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We investigate population and individual firing behaviors in sparsely synchronized rhythms (SSRs) in a spiking neural network of the hippocampal dentate gyrus (DG). The main encoding granule cells (GCs) are grouped into lamellar clusters. In each GC cluster, there is one inhibitory (I) basket cell (BC) along with excitatory (E) GCs, and they form the E-I loop. Winner-take-all competition, leading to sparse activation of the GCs, occurs in each GC cluster. Such sparsity has been thought to enhance pattern separation performed in the DG. During the winner-take-all competition, SSRs are found to appear in each population of the GCs and the BCs through interaction of excitation of the GCs with inhibition of the BCs. Sparsely synchronized spiking stripes appear successively with the population frequency $f_p~ (= 13$ Hz) in the raster plots of spikes. We also note that excitatory hilar mossy cells (MCs) control the firing activity of the GC-BC loop by providing excitation to both the GCs and the BCs. SSR also appears in the population of MCs via interaction with the GCs (i.e., GC-MC loop). Population behaviors in the SSRs are quantitatively characterized in terms of the synchronization measures. In addition, we investigate individual firing activity of GCs, BCs, and MCs in the SSRs. Individual GCs exhibit random spike skipping, leading to a multi-peaked inter-spike-interval histogram, which is well characterized in terms of the random phase-locking degree. On the other hand, both BCs and MCs show "intrastripe" burstings within stripes, together with "interstripe" random spike skipping. MC loss may occur during epileptogenesis. With decreasing the fraction of the MCs, changes in the population and individual firings in the SSRs are also studied. Finally, quantitative association between the population/individual firing behaviors in the SSRs and the winner-take-all competition is discussed., Comment: arXiv admin note: text overlap with arXiv:2105.06057

Subclinical lymph node (LN) metastasis is associated with poor survival outcome in oral cavity squamous cell carcinoma (OCC), which alleges elective neck LN dissection. Preoperative detection of metastatic LNs may improve prognosis and proper management of OCC. We examined the clinical usefulness of fluorine 18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) for the detection of occult neck LN metastasis in OCC patients in comparison with conventional CT/magnetic resonance (MR) imaging. A total of 178 OCC patients with negative neck palpation findings were assessed prospectively with 18F-FDG PET/CT and CT/MR imaging. Histopathological analyses of neck dissection samples served as reference. Diagnostic values of 18F-FDG PET/CT versus CT/MR imaging were compared with the McNemar test and logistic regression with generalized estimating equations. Forty-two patients (23.6%) had metastasis in 44 sides and 58 levels of the neck. The sensitivity for detection of occult metastasis was higher for 18F-FDG PET/CT than that for CT/MR imaging on a per-patient (69.1% vs 35.7%), per-side (70.5% vs 36.4%), and per-level (62.1% vs 29.3%) basis (all P ≤ 0.001). However, the specificity for metastatic detection was higher for CT/MR imaging than that for 18F-FDG PET/CT (all P

Metastatic lymph node (LN) burden is one of the most important prognosticators in human solid cancers, but has rarely been examined in laryngeal and hypopharyngeal cancers (LHC). We evaluated the nodal factors predictive of recurrence and survival in patients with LHC. This study included 141 consecutive patients who underwent primary surgery and neck dissection for previously untreated LHC at our tertiary referral centre. Nodal factors included the presence of pathological LN metastasis, number of positive LNs, LN ratio, and extra-nodal extension (ENE). Our proposed N classification was analysed by recursive partitioning analysis and compared with the AJCC and other N classifications using the c-index. Univariate and multivariate Cox proportional hazard regression analyses were used to define significant predictors of post-treatment disease-free survival (DFS) and overall survival (OS). Of the 141 patients, 66 (46.8%) had positive LNs, and 27 (19.1%) had ENE. In multivariate analyses, the number of positive LNs was strongly associated with DFS and OS outcomes (P

We consider a scale-free network of inhibitory Hindmarsh-Rose (HR) bursting neurons, and investigate coupling-induced cluster burst synchronization by varying the average coupling strength $J_0$. For sufficiently small $J_0$, non-cluster desynchronized states exist. However, when passing a critical point $J^*_c~(\simeq 0.16)$, the whole population is segregated into 3 clusters via a constructive role of synaptic inhibition to stimulate dynamical clustering between individual burstings, and thus 3-cluster desynchronized states appear. As $J_0$ is further increased and passes a lower threshold $J^*_l~(\simeq 0.78)$, a transition to 3-cluster burst synchronization occurs due to another constructive role of synaptic inhibition to favor population synchronization. In this case, HR neurons in each cluster exhibit burst synchronization. However, as $J_0$ passes an intermediate threshold $J^*_m~(\simeq 5.2)$, HR neurons begin to make intermittent hoppings between the 3 clusters. Due to the intermittent intercluster hoppings, the 3 clusters are integrated into a single one. In spite of break-up of the 3 clusters, (non-cluster) burst synchronization persists in the whole population, which is well visualized in the raster plot of burst onset times where bursting stripes (composed of burst onset times and indicating burst synchronization) appear successively. With further increase in $J_0$, intercluster hoppings are intensified, and bursting stripes also become smeared more and more due to a destructive role of synaptic inhibition to spoil the burst synchronization. Eventually, when passing a higher threshold $J^*_h~(\simeq 17.8)$ a transition to desynchronization occurs via complete overlap between the bursting stripes. Finally, we also investigate the effects of stochastic noise on both 3-cluster burst synchronization and intercluster hoppings., Comment: arXiv admin note: text overlap with arXiv:1803.07256, arXiv:1708.04543

Background: The accurate detection of distant metastases can facilitate appropriate treatment planning for patients with recurrent head and neck squamous cell carcinoma (HNSCC).Objectives: ...

Background/aims Endoscopic ultrasonography (EUS) is the most efficient imaging modality for gastric subepithelial tumors (SETs). However, abdominopelvic computed tomography (APCT) has other advantages in evaluating the characteristics, local extension, or invasion of SETs to adjacent organs. This study aimed to compare the diagnostic ability of EUS and APCT based on surgical histopathology results. Methods We retrospectively reviewed data from 53 patients who underwent both EUS and APCT before laparoscopic wedge resection for gastric SETs from January 2010 to December 2017 at a single institution. On the basis of histopathology results, we assessed the diagnostic ability of the 2 tests. Results The overall accuracy of EUS and APCT was 64.2% and 50.9%, respectively. In particular, the accuracy of EUS vs. APCT for the diagnosis of gastrointestinal stromal tumors (GISTs), leiomyomas, and ectopic pancreas was 83.9% vs. 74.2%, 37.5% vs. 0.0%, and 57.1% vs. 14.3%, respectively. Most of the incorrect diagnoses with EUS involved hypoechoic lesions originating in the fourth echolayer, with the most common misdiagnosed lesions being GISTs mistaken for leiomyomas and vice versa. Conclusion APCT showed a lower overall accuracy than EUS; however, APCT remains a useful modality for malignant/potentially malignant gastric SETs.

