Comparison of sentinel lymph node biopsy and elective neck dissection for early oral cavity squamous cell carcinoma patients with clinically node-negative necks: systematic review and meta-analysis.

OBJECTIVE: This study aimed to compare the prognostic utility of sentinel node biopsy and elective neck dissection in early stage clinically node-negative oral cavity squamous cell carcinoma patients. METHOD: PubMed, Scopus, Embase, Web of Science and Cochrane Library databases were searched up to March 2022. Hazard ratios, Kaplan-Meier curves, p-values and survival outcomes were extracted. RESULTS: Twelve studies involving 10 583 patients were included. No significant differences in overall survival between sentinel node biopsy and elective neck dissection groups were found. Heterogeneity was not detected in pooled overall survival, disease-free survival and disease-specific survival analyses (all I2 less than 50). In subgroup analyses by follow-up period, sentinel node biopsy and elective neck dissection had similar prognostic value. CONCLUSION: Sentinel node biopsy might be a valuable alternative to elective neck dissection for the management of early stage clinically node-negative oral cavity squamous cell carcinoma.

Relationship between the type of hormone replacement therapy and incidence of breast cancer in Korea.

OBJECTIVE: This study aimed to investigate the relationship between hormone replacement therapy (HRT) types and breast cancer (BC) incidence in postmenopausal women in Korea. METHODS: The nested case-control study used data from the National Health Insurance Service database. Among the women aged ≥50 years who menopaused between 2004 and 2007, BC incidence up to 2017 was analyzed in 36,446 women using or having used HRT for >1 year and in 36,446 women who did not use any HRT for more than 1 year. HRT types and duration were classified into three categories. RESULTS: BC risk (BCR) decreased with tibolone use for all ages. With HRT initiation in women aged ≥50 years, BCR was lower with tibolone and estrogen-progestogen therapy. HRT for <3 years showed lower BCR with tibolone, while higher BCR was observed with estrogen-only therapy. BCR was lower in women of all ages on HRT for >5 years than in the control group. CONCLUSIONS: For women in their 50s, tibolone use lowers BCR; for all ages, the use of any HRT for >5 years showed lower BCR in Korea. These divergent results from western countries could be associated with the specific characteristics of BC in Korea.

Liposomal irinotecan plus fluorouracil/leucovorin versus FOLFIRINOX as the second-line chemotherapy for patients with metastatic pancreatic cancer: a multicenter retrospective study of the Korean Cancer Study Group (KCSG).

BACKGROUND: There is no clear consensus on the recommended second-line treatment for patients with metastatic pancreatic cancer who have disease progression following gemcitabine-based therapy. We retrospectively evaluated the clinical outcomes of liposomal irinotecan (nal-IRI) plus fluorouracil/leucovorin (FL) and FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin) in patients who had failed on the first-line gemcitabine-based therapy. PATIENTS AND METHODS: From January 2015 to August 2019, 378 patients with MPC who had received nal-IRI/FL (n = 104) or FOLFIRINOX (n = 274) as second-line treatment across 11 institutions were included in this retrospective study. RESULTS: There were no significant differences in baseline characteristics between groups, except age and first-line regimens. With a median follow-up of 6 months, the median progression-free survival (PFS) was 3.7 months with nal-IRI/FL versus 4.6 months with FOLFIRINOX (P = 0.44). Median overall survival (OS) was 7.7 months with nal-IRI/FL versus 9.7 months with FOLFRINOX (P = 0.13). There was no significant difference in PFS and OS between the two regimens in the univariate and multivariate analyses. The subgroup analysis revealed that younger age (<70 years) was associated with better OS with FOLFIRINOX. In contrast, older age (≥70 years) was associated with better survival outcomes with nal-IRI/FL. Adverse events were manageable with both regimens; however, the incidence of grade 3 or higher neutropenia and peripheral neuropathy was higher in patients treated with FOLFIRINOX than with nal-IRI/FL. CONCLUSIONS: Second-line nal-IRI/FL and FOLFIRINOX showed similar effectiveness outcomes after progression following first-line gemcitabine-based therapy. Age could be the determining factor for choosing the appropriate second-line therapy.

