In this study, we engineered liposomal indocyanine green (ICG) to maximize its photothermal effects while maintaining the fluorescence intensity. Various liposomal formulations of ICG were prepared ...by varying the lipid composition and the molar ratio between total lipid and ICG, and their photothermal characteristics were evaluated under near-infrared irradiation. We showed that the ICG dispersity in the liposomal membrane and its physical interaction with phospholipids were the main factors determining the photothermal conversion efficiency. In phototherapeutic studies, the optimized formulation of liposomal ICG showed greater anticancer effects in a mouse tumor model compared with other liposomal formulations and the free form of ICG. Furthermore, we utilized liposomal ICG to visualize the metastatic lymph node around the primary tumor under fluorescence imaging guidance and ablate the lymph node with the enhanced photothermal effect, indicating the potential for selective treatment of metastatic lymph node.
Background
With improved short-term surgical outcomes, laparoscopic distal gastrectomy has rapidly gained popularity. However, the safety and feasibility of laparoscopic total gastrectomy (LTG) has ...not yet been proven due to the difficulty of the technique. This single-arm prospective multi-center study was conducted to evaluate the use of LTG for clinical stage I gastric cancer.
Methods
Between October 2012 and January 2014, 170 patients with pathologically proven, clinical stage I gastric adenocarcinoma located at the proximal stomach were enrolled. Twenty-two experienced surgeons from 19 institutions participated in this clinical trial. The primary end point was the incidence of postoperative morbidity and mortality at postoperative 30 days. The severity of postoperative complications was categorized according to Clavien–Dindo classification, and the incidence of postoperative morbidity and mortality was compared with that in a historical control.
Results
Of the enrolled patients, 160 met criteria for inclusion in the full analysis set. Postoperative morbidity and mortality rates reached 20.6% (33/160) and 0.6% (1/160), respectively. Fifteen patients (9.4%) had grade III or higher complications, and three reoperations (1.9%) were performed. The incidence of morbidity after LTG in this trial did not significantly differ from that reported in a previous study for open total gastrectomy (18%).
Conclusions
LTG performed by experienced surgeons showed acceptable postoperative morbidity and mortality for patients with clinical stage I gastric cancer.
Tumor-infiltrating lymphocytes (TILs) have been known for their strong prognostic and predictive significance in triple-negative breast cancer (TNBC). Several mechanisms for TIL influx in TNBC have ...been elucidated. Major histocompatibility complex class II (MHC-II) is an essential component of the adaptive immune system and is generally restricted to the surface of antigen-presenting cells. However, it has been reported that interferon-gamma signaling may induce MHC-II in almost all cell types, including those derived from cancer. We aimed to examine the relationship between MHC-II expression in tumor cells and the amount of TILs in 681 patients with TNBC. Further, the prognostic significance of MHC-II and the association of MHC-II with a couple of molecules involved in the interferon signaling pathway were investigated using immunohistochemical staining. Higher MHC-II expression in tumor cells was associated with the absence of lymphovascular invasion (p = 0.042); larger amounts of TILs (p < 0.001); frequent formations of tertiary lymphoid structures (p < 0.001); higher expression of myxovirus resistance gene A, one of the main mediators of the interferon signaling pathway (p < 0.001); and higher expression of double-stranded RNA-activated protein kinase, which can be induced by interferons (p = 0.008). Moreover, tumors that showed high MHC class I expression and any positivity for MHC-II had larger amounts of CD4- and CD8-positive T lymphocytes (p < 0.001). Positive MHC-II expression in tumor cells was associated with better disease-free survival in patients who had lymph node metastasis (p = 0.009). In conclusion, MHC-II expression in tumor cells was closely associated with an increase in TIL number and interferon signaling in TNBC. Further studies are warranted to improve our understanding regarding TIL influx, as well as patients' responses to immunotherapy.
•Psychometric function based on a normal distribution function.•Psychometric function based on a bivariate normal distribution function.•Psychometric function based on a non-central F-distribution ...function.•Four-interval oddity test is more powerful than the Triangle and Duo-trio tests.•Tables and R codes for data analysis using the four-interval oddity task.
