RBF-Based Camera Model Based on a Ray Constraint to Compensate for Refraction Error.

A camera equipped with a transparent shield can be modeled using the pinhole camera model and residual error vectors defined by the difference between the estimated ray from the pinhole camera model and the actual three-dimensional (3D) point. To calculate the residual error vectors, we employ sparse calibration data consisting of 3D points and their corresponding 2D points on the image. However, the observation noise and sparsity of the 3D calibration points pose challenges in determining the residual error vectors. To address this, we first fit Gaussian Process Regression (GPR) operating robustly against data noise to the observed residual error vectors from the sparse calibration data to obtain dense residual error vectors. Subsequently, to improve performance in unobserved areas due to data sparsity, we use an additional constraint; the 3D points on the estimated ray should be projected to one 2D image point, called the ray constraint. Finally, we optimize the radial basis function (RBF)-based regression model to reduce the residual error vector differences with GPR at the predetermined dense set of 3D points while reflecting the ray constraint. The proposed RBF-based camera model reduces the error of the estimated rays by 6% on average and the reprojection error by 26% on average.

Operation time as a simple indicator to predict the overcoming of the learning curve in gastric cancer surgery: a multicenter cohort study.

BACKGROUND: The aim of this study is to identify an indicator to predict the overcoming of the learning curve of distal gastrectomy in gastric cancer surgery. METHOD: A retrospective multicenter cohort study was conducted in 2100 patients who underwent radical distal gastrectomy performed by nine surgeons in eight hospitals between 2001 and 2006. For each surgeon, an individual CUSUM chart was formulated in terms of operation time or clinical outcomes, including severe complications, number of retrieved lymph nodes, positive resection margin, and hospital stay. The actual changing points (CPs) of the CUSUM charts were analyzed. Based on the CP, patients were divided into pre-CP and post-CP groups, and the clinicopathologic outcomes and survival data were compared between the groups. RESULTS: CP determined by operation time was more reliable than CP determined by a combination of clinical outcomes, as the former was correlated not only with short-term outcomes but also with survival. The outcomes were superior in the post-CP group in terms of numbers of harvested lymph nodes, sufficient lymph node harvesting (> 15), and negative proximal margins. In a survival analysis, the post-CP group showed better survival than the pre-CP group in stage II (76% vs 86.1% p = 0.010) and stage III (51.5% vs 60.6% p = 0.042). CONCLUSION: Overcoming the learning curve of distal gastrectomy for gastric cancer can be better predicted by operation time rather than by a combination of postoperative clinical parameters. It is recommended that surgeons initially operate on early stage cancer patients before overcoming the learning curve.

Applicability of Diffuse Ultrasound to Evaluation of the Water Permeability and Chloride Ion Penetrability of Cracked Concrete.

This study aims to explore the applicability of diffuse ultrasound to the evaluation of water permeability and chloride ion penetrability of cracked concrete. Lab-scale experiments were conducted on disk-shaped concrete specimens, each having a different width of a penetrating crack that was generated by splitting tension along the centerline. The average crack width of each specimen was determined using an image binarization technique. The diffuse ultrasound test employed signals in the frequency range of 200 to 440 kHz. The water flow rate was measured using a constant water-head permeability method, and the chloride diffusion coefficient was determined using a modified steady-state migration method. Then, the effects of crack width on the diffusion characteristics of ultrasound (i.e., diffusivity, dissipation), water flow rate, and chloride diffusion coefficient are investigated. The correlations between the water flow rate and diffuse ultrasound parameters, and between the chloride diffusion coefficient and diffuse ultrasound parameters, are examined. The results suggest that diffuse ultrasound is a promising method for assessing the water permeability and chloride ion penetrability of cracked concrete.

AraNet v2: an improved database of co-functional gene networks for the study of Arabidopsis thaliana and 27 other nonmodel plant species.

