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KRAS is the most frequently mutated oncogene in human lung adenocarcinomas (hLUAD), and activating mutations frequently co-occur with loss-of-function mutations in TP53 or STK11/LKB1. However, mutation of all three genes is rarely observed in hLUAD, even though engineered comutation is highly aggressive in mouse lung adenocarcinoma (mLUAD). Here, we provide a mechanistic explanation for this difference by uncovering an evolutionary divergence in the regulation of triosephosphate isomerase (TPI1). In hLUAD, TPI1 activity is regulated via phosphorylation at Ser21 by the salt inducible kinases (SIK) in an LKB1-dependent manner, modulating flux between the completion of glycolysis and production of glycerol lipids. In mice, Ser21 of TPI1 is a Cys residue that can be oxidized to alter TPI1 activity without a need for SIKs or LKB1. Our findings suggest this metabolic flexibility is critical in rapidly growing cells with KRAS and TP53 mutations, explaining why the loss of LKB1 creates a liability in these tumors. Significance: Utilizing phosphoproteomics and metabolomics in genetically engineered human cell lines and genetically engineered mouse models (GEMM), we uncover an evolutionary divergence in metabolic regulation within a clinically relevant genotype of human LUAD with therapeutic implications. Our data provide a cautionary example of the limits of GEMMs as tools to study human diseases such as cancers. This article is highlighted in the In This Issue feature, p. 799

Due to the low incidence and histologic diversity of salivary gland cancer, analyzing the incidence of salivary gland cancer is necessary to understand the macroscopic aspects. We intend to investigate the international trend of the reported incidence rate of salivary gland cancer. Using the Korea Central Cancer Registry data, the domestic change in the incidence rate was examined. As a result, a significant increasing trend was confirmed, consistent with the United States and Japan trends. The etiology of the change is unclear, and various factors that may influence the direction are reported. Additional research is needed to understand the pathophysiology of salivary gland cancer, and further efforts are required to understand salivary gland cancer.

To investigate the relationship between subjective voice changes and appendicular skeletal muscle in the elderly in Korea.Retrospective cross-sectional study.Population-based survey data were collected by the Korean National Health and Nutrition Examination Survey between January 2009 and December 2011.A total of 2611 participants (1081 men and 1530 women) aged 65 to 80 years were enrolled in the Korean National Health and Nutrition Examination Survey from 2009 to 2011. A 70-degree laryngeal endoscopy was performed to check for abnormalities in the larynx, while dual-energy x-ray absorptiometry was utilised to measure appendicular skeletal muscle mass. The correlation between subjective voice change and appendicular skeletal muscle index (ASMI) was analysed using a linear-by-linear association test and logistic regression analysis.When comparing ASMI according to the presence or absence of subjective voice change, elderly men showed significantly lower ASMI values when subjective voice change was present (p = .021). However, in women, the ASMI was not significantly lower in the presence of subjective voice changes (p = .365). We confirmed that subjective voice change was significantly lower in the highest quintile of ASMI compared to lowest quintile of ASMI in the men using logistic regression analysis (B 0.281, 95% confident interval 0.082-0.964, p .044).This study has shown that in Korean men aged65 years, subjective voice abnormality significantly increased as skeletal muscle mass decreased. Further longitudinal studies are needed to determine whether a correlation exists between objective voice test results and ASMI.

Microvascular decompression is the gold standard for the treatment of trigeminal neuralgia (TN). However, percutaneous techniques still play a role in treating patients with TN and offer several important advantages and efficiency in obtaining immediate pain relief, which is also durable in a less invasive and safe manner. Patients’ preference for a less invasive method can influence the procedure they will undergo. Neurovascular conflict is not always a prerequisite for patients with TN. In addition, recurrence and failure of the previous procedure can influence the decision to follow the treatment. Therefore, indications for percutaneous procedures for TN persist when patients experience idiopathic and episodic sharp shooting pain. In this review, we provide an overview of percutaneous procedures for TN and its outcome and complication.

