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The mechanism for the cutoff, an activity cliff at which long-chain alcohols lose their biological effects, has not been elucidated. Highly hydrophobic oleyl alcohol (C

BACKGROUND: Although a well-acknowledged component of curative surgery for lung cancer, investigators have recently questioned the need for mediastinal lymph node dissection (MLND) in early-stage lung cancer cases. As such, the accurate prediction of N2 stage prior to surgery has become increasingly critical. But diagnostic biomarkers predicting N2 metastases are deficient, which are urgently needed. METHODS: We extracted the data of non-small cell lung cancer (NSCLC) patients whose clinical information and follow-up data are complete and without preoperative induction therapy from the Surveillance, Epidemiology, and End Results (SEER) database. The SEER program registries routinely collect demographic and clinic data on patients. And the prognostic differences were analyzed according to the presence or absence of MLND in their lung resection using the R package. Subsequently, the correlations between pN2 metastasis and clinical characteristics were analyzed. In parallel, the long non-coding RNAs (lncRNAs) associated with pN2 status were screened in The Cancer Genome Atlas (TCGA) database by expression difference analysis between pN0-N1 and pN2 patients using limma. Their diagnostic efficiency for detecting N2 metastases was evaluated using receiver operating characteristic (ROC) curves, and a combined diagnostic model was constructed using logistic regression and ROC curve analyses in lung adenocarcinoma (LUAD). RESULTS: There were 16,772 patients in MLND group, and 2,699 cases in no-MLND group. The clinical data from SEER showed that the incidence of N2 metastasis was low in pT1 NSCLC (1,023/16,772, 6.10%), but the prognosis of no-MLND patients was poorer than those who underwent MLND (P

OBJECTIVESThis study aimed to determine the clinical characteristics for predicting low-grade cancer in radiologically solid predominant non-small-cell lung cancer (NSCLC) and compare the survival outcomes of wedge resection with those of anatomical resection for patients with and without these characteristics.METHODSConsecutive patients with clinical stages IA1–IA2 NSCLC showing radiologically solid predominance ≤2 cm at 3 institutions were retrospectively evaluated. Low-grade cancer was defined as the absence of nodal involvement and blood vessel, lymphatic and pleural invasion. The predictive criteria for low-grade cancer were established by multivariable analysis. The prognosis of wedge resection was compared with that of anatomical resection for patients who met the criteria, using the propensity score-matched analysis.RESULTSAmong 669 patients, multivariable analysis showed that ground-glass opacity (GGO) (P CONCLUSIONSThe radiologic criteria for GGO and a low maximum standardized uptake value could predict low-grade cancer, even in solid-dominant NSCLC sized ≤2 cm. Wedge resection could be an acceptable surgical option for patients with radiologically predicted indolent NSCLC showing a solid-dominant appearance.

Vascular invasion (VI) is a fundamental step toward the spread of cancer. Extracellular vesicles (EVs) promote cellular communication by shuttling cargo, such as microRNAs (miRNAs). However, whether EV-associated miRNAs serve as biomarkers for VI remains unclear. This study aimed to identify EV-associated miRNAs related to VI and validate the miRNA levels from patients with early-stage lung adenocarcinoma (LADC). Blood samples were collected from patients undergoing pulmonary resection for stage I LADC before surgery. The patients were classified into three groups according to the presence of VI and postoperative recurrence. Serum-derived EVs in the derivation cohort were used for small RNA sequencing, while the selected VI miRNA candidates were validated via real-time quantitative polymerase chain reaction using 44 patient and 16 healthy donor samples as the validation cohorts. Five miRNAs (miR-99b-3p, miR-26a-5p, miR-93-5p, miR-30d-5p, and miR-365b-3p) were assessed, and miR-30d-5p (p = 0.036) levels were significantly downregulated in the VI-positive group. MiR-30d-5p levels in healthy donors were lower than those in LADC patients. Patients with high miR-30d-5p levels had favorable survival compared to those with low miR-30d-5p levels. MiR-30d-5p level in EVs may serve as a promising biomarker for detecting VI in patients with early-stage LADC.