Arabidopsis thaliana is a reference plant that has been studied intensively for several decades. Recent advances in high-throughput experimental technology have enabled the generation of an unprecedented amount of data from A. thaliana, which has facilitated data-driven approaches to unravel the genetic organization of plant phenotypes. We previously published a description of a genome-scale functional gene network for A. thaliana, AraNet, which was constructed by integrating multiple co-functional gene networks inferred from diverse data types, and we demonstrated the predictive power of this network for complex phenotypes. More recently, we have observed significant growth in the availability of omics data for A. thaliana as well as improvements in data analysis methods that we anticipate will further enhance the integrated database of co-functional networks. Here, we present an updated co-functional gene network for A. thaliana, AraNet v2 (available at http://www.inetbio.org/aranet), which covers approximately 84% of the coding genome. We demonstrate significant improvements in both genome coverage and accuracy. To enhance the usability of the network, we implemented an AraNet v2 web server, which generates functional predictions for A. thaliana and 27 nonmodel plant species using an orthology-based projection of nonmodel plant genes on the A. thaliana gene network.

WormNet v3: a network-assisted hypothesis-generating server for Caenorhabditis elegans.

High-throughput experimental technologies gradually shift the paradigm of biological research from hypothesis-validation toward hypothesis-generation science. Translating diverse types of large-scale experimental data into testable hypotheses, however, remains a daunting task. We previously demonstrated that heterogeneous genomics data can be integrated into a single genome-scale gene network with high prediction power for ribonucleic acid interference (RNAi) phenotypes in Caenorhabditis elegans, a popular metazoan model in the study of developmental biology, neurobiology and genetics. Here, we present WormNet version 3 (v3), which is a new network-assisted hypothesis-generating server for C. elegans. WormNet v3 includes major updates to the base gene network, which substantially improved predictions of RNAi phenotypes. The server generates various gene network-based hypotheses using three complementary network methods: (i) a phenotype-centric approach to 'find new members for a pathway'; (ii) a gene-centric approach to 'infer functions from network neighbors' and (iii) a context-centric approach to 'find context-associated hub genes', which is a new method to identify key genes that mediate physiology within a specific context. For example, we demonstrated that the context-centric approach can be used to identify potential molecular targets of toxic chemicals. WormNet v3 is freely accessible at http://www.inetbio.org/wormnet.

The effect on incisional hernia of absorbable barbed suture for midline fascial closure in minimally invasive surgery for colorectal and gastric cancers: study protocol for a randomized controlled trial.

BACKGROUND: Incisional hernia following abdominal surgery is a frequent complication of midline laparotomy. This complication is strongly associated with the technique and material used for suture. While a monofilament absorbable suture is recommended to prevent incisional hernia, it can lead to suture loosening or surgical-knot breakage. Although barbed sutures can be an alternative suture material in abdominal fascial closure, evidence for its safety and effectiveness is lacking. Therefore, we designed a prospective randomized trial to evaluate the safety and efficacy of absorbable barbed sutures for midline fascia closure in minimally invasive surgery for colorectal and gastric cancers in comparison with conventional absorbable monofilament sutures. METHODS: A total of 312 patients who underwent minimally invasive surgery for colorectal and gastric cancers will be randomly allocated to either the absorbable barbed or monofilament suture group for abdominal fascia closure in a 1:1 ratio. The primary outcome is incisional hernia rate within 3 years after surgery, as verified by physical examination and computed tomography. Postoperative complications, including surgical site infection, postoperative pain, and quality of life, will be compared between two groups as secondary outcomes. The investigator will examine the patients until discharge and at 6, 12, 18, 24, and 36 months postoperatively. DISCUSSION: This is the first randomized controlled trial to compare absorbable barbed sutures with monofilament sutures for midline fascia closure in minimally invasive surgery. If absorbable barbed sutures demonstrate superior results to those of monofilament sutures, this type of suture material may be recommended as an alternative option for abdominal fascia closure. TRIAL REGISTRATION: KCT0007069. Registered on January 30, 2023.