Tumor multifocality or bilaterality is associated with increased risk of papillary thyroid carcinoma (PTC) recurrence. However, its prognostic value in clinical outcomes remains controversial. This study aimed to evaluate the association of multifocality or bilaterality with recurrence and survival after total thyroidectomy.This was a retrospective study of 2390 consecutive patients with pathologically confirmed PTC who underwent total thyroidectomy. Multifocality and bilaterality were decided based on the final pathology results, that is, if there were two or more tumor foci and bilateral location, respectively. Primary outcomes were recurrence-free survival (RFS). Cox proportional hazards regression analyses were used to assess the associations of multifocality, bilaterality, and other clinicopathological factors with RFS.Multifocal and bilateral PTC were found in 892 (37.3%) and 593 (24.8%) patients, respectively. Multivariate analyses showed that multifocality, lymphovascular invasion, N category, and number of positive lymph node (5) were significant independent variables predictive of RFS (all P 0.05). Multifocality was associated with adjusted hazard ratios for RFS of 1.93 (95% confidence interval = 1.33-2.80; P = 0.001). In a subset analysis, the prognostic value of multifocality was found to be significant in those patients with PTC 1 cm, but not in papillary thyroid microcarcinoma.Tumor multifocality is an independent risk factor of PTC recurrence after total thyroidectomy. This indicate a more progressive state of disease, being included in risk stratification.

OBJECTIVE To evaluate the prognostic values of tumor-related leukocytosis (TRL) as a reliable biomarker predictive of recurrence and survival after definitive surgery for oral cavity squamous cell carcinoma (OSCC). MATERIALS AND METHODS This retrospective study involved 322 patients who underwent tumor extirpation combined with neck dissection for treatment-naive OSCC between 2006 and 2014. Multivariate binary logistic regression analyses were used to analyze the relationship between TRL and pathological variables. Cox proportional hazard regression analyses were used to find associations between factors and disease-free survival (DFS) or overall survival (OS). RESULTS TRL was significantly related to advanced disease status, tumor size, invasion depth, poor differentiation, and T and N classifications, resulting in increased post-treatment recurrence rate, particularly in the distant site. Multivariate logistic regression analyses showed that only the T classification was significantly associated with baseline TRL (p = 0.018). Multivariate analyses also showed that the tumor depth of invasion, pathological N classification, extranodal extension, and TRL remained the independent variables predictive of DFS and OS (all p

BACKGROUND This study examined the risk factors of pharyngocutaneous fistula development and poor survival after salvage laryngectomy. METHODS Binary logistic regression analyses were carried out to analyze the relationship between post-salvage fistula development and variables. Univariate and multivariate Cox proportional hazard regression analyses were performed to evaluate prognostic factors associated with disease-free survival (DFS) and overall survival (OS) after salvage laryngectomy. RESULTS Multivariate analyses showed that previous radiotherapy and pre-salvage tracheostomy were the independent variables predictive of post-salvage fistula development (all P

Submandibular gland (SMG) carcinoma has an unfavorable clinical course and a low survival rate. Specific tumor and nodal findings might help predict posttreatment recurrence and survival in SMG carcinoma patients. This study evaluated factors predictive of posttreatment recurrence and survival in SMG carcinoma patients. This study enrolled 99 consecutive patients with previously untreated SMG carcinoma. All patients underwent tumor and metastatic lymph node resection along with or without radiation/chemo-radiation. The predictive clinical and pathological factors for disease-free survival (DFS), distant metastasis–free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were determined using univariate and multivariate Cox proportional hazards regression analyses. The median tumor size was 2.7 cm and 53 patients (53.5%) had high-grade tumors. The rates of initial nodal and distant metastasis at initial presentation or follow-up were 45.5% and 42.4%, respectively. The actuarial 5-year DFS, DMFS, DSS, and OS rates were 46.4%, 55.9%, 61.5%, and 59.7%, respectively. The independent factors associated with poor DFS, DMFS, DSS, and OS outcomes (all p

This study aimed to investigate the correlations between diffuse splenic Fluorine-18-fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography/computed tomography (PET/CT) and inflammatory markers and to evaluate the prognostic significance of splenic FDG uptake in rectal cancer patients who underwent curative surgery. We retrospectively analyzed the data from 161 patients who underwent splenic FDG PET/CT staging and subsequent curative surgical resection of rectal cancer between July 2006 and September 2014. The spleen-to-liver uptake ratio (S/L ratio) was calculated by dividing the spleen SUVmean by liver SUVmean. We found significant positive correlations between the S/L ratio and neutrophil-to-lymphocyte ratio (P = 0.013) and platelet-to-lymphocyte ratio (P = 0.007). In a Kaplan–Meier analysis, patients with S/L ratio ≤0.815 had a significantly higher recurrence-free survival rate than those with S/L ratio >0.815 (P = 0.028). Also, patients with S/L ratio ≤0.731 had a significantly higher overall survival rate than those with S/L ratio >0.731 (P = 0.036). In multivariate analysis, higher S/L ratio, as well as male, poor differentiation, higher TNM stage, perineural invasion, and larger tumor size, was independently predictive of cancer recurrence (>0.815 vs ≤0.815, hazard ratio [HR]: 2.04, P = 0.046). With regard to OS, S/L ratio was also an independent prognostic factor for death during follow-up (>0.731 vs ≤0.731, HR: 3.81, P = 0.017). Our results show significant correlations between S/L ratio on PET/CT and systemic inflammatory markers. Further, S/L ratio was an independent prognostic factor for predicting recurrence and death in patient with rectal cancer after curative surgery.

Alkaline hydrolysis was used to develop a liquid fertilizer which was then applied to hot pepper plants in field in order to assess its potential to be used as a fertilizer. The treatments were control (Cn), developed liquid fertilizer (DLF), inorganic fertilizer (NPK), and DLF + NPK treatments. The chemical properties of the final DLF product were a pH of 10.2, TN of 2.26%, and K of 6.12%, respectively. The length and weight of the plant in hot pepper cultivation were higher in the order of DLF + NPK > NPK > DLF > Cn treatment. The fresh weight of hot pepper under DLF + NPK treatment increased by 312% compared to control. Although the DLF showed a significant increase in fruit length and fruit fresh weight in the hot pepper cultivation compared to the control, the effect of DLF treatment on plant growth was limited due to the unbalanced N-to-P ratios in the DLF. In the potting experiment, the DLF could potentially be used as a supplement to inorganic fertilizer, demonstrating that alkaline hydrolysis is a promising technique for recycling bio-hazardous materials such as infected animal carcasses into value-added liquid fertilizer.