The four-interval oddity task is an extension of the Triangle method, which is the three-interval oddity task and is one of the most broadly used conventional sensory discrimination methods. It is a special case of the m-interval oddity task or the m-alternative odd-man-out task where m = 4. It is also a special situation of the unspecified ‘M + N’ with M = 3 and N = 1. Some new forms of the analytical psychometric function for the four-interval oddity task based on a normal distribution function, a bivariate normal distribution function, and a non-central F-distribution function are provided originally in this paper. The performance of the four-interval oddity task in both difference testing and similarity/equivalence testing is explored and compared with some unspecified forced-choice sensory discrimination methods including the Triangle. Tables and R codes are presented and provided for estimations of the probability of correct response, Pc, Thurstonian discriminal distance δ or d´, and the B value for estimating the variance of d´ for the four-interval oddity task.
The generalization capability of unsupervised domain adaptation can mitigate the need for extensive pixel-level annotations to train semantic segmentation networks by training models on synthetic ...data as a source with computer-generated annotations. Entropy-based adversarial networks are proposed to improve source domain prediction; however, they disregard significant external information, such as edges, which have the potential to identify and distinguish various objects within an image accurately. To address this issue, we introduce a novel approach to domain adaptation, leveraging the synergy of internal and external information within entropy-based adversarial networks. In this approach, we enrich the discriminator network with edge-predicted probability values within this innovative framework to enhance the clarity of class boundaries. Furthermore, we devised a probability-sharing network that integrates diverse information for more effective segmentation. Incorporating object edges addresses a pivotal aspect of unsupervised domain adaptation that has frequently been neglected in the past—the precise delineation of object boundaries. Conventional unsupervised domain adaptation methods usually center around aligning feature distributions and may not explicitly model object boundaries. Our approach effectively bridges this gap by offering clear guidance on object boundaries, thereby elevating the quality of domain adaptation. Our approach undergoes rigorous evaluation on the established unsupervised domain adaptation benchmarks, specifically in adapting SYNTHIA → Cityscapes and SYNTHIA → Mapillary. Experimental results show that the proposed model attains better performance than state-of-the-art methods. The superior performance across different unsupervised domain adaptation scenarios highlights the versatility and robustness of the proposed method.
•Establishing dataset creation via edge extraction from segmentation maps.•Pioneering dual transmission of edge and depth-semantic probabilities.•Surpassing prior techniques in S2R benchmark dataset performance.
•The d′A expectation profile effectively quantified consumer-expected attributes.•The d′A expectation profile pinpointed key attributes for overall satisfaction.•Satisfaction drivers were identified ...from PLSR and LSA using product sensory tests.•The d′A expectation profile provided better optimization insights than PLSR or LSA.•Expected profile valence can be customized for target consumers.
Understanding consumer requirements with respect to the sensory attributes of food and the sentimental consequences is critical for enhancing consumer satisfaction and achieving market success. A recent innovation, the signal detection expectation profiling method, introduced by Lee, Kim, van Hout, and Lee (2021), utilizes the two-step rating-based ‘double-faced applicability (DFA)’ test to create expectation profiles for product attributes, quantified by d′A output measures. This study aimed to demonstrate and test the usage and efficacy of the d′A expectation profiling method to provide insight for product development. The efficiency of this approach for using a two-step rating-based DFA was examined first and the information guided by the d′A expectation profiling output measures was compared to satisfaction drivers identified through partial least square (PLS) regression and landscape segmentation analysis (LSA), commonly used to link consumer satisfaction/liking and sensory perception. Consumer expectations and satisfaction/sensory evaluations of six different mayonnaise products formed the dataset. Overall, the d′A expectation profiles effectively identified the key attributes significantly impacting overall satisfaction, aligning with the results of the PLS regression and LSA. The advantage of d′A expectation profiles lies in their quantitative representation of the degree of expected sensory attributes, extending beyond the scope of actual evaluated products and offering actionable insights for product optimization. Furthermore, by incorporating custom attributes (descriptor pairs) based on the hedonic valence of target consumers, the d′A expectation profile showcases the potential for effectively addressing consumer-relevant attributes tailored to specific target consumer groups.
•An analytical psychometric function for the dual reference duo-trio (DRDT).•Two forms of the analytical psychometric function for the DRDT.•Tables and R codes for Pc,d', and variance of d' (B value) ...based on the function.
The dual reference duo-trio (DRDT) is an improved balanced-reference duo-trio method, in which two same references are presented in a test but the reference is changed across the tests. The performance of the DRDT has been investigated theoretically based on a simulation-derived psychometric function in a previous paper published in this journal. The DRDT method is more powerful than the conventional duo-trio and the triangle methods. This paper derives an analytical psychometric function for the DRDT. Another form of the psychometric function for the DRDT is also derived based on the Torgerson’s method of triads. Tables and R codes are provided for presentations and calculations of Pc, δ (or d'), and variance of d' (B-value) based on the analytical psychometric function for the method.
