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Background: To use the apparent diffusion coefficient (ADC) as reliable biomarkers, validation of MRI equipment performance and clinical acquisition protocols should be performed prior to application in patients. This study aims to validate various MRI equipment and clinical brain protocols for diffusion weighted imaging (DWI) using commercial phantom, and confirm the validated protocols in patients' images. Methods: The performance of four different scanners and clinical brain protocols were validated using a Quantitative Imaging Biomarker Alliance (QIBA) diffusion phantom and cloud-based analysis tool. We evaluated the performance metrics regarding accuracy and repeatability of ADC measurement using QIBA profile. The validated clinical brain protocols were applied to 17 patients, and image quality and repeatability of ADC were assessed. Results: The MRI equipment performance of all four MRI scanners demonstrated high accuracy in ADC measurement (ADC bias, −2.3% to −0.4%), excellent linear correlation to the reference ADC value (slope, 0.9 to 1.0; R2, 0.999–1.000), and high short-term repeatability [within-subject-coefficient-of-variation (wCV), 0% to 0.3%]. The clinical protocols were also validated by fulfilling QIBA claims with high accuracy (ADC bias, −3.1% to −0.7%) and robust repeatability (wCV, 0% to 0.1%). Brain DWI acquired using the validated clinical protocols showed ideal image quality (mean score ≥ 2.9) and good repeatability (wCV, 1.8–2.2). Conclusions: The whole process of standardization of DWI demonstrated the robustness of ADC with high accuracy and repeatability across diverse MRI equipment and clinical protocols in accordance with the QIBA claims. [ABSTRACT FROM AUTHOR]

Chemical exchange saturation transfer with glutamate (GluCEST) imaging is a novel technique for the non-invasive detection and quantification of cerebral Glu levels in neuromolecular processes. Here we used GluCEST imaging and 1H magnetic resonance spectroscopy (1H MRS) to assess in vivo changes in Glu signals within the hippocampus in a rat model of depression induced by a forced swim test. The forced swimming test (FST) group exhibited markedly reduced GluCEST-weighted levels and Glu concentrations when examined using 1H MRS in the hippocampal region compared to the control group (GluCEST-weighted levels: 3.67 ± 0.81% vs. 5.02 ± 0.44%, p < 0.001; and Glu concentrations: 6.560 ± 0.292 μmol/g vs. 7.133 ± 0.397 μmol/g, p = 0.001). Our results indicate that GluCEST imaging is a distinctive approach to detecting and monitoring Glu levels in a rat model of depression. Furthermore, the application of GluCEST imaging may provide a deeper insight into the neurochemical involvement of glutamate in various psychiatric disorders. [ABSTRACT FROM AUTHOR]

We propose a self-supervised machine learning (ML) algorithm for sequence-type classification of brain MRI using a supervisory signal from DICOM metadata (i.e., a rule-based virtual label). A total of 1787 brain MRI datasets were constructed, including 1531 from hospitals and 256 from multi-center trial datasets. The ground truth (GT) was generated by two experienced image analysts and checked by a radiologist. An ML framework called ImageSort-net was developed using various features related to MRI acquisition parameters and used for training virtual labels and ML algorithms derived from rule-based labeling systems that act as labels for supervised learning. For the performance evaluation of ImageSort-net (MLvirtual), we compare and analyze the performances of models trained with human expert labels (MLhumans), using as a test set blank data that the rule-based labeling system failed to infer from each dataset. The performance of ImageSort-net (MLvirtual) was comparable to that of MLhuman (98.5% and 99%, respectively) in terms of overall accuracy when trained with hospital datasets. When trained with a relatively small multi-center trial dataset, the overall accuracy was relatively lower than that of MLhuman (95.6% and 99.4%, respectively). After integrating the two datasets and re-training them, MLvirtual showed higher accuracy than MLvirtual trained only on multi-center datasets (95.6% and 99.7%, respectively). Additionally, the multi-center dataset inference performances after the re-training of MLvirtual and MLhumans were identical (99.7%). Training of ML algorithms based on rule-based virtual labels achieved high accuracy for sequence-type classification of brain MRI and enabled us to build a sustainable self-learning system. [ABSTRACT FROM AUTHOR]