Discrepancies between radiological whole tumor size (RTS) and pathological whole tumor size (PTS) are sometimes observed. Unexpected pathological upsize may lead to insufficient margins during procedures like sub lobar resections. Therefore, this study aimed to investigate the current status of these discrepancies and identify factors resulting in pathological upsize in patients with early-stage non-small cell lung cancer (NSCLC). Data from a multicenter database of 3092 patients with clinical stage 0-IA NSCLC who underwent pulmonary resection were retrospectively analyzed. Differences between the RTS and PTS were evaluated using Pearson's correlation analysis and Bland-Altman plots. Unexpected pathological upsize was defined as an upsize of ≥1 cm when compared to the RTS, and the predictive factors of this upsize were identified based on multivariable analyses. The RTS and PTS showed a positive linear relationship (r = 0.659), and the RTS slightly overestimated the PTS. The Bland-Altman plot showed 131 of 3092 (5.2%) cases were over the upper 95% limits of agreement. In multivariable analyses, a maximum standardized uptake value (SUV

A total of 100 patients were retrospectively analyzed with magnetic resonance imaging-ultrasonography (MRI-US) fusion biopsy(KOELIS, TRINITY®) at our institution between October 2019 and May 2020. The median patient age was 71 years, median prostate specific antigen (PSA) level was 7.4 ng/ml, and median PSA-density was 0.183 mg/ml. Sixty-one of the patients were positive for cancer ; 14 of them were positive by targeted biopsy only, 9 were positive by systematic biopsy only, and 38 were positive by both. Clinically significant prostate cancer (CPSC ; Gleason Score ≥3＋4 and % core ≥50%) was detected by target biopsies in 46 patients and by systematic biopsies in 33 patients. The positive core detection rate for CSPC was 32.5% for targeted biopsies and 7.0% for systematic biopsies(P＜0.0001), with a significantly higher rate for targeted biopsies. These results indicate that in MRI-US fusion biopsy, targeted biopsy has a higher detection rate for cancer and a significantly higher detection rate for clinically significant prostate cancer compared with systematic biopsy.

Background Staple-line coverage is an effective method for prevention of postoperative recurrence of pneumothorax. However, the recurrence rate in young patients is still unsatisfactory using this method. Moreover, there is no consensus about the optimal material for use in this technique. To explore new material for this technique, we conducted this study to evaluate the safety of an absorbable topical collagen hemostat (INTEGRAN®) for staple-line coverage in pneumothorax surgery in young patients. Methods A single-arm prospective interventional study was performed in 25 patients (age 18,000/mm3 and/or CRP >15 mg/dL, or acute empyema within 30 postoperative days) was defined as the primary endpoint. The 1-year postoperative rates of recurrence and of new bullae around the staple-line were also measured. Results The median age was 19 years old. None of the patients had a body temperature ≥38 ℃ continuing for ≥2 days, extra-abnormal examination data, and acute empyema findings. At 1-year postoperatively, the recurrence rate was 12.0%, and the rate of new bullae around the staple-line was 16.7%. Conclusions This study showed the safety of use of INTEGRAN® for staple-line coverage in pneumothorax surgery in young adults. The short-term recurrence rate was acceptable given the high-risk cohort examined in the study. A prospective randomized controlled study is needed for evaluation of the efficacy of INTEGRAN® for prevention of recurrence of PSP. Trial registration UMIN000026530 at UMIN Clinical Trials Registry.

There are few reports on the utility of the maximum standardized uptake value (SUVmax) for predicting the prognosis of early-stage lung adenocarcinoma based on the latest tumor-node-metastasis (TNM) classification. This study aimed to determine whether clinicopathologic factors, including the SUVmax, affect prognosis in these patients.We enrolled 527 patients with c-stage IA lung adenocarcinoma who underwent lobectomy or greater resection between 2011 and 2017. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan-Meier curves and compared using the log-rank test. Factors associated with RFS and OS were determined using the Cox proportional hazards model.RFS was significantly different based on tumor stage. In contrast, there was no significant difference in OS between patients with stage IA2 and IA3 disease (p = 0.794), although there were significant differences in OS between patients with stage IA1 and IA2 disease (p = 0.024) and between patients with stage IA1 and IA3 disease (p = 0.012). Multivariate analysis demonstrated that SUVmax was independently associated with both RFS and OS among patients with c-stage IA lung adenocarcinoma (RFS, p = 0.017; OS, p = 0.047). Further, even though there was no significant difference in OS between patients with stage IA2 and IA3 disease (n = 410), SUVmax was able to stratify patients with high and low RFS and OS among these patients (RFS, p 0.001; OS, p 0.001).SUVmax was an important preoperative factor to evaluate prognosis among patients with c-stage IA lung adenocarcinoma as well as the current TNM classification.