Retrograde signaling by a mtDNA-encoded non-coding RNA preserves mitochondrial bioenergetics.

Alveolar epithelial type II (AETII) cells are important for lung epithelium maintenance and function. We demonstrate that AETII cells from mouse lungs exposed to cigarette smoke (CS) increase the levels of the mitochondria-encoded non-coding RNA, mito-RNA-805, generated by the control region of the mitochondrial genome. The protective effects of mito-ncR-805 are associated with positive regulation of mitochondrial energy metabolism, and respiration. Levels of mito-ncR-805 do not relate to steady-state transcription or replication of the mitochondrial genome. Instead, CS-exposure causes the redistribution of mito-ncR-805 from mitochondria to the nucleus, which correlated with the increased expression of nuclear-encoded genes involved in mitochondrial function. These studies reveal an unrecognized mitochondria stress associated retrograde signaling, and put forward the idea that mito-ncRNA-805 represents a subtype of small non coding RNAs that are regulated in a tissue- or cell-type specific manner to protect cells under physiological stress.

Long-term mortality of patients with tuberculosis in Korea.

BACKGROUND: Long-term mortality following tuberculosis (TB) diagnosis in Korea remains unclear.METHODS: The present study used data from the National Health Insurance Service database, an extensive health-related database including most Korean residents. TB patients were identified using International Classification of Diseases, Tenth Revision coding (A15-19, U88.0-88.1) and the type of anti-TB drug(s) between 2003 and 2016. Long-term mortality and causes of death in TB patients were analysed.RESULTS: A total of 357 211 individuals had TB over the period from 2003 to 2016 and 103 682 died. The mean age of the cohort was 54.7 ± 20.7 years, and 59.8% were male. The survival probability of TB patients at 1, 5, and 10 years after diagnosis was 87.8%, 75.3%, and 63.3%, respectively. High mortality and TB-related death rates were especially prominent in the early stages after TB diagnosis. The overall standardized mortality ratio of TB patients to the general Korean population was 3.23 (95% confidence interval 3.21-3.25).CONCLUSION: Mortality in TB patients was especially high in the early stages of disease after TB diagnosis, and mostly due to TB. This figure was approximately three-times higher than the mortality rate in the general population.

Incidence, survival, and risk of cardiovascular events in adult inflammatory myopathies in South Korea: a nationwide population-based study.

OBJECTIVE: Epidemiological studies on inflammatory myopathies (IMs) show widely variable results, and studies on Asians are lacking. Despite emerging interest in the cardiovascular disease (CVD) risk associated with IMs, the prevalence of CVD in IM patients and its impact on mortality remain unclear. We conducted a nationwide, population-based study on the incidence, mortality, and associated major CVD events of IMs in the Republic of Korea over 11 years. METHOD: Using the nationwide, population-based National Health Insurance claims database and the Rare Intractable Disease registration programme, we estimated incidence, mortality, and CVD occurrence. Survival was examined using the Kaplan-Meier method. Mortality rate in IMs with CVD was analysed by Cox proportional hazards regression. RESULTS: There were 3014 incident cases, 640 of whom died during the study period. The mean annual incidence was 7.16/106. Dermatomyositis (DM) and polymyositis (PM) had 5 year survival rates of 76.8% and 79.3%, respectively. Cardiovascular events occurred in 155 patients and 40.6% of IM patients with CVD died. Acute myocardial infarction in men had the highest risk of any CVD event in both DM [standardized incidence ratio (SIR) 4.2, 95% confidence interval (95% CI) 2.4-7.2] and PM (SIR 3.5, 95% CI 1.8-7.0). Haemorrhagic stroke had the highest hazard ratio (HR) in both DM (HR 2.31, 95% CI 1.13-4.70) and PM patients (HR 2.10, 95% CI 1.03-4.27) compared with the general population with CVD. CONCLUSION: We found persistently low incidence, poor survival, and high major CVD incidence in IMs, and increased mortality in IMs with CVD.

The Processing Time for Recanalization and Size of Ischemic Lesions on DWI is Related With Complete Reperfusion After Mechanical Thrombectomy.