We compared the predictive ability of our proposed N classification with that of the American Joint Committee on Cancer (AJCC) nodal (N) classification for oral cavity squamous cell carcinoma (OCC).We assessed 345 OCC patients who underwent primary tumor extirpation and neck lymph node (LN) dissection. N classification was analyzed by recursive partitioning analysis and compared with the AJCC N classification by c-index. Cox proportional hazards regression analyses were used to determine associations between tumor or nodal factors and disease-free survival (DFS) or overall survival (OS).Positive LNs were found in 149 patients (43.2%). In multivariate models, the number of positive LNs and LN ratio strongly associated with DFS and OS (P 0.001). Our new N classification was proposed with four categories of N0, N1 (1 positive LN), N2 (2-4 positive LNs or extranodal extension 2 mm), and N3 (≥5 positive LNs). The c-index for the proposed N classification showed improvement in survival predictions (0.735; 95% CI, 0.703-0.767) compared with the AJCC N classification (0.701; 0.667-0.735).The number of positive LNs and LN ratios strongly associated with posttreatment recurrence and survival for OCC. Using positive LN numbers with the N classification improves OCC survival predictions.

The role of p53 in genotoxic therapy-induced metabolic shift in cancers is not yet known. In this study, we investigated the role of p53 in the glycolytic shift in head and neck squamous cell carcinoma cell lines following irradiation. Isogenic p53-null radioresistant cancer cells established through cumulative irradiation showed decreased oxygen consumption and increased glycolysis with compromised mitochondria, corresponding with their enhanced sensitivity to drugs that target glycolysis. In contrast, radioresistant cancer cells with wild-type p53 preserved their primary metabolic profile with intact mitophagic processes and maintained their mitochondrial integrity. Moreover, we identified a previously unappreciated link between p53 and mitophagy, which limited the glycolytic shift through the BNIP3-dependent clearance of abnormal mitochondria. Thus, drugs targeting glycolysis could be used as an alternative strategy for overcoming radioresistant cancers, and the p53 status could be used as a biomarker for selecting participants for clinical trials.

Objectives Current guidelines recommend chest computed tomography (CT) with locoregional CT/magnetic resonance imaging for patients with head and neck squamous cell carcinoma (HNSCC), and 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET)/CT is suggested for stage III–IV patients. However, whole body screening with 18F-FDG PET/CT may provide better detection of distant metastases and synchronous cancer than conventional imaging. We evaluated the utility of 18F-FDG PET/CT in detecting distant metastasis and synchronous cancer. Methods This prospective study enrolled 740 consecutive patients with previously untreated HNSCC diagnosed between September 2010 and December 2015. Synchronous cancer was histologically confirmed and distant metastases were confirmed by biopsy or serial imaging follow-ups. McNemar test was used to compare the true-positive detection rates of chest radiography (CXR) + head and neck CT (hnCT) (A) versus 18F-FDG PET/CT (C) and chest CT + hnCT (B) versus 18F-FDG PET/CT. Results Distant metastases and synchronous cancer were found in 23 (3.1%) and 55 (7.4%) patients, respectively. A, B, and C detected distant metastases in 10 (1.3%), 19 (2.6%), and 21 (2.8%) patients, respectively. The absolute differences were 1.5% (A versus C, P = 0.003) and 0.3% (B versus C, P = 0.687). A, B, and C detected synchronous cancer in 15 (2.0%), 22 (2.9%), and 36 (4.9%) patients, respectively. The absolute differences were 2.8% (A versus C, P Conclusions 18F-FDG PET/CT detected more distant metastases and synchronous cancer than CXR + hnCT and more synchronous cancer than chest CT + hnCT.

Stress exposure is a major risk factor for mental disorders such as depression. Because of the limitations of classical antidepressants such as side effects, low efficacy, and difficulty in long-term use, new natural medicines and bioactive molecules from plants with greater safety and efficacy have recently attracted attention. Luteolin-7-O-glucuronide (L7Gn), a bioactive molecule present in Perilla frutescens, is known to alleviate severe inflammatory responses and oxidative stress in macrophages. However, its antistress and antidepressant effects have not been elucidated. The present study aims to explore the antidepressant the effect of L7Gn on stress-induced behaviors and the underlying mechanism in a mouse sleep deprivation (SD) model. L7Gn treatment improved depression-like and stress coping behaviors induced by SD stress, as confirmed by the tail suspension test and forced swimming test. Furthermore, L7Gn treatment reduced the blood corticosterone and hippocampal proinflammatory cytokine levels which were increased by SD stress, and L7Gn also increased the mRNA and protein levels of hippocampal brain-derived neurotrophic factor (BDNF) which were reduced by SD stress. Additionally, treatment with L7Gn resulted in increases in the phosphorylation of tropomyosin-related kinase B (TrkB), extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB), which are downstream molecules of BDNF signaling. These findings suggest that L7Gn have therapeutic potential for SD-induced stress, via activating the BDNF signaling.

Conventional chemotherapy with maximum tolerated dose (MTD) has shown confident anti-cancer effect and when combined with targeted therapy, immunotherapy. Yet, understanding about how the MTD regimen is optimized has lacked due to its high tumor burdens. In this study, the oral doxorubicin (DOX) formulation was shown to improve oral bioavailability by 12.1% and sustain the metronomic concentration through the flexible protocol. Since the optimizing dose and schedules of DOX in metronomic chemotherapy (MCT) is essential to maximize efficacy and minimize toxicity, which is determined by the exposure of drugs based on pharmacokinetic-pharmacodynamic (PK/PD) correlation, we developed an integrated systemic mathematical model that can evaluate the anti-tumor effect and the toxicity of oral DOX formulation simultaneously. Oral physiologically-based pharmacokinetic (PBPK) models were established with dose dependency, and creatine kinase-MB (CK-MB) and tumor growth profiles were assessed as markers for toxicodynamic (TD) and PD models, respectively. Each model was validated and then integrated into the PK-TD/PD model and the effects of various oral metronomic regimens were predicted. In conclusion, the finalized oral metronomic dosing regimen (10 mg/kg, QD) showed 83.3% tumor growth inhibition without cardiotoxicity. In this study, we defined the MCT regimen using a mathematical model and suggested a dose selection method for developing oral drugs from injections, to efficiently utilize the preclinical results and apply to clinical practice. Citation Format: Seho Kweon, Yoo-Seong Jeong, Yoon Gun Ko, Seung Woo Chung, Ha Kyeong Lee, Suk-Jae Chung, Youngro Byun, Sang Yoon Kim. Metronomic dose-finding approach of oral chemotherapy by experimentally-driven integrated mathematical modeling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2730.