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is an important treatment for lung adenocarcinoma patients withTumor tissues were collected from stage IV lung adenocarcinoma patients withT790M mutation rates were 37.93% (11/29) and 42.50% (17/40) in theAfter resistance to the first-generation EGFR-TKI treatment, the occurrence of T790M mutation may be related to the expression of EGFR mutant protein in patients with

OBJECTIVES This study aimed to analyse the risk of death from non-lung cancer after segmentectomy or lobectomy for early-stage lung cancer. METHODS A total of 1385 patients underwent lobectomy or segmentectomy for clinical stage 0–I primary lung cancer, with no evidence of recurrence after surgery, between January 2008 and December 2018. Risk factors for non-lung cancer deaths (NLCD) were analysed using multivariable logistic regression analysis. The overall survival (OS) of patients with low and high comorbidities who underwent lobectomy and segmentectomy was compared using a log-rank test. RESULTS Patients with NLCD (n = 126) were more likely to have undergone lobectomy than patients with non-recurrence survival (n = 1259). Multivariable analysis revealed that age (≥65 years), smoking index (≥600), body mass index (≤18.5 kg/m2), interstitial pneumonia, values for percentage of predicted vital capacity (≤9.4%) and lobectomy were risk factors for NLCD. Patients who underwent segmentectomy had significantly better 5-year OS than those who underwent lobectomy, after propensity score matching (94.6% vs 90.4%, P = 0.027). Patients with high comorbidities (patients with ≥2 of the following risks: age ≥65 years, smoking index ≥600, body mass index ≤18.5 kg/m2, Charlson Comorbidity Index ≥1, values for percentage of predicted vital capacity ≤96.4%) who underwent segmentectomy had a better 5-year OS than those who underwent lobectomy (92.8% vs 87.8%, P = 0.016). However, there was no difference in 5-year OS between segmentectomy and lobectomy in patients with low comorbidities (98.5% vs 97.4%, P = 0.867). CONCLUSIONS The impact of lobectomy and segmentectomy on NLCD depends on the extent of the patients’ comorbidities.

Several methods for chest drainage after pulmonary resection of malignant lung tumors exist, but consensus on the ideal method has not been reached.We conducted a multicenter prospective observational study. We enrolled 2200 patients who underwent lung resection for lung tumors. Of the 1470 patients who underwent anatomic resection, 347 showed air leak on the morning of postoperative day 1. They were assigned to 3 groups according to the chest drainage method on postoperative day 1.Of 347 patients with postoperative air leaks, 107 (30.8%), 179 (51.6%), and 61 (17.6%) were assigned to water seal, continuous suction, and digital drainage, respectively. The median postoperative air leak duration was significantly longer with digital drainage (4.0 days) than with either water seal (2.5 days) or continuous suction (3.0 days; P = .009). Chest tubes were required for significantly more days on average with digital drainage (6.0 days) than with water seal (4.0 days) or continuous suction (4.0 days; P = .003). Prolongation of air leak duration was significantly more likely to occur in patients with body mass index18.5 kg/mWater seal was associated with significantly shorter duration of postoperative air leak and chest drainage compared with continuous suction and digital drainage.