Low-k SiOx/AlOx Nanolaminate Dielectric on Dielectric Achieved by Hybrid Pulsed Chemical Vapor Deposition.

Selective and smooth low-k SiOx/AlOx nanolaminate dielectric on dielectric (DOD) was achieved by a hybrid water-free pulsed CVD process consisting of 50 pulses of ATSB (tris(2-butoxy)aluminum) at 330 °C and a 60 s TBS (tris(tert-butoxy)silanol) exposure at 200 °C. Aniline selective passivation was demonstrated on W surfaces in preference to Si3N4 and SiO2 at 300 °C. At 200 °C, TBS pulsed CVD exhibited no growth on W or SiO2, but its growth was catalyzed by AlOx. Using a two-temperature pulsed CVD process, ∼2.7 nm selective SiOx/AlOx nanolaminate was deposited on Si3N4 in preference to aniline passivated W. Nanoselectivity was confirmed and demonstrated on nanoscale W/SiO2 patterned samples by TEM analysis. For a 1:1 Si:Al ratio, a dielectric constant (k) value of 3.3 was measured. For a 2:1 Si:Al ratio, a dielectric constant (k) value of 2.5 was measured. The k value well below that of Al2O3 and SiO2 is consistent with the formation of a low-density, low-k SiO2/Al2O3 nanolaminate in a purely thermal process. This is the first report of a further thermal CVD process for deposition of a low-k dielectric and the first report for a selective low-k process on the nanoscale.

Artificial intelligence-powered spatial analysis of tumor-infiltrating lymphocytes for prediction of prognosis in resected colon cancer.

Tumor-infiltrating lymphocytes (TIL) have been suggested as an important prognostic marker in colorectal cancer, but assessment usually requires additional tissue processing and interpretational efforts. The aim of this study is to assess the clinical significance of artificial intelligence (AI)-powered spatial TIL analysis using only a hematoxylin and eosin (H&E)-stained whole-slide image (WSI) for the prediction of prognosis in stage II-III colon cancer treated with surgery and adjuvant therapy. In this retrospective study, we used Lunit SCOPE IO, an AI-powered H&E WSI analyzer, to assess intratumoral TIL (iTIL) and tumor-related stromal TIL (sTIL) densities from WSIs of 289 patients. The patients with confirmed recurrences had significantly lower sTIL densities (mean sTIL density 630.2/mm2 in cases with confirmed recurrence vs. 1021.3/mm2 in no recurrence, p < 0.001). Additionally, significantly higher recurrence rates were observed in patients having sTIL or iTIL in the lower quartile groups. Risk groups defined as high-risk (both iTIL and sTIL in the lowest quartile groups), low-risk (sTIL higher than the median), or intermediate-risk (not high- or low-risk) were predictive of recurrence and were independently associated with clinical outcomes after adjusting for other clinical factors. AI-powered TIL analysis can provide prognostic information in stage II/III colon cancer in a practical manner.

Pharmacological Properties of Jaeumgeonbi-Tang on Redox System and Stress-Related Hormones in Chronic Subjective Dizziness: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial.

Jaeumgeonbi-Tang (JGT), a traditional herbal medicine, has been used to treat dizziness and vertigo in Korea and China for hundreds of years. The purpose of this study was to evaluate the pharmacological properties of JGT in chronic subjective dizziness (CSD) patients. A randomized, double-blind, parallel-group and placebo-controlled trial was performed with a total of 50 CSD patients. The patients were randomly assigned to one of two groups: JGT or placebo (n = 25 for each). All participants received the treatment (placebo or JGT, 24 g/day) for 4 weeks. We analyzed the serum levels of oxidative stressors, antioxidants, and stress hormones. Serum levels of lipid peroxidation, but not nitric oxide, were significantly decreased in the JGT group. JGT not only prevented the decline of serum total glutathione contents and total antioxidant capacity, but it also increased superoxide dismutase and catalase activities. Serum levels of stress hormones including cortisol, adrenaline, and serotonin were notably normalized by JGT treatment, but noradrenaline levels were not affected. Regarding the safety and tolerability of JGT, we found no allergic, adverse, or side effects in any of the participants. JGT showed beneficial effects on CSD patients by improving redox status and balancing psycho-emotional stress hormones.