Claudin-1 (CLDN1), a major component of tight junction complexes in the epithelium, maintains cellular polarity, and plays a critical role in cell-to-cell communication as well as epithelial cell homeostasis. Although the role of CLDN1 has been widely studied in cancer, its role in the progression and the exact regulatory mechanisms, remain controversial. Using next-generation sequencing, we first analyzed the expression profiles of tumor/non-tumor paired tissue in patients with head and neck squamous cell carcinoma (HNSC) from public and local cohorts and found out that CLDN1 is upregulated in tumors compared to normal tissues. Next, its correlation with lymph node metastasis and poor prognosis was validated in the retrospective cohort, which collectively suggests CLDN1 as an oncogene in HNSC. As expected, the knockdown of CLDN1 inhibited invasive phenotypes by downregulating epithelial-to-mesenchymal transition (EMT) in vitro. To ascertain the regulatory mechanism of CLDN1 in HNSC analysis of GO term enrichment, KEGG pathways, and curated gene sets were used. As a result, CLDN1 was negatively associated with AMP-activated protein kinase (AMPK) and positively associated with transforming growth factor-β (TGF-β) signaling. In vitro mechanistic assay showed that CLDN1 inhibited AMPK phosphorylation by regulating AMPK upstream phosphatases, which led to inhibition of Smad2 activity. Intriguingly, the invasive phenotype of cancer cells increased by CLDN1 overexpression was rescued by AMPK activation, indicating a role of the CLDN1/AMPK/TGF-β/EMT cascade in HNSC. Consistently in vivo, CLDN1 suppression significantly inhibited the tumor growth, with elevated AMPK expression, suggesting the novel observation of oncogenic CLDN1-AMPK signaling in HNSC.

Energy storage systems are an effective solution to manage the intermittency of renewable energies, balance supply, and demand. Numerous studies recommend adopting a shared energy storage system (ESS) as opposed to multiple single ESSs because of their high prices and inefficiency. Thus, this study examines a shared storage system in a grid-connected microgrid. By modifying the power outputs of the energy resources, this work intends to implement an economic dispatch of a shared ESS in order to satisfy the power balance and lower the overall cost of electricity. In this context, an optimization problem was formulated and developed using a mixed-integer linear programming (MILP) model. Furthermore, a pilot project (the Solar Decathlon Africa Village) in the Green & Smart Building Park (GSBP), Benguerir, Morocco, was employed to evaluate and verify the proposed approach. Some comparable scenarios were therefore run in a MATLAB environment. The collected findings demonstrate the efficacy of the developed algorithm in terms of optimizing energy cost reductions and enhancing the integration of renewable resources into the Moroccan energy mix.

Renal infarction is a condition caused by sudden disturbance of renal arterial blood flow, which occurs frequently in cardioembolic disease, renal artery injury (trauma, Marfan syndrome, rarely Ehlers-Danlos syndrome), and in association with a hypercoagulable state. Ehlers-Danlos syndrome is a rare hereditary connective tissue disease characterized by skin fragility, hyperelasticity, hypermobility of small joints, and easy bruising. Among the subtypes, vascular Ehlers-Danlos syndrome is a very rare genetic disease caused by a mutation in the COL3A1 gene. As blood vessels are fragile due dysfunctional collagen synthesis, complications of bleeding due to arterial dissection or rupture are common in patients with this disease. Here, we report a case of vascular Ehlers-Danlos syndrome diagnosed based on a renal infarction caused by thrombus and renal artery injury; we also present a review of the relevant literature.

Purpose: To evaluate CT findings to predict incomplete (R1 or R2) resection and poor survival in patients with perihilar cholangiocarcinoma using pre-operative CT.Materials and Methods: From 2006 to 2012, a total of 139 patients with perihilar cholangiocarcinoma who underwent pre-operative multiphase CT and subsequent curative-intent surgery were included. After two radiologists independently reviewed CT findings including the likelihood of bile duct (BD) involvement from intrapancreatic common bile duct (CBD) to bilateral second-order branches and peritumoral fat stranding using a 5-point scale, vessel involvement (no, abutment, encasement), and LN involvement, imaging findings were finalized by a consensus of two radiologists. When the likelihood scale of 4 or more on preoperative CT was regarded as BD involvement, the diagnostic ability of CT was analyzed by the receiver operating curve using histopathologic results as a reference standard. Residual tumor categorized into no residual tumor (R0) and residual tumor (R+; R1 or R2). Predictive factors of R+ resection on pre-operative CT were analyzed by logistic regression. Cox proportional hazard model was used to determine the prognostic factor for overall survival by using pre-operative CT findings and laboratory results.Results: Seventy-one patients were R0 and sixty-eight patients were R+ resection. For resectability evaluation, mid-CBD involvement (score ≥ 4) in pre-operative CT was significant factor for R+ resection in multivariable analysis (P < 0.01) with substantial interobserver agreement. In multivariable Cox regression, intrapancreatic CBD involvement (score ≥ 4, hazard ratio [HR] = 1.81, P < 0.01) as well as elevated total bilirubin (HR = 1.53, P = 0.04) and CA 19-9 level (HR = 1.75, P < 0.01) were significant predictors for poor survival. Diagnostic ability to predict mid-CBD and intrapancreatic CBD involvement on pre-operative CT were 0.71 and 0.72 (AUC values).Conclusions: Distal longitudinal extent of perihilar cancer on pre-operative CT is a significant factor for margin positive resection and poor survival on curative-intent surgery.

