Nutritional index in relation to prognosis of endometrial cancer.

Objective: Evaluate the prognostic value of the prognostic nutritional index (PNI) in patients with endometrial cancer (EC). Method: Laboratory and clinicopathological data from 370 patients who were diagnosed with EC between January 2010 and December 2021 were reviewed. The PNI was analyzed for correlations with recurrence and survival. The receiver operating characteristic curves were generated for the PNI. Optimal cut-off values were determined as the points at which the Youden index (sensitivity + specificity - 1) was maximal. Based on the results of the ROC curve analysis, the patients were grouped into high and low PNI groups. Differences in the clinicopathological characteristics between patients with high and low PNI were compared between the two groups. The effects of the prognostic factors were analyzed using univariate and multivariate Cox proportional hazards model. Results: The optimal cutoff value of the PNI was 52.74 for DFS (area under the curve: 0.817; 95% CI: 0.738-0.858, p <0.001). Significantly more patients in the low PNI group experienced recurrence (30.6% vs. 5.2%, p <0.001) and cancer-related death (17.8% vs. 2.8%, p <0.001). In multivariate analysis, PNI were independent prognostic factors for both DFS and overall survival OS. Conclusion: Low PNI was significantly associated with worse clinical outcomes in patients with EC. Our findings demonstrate that the PNI may be clinically reliable and useful as a prognostic marker for patients with EC. Further large-scale prospective studies are needed to confirm our findings.

Is there a relationship between surgical proficiency and oncologic outcome of minimally invasive radical hysterectomy for early-stage cervical cancer?

Objective: Investigate the relationship between surgical proficiency and oncological outcomes of minimally invasive surgery (MIS) in the treatment of early-stage cervical cancer. Methods: This retrospective study included patients with cervical cancer stage IB1, IB2 who were treated with minimally invasive radical hysterectomy from January 2010 to Dec 2020. Patients were divided into two groups based on the year of surgery: phase 1 (from January 2010 to December 2015) and phase 2 (from January 2016 to December 2020). Oncologic outcomes were compared between the groups. Results: In total, 142 patients were included in the final analysis. 73 and 69 patients underwent surgery in phase 1 (51.4%) and phase 2 (48.6%), respectively. Twelve recurrences (12/142, 8.5%) were observed in the entire cohort: ten (13.7%) in phase 1 and two (2.9%) in phase 2. The recurrence rate was significantly higher in phase 1 (p = 0.021). And the phase 1 group showed significantly shorter disease-free survival than the phase 2 group (p = 0.049). In the multivariate analysis, surgical proficiency, represented by the phase of operation, was the only significant predictor of disease-free survival (HR = 0.244, p = 0.042). Conclusions: Surgical proficiency in MIS is a significant factor associated with the outcomes in early-stage cervical cancer. More favorable outcomes can be obtained after operating on a certain number of MIS cases.

Improved multi-echo gradient echo myelin water fraction mapping using complex-valued neural network analysis.

PURPOSE: Previously, an artificial neural network method was introduced to estimate quantitative myelin water fraction (MWF) using multi-echo gradient-echo data. However, the fiber orientation of white matter with respect to B0 could bias the quantification of MWF. Here, we developed an advanced workflow for MWF estimation that could improve the quantification of MWF. METHODS: To adopt fiber orientation effects, a complex-valued neural network with complex-valued operation was used. In addition, to compensate for the bias from different scan parameters, a signal model incorporating the T1 value was devised for training data generation. At the testing stage, a voxel-spread function approach was utilized for spatial B0 artifact correction. Finally, dropout-based variational inference was implemented for uncertainty estimates on the network model to provide a confidence interpretation of the output. RESULTS: According to simulation and in vivo analysis, the proposed method suggests improved quality of MWF estimation by correcting the bias and artifacts. The proposed complex-valued neural network approach can alleviate the dependency of fiber orientation effects compared to previous artificial neural network method. Uncertainty estimates provides information different from fitting error that can be used as a confidence level of the resulting MWF values. CONCLUSION: An improved MWF mapping using complex-valued neural network analysis has been proposed.

Triphenylphosphonium conjugation to a TRAP1 inhibitor, 2-amino-6-chloro-7,9-dihydro-8H-purin-8-one increases antiproliferative activity.