Long-Term Survival Outcomes of Elderly Patients Treated With S-1 or Capecitabine Plus Oxaliplatin for Stage II or III Gastric Cancer: A Multicenter Cohort Study.

Purpose: Tegafur/gimeracil/oteracil (S-1) and capecitabine plus oxaliplatin (CAPOX) are standard adjuvant chemotherapies (ACs) administered after gastrectomy to patients with stage II or III gastric cancer. However, the efficacy of AC in elderly patients remains unclear. The objective of this retrospective multicenter cohort study was to compare the efficacies of S-1 and CAPOX AC in patients aged ≥70 years. Materials and Methods: Nine hundred eighty-three patients who were treated with AC using S-1 (768 patients) or CAPOX (215 patients) were enrolled in this study. Each patient underwent AC after curative gastrectomy for stage II or III gastric cancer at one of 27 hospitals in the Republic of Korea between January 2012 and December 2013. Relapse-free survival (RFS) and overall survival (OS) were analyzed according to AC regimen and age group. Results: Of the 983 patients, 254 (25.8%) were elderly. This group had a similar RFS (P=0.099) but significantly poorer OS (p=0.003) compared with the non-elderly group. Subgroup analysis of the non-elderly group revealed no AC-associated differences in survival. Subgroup analysis of the elderly group revealed significantly better survival in the S-1 group than in the CAPOX group (RFS, P<0.001; OS, P<0.001). Multivariate analysis revealed that the CAPOX regimen was an independent poor prognostic factor for RFS (hazard ratio [HR], 1.891; 95% confidence interval [CI], 1.072-3.333; P=0.028) and OS (HR, 2.970; 95% CI, 1.550-5.692; P=0.001). Conclusions: This multicenter observational cohort study found significant differences in RFS and OS between S-1 and CAPOX AC among patients with gastric cancer aged ≥70 years.

Chronologic trends of cancer-related lymph node research in PubMed: informetrics analysis.

PURPOSE: Given the long history of investigation into cancer and its relevance to the lymph node (LN), it would be meaningful to plot the trends of research on cancer-related LN. METHODS: Queries such as "cancer," "lymph node," and "cancer and lymph node" were submitted to PubMed to collect articles on cancer and LN published between 1945 and 2017. The collected articles were then extracted by an automatic web crawler and examined through informetrics and linguistic analysis. RESULTS: The number of articles related to cancer was 2,795,476 and 127,897 articles (4.6%) were found to be relevant to LN. With regard to cancer types, breast cancer was the most studied (37%), followed by gastric cancer (17%). With regard to the subjects in which the surgeon is interested, LN metastasis (57%) was found to be the topic most discussed, followed by LN dissection (22%) and sentinel LN (17%). Publications on LN metastasis gradually increased over time from 1988 to 2017 although those on sentinel LN and LN dissection have stagnated since the early 2000s. CONCLUSION: Although research on cancer was abundant, only a small portion was dedicated to investigating its relevance to LN. Western countries had led the research on cancer-related LN, but Asian countries began to participate as major players, expanding their contributions. While LN metastasis, one of the major cancer-related LN topics, showed a steady increase, those involved in oncologic surgery such as LN dissection and sentinel LN did not.

Gait Disturbance Improvement and Cerebral Cortex Rearrangement by Acupuncture in Parkinson's Disease: A Pilot Assessor-Blinded, Randomized, Controlled, Parallel-Group Trial.

