamen between brains processed by early image and MRI compared to that between delayed image and MRI. Conclusion The early-phase [18F]FP-CIT PET can be utilized for spatial normalization of delayed PET image when the MRI image is unavailable and presents better performance than the delayed template-based method in quantitation of putaminal binding ratio.

Remote cerebellar hemorrhage (RCH) is a rare complication of neurosurgical procedures and is characterized by a typical bleeding pattern defined as the “zebra sign.” Only few cases of RCH have been reported in the English literature, and its pathophysiology remains unclear. In this report, we present the cases of three patients with RCH after three different procedures: burr-hole trephination and chronic subdural hematoma evacuation of bilateral cerebral convexity with subsequent subdural drain insertion, lumbar drainage for cerebrospinal fluid divergence for thoracic endovascular aortic repair, and combined bypass surgery for moyamoya disease.

Rab40 proteins are an atypical subgroup of Rab GTPases containing a unique suppressor of the cytokine signaling (SOCS) domain that is recruited to assemble the CRL5 E3 ligase complex for proteolytic regulation in various biological processes. A nonsense mutation deleting the C-terminal SOCS box in the RAB40B gene was identified in a family with axonal peripheral neuropathy (Charcot-Marie-Tooth disease type 2), and pathogenicity of the mutation was assessed in model organisms of zebrafish and Drosophila. Compared to control fish, zebrafish larvae transformed by the human mutant hRAB40B-Y83X showed a defective swimming pattern of stalling with restricted localization and slower motility. We were consistently able to observe reduced labeling of synaptic markers along neuromuscular junctions of the transformed larvae. In addition to the neurodevelopmental phenotypes, compared to normal hRAB40B expression, we further examined ectopic expression of hRAB40B-Y83X in Drosophila to show a progressive decline of locomotion ability. Decreased ability of locomotion by ubiquitous expression of the human mutation was reproduced not with GAL4 drivers for neuron-specific expression but only when a pan-glial GAL4 driver was applied. Using the ectopic expression model of Drosophila, we identified a genetic interaction in which Cul5 down regulation exacerbated the defective motor performance, showing a consistent loss of SOCS box of the pathogenic RAB40B. Taken together, we could assess the possible gain-of-function of the human RAB40B mutation by comparing behavioral phenotypes in animal models; our results suggest that the mutant phenotypes may be associated with CRL5-mediated proteolytic regulation.

Purpose: This study compared the diagnostic performance of quantitative ultrasonography (QUS) with that of conventional ultrasonography (US) in assessing hepatic steatosis among individuals undergoing health screening using magnetic resonance imaging–derived proton density fat fraction (MRI-PDFF) as the reference standard. Methods: This single-center prospective study enrolled 427 participants who underwent abdominal MRI and US. Measurements included the attenuation coefficient in tissue attenuation imaging (TAI) and the scatter-distribution coefficient in tissue scatter-distribution imaging (TSI). The correlation between QUS and MRI-PDFF was evaluated. The diagnostic capabilities of QUS, conventional B-mode US, and their combined models for detecting hepatic fat content of ≥5% (MRI-PDFF ≥5%) and ≥10% (MRI-PDFF ≥10%) were compared by analyzing the areas under the receiver operating characteristic curves. Additionally, clinical risk factors influencing the diagnostic performance of QUS were identified using multivariate linear regression analyses. Results: TAI and TSI were strongly correlated with MRI-PDFF (r=0.759 and r=0.802, respectively; both P<0.001) and demonstrated good diagnostic performance in detecting and grading hepatic steatosis. The combination of QUS and B-mode US resulted in the highest areas under the ROC curve (AUCs) (0.947 and 0.975 for detecting hepatic fat content of ≥5% and ≥10%, respectively; both P<0.05), compared to TAI, TSI, or B-mode US alone (AUCs: 0.887, 0.910, 0.878 for ≥5% and 0.951, 0.922, 0.875 for ≥10%, respectively). The independent determinants of QUS included skinliver capsule distance (β=7.134), hepatic fibrosis (β=4.808), alanine aminotransferase (β=0.202), triglyceride levels (β=0.027), and diabetes mellitus (β=3.710). Conclusion QUS is a useful and effective screening tool for detecting and grading hepatic steatosis during health checkups.