Tumor-necrosis-factor-receptor associated protein 1 (TRAP1), a mitochondrial paralog of heat shock protein 90 family proteins, is overexpressed in many cancer cells and supports tumorigenesis by rewiring vital metabolic and cell death pathways. The triphenylphosphonium moiety is used to deliver therapeutic cargo to increase drug uptake into mitochondria. Various aryl- or alkyl-substituted phosphonium analogs were conjugated with TRAP1-selective inhibitors 4a-c to optimize anticancer activity. Among these various phosphonium-conjugated compounds, (6-(2-amino-9-(4-bromo-2-fluorobenzyl)-6-chloro-8-oxo-8,9-dihydro-7H-purin-7-yl)hexyl)triphenylphosphornium (6a) was identified as a potential anticancer agent. Compound 6a had IC50 values of 0.30-3.24 µM in seven different cancer cell lines and potently suppressed tumor growth without any noticeable in vivo toxicity in a nude mouse model xenografted with PC3 prostate cancer cells.

Development of pyrazolo[3,4-d]pyrimidine-6-amine-based TRAP1 inhibitors that demonstrate in vivo anticancer activity in mouse xenograft models.

TNF Receptor Associated Protein 1 (TRAP1) is a mitochondrial paralog of Hsp90 related to the promotion of tumorigenesis in various cancers via maintaining mitochondrial integrity, reducing the production of reactive oxygen species, and reprogramming cellular metabolism. Consequently, Hsp90 and TRAP1 have been targeted to develop cancer therapeutics. Herein, we report a series of pyrazolo[3,4-d]pyrimidine derivatives that are mitochondria-permeable TRAP1 inhibitors. Structure-based drug design guided the optimization of potency, leading to the identification of compounds 47 and 48 as potent TRAP1 and Hsp90 inhibitors with good metabolic and plasma stability as well as acceptable CYP and hERG inhibition. X-ray co-crystallization studies confirmed both 47 and 48 interact with the ATP binding pocket in the TRAP1 protein. Compounds 47 and 48 demonstrated excellent anticancer efficiency in various cancer cells, with limited toxicity over normal hepatocyte and prostate cells. Mouse PC3 xenograft studies showed 47 and 48 significantly reduced tumor growth.

Resilience and Overcoming Experiences of Coronavirus Disease 2019 Patients Hospitalized in a Single-Room Isolation Ward: A Mixed-Methods Study.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has caused patients to suffer from various physical and psychological symptoms and social challenges, but the impact was harder for those COVID-19 patients receiving treatment in single-room isolation wards in South Korea. This study aimed to investigate resilience, anxiety, depression, and sleep quality of those patients and the relationships between those variables, and explore the patients' experience of resilience during the COVID-19 treatment in single-room isolation wards. METHODS: This study employed a mixed-methods approach, collecting quantitative data through surveys and qualitative data through semistructured interviews conducted between May and October 2022. Quantitative surveys encompassing disease-specific and demographic information, visual analog scales to assess anxiety, depression, and sleep quality, and the Connor-Davidson resilience scale were administered to patients (N = 153). Qualitative thematic analyses were conducted following interviews with a subset of patients (N = 13) belonging to the high-resilience group. RESULTS: Resilience exhibited a negative correlation with anxiety and depression, while showing a positive correlation with sleep quality. Factors affecting resilience include having a spouse, educational attainment, and depression. The qualitative thematic analysis results were categorized into: (1) facing the reality of being isolated in a room; (2) struggling to accept and adapt to isolation; and (3) seeking connections in isolation. CONCLUSIONS: This research sheds light on the challenges faced by individuals in isolation and underscores the crucial role of resilience in overcoming such challenges. The resilience observed in these patients is grounded in both interpersonal and profound spiritual connections. These findings underscore the necessity for nurses to develop customized strategies to alleviate the impacts of social isolation.

Quantification of the Carbon-Coating Effect on the Interfacial Behavior of Graphite Single Particles.