We aimed to investigate long-term cardiovascular sequelae after coronary artery bypass grafting (CABG) in patients with subclinical hypothyroidism (SCH). All-cause and cardiovascular-related mortality, and cardiovascular events were retrospectively reviewed in 222 euthyroid and 36 SCH patients who underwent CABG. During a mean follow-up period of 8.2 ± 4.1 years, there were 90 incidents of all-cause deaths, 20 cardiovascular-related deaths, 70 major cardiovascular adverse events, 6 myocardial infarctions, 12 unstable anginas, 31 strokes, 23 hospitalizations due to heart failure, 15 atrial fibrillation (AF) events, and 27 coronary revascularizations. The incidence rate of coronary revascularization was significantly higher in patients with SCH (n = 6, 16.6%) than in euthyroid patients (n = 20, 9.0%), with a hazard ratio (HR) of 3.179 (95% confidence interval [CI] 1.174, 8.605; p = 0.023) after adjustment. In subgroup analysis, SCH patients who experienced postoperative AF within 3 months after CABG surgery had a significantly higher risk of coronary revascularization (n = 4, 25.0%) than euthyroid patients without AF (n = 14, 8.9%) after adjustment (HR 11.759, 95% CI 2.747, 50.343, p = 0.001). The frequency of fatal or nonfatal unstable angina was also higher in patients with SCH (n = 2, 12.5%) than in euthyroid patients (n = 4, 2.5%) (HR 16.999, 95% CI 2.242, 128.860, p = 0.006). In conclusion, preoperative SCH is associated with less favorable cardiovascular outcomes, especially coronary revascularization after CABG. Moreover, SCH patients who develop postoperative AF exhibit significantly increased risks of unstable angina and coronary revascularization. Preoperative evaluation of thyroid function may be helpful for predicting long-term outcomes after CABG.

Objectives The current study aims to determine the correlation between nutritional status upon presentation and disease severity, as well as treatment and survival outcomes. Methods Patients who were diagnosed with deep neck infection, underwent at least one surgical drainage/debridement, and had more than 1 week of hospitalization at a tertiary medical center from 2007 to 2015 were retrospectively included. Thereafter, initial serum albumin, C-reactive protein (CRP), and body mass index (BMI) were reviewed. Results A total of 135 patients were included in the final analysis. Accordingly, the proportion of patients with simultaneous mediastinitis (21.0%), necrotizing fasciitis (12.9%), disease extent >1 cervical level (72.6%), mean CRP (22.4 mg/dL), mean length of hospitalization (25.0 days), and mean 1-week follow-up CRP (7.2 mg/dL) was significantly higher in the hypoalbuminemia group (initial serum albumin 1 cervical level (2.12), initial serum CRP over 20 mg/dL (3.79), hospitalization of more than 14 days (4.10), 1-week follow-up CRP over 5 mg/dL (3.78), and increased duration for an over 50% decrease in initial CRP (2.70) (all P

The recently published 8th edition of the American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) staging system was significantly updated following the thyroid cancer-related guidelines to provide better predictability of survival but not focus on recurrence. Therefore, we compared the predictive values of the 7th and 8th editions of the AJCC staging systems for recurrence-free survival (RFS) and overall survival (OS) after thyroidectomy for papillary thyroid carcinoma (PTC).This retrospective study included 2930 patients who underwent thyroidectomy and neck dissection for previously untreated PTC between 2006 and 2014. TNM stage was defined according to 7th and 8th editions. Univariate and multivariate Cox proportional hazard regression analyses were used to identify associations between variables and RFS or OS. Multivariate models for the AJCC TNM stages were adjusted for clinical and pathological variables.A significant number of patients classified as T3 with overall TNM stages II-IV in the AJCC 7th edition were down-staged in the 8th edition. Unadjusted T classification and overall TNM staging in both the 7th and 8th editions were significantly associated with RFS and OS rates (P 0.001). After adjustment for clinicopathological factors, the overall TNM stage according to the AJCC 8th edition, but not the 7th edition, remained significantly associated with RFS and OS (P 0.05), with better predictability of recurrence and survival, in patients with PTC.The 8th edition AJCC staging system down-staged a large proportion of PTC patients, resulting in better predictability of recurrence and survival compared to the previous staging system.This study compared the abilities of the 7th and 8th edition AJCC staging systems to predict recurrence and overall survival in 2930 patients with papillary thyroid carcinoma. The updated guidelines down-staged a large proportion of patients, resulting in better prediction of recurrence and survival than the previous staging system.

Studies regarding the best strategy to determine appropriate femoral component rotation during bilateral total knee arthroplasty (TKA) in wind swept deformities (WSD) are very limited. The purpose of this study was (1) to evaluate whether femoral rotational profiles differ between varus and valgus osteoarthritic knees in WSD and (2) to analyze the correlation between femoral rotational profiles and coronal radiologic parameters.A total of 40 patients who were diagnosed with bilateral knee osteoarthritis with WSD between January 2010 and December 2020 at a single institution were retrospectively reviewed. On axial computed tomography scans, femoral rotational profile parameters such as the clinical transepicondylar axis (cTEA) and anterior-posterior (AP) axis were compared between valgus and varus osteoarthritic knees. In standing full-limb AP radiographs, coronal radiographic parameters including hip-knee-ankle angle (HKA), valgus correction angle (VCA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), and joint line convergence angle (JLCA) were measured in both knees. The correlation between the varus-valgus cTEA difference, and differences in coronal radiologic parameters was analyzed.In valgus osteoarthritic knees, cTEA was significantly increased compared to varus osteoarthritic knees by 1.5° (valgus: 7.65° ± 1.82°, varus: 6.15° ± 1.58°, p 0.001). All coronal radiologic parameters, including HKA, LDFA, MPTA, JLCA, and VCA, were significantly different between valgus and varus knees. In correlation analysis, the varus-valgus cTEA difference was significantly correlated with LDFA (r = 0.365, p = 0.021), MPTA (r = 0.442, p = 0.004), and HKA differences (r = 0.693, p 0.001), with the HKA difference showing the strongest correlation with the cTEA difference.In bilateral knee osteoarthritis with WSD, valgus knees showed significantly increased cTEA compared to varus knees, and the cTEA difference positively correlated with the HKA difference between valgus and varus knees. To determine the optimal femoral component rotation during TKA in WSD, assessment of cTEA with pre-operative CT scans or careful intra-operative measurement is recommended, especially in patients with large HKA difference.III, Retrospective cohort study.