Recent studies demonstrated that modified thrombolysis in cerebral infarction (TICI) 3 reperfusion have better functional outcomes than modified TICI 2b after mechanical thrombectomy in acute ischemic stroke with large vessel occlusion. The purpose of this study was to determine significant factors to forecast the presence of complete reperfusion after mechanical thrombectomy based on multimodal magnetic resonance imaging (MRI). We investigated 96 consecutive patients with acute large intracranial artery occlusion of anterior circulation who based on multimodal MRI. Also, we compared clinical and radiologic parameters between patients with modified TICI 3 and those with modified TICI 0-2b. Among 96 eligible subjects received mechanical thrombectomy, 39 patients (40.6%) showed complete reperfusion and 57 partial or nonreperfusion (mTICI 2b-26, mTICI 2a-9, mTICI 1-8, and mTICI 0-14) after mechanical thrombectomy. Patients with mTICI 3 had significantly smaller initial Diffusion weighted images (DWI) lesion volume (P < .01) and much shorter time interval from onset to reperfusion (P < .01) than those patients with mTICI (0-2b). In multivariate analysis, smaller initial DWI volume (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.23-2.57; P < .01) and faster reperfusion time (OR, 1.07; 95% CI 1.01-1.14; P = .015) had an independence significance for complete reperfusion after mechanical thrombectomy. In this study, the ischemic lesion volume on DWI and faster processing time are critical factor to predict the state of complete reperfusion after mechanical thrombectomy.

Urinary vitamin D-binding protein, a novel biomarker for lupus nephritis, predicts the development of proteinuric flare.

Lupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE). Conventional biomarkers for assessing renal disease activity are imperfect in predicting clinical outcomes associated with LN. The aim of this study is to identify urinary protein biomarkers that reliably reflect the disease activity or predict clinical outcomes. A quantitative proteomic analysis was performed to identify protein biomarker candidates that can differentiate between SLE patients with and without LN. Selected biomarker candidates were further verified by enzyme-linked immunosorbent assay using urine samples from a larger cohort of SLE patients ( n = 121) to investigate their predictive values for LN activity measure. Furthermore, the association between urinary levels of a selected panel of potential biomarkers and prognosis of LN was assessed with a four-year follow-up study of renal outcomes. Urinary vitamin D-binding protein (VDBP), transthyretin (TTR), retinol binding protein 4 (RBP4), and prostaglandin D synthase (PTGDS) were significantly elevated in SLE patients with LN, especially in patients with active LN ( n = 21). Among them, VDBP well correlated with severity of proteinuria (rho = 0.661, p < 0.001) and renal SLE Disease Activity Index (renal SLEDAI) (rho = 0.520, p < 0.001). In the four-year follow-up, VDBP was a significant risk factor (hazard ratio 9.627, 95% confidence interval 1.698 to 54.571, p = 0.011) for the development of proteinuric flare in SLE patients without proteinuria ( n = 100) after adjustments for multiple confounders. Urinary VDBP correlated with proteinuria and renal SLEDAI, and predicted the development of proteinuria.

Efficacy and safety findings from DREAM: a phase III study of DHP107 (oral paclitaxel) versus i.v. paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy.

Background: Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure. Methods and materials: Patients were randomized 1 : 1 to DHP107 (200 mg/m2 orally twice daily days 1, 8, 15 every 4 weeks) or i.v. paclitaxel (175 mg/m2 day 1 every 3 weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6 weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25. Results: Baseline characteristics were balanced in the 236 randomized patients (n = 118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7-4.0) months for DHP107 and 2.6 (95% CI 1.8-2.8) months for paclitaxel (hazard ratio [HR] = 0.85; 95% CI 0.64-1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR = 0.93; 95% CI 0.70-1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1 - 11.5) months for DHP107 versus 8.9 (95% CI 7.1-12.2) months for paclitaxel (HR = 1.04; 95% CI 0.76-1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%). Conclusions: DHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC. ClinicalTrials.gov: NCT01839773.

Different functional genes of upper airway microbiome associated with natural course of childhood asthma.