BACKGROUND: Parkinson's disease (PD) leads to impaired mobility and limited independence. OBJECTIVE: We investigated the effects of acupuncture on gait disturbance and analyzed hemodynamic changes caused by acupuncture in the cerebral cortex of patients with PD. METHODS: Participants (n = 26) with gait disturbance due to PD were randomly assigned to the intervention (acupuncture twice a week for 4 weeks + conventional therapy) or control (conventional therapy) groups. We analyzed gait parameters using the GAITRite system and hemodynamic responses in the cerebral cortices using functional near-infrared spectroscopy, Unified Parkinson's Disease Rating Scale (UPDRS) scores, neurotransmitter levels, as well as the immediate effects of acupuncture in patients with PD. RESULTS: The participants tended to walk with hypometric gait (high cadence, short steps) overground. After acupuncture treatment, those in the intervention group showed a significant reduction in cadence and the UPDRS scores involving "walking and balance" compared with those in the control group (P = .004 and P = .020, respectively); the stride, swing, and single support times were significantly increased (P = .006, P = .001, and P = .001, respectively). Oxyhemoglobin levels in the intervention group while walking on a treadmill were significantly increased in the prefrontal and supplementary motor areas. The oxyhemoglobin levels in the prefrontal cortex and swing time revealed significant positive correlations. CONCLUSIONS: Our findings indicated that acupuncture tended to improve hypometric gait and rearranged activation of the cerebral cortex. Thus, acupuncture may be a useful complementary treatment for gait disturbance, including hypometric gait, in patients with PD. Trial Registration Number. Clinical Research Information Service (KCT0002603), https://cris.nih.go.kr/cris/index.jsp.

Adjustment of N stages of gastric cancer by the ratio between the metastatic and examined lymph nodes.

BACKGROUND: The present study attempted to determine whether N stage could be adjusted for the differences in survival rates based on the ratio between the examined and metastatic lymph nodes (LN ratio). METHODS: Five hundred and twenty-nine patients with both >15 lymph nodes examined and >or= N1 after R0 resection were enrolled in the present study. To determine the cutoff LN ratio, the ratios at each N stage were compared at intervals of 10% with the log-rank test of Kaplan-Meier estimates of the survival curves. RESULTS: The 5-year survival rate of patients with N1 was 71.7%. Those of N2 patients with LN ratio of <60% (n = 116) and >or=60% (n = 3) were 37.0% and 0%, respectively. Those of N3 patients with LN ratio of <30% (n = 32), between 30% and 60% (n = 67), and >or=60% (n = 26) were 31.0%, 16.3%, and 0%, respectively. Thus, adjusted N2 was obtained from the sum of N2 < 60% and N3 < 30%. N3 with an LN ratio between 30% and 60% was regarded as adjusted N3. N2 and N3 patients with an LN ratio of >or=60% were regarded as adjusted T4. The 5-year survival rate in patients with adjusted N2, N3, and N4 were 35.7%, 16.3%, and 0%, respectively. Multivariate analysis showed adjusted N stage and tumor depth were significant independent prognostic factors. CONCLUSIONS: The results of this study suggest that, since stage migration can be induced in the N staging system, such stage migration can be adjusted by the LN ratio based on the survival rate.

Prognostic factors for survival in patients with hepatic recurrence after curative resection of gastric cancer.