A number of studies have been made on the sleep characteristics of children born preterm in an attempt to develop methods to address the sleep problems commonly observed among such children. However, the reported sleep characteristics from these studies vary depending on the observation methods used, i.e., actigraphy, polysomnography and questionnaire. In the current study, to obtain reliable data on the sleep characteristics of preterm-born children, we investigated the difference in sleep properties between 97 preterm and 97 term toddlers of approximately 1.5 years of age using actigraphy. Actigraphy units were attached to the toddlers’ waists with an adjustable elastic belt for 7 consecutive days, and a child sleep diary was completed by their parents. In the study, we found that preterm toddlers had more nocturnal awakenings and more daytime activity, suggesting that preterm-born children may have a different process of sleep development in their early development.

Objectives This retrospective study aimed to elucidate the effect of epidermal growth factor receptor (EGFR) gene mutations on the prognosis of patients with pathological stage II–IIIA primary lung cancer after curative surgery. Materials and methods We enrolled 539 patients with p-stage II–IIIA (8th edition tumor–node–metastasis [TNM] classification) lung cancer who underwent curative resection at Kanagawa Cancer Center between January 2010 and December 2020 and whose tumors were tested for EGFR mutations. Relapse-free survival (RFS) and overall survival (OS) of patients with EGFR-mutant lung cancer (Mt, n = 126) including EGFR exon 21 L858R point mutation and EGFR exon 19 deletion mutation and EGFR mutation-wild lung cancer (Wt, n = 413) were analyzed using Kaplan–Meier curves and compared using a log-rank test. Cox regression analysis was performed to evaluate the effects of EGFR gene mutations on RFS and OS at each stage. Results There were 56/256 patients with p-stage II EGFR-Mt/Wt and 70/157 patients with p-stage IIIA EGFR-Mt/Wt. The 5-year RFS rate of patients with EGFR-Mt/Wt was 46.6%/52.0% (p = 0.787) for p-stage II and 17.4%/29.7% (p = 0.929) for p-stage IIIA. The 5-year OS rate was 92.0%/65.7% (p = 0.001) for p-stage II and 56.0%/39.3% (p = 0.016) for p-stage IIIA. EGFR-Mt was not an independent prognostic factor for OS of patients with p-stage IIIA lung cancer (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.51–1.76; p = 0.872); however, EGFR-Mt was an independent favorable prognostic factor for OS of patients with p-stage II lung cancer (HR, 0.59; 95% CI, 0.36–0.96; p = 0.034). Conclusion The OS of lung cancer patients with p-stage II or IIIA, classified according to the 8th edition TNM classification, was remarkably favorable. Incorporating EGFR mutations to the anatomical TNM classification may lead to a more accurate prognosis prediction.

Background: The staging of patients with a tumor of diameter 4.1–5.0 cm and no lymphatic/distant metastases have been up-graded to stage IIA in the latest 8th edition of the TNM staging system. However, the efficacy of adjuvant tegafur-uracil (UFT) therapy in these patients, which has been recommended in the guideline issued by The Japan Lung Cancer Society, remains unclear. We evaluated the efficacy of adjuvant UFT therapy among a cohort by retrospective analyses of multicentric database. Methods: In 2005–2007, 130 patients with p-stage IB non-small cell lung cancer (NSCLC) (diagnosed according to the 7th edition of the TNM staging system) and tumor size of ≥3.1 cm underwent anatomic complete resection at nine of our affiliated hospitals. We retrospectively reviewed the clinicopathological characteristics and the outcomes among these patients. Results: Ninety-eight patients had tumor size of 3.1–4.0 cm (T2a group), whereas 32 patients had tumor size >4.0 cm (T2b group). Overall, patients who received adjuvant UFT showed a tendency of better outcomes than patients who did not [hazard ratio (HR) 0.564; 95% confidence interval (CI), 0.257–1.238, P=0.147]. In subgroup analyses, patients who received adjuvant UFT also tended to show better outcomes than those who did not in both T2a group and T2b group (HR 0.504; 95% CI, 0.202–1.255, P=0.132 in T2a group and HR 0.855; 95% CI, 0.181–4.033, P=0.843 in T2b group, respectively). Conclusions: Our results suggest that adjuvant UFT therapy have the potential to improve postoperative outcomes even in patients with p-stage IIA disease, as classified according to the 8th edition of the TNM staging system.