BACKGROUND: Microbial colonization of the airway plays a role in the pathogenesis of asthma; however, the effect of the upper airway microbiome on childhood asthma is not fully understood. We analyzed the metagenome of airway microbiome to understand the associated role of upper airway microbiome with the natural course of childhood asthma. METHODS: Nasopharyngeal swabs were collected from children with asthma, those in asthma remission, and control groups. High-throughput sequencing was used to examine the structure and functional dynamics of the airway microbiome with respect to asthma phenotypes. RESULTS: The composition of microbiota differed among healthy control, asthma, and remission groups. The relative abundance of Streptococcus was negatively associated with FEV1% predicted (P = .023) and that of Staphylococcus was negatively associated with methacholine PC20 (P = .013). Genes related to arachidonic acid metabolites, lysine residues, and glycosaminoglycans in the microbiome could be associated with airway inflammation. In particular, genes related to synthesis of anti-inflammatory prostaglandin E2 (PGE2 ) were not detected from the airway microbiome in the asthma group. CONCLUSIONS: These data suggest that alterations in the composition and function of the upper airway microbiome could be related with the natural course of asthma in children.

Pre-stroke glycemic control is associated with early neurologic deterioration in acute atrial fibrillation-related ischemic stroke.

BACKGROUND: It has been suggested that AF-related ischemic stroke (IS) that is accompanied by atherosclerotic burden have poorer outcomes. The aim of this study was to investigate the importance of pre-stroke glycemic control (PSGC) on the early neurologic deterioration (END) of patients with acute AF-related IS. METHODS: We retrospectively recruited 121 patients with AF-related IS who also had Diabetes mellitus (DM). The HbA1C level was measured in all subjects. END was defined as an increase in the National Institute of Health Stroke Scale (NIHSS) score of 4 NIHSS points within 7 days of symptom onset compared to the initial NIHSS score. RESULTS: In this study, 20.7% (25 patients) were classified as having a poor PSGC status with a HbA1C level above 8.0%. In the univariate analysis, a poor PSGC status (p < 0.01), smoking (p = 0.01), severe neurologic deficits at admission (p = 0.01), and a larger size of ischemic lesions on DWI (p < 0.01) were associated with the occurrence of END. In the multivariate model, a poor PSGC status (p = 0.02) and larger size of ischemic lesions on MRI (p < 0.01) were independent predictors of END in acute AF-related IS. CONCLUSION: The HbA1c level upon admission was independently associated with significant prediction of END in acute AF-related IS.

Randomized multicentre trial comparing external and internal pancreatic stenting during pancreaticoduodenectomy.

BACKGROUND: There is no consensus on the best method of preventing postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). This multicentre, parallel group, randomized equivalence trial investigated the effect of two ways of pancreatic stenting after PD on the rate of POPF. METHODS: Patients undergoing elective PD or pylorus-preserving PD with duct-to-mucosa pancreaticojejunostomy were enrolled from four tertiary referral hospitals. Randomization was stratified according to surgeon with a 1 : 1 allocation ratio to avoid any related technical factors. The primary endpoint was clinically relevant POPF rate. Secondary endpoints were nutritional index, remnant pancreatic volume, long-term complications and quality of life 2 years after PD. RESULTS: A total of 328 patients were randomized to the external (164 patients) or internal (164) stent group between August 2010 and January 2014. The rates of clinically relevant POPF were 24·4 per cent in the external and 18·9 per cent in the internal stent group (risk difference 5·5 per cent). As the 90 per cent confidence interval (-2·0 to 13·0 per cent) did not fall within the predefined equivalence limits (-10 to 10 per cent), the clinically relevant POPF rates in the two groups were not equivalent. Similar results were observed for patients with soft pancreatic texture and high fistula risk score. Other postoperative outcomes were comparable between the two groups. Five stent-related complications occurred in the external stent group. Multivariable analysis revealed that soft pancreatic texture, non-pancreatic disease and high body mass index (23·3 kg/m2 or above) predicted clinically relevant POPF. CONCLUSION: External stenting after PD was associated with a higher rate of clinically relevant POPF than internal stenting. Registration number: NCT01023594 (https://www.clinicaltrials.gov).

Increased levels of brain serotonin correlated with MMP-9 activity and IL-4 levels resulted in severe experimental autoimmune encephalomyelitis (EAE) in obese mice.