BACKGROUND: This study was done to evaluate the prognostic factors that may affect the survival of patients with recurrent hepatic metastasis after curative resection of gastric cancer. METHODS: We reviewed the medical records of 73 patients with recurrent hepatic metastasis after surgical treatment of gastric cancer from January 1995 to December 2005. Prognostic factors were classified into three groups: primary tumor factors, recurrent hepatic factors, and treatment factors. The prognostic values of these factors were assessed using univariate and multivariate analyses by the log-rank test in the Kaplan-Meier method and Cox's proportional hazard model. RESULTS: The overall median survival rate of the 73 study patients was 20.0 months [95% confidence interval (CI) 15.4-24.6 months]. The median survival rate after diagnosis of recurrent hepatic metastasis was 5 months (95% CI 3.5-6.5 months). Univariate analysis showed that the favorable prognostic factors were stage I and II among the primary tumor factors, no extrahepatic metastasis and unilobar distribution among the recurrent hepatic factors, and radiofrequency ablation (RFA) +/- chemotherapy among the treatment factors when operative treatment had been excluded. The independent favorable prognostic factors revealed by the multivariate analysis were no extrahepatic metastasis and RFA +/- chemotherapy. The median survival rate of patients who had two favorable prognostic factors was 27 months (95% CI 0-66.38 months). CONCLUSIONS: Improvement in the survival rate can be expected with RFA +/- chemotherapy for patients with recurrent gastric cancer in the liver without extrahepatic metastasis.

Clinical results after implantation of a spherical aberration-free intraocular lens: effect of contrast sensitivity and wavefront aberration--a clinical comparative study.

PURPOSE: To compare the clinical results of the spherical aberration-free Akreos AO (Bausch & Lomb) with the Akreos Adapt (Bausch & Lomb), the parent model of spherical optic design. METHODS: Fifty patients (100 eyes) were randomly assigned to bilaterally receive Akreos AO or Akreos Adapt intraocular lenses (IOLs) after phacoemulsification. At 6 months postoperatively, best-corrected contrast sensitivities were determined at 3, 4.8, 7.5, 12 and 19 cycles per degree using a Visual Capacity Analyzer (L2 Informatique) under mesopic (5 cd/m(2)) and photopic (100 cd/m(2)) conditions with undilated pupils. Wavefront analysis of total aberration was performed with the WaveScan WaveFront System (Advanced Medical Optics VISX). RESULTS: Postoperative contrast sensitivities were not statistically different under mesopic and photopic conditions. On the other hand, fourth-order spherical aberration was lower in the AO group than the Adapt group with only a marginal difference (p = 0.048). Other higher-order aberrations such as coma and trefoil were not significantly different between the two groups (p = 0.657, 0.614). The questionnaire on subjective visual quality in terms of glare disability, distant vision and night driving did not reveal an improved visual function in the AO group. CONCLUSION: The spherical aberration-free Akreos AO IOL did not show improved visual quality compared with its spherical counterpart.

Beta wave enhancement neurofeedback improves cognitive functions in patients with mild cognitive impairment: A preliminary pilot study.

BACKGROUND: Mild cognitive impairment (MCI) is a symptom characterizing cognitive decline and a transitional state between normal aging and dementia; however, there is no definitive diagnosis and treatment for MCI. Neurofeedback (NF), which is a training mechanism that employs operant conditioning to regulate brain activity, has been increasingly investigated concerning its beneficial effects for dementia and MCI. METHODS: This study investigated cognitive improvement and hemodynamic changes in the prefrontal cortex (PFC) following NF training in patients with MCI. Five patients with MCI received NF training for enhanced beta band activity in the dorsolateral PFC-16 sessions for 8 weeks-with each session divided into 9 5-minute trials. The primary outcome measure was a cognitive assessment tool: the Korean version of the Montreal Cognitive Assessment. The secondary outcome measures were the Central Nervous System Vital Signs for neurocognitive testing, hemodynamic changes using functional near-infrared spectroscopy in the PFC during a working-memory task, and Beck Depression Inventory scores. RESULTS: After completing the training, patients' cognitive function significantly improved in domains such as composite memory, cognitive flexibility, complex attention, reaction time, and executive function. Increased electroencephalogram beta power was observed over NF training sessions (Spearman rank correlation test: r = 0.746, P = .001). The threshold value for gaining positive feedback from pre-NF baseline on beta power significantly increased (Spearman rank correlation test: r = 0.805, P = .001). Hemodynamic response in PFC changed after NF training, and individual differences were identified. Specifically, hypoactivation of the hemodynamic response by emotional distraction recovered following NF training. CONCLUSION: We suggest that patients' cognitive processing efficiency was improved by the NF training. These beneficial results suggest that NF training may have potential therapeutic applications to prevent the progression from MCI to dementia. TRIAL REGISTRATION NUMBER: Clinical Research Information Service (KCT0003433).