EPHA3, a member of the EPH family, is overexpressed in various cancers. We demonstrated previously that EPHA3 is associated with radiation resistance in head and neck cancer via the PTEN/Akt/EMT pathway, the inhibition of EPHA3 significantly enhances the efficacy of radiotherapy in vitro and in vivo. In this study, we investigated the mechanisms of PTEN regulation through EPHA3-related signaling. Increased DNA methyltransferase 1 (DNMT1) and enhancer of zeste homolog 2 (EZH2) levels, along with increased histone H3 lysine 27 trimethylation (H3K27me3) levels, correlated with decreased levels of PTEN in radioresistant head and neck cancer cells. Furthermore, PTEN is regulated in two ways: DNMT1-mediated DNA methylation, and EZH2-mediated histone methylation through EPHA3/C-myc signaling. Our results suggest that EPHA3 could display a novel regulatory mechanism for the epigenetic regulation of PTEN in radioresistant head and neck cancer cells.

Tumors are composed of subpopulations of cancer cells with functionally distinct features. Intratumoral heterogeneity limits the therapeutic effectiveness of cancer drugs. To address this issue, it is important to understand the regulatory mechanisms driving a subclonal variety within a therapy-resistant tumor. We identified tumor subclones of HN9 head and neck cancer cells showing distinct responses to radiation with different levels of p62 expression. Genetically identical grounds but epigenetic heterogeneity of the p62 promoter regions revealed that radioresistant HN9-R clones displayed low p62 expression via the creation of repressive chromatin architecture, in which cooperation between DNMT1 (DNA methyltransferases 1) and HDAC1 (histone deacetylases 1) resulted in DNA methylation and repressive H3K9me3 and H3K27me3 marks in the p62 promoter. Combined inhibition of DNMT1 and HDAC1 by genetic depletion or inhibitors enhanced the suppressive effects on proliferative capacity and in vivo tumorigenesis following irradiation. Importantly, ectopically p62-overexpressed HN9-R clones increased the induction of senescence along with p62-dependent autophagy activation. These results demonstrate the heterogeneous expression of p62 as the key component of clonal variation within a tumor against irradiation. Understanding the epigenetic diversity of p62 heterogeneity among subclones allows for improved identification of the functional state of subclones and provides a novel treatment option to resolve resistance to current therapies.

PURPOSE The aims of this study were to evaluate the degree of cortical thinning and the tumor area in simple radiographs in patients with enchondroma of the hand combined with pathologic fracture and to determine the surgical outcome of simultaneous tumor curettage and internal fixation of fracture. METHODS We enrolled 23 bone lesions of 21 patients diagnosed with enchondroma of the hand. Of them, 9 bone lesions of 8 patients had pathologic fracture. We evaluated the degree of cortical thinning and tumor area in simple radiographs and compared them between patients with and without pathologic fracture. For patients with pathologic fracture, we performed curettage of the tumor through the fracture site and fixed the fracture using K-wires. We then evaluated the clinical outcome of these patients using the visual analog scale to measure pain intensity and Takigawa's criteria 1 year after surgery. RESULTS There was a significant difference in the degree of cortical thinning between the 2 groups (P < 0.001); however, there was no significant difference in the percentage of tumor area (P = 0.259). The average time from surgery to bony union was 8.5 weeks in patients with pathologic fracture. The patients reported that they could return to their previous activities of daily living within 12 weeks of surgery. The average visual analog scale score was 0.6 at 1 year after surgery, and 6 patients were graded as excellent and 2 as good according to Takigawa's criteria. CONCLUSIONS Cortical thinning seems to be related to pathologic fracture. Our scoring system for cortical thinning may be helpful in evaluating the risk for pathologic fracture. Early 1-stage surgical treatment for pathologic hand fracture with enchondroma is a very useful method with satisfactory outcomes that could shorten the treatment period.

Here we report a novel combination of a caspase-cleavable peptide-doxorubicin conjugate (MPD-1) with CD47-antagonizing nanocage therapeutics for the treatment of microsatellite-stable (MSS) colorectal cancer (CRC). MPD-1 (i) upregulated markers of immunogenic cell death (ICD) in tumor, and increased co-stimulatory markers on dendritic cells (DCs), (ii) enhanced CD8+ T cell infiltration and antigen presenting cell (APC) activation, and (iii) showed negligible off-target immune-related toxicity compared to free dox. Then, the CD47 antagonist FS nanocage, a SIRPα-expressing ferritin nanocage, was co-administered with MPD-1 that resulted in 95.2% (p < 0.001) tumor growth inhibition in an established CRC model. T cell-mediated elimination of tumors was also confirmed by the tumor-specific activation of T cells detected by IFNγ and tumor-free mice were observed (95%) that bared a memory response when re-challenged. The strategically developed MPD-1 is an ideal adjuvant to immunotherapy and the combination with FS nanocage triggers potent immunity against MSS CRC. In summary, we present an approach to initiate and stimulate immune-mediated eradication of cancer cells using synergistic immunogenic agents targeting the MSS CRC.

Livestock manure has been widely used in agriculture to improve soil productivity and quality. However, intensive application can significantly enhance soil nitrogen (N) availability and facilitate ammonia (NH

Currently, there is great interest in the development of ways to achieve the benefits of radiation treatments with reduced negative effects. The present study demonstrates the utilization of radio-luminescent particles (RLPs) as a means to achieve radio-sensitization and enhancement and their ability to affect head- and neck-cancer-cell cultures (in vitro) and xenografts (in vivo). Our approach utilizes a naturally abundant radio-luminescent mineral, calcium tungstate (CaWO

We investigate disynaptic effect of the hilar cells on pattern separation in a spiking neural network of the hippocampal dentate gyrus (DG). The principal granule cells (GCs) in the DG perform pattern separation, transforming similar input patterns into less-similar output patterns. The hilus consists of excitatory mossy cells (MCs) and inhibitory HIPP (hilar perforant path-associated) cells. Here, we consider the disynaptic effects of the MCs and the HIPP cells on the GCs, mediated by the inhibitory basket cells (BCs); MC $\rightarrow$ BC $\rightarrow$ GC and HIPP $\rightarrow$ BC $\rightarrow$ GC. By changing synaptic strength $K^{\rm (BC, X)}$ ( X = MC or HIPP) from the default value ${K^{\rm (BC, X)}}^*$, we study the change in the pattern separation degree ${\cal S}_d$. When decreasing $K^{\rm (BC, MC)}$ or independently increasing $K^{\rm (BC, HIPP)}$ from their default values, ${\cal S}_d$ is found to decrease (i.e., pattern separation is reduced). On the other hand, as $K^{\rm (BC, MC)}$ is increased or independently $K^{\rm (BC, HIPP)}$ is decreased from their default values, pattern separation becomes enhanced (i.e., ${\cal S}_d$ increases). In this way, the disynaptic effects of the MCs and the HIPP cells on the pattern separation are opposite ones. Thus, when simultaneously varying both $K^{\rm (BC, MC)}$ and $K^{\rm (BC, HIPP)}$, as a result of balance between the two competing disynaptic effects of the MCs and the HIPP cells, ${\cal S}_d$ forms a bell-shaped curve with an optimal maximum at their default values. Moreover, the population and individual behaviors of the sparsely synchronized rhythm of the GCs are found to be strongly correlated with the pattern separation degree ${\cal S}_d$. Consequently, the larger the synchronization and the random phase-locking degrees of the sparsely synchronized rhythm is, the more the pattern separation becomes enhanced., Comment: arXiv admin note: text overlap with arXiv:2106.00172, arXiv:2105.06057