Background
Understanding the natural progression of untreated gastric cancer is critical for determining the disease prognosis as well as treatment options and timing. The aim of this study is to ...analyze the natural history of gastric cancer.
Patients and Methods
We included patients with gastric cancer who had not received any treatment and were staged using endoscopy/endoscopic ultrasonography and computed tomography on at least two follow-up visits during intervals of nontreatment. Tumor volumes were also measured in addition to the staging. Survival of each stage at diagnosis was also analyzed.
Results
A total of 101 patients were included. The mean follow-up period was 35.1 ± 34.4 months. The gastric cancer doubling time was 11.8 months for
T
1 and 6.2 months for
T
4. The progression time from early gastric cancer to advanced gastric cancer was 34 months. It decreased as the stages advanced: from 34 months between tumor-nodes-metastasis stage I and II to 1.8 months between stage III and IV. No variable was identified as a risk factor for cancer progression. The 5-year survival rates of untreated patients were 46.2% in stage I and 0% in stage II, stage III, and stage IV.
Conclusions
The progression and doubling times of gastric cancer shorten as the stages advance. Objective data reported in this study can be a critical factor in determining treatment timing and screening interval.
Background
The comprehensive complication index (CCI) integrates all complications of the Clavien–Dindo classification (CDC) and offers a metric approach to measure morbidity. The aim of this study ...was to evaluate the CCI at a high-volume center for gastric cancer surgery and to compare the CCI to the conventional CDC.
Methods
Clinical factors were collected from the prospective complication data of gastric cancer patients who underwent radical gastrectomy at Seoul National University Hospital from 2013 to 2014. CDC and CCI were calculated, and risk factors were investigated. Correlations and generalized linear models of hospital stay were compared between the CCI and CDC. The complication monitoring model with cumulative sum control-CCI (CUSUM-CCI) was displayed for individual surgeons, for comparisons between surgeons, and for the institution.
Results
From 1660 patients, 583 complications in 424 patients (25.5%) were identified. The rate of CDC grade IIIa or greater was 9.7%, and the overall CCI was 5.8 ± 11.7. Age, gender, Charlson score, combined resection, open method, and total gastrectomy were associated with increased CCI (
p
< 0.05). The CCI demonstrated a stronger relationship with hospital stay (
ρ
= 0.721,
p
< 0.001) than did the CDC (
ρ
= 0.634,
p
< 0.001). For prolonged hospital stays (≥30 days), only the CCI showed a moderate correlation (
ρ
= 0.544,
p
= 0.024), although the CDC did not. The CUSUM-CCI model displayed dynamic time–event differences in individual and comparison monitoring models. In the institution monitoring model, a gradual decrease in the CCI was observed.
Conclusions
The CCI is more strongly correlated with postoperative hospital stay than is the conventional CDC. The CUSUM-CCI model can be used for the continuous monitoring of surgical quality.
Cannabidiol (CBD), one of the compounds present in the marijuana plant, has anti-tumor properties, but its mechanism is not well known. This study aimed to evaluate the apoptotic action of CBD in ...colorectal cancer (CRC) cells, and focused on its effects on the novel pro-apoptotic Noxa-reactive oxygen species (ROS) signaling pathway. CBD experiments were performed using the CRC cell lines HCT116 and DLD-1. CBD induced apoptosis by regulating many pro- and anti-apoptotic proteins, of which Noxa showed significantly higher expression. To understand the relationship between Noxa and CBD-induced apoptosis, Noxa levels were downregulated using siRNA, and the expression of apoptosis markers decreased. After ROS production was blocked, the level of Noxa also decreased, suggesting that ROS is involved in the regulation of Noxa, which along with ROS is a well-known pro-apoptotic signaling agents. As a result, CBD induced apoptosis in a Noxa-and-ROS-dependent manner. Taken together, the results obtained in this study re-demonstrated the effects of CBD treatment in vivo, thus confirming its role as a novel, reliable anticancer drug.
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•Our results strongly suggest, for the first time, that CBD can cause Noxa-induced cell death.•CBD induced apoptotic cell death via ROS/Endoplasmic Reticulum stress-regulated Noxa activation in colorectal cancer cells.•These results suggest that CBD has important implications for the potential treatment of human CRC.
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