Prognostic significance of intraoperative macroscopic serosal invasion finding when it shows a discrepancy in pathologic result gastric cancer.

PURPOSE: Depth of wall invasion is an important prognostic factor in patients with gastric cancer, whereas the prognostic significance of intraoperative macroscopic serosal invasion (mSE) findings remain unclear when they show a discrepancy in pathologic findings. This study, therefore, assessed the prognostic significance of mSE. METHODS: Data from cohort of 2,835 patients with resectable gastric cancer who underwent surgery between 1990 and 2010 were retrospectively reviewed. RESULTS: The overall accuracy of mSE and pathologic results was 83.4%. The accuracy of mSE was 75.5% in pT2. On the other hand, the accuracy of pT3 dropped to 24.5%. According to mSE findings (+/-), the 5-year disease-specific survival (DSS) rate differed significantly in patients with pT2 (+; 74.2% vs. -; 92.0%), pT3 (+; 76.7% vs. -; 91.8%) and pT4a (+; 51.3% vs. -; 72.8%) (P < 0.001 each), but not in patients with T1 tumor. Multivariate analysis showed that mSE findings (hazard ratio [HR], 2.275; 95% confidence interval [CI], 1.148-4.509), tumor depth (HR, 6.894; 95% CI, 2.325-20.437), nodal status (HR, 5.206; 95% CI, 2.298-11.791), distant metastasis (HR, 2.881; 95% CI, 1.388-6.209), radical resection (HR, 2.002; 95% CI, 1.017-3.940), and lymphatic invasion (HR, 2.713; 95% CI, 1.424-5.167) were independent predictors of 5-year DSS rate. CONCLUSION: We observed considerable discrepancies between macroscopic and pathologic diagnosis of serosal invasion. However, macroscopic diagnosis of serosal invasion was independently prognostic of 5-year DSS. It suggests that because the pathologic results could not be perfect and the local inflammatory change with mSE(+) could affect survival, a combination of mSE(+/-) and pathologic depth may be predictive of prognosis in patients with gastric cancer.

APIP, an ERBB3-binding partner, stimulates erbB2-3 heterodimer formation to promote tumorigenesis.

Despite the fact that the epidermal growth factor (EGF) family member ERBB3 (HER3) is deregulated in many cancers, the list of ERBB3-interacting partners remains limited. Here, we report that the Apaf-1-interacting protein (APIP) stimulates heregulin-ß1 (HRG-ß1)/ERBB3-driven cell proliferation and tumorigenesis. APIP levels are frequently increased in human gastric cancers and gastric cancer-derived cells. Cell proliferation and tumor formation are repressed by APIP downregulation and stimulated by its overexpression. APIP's role in the ERBB3 pathway is not associated with its functions within the methionine salvage pathway. In response to HRG-ß1, APIP binds to the ERBB3 receptor, leading to an enhanced binding of ERBB3 and ERBB2 that results in sustained activations of ERK1/2 and AKT protein kinases. Furthermore, HRG-ß1/ERBB3-dependent signaling is gained in APIP transgenic mouse embryonic fibroblasts (MEFs), but not lost in Apip-/- MEFs. Our findings offer compelling evidence that APIP plays an essential role in ERBB3 signaling as a positive regulator for tumorigenesis, warranting future development of therapeutic strategies for ERBB3-driven gastric cancer.

Intrathecal neostigmine reduces the zymosan-induced inflammatory response in a mouse air pouch model via adrenomedullary activity: involvement of spinal muscarinic type 2 receptors.