The aim of this study was to investigate the role of monoamine neurotransmitters on the severity of experimental autoimmune encephalomyelitis (EAE) in obese mice. EAE was induced in mice with normal diets (ND-EAE) and obese mice with high-fat diets (HFD-EAE) through the immune response to myelin oligodendrocyte glycoprotein (MOG) (35-55). The levels of dopamine (DA), serotonin (5-HT) and their metabolites in different anatomical brain regions were measured by high-performance liquid chromatography. The plasma and tissue NADPH oxidase and matrix metalloproteinases (MMP)-9 activities were analyzed by fluorescence spectrophotometry. The cumulative disease index and disease peaks were significantly higher in HFD-EAE compared with those in ND-EAE. Significantly higher 5-HT levels and lower 5-HT turnovers 5-hydroxyindole acetic acid ((5-HIAA)/5-HT) were found in the brains of HFD-EAE mice compared with those found in the HFD-CON and ND-EAE mice brains. Moreover, increased DA levels were observed in the caudate nucleus of the HFD-EAE mice compared with the control and ND-EAE mice. The NADPH oxidase and MMP-9 activities in the plasma and tissues were significantly higher in both the ND-EAE and HFD-EAE groups than in their respective controls. The cytokine levels in the plasma, tissues, and cultured splenocytes were found to be significantly altered in EAE mice compared with control mice. Moreover, HFD-EAE mice exhibited significantly higher MMP-9 activity and lower IL-4 levels than ND-EAE mice and were significantly correlated with brain 5-HT levels. In conclusion, the increased 5-HT levels in the brain significantly correlated with MMP-9 activity and IL-4 levels play an important role in the exacerbation of disease severity in HFD-EAE mice.

Retinal vessel structure measurement using spectral-domain optical coherence tomography.

PURPOSE: To assess the reliability and validity of spectral-domain optical coherence tomography (SD-OCT) measurements of retinal vessel lumen diameters and wall thicknesses. METHODS: SD-OCT was used to characterize the circular region around the optic disc of 40 eyes (20 subjects). The inner and outer sides (vitreal and choroidal sides) of the vessel wall and the luminal diameter were measured using intensity graphs. RESULTS: Mean arterial and venous luminal diameters were 95.1±16.1 and 132.6±17.8 µm, respectively. The wall thicknesses of inner and outer sides of the artery were 23.9±4.9 and 21.2±3.5 µm, respectively. The wall thicknesses of the inner and outer sides of the vein were 20.7±4.2 and 16.3±4.3 µm, respectively. There were significant differences between the inner and outer wall thicknesses in both the artery and vein (P<0.01). Intra- and interobserver intraclass correlation coefficients (ICCs) for lumen measurements were >0.95, and for wall thicknesses were >0.85, except for the outer wall thickness measurements. The mean value of outer and inner wall thicknesses showed good reproducibility, with ICCs of >0.85. CONCLUSION: Intensity graph-assisted measurements using SD-OCT provided more objective information in finding boundaries of vessels. Luminal diameters and wall thicknesses obtained with OCT showed good overall reproducibility, with inner wall thicknesses being thicker, and with better reproducibility compared with outer wall thicknesses, where ICC values were the lowest among the inner wall thicknesses, mean thicknesses of inner and outer walls, and luminal diameters. When using SD-OCT measurements, caution is therefore advised when using only the outer wall as representative of the wall thicknesses.

Portal vein patency after pancreatoduodenectomy for periampullary cancer.