We consider two inhibitory (I) and excitatory (E) populations with I to E and E to I interpopulation spike-timing-dependent plasticity (STDP). By changing the noise intensity D, we study the effect of interpopulation STDPs on fast sparsely synchronized rhythms that appear in the two I- and E-populations. Long-term potentiation (LTP) and long-term depression (LTD) for population-averaged values of saturated interpopulation synaptic strengths are thus found to take place. Then, the degree of fast sparse synchronization changes due to the effects of LTP and LTD. In a broad region of intermediate D, the degree of good synchronization (with larger synchronization degree) gets decreased. On the other hand, in a region of large D, the degree of bad synchronization (with smaller synchronization degree) becomes increased. As a result, an “equalization effect” in interpopulation synaptic plasticity occurs in each I- or E-population, where the synchronization degree gets nearly the same in a wide range of D.

We consider a biological network of the hippocampal dentate gyrus (DG). The DG is a pre-processor for pattern separation which facilitates pattern storage and retrieval in the CA3 area of the hippocampus. The main encoding cells in the DG are the granule cells (GCs) which receive the input from the entorhinal cortex (EC) and send their output to the CA3. We note that the activation degree of GCs is so low (~ 5%). This sparsity has been thought to enhance the pattern separation. We investigate the dynamical origin for winner-take-all (WTA) competition which leads to sparse activation of the GCs. The whole GCs are grouped into lamellar clusters. In each GC cluster, there is one inhibitory (I) basket cell (BC) along with excitatory (E) GCs. There are three kinds of external inputs into the GCs; the direct excitatory EC input, the indirect inhibitory EC input, mediated by the HIPP (hilar perforant path-associated) cells, and the excitatory input from the hilar mossy cells (MCs). The firing activities of the GCs are determined via competition between the external E and I inputs. The E-I conductance ratio (given by the time average of the external E to I conductances) may represents well the degree of such external E-I input competition. It is thus found that GCs become active when their is larger than a threshold , and then the mean firing rates of the active GCs are strongly correlated with . In each GC cluster, the feedback inhibition of the BC may select the winner GCs. GCs with larger than the threshold survive, and they become winners; all the other GCs with smaller become silent. In this way, WTA competition occurs via competition between the firing activity of the GCs and the feedback inhibition from the BC in each GC cluster. In this case, the hilar MCs are also found to play an essential role of enhancing the WTA competition in each GC cluster by exciting both the GCs and the BC.PACS numbers: 87.19.lj, 87.19.lm, 87.19.lv

To analyze the factors influencing visual field recovery in patients with pituitary adenoma following surgical treatment.We retrospectively reviewed 144 eyes of 72 patients with pituitary adenoma who had been followed up for more than 6 months following surgery between January 2016 and December 2019. Pre and postoperative visual acuity, visual field test and retinal nerve fiber layer (RNFL) thickness were investigated. We defined recovery of visual field defects as being an improvement in mean deviation (MD) of 2 dB or more.The average age of the 72 patients (144 eyes) was 51.94 ± 14.69 years, making for 37 patients in the recovery group and 35 patients in the non-recovery group. Preoperative MD, pattern standard deviation (PSD), and visual field indexes (VFI) were negatively correlated to postoperative MD, PSD and VFI changes and positively correlated to postoperative MD, PSD, and VFI values. Using multiple regression analysis, a shorter duration of symptoms (Odds ratio [OR], 0.990; p = 0.033), higher preoperative MD values (OR, 0.871; p = 0.025), and thicker temporal RNFL (OR, 1.068; p = 0.048) were associated with a visual field recovery following surgery.The prognosis for visual field recovery is favorable for patients who have a short period from symptom onset to surgery, a higher MD value of preoperative VF, and a thicker peripapillary temporal RNFL thickness. Therefore, the preoperative MD, temporal RNFL thickness, and the symptom period can be predictive variables affecting postoperative visual field recovery.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has attracted attention as a potential candidate for cancer therapy. However, many primary cancers are resistant to TRAIL, even when combined with standard chemotherapy. The mechanism of TRAIL resistance in cancer cells has not been fully elucidated. The TRAIL death receptor (DR) 3&prime, untranslated region (3&prime, UTR) is reported to contain AU-rich elements (AREs) that are important for regulating DR mRNA stability. However, the mechanisms by which DR mRNA stability is determined by its 3&prime, UTR are unknown. We demonstrate that tristetraprolin (TTP), an ARE-binding protein, has a critical function of regulating DR mRNA stability. DR4 mRNA contains three AREs and DR5 mRNA contains four AREs in 3&prime, UTR. TTP bound to all three AREs in DR4 and ARE3 in DR5 and enhanced decay of DR4/5 mRNA. TTP overexpression in colon cancer cells changed the TRAIL-sensitive cancer cells to TRAIL-resistant cells, and down-regulation of TTP increased TRAIL sensitivity via DR4/5 expression. Therefore, this study provides a molecular mechanism for enhanced levels of TRAIL DRs in cancer cells and a biological basis for posttranscriptional modification of TRAIL DRs. In addition, TTP status might be a biomarker for predicting TRAIL response when a TRAIL-based treatment is used for cancer.

The manner in which p53 maintains redox homeostasis and the means by which two key metabolic elements, glucose and glutamine, contribute to p53-dependent redox stability remain unclear. To elucidate the manner in which p53 deals with glucose-deprived, reactive oxygen species (ROS)-prone conditions in this regard, two isogenic cancer subclones (HN3R-A and HN3R-B) bearing distinct p53 mutations as an in vitro model of intratumoral p53 heterogeneity were identified. Following cumulative irradiation, the subclones showed a similar metabolic shift to aerobic glycolysis and increasing NADPH biogenesis for cellular defense against oxidative damage irrespective of p53 status. The radioresistant cancer cells became more sensitive to glycolysis-targeting drugs. However, in glucose-deprived and ROS-prone conditions, HN3R-B, the subclone with the original p53 increased the utilization of glutamine by GLS2, thereby maintaining redox homeostasis and ATP. Conversely, HN3R-A, the p53-deficient radioresistant subclone displayed an impairment in glutamine usage and high susceptibility to metabolic stresses as well as ROS-inducing agents despite the increased ROS scavenging system. Collectively, our findings suggest that p53 governs the alternative utilization of metabolic ingredients, such as glucose and glutamine, in ROS-prone conditions. Thus, p53 status may be an important biomarker for selecting cancer treatment strategies, including metabolic drugs and ROS-inducing agents, for recurrent cancers after radiotherapy.