Intrathecal (IT) injection of neostigmine (a cholinesterase inhibitor) has been reported to produce a significant anti-nociceptive effect in a number of inflammatory pain models. However, a potential anti-inflammatory effect of IT neostigmine in these models has not been investigated. In the present study, we have examined the 'anti-inflammatory effect of IT injection of neostigmine' (AI-NEO) using a standard mouse air pouch model by evaluating the effect of AI-NEO on zymosan-induced leukocyte migration and myeloperoxidase (MPO) release. IT neostigmine was found to suppress both leukocyte migration and MPO degranulation in a dose dependent manner. We then established which subtypes of cholinergic receptors were involved in this AI-NEO. IT pretreatment with atropine (a muscarinic receptor antagonist) but not hexamethonium (a nicotinic receptor antagonist) completely blocked the IT neostigmine anti-inflammatory effect. Subsequent experiments showed that IT pretreatment with methoctramine (a muscarinic type 2 (M2) receptor antagonist), but not pirenzepine (M1 receptor antagonist) or 4-DAMP (M3 receptor antagonist), suppressed the AI-NEO. We then evaluated whether adrenal glandular activity was important in the AI-NEO. Adrenalectomy significantly blocked the AI-NEO, while intraperitoneal pretreatment with the beta-adrenoceptor antagonist (propranolol), but not the corticosteroid antagonist (RU486) reversed AI-NEO. In conclusion, these results indicate that IT neostigmine facilitates the activation of spinal M2 receptors and this activation ultimately leads to release of adrenal catecholamines which contribute to the anti-inflammatory effect observed at the site of tissue inflammation.

Pretreatment F-18 FDG PET/CT Parameters to Evaluate Progression-Free Survival in Gastric Cancer.

PURPOSE: We performed this study to evaluate the predictive value of pretreatment F-18 FDG PET/CT for progression-free survival (PFS) in patients with gastric cancer. METHODS: Of 321 patients with a diagnosis of gastric cancer, we retrospectively enrolled 97 patients (men:women = 61:36, age 59.8 ± 13.2 years), who underwent pretreatment F-18 fluoro-2-deoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) from January 2009 to December 2009. Maximum standardized uptake value (SUVmax) was measured for each case with detectable primary lesions. In the remaining non-detectable cases, SUVmax was measured from the corresponding site seen on gastroduodenoscopy for analysis. In subgroup analysis, metabolic tumor volume (MTV) was measured in 50 patients with clearly distinguishable primary lesions. SUVmax, stage, depth of tumor invasion and presence of lymph node metastasis were analyzed in terms of PFS. Receiver operating characteristic (ROC) curves were used to find optimal cutoff values of SUVmax and MTV for disease progression. The relationship between SUVmax, MTV and PFS was analyzed using the Kaplan-Meier with log-rank test and Cox's proportional hazard regression methods. RESULTS: Of 97 patients, 15 (15.5 %) had disease progression. The mean follow-up duration was 29.6 ± 10.2 months. The mean PFS of low SUVmax group (≤5.74) was significantly longer than that of the high SUVmax group (>5.74) (30.9 ± 8.0 vs 24.3 ± 13.6 months, p = 0.008). In univariate analysis, stage (I vs II, III, IV), depth of tumor invasion (T1 vs T2, T3, T4), presence of lymph node metastasis and SUVmax (>5.74 vs ≤5.74) were significantly associated with recurrence. In multivariate analysis, high SUVmax (>5.74) was the only poor prognostic factor for PFS (p = 0.002, HR 11.03, 95 % CI 2.48-49.05). Subgroup multivariate analysis revealed that high MTV (>16.42) was the only poor prognostic factor for PFS (p = 0.034, HR 3.59, 95 % CI 1.10-11.71). CONCLUSION: In gastric cancer, SUVmax measured by pretreatment F-18 FDG PET/CT has a significant predictive value for PFS. In addition, if MTV is measurable, high MTV is an independent factor for disease progression.