Featured Application: New sanitary treatment using ethyl formate fumigation on importing/exporting agricultural machinery as an alternative to methyl bromide. With an increase in the international trade of agricultural and non-agricultural products, there is an increase in the possibility of introducing hitchhiking insect pests such as Halyomorpha halys, which has been detected on imported vehicles and agricultural machinery. Although methyl bromide (MB) is provisionally used to control invasive pests, it is classified as a restricted chemical owing to its potential to deplete the ozone layer and pose health risks to humans in cases of inadequate ventilation, as well as concerns regarding consumer safety. Therefore, this study investigated ethyl formate's (EF's) efficacy against H. halys and its efficacy and sorption, as an alternative to MB, on main electronic components, including alternators, ignition coils, and motors. Fumigation with 35 and 70 g/m3 EF for 4 h at 15 °C had no damage on the main electronic components as evaluated using various operation tests. In a commercial trial, H. halys infestation was effectively controlled with 35 g/m3 EF fumigated for 4 h at 23 °C using a 30 m3 polyvinyl chloride tarpaulin fumigation chamber. After ventilation, the EF concentration decreased below the safety level within 10 min and reached the zero level within 40 min for worker safety. This novel sanitary treatment using EF fumigation on imported agricultural machinery could be an effective method without causing mechanical damage. [ABSTRACT FROM AUTHOR]

Target identification is a crucial process in drug development, aiming to identify key proteins, genes, and signal pathways involved in disease progression and their relevance in potential therapeutic interventions. While C-C chemokine receptor 8 (CCR8) has been investigated as a candidate anti-cancer target, comprehensive multi-omics analyzes across various indications are limited. In this study, we conducted an extensive bioinformatics analysis integrating genomics, proteomics, and transcriptomics data to establish CCR8 as a promising anti-cancer drug target. Our approach encompassed data collection from diverse knowledge resources, gene function analysis, differential gene expression profiling, immune cell infiltration assessment, and strategic prioritization of target indications. Our findings revealed strong correlations between CCR8 and specific cancers, notably Breast Invasive Carcinoma (BRCA), Colon Adenocarcinoma (COAD), Head and Neck Squamous Cell Carcinoma (HNSC), Rectum adenocarcinoma (READ), Stomach adenocarcinoma (STAD), and Thyroid carcinoma (THCA). This research advances our understanding of CCR8 as a potential target for anti-cancer drug development, bridging the gap between molecular insights and creating opportunities for personalized treatment of solid tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: Recognized as a promising target for anti-cancer treatment, PGF has the potential to overcome resistance to existing angiogenesis inhibitors. In this study, we aimed to identify target indications for PGF across various cancer types using bioinformatics analysis. We analyzed PGF gene function, molecular pathways, protein interactions, gene expression, mutations, survival prognosis, and tumor immune infiltration associated with PGF. The identified target diseases for PGF inhibitors included adrenocortical carcinoma, kidney cancers, liver hepatocellular carcinoma, stomach adenocarcinoma, and uveal melanoma. These findings highlight the potential of targeting PGF as a therapeutic strategy in these specific cancer types. The expression of the placental growth factor (PGF) in cancer cells and the tumor microenvironment can contribute to the induction of angiogenesis, supporting cancer cell metabolism by ensuring an adequate blood supply. Angiogenesis is a key component of cancer metabolism as it facilitates the delivery of nutrients and oxygen to rapidly growing tumor cells. PGF is recognized as a novel target for anti-cancer treatment due to its ability to overcome resistance to existing angiogenesis inhibitors and its impact on the tumor microenvironment. We aimed to integrate bioinformatics evidence using various data sources and analytic tools for target-indication identification of the PGF target and prioritize the indication across various cancer types as an initial step of drug development. The data analysis included PGF gene function, molecular pathway, protein interaction, gene expression and mutation across cancer type, survival prognosis and tumor immune infiltration association with PGF. The overall evaluation was conducted given the totality of evidence, to target the PGF gene to treat the cancer where the PGF level was highly expressed in a certain tumor type with poor survival prognosis as well as possibly associated with poor tumor infiltration level. PGF showed a significant impact on overall survival in several cancers through univariate or multivariate survival analysis. The cancers considered as target diseases for PGF inhibitors, due to their potential effects on PGF, are adrenocortical carcinoma, kidney cancers, liver hepatocellular carcinoma, stomach adenocarcinoma, and uveal melanoma. [ABSTRACT FROM AUTHOR]