BACKGROUND: The fate of the portal vein (PV) after pancreatoduodenectomy, especially its long-term patency and associated complications, has received little attention. The aim of this study was to explore the long-term patency rate of the PV after pancreatoduodenectomy, focusing on risk factors for PV stenosis/occlusion and associated complications. METHODS: Serial CT images of patients who underwent pancreatoduodenectomy for periampullary cancer between January 2000 and June 2012 in a single institution were evaluated for PV stenosis or occlusion. RESULTS: A total of 826 patients were enrolled. The PV stenosis/occlusion rate after pancreatoduodenectomy was 19.6 per cent and the 5-year patency rate 69.9 per cent. The most frequent cause of PV stenosis/occlusion was local recurrence followed by postoperative change and PV thrombosis. Patients who underwent PV resection had a higher PV stenosis/occlusion rate than those who did not (51 versus 17.4 per cent; P < 0.001). The 3-year patency rate was highest in patients with cancer of the ampulla of Vater and lowest in patients with pancreatic cancer (91.9 versus 55.5 per cent respectively; P < 0.001). Multivariable analysis showed that risk factors for PV stenosis/occlusion included primary tumour location, chemoradiotherapy and PV resection. PV stenosis or occlusion without disease recurrence was observed in 17.3 per cent of the patients. PV resection and grade B or C pancreatic fistula were independent risk factors for PV stenosis/occlusion. Among 162 patients with PV stenosis or occlusion, five (3.1 per cent) had fatal recurrent gastrointestinal bleeding. CONCLUSION: PV stenosis or occlusion is common after pancreatoduodenectomy, particularly if the PV has been resected and/or chemoradiotherapy was given after surgery. Although recurrence is the most frequent cause of PV stenosis/occlusion, this complication is found in a significant proportion of patients without disease recurrence.

Crucial role of calbindin-D28k in the pathogenesis of Alzheimer's disease mouse model.

Calbindin-D28k (CB), one of the major calcium-binding and buffering proteins, has a critical role in preventing a neuronal death as well as maintaining calcium homeostasis. Although marked reductions of CB expression have been observed in the brains of mice and humans with Alzheimer disease (AD), it is unknown whether these changes contribute to AD-related dysfunction. To determine the pathogenic importance of CB depletions in AD models, we crossed 5 familial AD mutations (5XFAD; Tg) mice with CB knock-out (CBKO) mice and generated a novel line CBKO·5XFAD (CBKOTg) mice. We first identified the change of signaling pathways and differentially expressed proteins globally by removing CB in Tg mice using mass spectrometry and antibody microarray. Immunohistochemistry showed that CBKOTg mice had significant neuronal loss in the subiculum area without changing the magnitude (number) of amyloid ß-peptide (Aß) plaques deposition and elicited significant apoptotic features and mitochondrial dysfunction compared with Tg mice. Moreover, CBKOTg mice reduced levels of phosphorylated mitogen-activated protein kinase (extracellular signal-regulated kinase) 1/2 and cAMP response element-binding protein at Ser-133 and synaptic molecules such as N-methyl-D-aspartate receptor 1 (NMDA receptor 1), NMDA receptor 2A, PSD-95 and synaptophysin in the subiculum compared with Tg mice. Importantly, this is the first experimental evidence that removal of CB from amyloid precursor protein/presenilin transgenic mice aggravates AD pathogenesis, suggesting that CB has a critical role in AD pathogenesis.

Validation of international consensus guidelines for the resection of branch duct-type intraductal papillary mucinous neoplasms.

BACKGROUND: Classifications of intraductal papillary mucinous neoplasm (IPMN) remain ambiguous, especially for the mixed type. Factors predicting malignancy remain unclear. The aim of this study was to evaluate the usefulness of factors predicting malignancy in the new international consensus guidelines for resection of branch duct-type (BD)-IPMN and to compare them with those in the previous version. METHODS: A prospectively collected database of patients with biopsy-proven BD-IPMN was analysed to compare factors between the first and second consensus guidelines, particularly as predictors of malignancy. RESULTS: Of 350 patients with BD-IPMN, sensitivity (0.724) and balanced accuracy (0.751) of the second guidelines were superior to those (0.639 and 0.730) in the first version at the expense of slightly reduced specificity (0.779 versus 0.822 for the first version) by random forest models. Multiple logistic regression analysis showed that main pancreatic duct dilatation greater than 5 mm (hazard ratio (HR) 4.54, 95 per cent confidence interval 2.45 to 8.41; P < 0.001), mural nodules (HR 6.27, 3.27 to 12.01; P < 0.001) and carbohydrate antigen 19-9 level above 37 units/ml (HR 4.03, 1.83 to 8.90; P = 0.001) were independent predictors of BD-IPMN malignancy. CONCLUSION: The new consensus guidelines provide better sensitivity, performance of factors predicting malignancy, and balanced accuracy in the diagnosis of BD-IPMN malignancy. Size alone was limited in predicting malignancy. Variability in clinical significance of the individual factors associated with a risk of malignancy indicates the need for a tailored approach in the management of patients with BD-IPMN.