Background/Aims: Point mutations in the 23S ribosomal RNA gene have been associated with Helicobacter pylori clarithromycin resistance. This study aimed to detect the prevalence of these point mutations and to investigate the role of different point mutations in the success of eradication therapy. Methods: We retrospectively investigated a total of 464 consecutive patients who underwent an endoscopic examination and dual-priming oligonucleotide-based multiplex polymerase chain reaction for H. pylori between June 2014 and October 2019. For 289 patients with negative point mutations, standard triple therapy was used in 287 patients, and the bismuth-quadruple regimen was used in two patients. For 175 patients with positive point mutations (A2142G, A2143G, and both mutations), standard triple and bismuth-quadruple therapies were used in 37 patients and 138 patients, respectively. Results: The eradication rates of standard triple and bismuth-quadruple therapies showed no significant difference in mutation-negative patients or those with the A2142G point mutation. However, the eradication rate with bismuth-quadruple therapy was significantly higher than that with standard triple therapy in the group with the A2143G mutation or with the double mutation. The eradication rates for standard triple and bismuth-quadruple therapies, respectively, were 25.8% and 92.1% in the per-protocol group (p

To develop a deep learning method to predict visual field (VF) from wide-angle swept-source optical coherence tomography (SS-OCT) and compare the performance of three Google Inception architectures. Three deep learning models (with Inception-ResNet-v2, Inception-v3, and Inception-v4) were trained to predict 24-2 VF from the macular ganglion cell-inner plexiform layer and the peripapillary retinal nerve fibre layer map obtained by SS-OCT. The prediction performance of the three models was evaluated by using the root mean square error (RMSE) between the actual and predicted VF. The performance was also compared among different glaucoma severities and Garway-Heath sectorizations. The training dataset comprised images of 2220 eyes from 1120 subjects, and the test dataset was obtained from another 305 subjects (305 eyes). In all subjects, the global prediction errors (RMSEs) were 4.44 ± 2.09 dB, 4.78 ± 2.38 dB, and 4.85 ± 2.66 dB for the Inception-ResNet-v2, Inception-v3, and Inception-v4 architectures, respectively, and the prediction error of Inception-ResNet-v2 was significantly lower than the other two (P

We consider a cerebellar ring network for the optokinetic response (OKR), and investigate the effect of diverse recoding of granule (GR) cells on OKR by varybing the connection probability pc from Golgi to GR cells. For an optimal value of , individual GR cells exhibit diverse spiking patterns which are in-phase, anti-phase, or complex out-of-phase with respect to their population-averaged firing activity. Then, these diversely-recoded signals via parallel fibers (PFs) from GR cells are effectively depressed by the error-teaching signals via climbing fibers from the inferior olive which are also in-phase ones. Synaptic weights at in-phase PF-Purkinje cell (PC) synapses of active GR cells are strongly depressed via strong long-term depression (LTD), while those at anti-phase and complex out-of-phase PF-PC synapses are weakly depressed through weak LTD. This kind of “effective” depression (i.e., strong/weak LTD) at the PF-PC synapses causes a big modulation in firings of PCs, which then exert effective inhibitory coordination on the vestibular nucleus (VN) neuron (which evokes OKR). For the firing of the VN neuron, the learning gain degree ℒg, corresponding to the modulation gain ratio, increases with increasing the learning cycle, and it saturates at about the 300th cycle. By varying pc from , we find that a plot of saturated learning gain degree versus pc forms a bell-shaped curve with a peak at (where the diversity degree in spiking patterns of GR cells is also maximum). Consequently, the more diverse in recoding of GR cells, the more effective in motor learning for the OKR adaptation.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive head and neck malignancy. The aim of this study was to elucidate the role of periostin (POSTN) in the epithelial-to-mesenchymal transition (EMT) process mediating the acquisition of radioresistance in HNSCC.The expression levels of EMT hallmark genes including POSTN and Erk/Akt signaling pathways were compared between radiosensitive and radioresistant HNSCC cells.POSTN mRNA expression was higher in radioresistant HNSCC cells, and silencing POSTN significantly impaired their invasiveness under the effect of EMT process represented by up-regulation of mesenchymal markers and down-regulation of an epithelial marker. Expression levels of Erk and Akt were higher in radioresistant cells.POSTN in association with the Erk and Akt signaling pathways was up-regulated during the EMT process, leading to the conversion of radiosensitive to radioresistant HNSCC cells. POSTN may be a key marker for predicting the radioresistance and therapeutic target of HNSCC.

Oral cavity squamous cell carcinoma (OCC) can spread to the neck without apparent lymphadenopathy. Pretreatment detection or prediction of occult metastasis might contribute to proper management of clinically node-negative (cN0) OCC. We examined the role of tumour quantitative 18-fluorodeoxyglucose (This study included 130 cN0 OCC patients who underwentPathological cervical metastasis (pN +) was found in 29 (22.3%) patients. Age, tumour differentiation, lymphovascular invasion, and T classification were significantly associated with pN + (all P 0.05). After adjustment for these factors, MTV and TLG independently predicted pN + (P 0.05). Invasion depth, lymphovascular invasion, T and N classifications, and overall TNM stage were significantly associated with OS. After adjustment for these factors, SUVTumour

Pre- and post-treatmentThis prospective study involved 225 patients with previously untreated advanced-stage HNSCC who underwent primary surgery with or without postoperative radiotherapy or chemoradiotherapy. The patients also hadPPV and NPV for post-treatment PET/CT for overall recurrence were 75.8% and 98.7%, respectively. A positive post-treatment PET/CT was an independent predictive factor for overall and disease-free survival (both P 0.001). Five-year overall survival rates for patients with positive and negative PET/CT were 48.1% and 92.3%, respectively. Corresponding 5-year disease-free survival rates were 22.5% and 82.4%, respectively. Perineural invasion, positive resection margin, positive pathological node, and extranodal extension were the independent predictors of positivePost-treatment