Purpose: This study compared the diagnostic performance of quantitative ultrasonography (QUS) with that of conventional ultrasonography (US) in assessing hepatic steatosis among individuals undergoing health screening using magnetic resonance imaging–derived proton density fat fraction (MRI-PDFF) as the reference standard. Methods: This single-center prospective study enrolled 427 participants who underwent abdominal MRI and US. Measurements included the attenuation coefficient in tissue attenuation imaging (TAI) and the scatter-distribution coefficient in tissue scatter-distribution imaging (TSI). The correlation between QUS and MRI-PDFF was evaluated. The diagnostic capabilities of QUS, conventional B-mode US, and their combined models for detecting hepatic fat content of ≥5% (MRI-PDFF ≥5%) and ≥10% (MRI-PDFF ≥10%) were compared by analyzing the areas under the receiver operating characteristic curves. Additionally, clinical risk factors influencing the diagnostic performance of QUS were identified using multivariate linear regression analyses. Results: TAI and TSI were strongly correlated with MRI-PDFF (r=0.759 and r=0.802, respectively; both P<0.001) and demonstrated good diagnostic performance in detecting and grading hepatic steatosis. The combination of QUS and B-mode US resulted in the highest areas under the ROC curve (AUCs) (0.947 and 0.975 for detecting hepatic fat content of ≥5% and ≥10%, respectively; both P<0.05), compared to TAI, TSI, or B-mode US alone (AUCs: 0.887, 0.910, 0.878 for ≥5% and 0.951, 0.922, 0.875 for ≥10%, respectively). The independent determinants of QUS included skinliver capsule distance (β=7.134), hepatic fibrosis (β=4.808), alanine aminotransferase (β=0.202), triglyceride levels (β=0.027), and diabetes mellitus (β=3.710). Conclusion QUS is a useful and effective screening tool for detecting and grading hepatic steatosis during health checkups.

Purpose: This study compared the diagnostic performance of quantitative ultrasonography (QUS) with that of conventional ultrasonography (US) in assessing hepatic steatosis among individuals undergoing health screening using magnetic resonance imaging–derived proton density fat fraction (MRI-PDFF) as the reference standard. Methods: This single-center prospective study enrolled 427 participants who underwent abdominal MRI and US. Measurements included the attenuation coefficient in tissue attenuation imaging (TAI) and the scatter-distribution coefficient in tissue scatter-distribution imaging (TSI). The correlation between QUS and MRI-PDFF was evaluated. The diagnostic capabilities of QUS, conventional B-mode US, and their combined models for detecting hepatic fat content of ≥5% (MRI-PDFF ≥5%) and ≥10% (MRI-PDFF ≥10%) were compared by analyzing the areas under the receiver operating characteristic curves. Additionally, clinical risk factors influencing the diagnostic performance of QUS were identified using multivariate linear regression analyses. Results: TAI and TSI were strongly correlated with MRI-PDFF (r=0.759 and r=0.802, respectively; both P<0.001) and demonstrated good diagnostic performance in detecting and grading hepatic steatosis. The combination of QUS and B-mode US resulted in the highest areas under the ROC curve (AUCs) (0.947 and 0.975 for detecting hepatic fat content of ≥5% and ≥10%, respectively; both P<0.05), compared to TAI, TSI, or B-mode US alone (AUCs: 0.887, 0.910, 0.878 for ≥5% and 0.951, 0.922, 0.875 for ≥10%, respectively). The independent determinants of QUS included skinliver capsule distance (β=7.134), hepatic fibrosis (β=4.808), alanine aminotransferase (β=0.202), triglyceride levels (β=0.027), and diabetes mellitus (β=3.710). Conclusion QUS is a useful and effective screening tool for detecting and grading hepatic steatosis during health checkups.