Split-gate organic field-effect transistors for high-speed operation.

Split-gate organic field-effect transistors have been developed for high-speed operation. Owing to the combination of reduced contact resistance and minimized parasitic capacitance, the devices have fast switching characteristics. The cutoff frequencies for the vacuum-evaporated devices and the solution-processed devices are 20 and 10 MHz, respectively. A speed of 10 MHz is the fastest device reported so far among solution-processed organic transistors.

Effects of Lactobacillus rhamnosus on asthma with an adoptive transfer of dendritic cells in mice.

AIM: This study was designed to investigate whether the protective effects of Lactobacillus rhamnosus (Lcr35) on allergic asthma are associated with the adoptive transfer of dendritic cells (DCs) and regulatory T cells (Tregs), using a mouse experimental model of asthma. METHODS AND RESULTS: BALB/c mice were orally administered Lcr35 or intravenously treated with in vivo Lcr35-treated DCs daily and were then sensitized and challenged with ovalbumin (OVA) in accordance with a model of asthma protocol. Both the oral application of Lcr35 and intravenous administration of Lcr35-treated DCs suppressed all aspects of the asthmatic response, including bronchial hyperresponsiveness (BHR), total cell counts in the bronchoalveolar lavage (BAL) fluid, the production of OVA-specificimmunoglobulin E (IgE), and pulmonary eosinophilic inflammation. The mechanism of action of Lcr35 is related to Tregs, which suppress the Th2 response in the respiratory organs, and this is mediated by DCs in the mouse model of asthma. CONCLUSIONS: These results confirm that the mechanism underlying the effects of Lcr35 on asthma involves the adoptive transfer of DCs. SIGNIFICANCE AND IMPACT OF THE STUDY: This finding broadens the possibility that Lcr35 has potential as an alternative therapeutic approach to the treatment of human asthma.

ZNF313 is a novel cell cycle activator with an E3 ligase activity inhibiting cellular senescence by destabilizing p21(WAF1.).

ZNF313 encoding a zinc-binding protein is located at chromosome 20q13.13, which exhibits a frequent genomic amplification in multiple human cancers. However, the biological function of ZNF313 remains largely undefined. Here we report that ZNF313 is an ubiquitin E3 ligase that has a critical role in the regulation of cell cycle progression, differentiation and senescence. In this study, ZNF313 is initially identified as a XIAP-associated factor 1 (XAF1)-interacting protein, which upregulates the stability and proapoptotic effect of XAF1. Intriguingly, we found that ZNF313 activates cell cycle progression and suppresses cellular senescence through the RING domain-mediated degradation of p21(WAF1). ZNF313 ubiquitinates p21(WAF1) and also destabilizes p27(KIP1) and p57(KIP2), three members of the CDK-interacting protein (CIP)/kinase inhibitor protein (KIP) family of cyclin-dependent kinase inhibitors, whereas it does not affect the stability of the inhibitor of CDK (INK4) family members, such as p16(INK4A) and p15(INK4B). ZNF313 expression is tightly controlled during the cell cycle and its elevation at the late G1 phase is crucial for the G1-to-S phase transition. ZNF313 is induced by mitogenic growth factors and its blockade profoundly delays cell cycle progression and accelerates p21(WAF1)-mediated senescence. Both replicative and stress-induced senescence are accompanied with ZNF313 reduction. ZNF313 is downregulated during cellular differentiation process in vitro and in vivo, while it is commonly upregulated in many types of cancer cells. ZNF313 shows both the nuclear and cytoplasmic localization in epithelial cells of normal tissues, but exhibits an intense cytoplasmic distribution in carcinoma cells of tumor tissues. Collectively, ZNF313 is a novel E3 ligase for p21(WAF1), whose alteration might be implicated in the pathogenesis of several human diseases, including cancers.