After being translocated into the ER lumen, membrane and secretory proteins are transported from the ER to the early Golgi by COPII vesicles. Incorporation of these cargo proteins into COPII vesicles are facilitated either by direct interaction of cargo proteins with COPII coat proteins or by ER exit adaptor proteins which mediate the interaction of cargo proteins with COPII coat proteins. Svp26 is one of the ER exit adaptor proteins in yeast Saccharomyces cerevisiae. ER exit of several type II membrane proteins have been reported to be facilitated by Svp26. We demonstrate here that efficient incorporation of Mnt2 and Mnt3 into COPII vesicles is also dependent on the function of Svp26. Mnt2 and Mnt3 are Golgi-localized α-1,3-mannosyltransferases with type II membrane topology involved in protein O-glycosylation. Immunoisolation of the yeast Golgi subcompartments quantitatively showed that Mnt2 and Mnt3 are more abundant in the early Golgi fraction than in the late Golgi fraction. Subcellular fractionation and fluorescence microscopy showed that deletion of the SVP26 gene results in the accumulation of Mnt2 and Mnt3 in ER. Using an in vitro COPII vesicle formation assay, we further demonstrate that Svp26 facilitates incorporation of Mnt2 and Mnt3 into COPII vesicles. Finally, we showed that Mnt2 and Mnt3 were co-immunoprecipitated with Svp26 from digitonin-solubilized membranes. These results indicate that Svp26 functions as an ER exit adaptor protein of Mnt2 and Mnt3.

We consider the matrix regularization of scalar fields on a Riemann surface with a general gauge-field background. We propose a construction of the fuzzy version of the Laplacian., 23 pages

OBJECTIVES The objective of this study was to determine the variation in intrapleural pressure (IPP) with and without air leakage using a digital chest drainage system (DCS) for each pressure setting. METHODS In this retrospective single-centre study, we analysed 49,553 h of air leakage after anatomical lung resection in 714 patients between 2018 and 2020. The transition of mean IPP and mean air leak flow was monitored using DCS, and the association between mean IPP and mean air leak flow was examined. The relationship between the transition of mean IPP and air leakage according to the varying suction pressures on DCS was also investigated. RESULTS Overall, 272 patients (38.1%) showed air leakage after surgery. The mean IPP in patients without air leakage was −12.0 ± 2.9 cmH2O and maintained at about −12 cmH2O constantly, while the mean IPP in patients with air leakage was −8.3 ± 1.9 cmH2O, which changed to −12 cmH2O instantly if air leakage disappeared (P CONCLUSIONS The change in IPP on a DCS is useful for detecting air leakage. Furthermore, management with a mild suction setting on DCS makes it easy to recognize the disappearance of postoperative air leakage.

BACKGROUND: Staple-line coverage is an effective method for prevention of postoperative recurrence of pneumothorax. However, the recurrence rate in young patients is still unsatisfactory using this method. Moreover, there is no consensus about the optimal material for use in this technique. To explore new material for this technique, we conducted this study to evaluate the safety of an absorbable topical collagen hemostat (INTEGRAN(®)) for staple-line coverage in pneumothorax surgery in young patients. METHODS: A single-arm prospective interventional study was performed in 25 patients (age 18,000/mm(3) and/or CRP >15 mg/dL, or acute empyema within 30 postoperative days) was defined as the primary endpoint. The 1-year postoperative rates of recurrence and of new bullae around the staple-line were also measured. RESULTS: The median age was 19 years old. None of the patients had a body temperature ≥38 ℃ continuing for ≥2 days, extra-abnormal examination data, and acute empyema findings. At 1-year postoperatively, the recurrence rate was 12.0%, and the rate of new bullae around the staple-line was 16.7%. CONCLUSIONS: This study showed the safety of use of INTEGRAN(®) for staple-line coverage in pneumothorax surgery in young adults. The short-term recurrence rate was acceptable given the high-risk cohort examined in the study. A prospective randomized controlled study is needed for evaluation of the efficacy of INTEGRAN(®) for prevention of recurrence of PSP. TRIAL REGISTRATION: UMIN000026530 at UMIN Clinical Trials Registry