BACKGROUND American Thyroid Association (ATA) proposed management guidelines for differentiated thyroid cancer, including a three-tiered risk stratification system for structural recurrence. This study aimed to compare the various 2015 ATA criteria for the strength of association with the recurrence of high-risk papillary thyroid carcinoma (PTC). STUDY DESIGN This study included 545 consecutive patients who underwent total thyroidectomy plus neck dissection and radioactive iodine ablation (RAI) for previously untreated high-risk PTC. The association of recurrence-free survival (RFS) with clinicopathological factors was evaluated by univariate and multivariate Cox proportional hazard regression analyses. RESULTS During a follow-up median period of 89 months, 90 (16.5%) patients had any-site recurrence. Of the high-risk factors, high stimulated thyroglobulin (sTg) level and >3-cm sized lymph nodes (LNs) were significantly associated with recurrence (all P

Lung cancer is the deadliest cancer worldwide, mainly due to its advanced stage at the time of diagnosis. A non-invasive method for its early detection remains mandatory to improve patients&rsquo, survival. Plasma levels of 351 proteins were quantified by Liquid Chromatography-Parallel Reaction Monitoring (LC-PRM)-based mass spectrometry in 128 lung cancer patients and 93 healthy donors. Bootstrap sampling and least absolute shrinkage and selection operator (LASSO) penalization were used to find the best protein combination for outcome prediction. The PanelomiX platform was used to select the optimal biomarker thresholds. The panel was validated in 48 patients and 49 healthy volunteers. A 6-protein panel clearly distinguished lung cancer from healthy individuals. The panel displayed excellent performance: area under the receiver operating characteristic curve (AUC) = 0.999, positive predictive value (PPV) = 0.992, negative predictive value (NPV) = 0.989, specificity = 0.989 and sensitivity = 0.992. The panel detected lung cancer independently of the disease stage. The 6-protein panel and other sub-combinations displayed excellent results in the validation dataset. In conclusion, we identified a blood-based 6-protein panel as a diagnostic tool in lung cancer. Used as a routine test for high- and average-risk individuals, it may complement currently adopted techniques in lung cancer screening.

Metronomic chemotherapy, which is defined as a low-dose and frequent administration of cytotoxic drugs without drug-free breaks, has been recently emerged as an alternative to traditional MTD therapy and has shown therapeutic benefit in breast cancer patients in numbers of clinical studies. Unlike MTD, metronomic chemotherapy acts by multiple mechanisms including antiangiogenic effect and immunomodulation, but the direct cytotoxic effect only playing a minor role due to the lowered dose. In this light, within the limits of p53-deficient breast cancer, we demonstrate the enhanced anticancer effect of metronomic chemotherapy using doxorubicin when combined with Chk1 inhibitor MK-8776 by specifically augmenting the direct cytotoxic effect on cancer cells. Since the oral drug is greatly favored in metronomic chemotherapy due to the frequent and potential long-term administration, we prepared an oral doxorubicin by producing an ionic complex with deoxycholic acid, which showed sufficient bioavailability and anticancer effect when administered orally. MK-8776 selectively enhanced the cytotoxic effect of low-concentration doxorubicin in p53-deficient breast cancer cells by abrogating the Chk1-dependent cell cycle arrest in vitro. Consistently, combining MK-8776 significantly improved the anticancer effect of the daily administered oral doxorubicin in p53-deficient breast cancer xenografts especially in a lower dose of doxorubicin without evident systemic toxicities. Combination therapy of MK-8776 and metronomic oral doxorubicin would be thus promising in the treatment of p53-deficient breast cancer benefited from the augmented direct cytotoxic effect and low risk of toxicities.

High-grade salivary gland carcinoma (SGC) shows a high rate of metastasis and post-treatment recurrence, resulting in poor patient survival. Therefore, we evaluated the utility of pre-treatment 18F-FDG PET/CT parameters in predicting metastasis, tumor progression, and survival of high-grade SGC patients. This observational study included 75 patients with previously untreated high-grade SGC who underwent pre-treatment 18F-FDG PET/CT scanning and subsequent treatment. Standardized uptake values (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured on pre-treatment 18F-FDG PET/CT. Logistic regression analysis was used to identify the relationship of these factors with metastasis. Cox proportional hazard regression analyses were used to identify associations between PET parameters and both progression-free survival (PFS) and overall survival (OS). A total of 36 (48%) patients had neck or distant metastases at initial staging. After controlling for clinical factors, MTV (> 8.8 mL) was an independent factor for initial metastasis (adjusted odds ratio 4.80, 95% confidence interval 1.09–21.20; P = 0.039). All PET parameters of SUVmax (> 4.3), SUVmean (> 3.0), SUVpeak (3.9), MTV (> 8.8 mL), and TLG (> 31.1 g) were significant variables for PFS (all P

Tumour size and extrathyroidal extension (ETE) may impact papillary thyroid carcinoma (PTC) outcomes. We therefore examined the prognostic value of tumour size and ETE for predicting posttreatment recurrence in PTC patients.A total of 2,902 patients who underwent thyroidectomy for previously untreated T1-T3 PTC (7th edition American Joint Committee on Cancer) at our tertiary referral center were included. Univariate and multivariate Cox proportional hazard regression analyses were used to determine significant factors predictive of posttreatment recurrence-free survival (RFS).In univariate analysis, tumour factors (including tumour size, multifocality, ETE, and lymphovascular invasion), nodal factors (including positive lymph node number, lymph node ratio, and extranodal extension), and MACIS (metastases, age, completeness of resection, invasion, and size) scores were significantly associated with RFS outcomes (P 0.001). In multivariate analysis, tumour size4 cm (P 0.001) and multifocality (P = 0.038) were the independent factors of RFS. Nodal factors and MACIS scores were also independent factors of RFS.Tumour size impacts RFS after thyroidectomy in T1-T3 PTC patients.

Background The aim of this study is to investigate the relationship between gender-specific and obesity-related airway anatomy in patients with obstructive sleep apnea (OSA) by using cephalometric analyses. Methods We retrospectively evaluated 206 patients with suspected OSA undergoing polysomnography and anthropometric measurements such as body mass index, neck circumference, and waist-hip ratio. We checked lateral cephalometry to measure tissue landmarks including angle from A point to nasion to B point (ANB), soft palate length (SPL), soft palate thickness (SPT), retropalatal space (RPS), retrolingual space (RLS), and mandibular plane to hyoid (MPH). Results Male with OSA showed significantly increased SPL (P = .006) compared with controls. SPL and MPH had significant correlation with apnea-hypopnea index (AHI) and central obesity. Female with OSA showed significantly increased ANB (P = .013) and SPT (P = .004) compared with controls. The receiver operating characteristic curves revealed that SPT in male and ANB and SPT in female were significant in model 1 (AHI ≥ 5) and model 2 (AHI ≥ 15). MPH was also significant for male in model 2. Conclusion Male and female with OSA had distinct anatomic features of the upper airway and different interactions among soft palate, mandible, and hyoid bone.