The effect of carbon coating on the interfacial charge transfer resistance of natural graphite (NG) was investigated by a single-particle measurement. The microscale carbon-coated natural graphite (NG@C) particles were synthesized by the simple wet-chemical mixing method using a phenolic resin as the carbon source. The electrochemical test results of NG@C using the conventional composite electrodes demonstrated desirable rate capability, cycle stability, and enhanced kinetic property. Moreover, the improvements in the composite electrodes were confirmed with the electrochemical parameters (i.e., charge transfer resistance, exchange current density, and solid phase diffusion coefficient) analyzed by a single-particle measurement. The surface carbon coating on the NG particles reduced the interfacial charge transfer resistance (Rct) and increased the exchange current density (i0). The Rct decreased from 81-101 (NG) to 49-67 Ω cm2 (NG@C), while i0 increased from 0.25-0.32 (NG) to 0.38-0.52 mA cm-2 (NG@C) after the coating process. The results suggested both electrochemically and quantitatively that the outer uniformly coated surface carbon layer on the graphite particles can improve the solid-liquid interface and other kinetic parameters, therefore enhancing the rate capabilities to obtain the high-power anode materials.

Predicting the eyebrow from the orbit using three-dimensional CT imaging in the application of forensic facial reconstruction and identification.

Eyebrows are the most important facial feature in facial recognition with its shape rated to be more helpful than color or density for facial reconstruction or approximation. However, little extant research has estimated the position and morphological territory of the eyebrow from the orbit. Three-dimensional craniofacial models, produced from CT scans of 180 Koreans autopsied at the National Forensic Service Seoul Institute, were used to conduct metric analyses of subjects (125 males and 55 females) between 19 and 49 (mean 35.1) years. We employed 18 craniofacial landmarks to examine the morphometry of the eyebrow and orbit with 35 pairs of distances per subject measured between landmark and reference planes. Additionally, we used linear regression analyses to predict eyebrow shape from the orbit for every possible combination of variables. The morphology of the orbit has more influence on the position of the superior margin of the eyebrow. In addition, the middle part of the eyebrow was more predictable. The highest point of the eyebrow in female was located more medially than the male. Based on our findings, the equations for estimating the position of the eyebrow from the shape of the orbit is useful information for face reconstruction or approximation.

Palladium-Catalyzed α-Arylation of Cyclic ß-Dicarbonyl Compounds for the Synthesis of CaV1.3 Inhibitors.

Cyclic α-aryl ß-dicarbonyl derivatives are important scaffolds in medicinal chemistry. Palladium-catalyzed coupling reactions of haloarenes were conducted with diverse five- to seven-membered cyclic ß-dicarbonyl derivatives including barbiturate, pyrazolidine-3,5-dione, and 1,4-diazepane-5,7-dione. The coupling reactions of various para- or meta-substituted aryl halides occurred efficiently when Pd(t-Bu3P)2, Xphos, and Cs2CO3 were used under 1,4-dioxane reflux conditions. Although the couplings of ortho-substituted aryl halides with pyrazolidine-3,5-dione and 1,4-diazepane-5,7-dione were moderate, the coupling with barbiturate was limited. Using the optimized reaction conditions, we synthesized several 5-aryl barbiturates as new scaffolds of CaV1.3 Ca2+ channel inhibitors. Among the synthesized molecules, 14e was the most potent CaV1.3 inhibitor with an IC50 of 1.42 µM.

Craniofacial anthropometric investigation of relationships between the nose and nasal aperture using 3D computed tomography of Korean subjects.

This study investigated the relationships of morphology and locations of the nose and nasal aperture by using major craniofacial landmarks on the human skull and face for craniofacial reconstruction/approximation of Koreans. In the frontal view, the positions of bony landmarks on the skull, including the nasal aperture, were correlated with the positions of nasal landmarks vertical to the transverse plane. In profile, the positions of bony landmarks on the skull were correlated with the positions of nasal landmarks horizontal to the coronal plane. Overall, 26 of the 76 measurements demonstrated significant correlations between the corresponding landmarks on the nose and nasal aperture. Simple regression equations were produced from the results. This study showed that the nose and nasal aperture are significantly related to each other in terms of their morphology and location in Koreans. The prediction guidelines, produced as regression formulas, can be applied to craniofacial reconstruction/approximation and bio-anthropological research of Korean skulls. The study results can also be used clinically in rhinoplasty and nasal reconstruction surgery.