Background and objective This study was conducted to determine the preferences in flower jewelry by conducting a survey using conjoint analysis on the perception of flower jewelry and provide basic data for development of flower jewelry products. Methods For the conjoint analysis, four attributes of flower jewelry were selected. Attribute 1 was related to the main material of flower jewelry, presented in three levels: cut flowers, potted flowers, and processed flowers. Attribute 2 was related to wearing area presented in five levels of wearing area: hair, neck, ear, arm (wrist) and chest (shoulder). Attribute 3 was related to price provided for selling products in flower shops, presented in three levels: less than 30,000 won, 50,000–70,000 won, and more than 100,000 won. Attribute 4 was related to flower jewelry wearing time, presented in three levels: less than 6 hours, 12–24 hours, and more than 24 hours. After extracting 25 profiles through orthogonal design, a questionnaire survey was conducted on 402 general participants, from which the responses of 343 participants were analyzed. Results By attribute of flower jewelry, the respondents attached most importance to price (34.14%), followed by wearing area (29.18%), wearing time (18.51%), and material (18.17%), proving that the general public attached most importance to price (Pearson’s R = .987, p = .000). The preference in levels by attribute was highest for processed flowers in material, less than 30,000 won in price, hair in wearing area, and 12–24 hours in wearing time. Conclusion By making flower jewelry based on the results of the analysis, it would be possible to help increase items sold in flower shops as well as their income.

To measure the prevalence of adrenal nodules detected on staging CT in patients with resectable colorectal cancer, and the proportion of patients with malignant nodules among them.This retrospective study included 6474 patients (median age, 65; interquartile range, 56-73; 3902 men) who underwent staging CT for colorectal cancer between May 2003 and December 2018. The patients had potentially resectable colorectal cancer, including resectable hepatic or pulmonary metastases. Through retrospective CT image review, patients with adrenal nodules were identified for the prevalence of adrenal nodule. Among patients with adrenal nodules, per-patient proportions of malignant nodules, adrenal metastasis from colorectal cancer, and additional adrenal examinations (biopsy or imaging tests) were measured. A secondary analysis was performed using data from the official CT reports.The prevalence of adrenal nodules was 5.6% (363 of 6474; 95% CI: 5.1, 6.2). The proportions of malignant nodules and adrenal metastasis from colorectal cancer were 0.8% (3 of 363; 0.2, 2.4) and 0.3% (1 of 363; 0.0, 1.5), respectively. 6.1% (22 of 363; 3.8, 9.0) of the patients underwent additional adrenal examination. According to official CT reports, the prevalence of adrenal nodules and proportions of malignant nodules, adrenal metastasis from colorectal cancer, and additional adrenal examination were 1.9% (125 of 6474; 1.6, 2.3), 1.6% (2 of 125; 0.2, 5.7), 0% (0 of 125; 0.0, 2.9), and 10.4% (1 of 125; 5.7, 17.1), respectively.Adrenal nodules detected in staging CTs in patients with otherwise resectable colorectal cancers are rarely malignant.• Among 6474 patients who underwent staging CT and had potentially resectable colorectal cancer, 363 had adrenal nodules (≥ 10 mm) detected in retrospective CT image review. • Three out of the 363 patients with adrenal nodules detected on staging CT had malignant adrenal nodules, one of whom had metastasis from colorectal cancer.