Glutamate-weighted chemical exchange saturation transfer (GluCEST) is a useful imaging tool to detect glutamate signal alterations caused by neuroinflammation. This study aimed to visualize and quantitatively evaluate hippocampal glutamate alterations in a rat model of sepsis-induced brain injury using GluCEST and proton magnetic resonance spectroscopy (1H-MRS). Twenty-one Sprague Dawley rats were divided into three groups (sepsis-induced groups (SEP05, n = 7 and SEP10, n = 7) and controls (n = 7)). Sepsis was induced through a single intraperitoneal injection of lipopolysaccharide (LPS) at a dose of 5 mg/kg (SEP05) or 10 mg/kg (SEP10). GluCEST values and 1H-MRS concentrations in the hippocampal region were quantified using conventional magnetization transfer ratio asymmetry and a water scaling method, respectively. In addition, we examined immunohistochemical and immunofluorescence staining to observe the immune response and activity in the hippocampal region after LPS exposure. The GluCEST and 1H-MRS results showed that GluCEST values and glutamate concentrations were significantly higher in sepsis-induced rats than those in controls as the LPS dose increased. GluCEST imaging may be a helpful technique for defining biomarkers to estimate glutamate-related metabolism in sepsis-associated diseases. [ABSTRACT FROM AUTHOR]

This study proposes a markerless Augmented Reality (AR) surgical framework for breast lesion removal using a depth sensor and 3D breast Computed Tomography (CT) images. A patient mesh in the real coordinate system is acquired through a patient 3D scan using a depth sensor for registration. The patient mesh on the virtual coordinate system is obtained by contrast-based skin segmentation in 3D mesh generated from breast CT scans. Then, the nipple area is detected based on the gradient in the segmented skin area. The region of interest (ROI) is set based on the detection result to select the vertices in the virtual coordinate system. The mesh on the real and virtual coordinate systems is first aligned by matching the center of mass, and the Iterative Closest Point (ICP) method is applied to perform more precise registration. Experimental results of 20 patients' data showed 98.35 ± 0.71% skin segmentation accuracy in terms of Dice Similarity Coefficient (DSC) value, 2.79 ± 1.54 mm nipple detection error, and 4.69 ± 1.95 mm registration error. Experiments using phantom and patient data also confirmed high accuracy in AR visualization. The proposed method in this study showed that the 3D AR visualization of medical data on the patient's body is possible by using a single depth sensor without having to use markers. [ABSTRACT FROM AUTHOR]

The properties of porous and lightweight ceramic foam that can be cured at room temperature using metakaolin-based geopolymers were studied. A geopolymer slurry was prepared using metakaolin and a potassium-based alkaline medium at room temperature, and the obtained viscous paste was expanded via gaseous methods, by means of the decomposition of peroxide at room temperature. Therefore, geopolymer (GP) foam developed in this study through multivariate geopolymer, foaming agents, and surfactants can be cured at room temperature (within 5 days) without a separate heat treatment process. The homogeneous micropores were obtained through the stabilization of the interface between geopolymer slurry and oxygen gas bubbles generated through the base-catalyzed decomposition of hydrogen peroxide. The porosity was confirmed to be 29% and 54% before and after using sodium dodecyl sulfate (SDS). The compressive strengths and densities were 1.57 MPa and 0.75 g/cm3 for GP foam without SDS, and 3.63 MPa and 0.48 g/cm3 for GP foam with SDS. Through the mercury intrusion porosimetry analysis, the pores were further refined from 100 µm to 30 µm when SDS was used, and at the same time, the variation of pore size was minimized, so that a relatively uniform pore size was maintained. In addition, the thermal conductivity is 0.0803 W/m·K and the pore size is 33.2 μ m , which is smaller in pore diameter than the geopolymer containing only hydrogen peroxide. As a result, although the hydrogen peroxide alone sample has excellent thermal conductivity, the use of a surfactant is recommended for fine micropore size control. While reducing the non-uniform distribution of pores and the size of micropores generated through the direct foaming method as an inorganic binder, the possibility of an insulation finish was also confirmed by reducing the weight. [ABSTRACT FROM AUTHOR]

Exotic ants and termites, including Solenopsis invicta, are frequent hitchhikers intercepted from miscellaneous nonfood commodities. In particular, S. invicta has been intercepted in Korea in imported nursery plants, stone, and lumber products, which increases the potential for establishment of this destructive invasive pest in Korea. In this study, we conducted commercial-scale fumigation trials to evaluate ethyl formate (EF) as a potential alternative of methyl bromide using two species of imported rubber plants and pieces of marble as representative good and workers of Reticulitermes speratus as an EF-resistant surrogate for S. invicta. An EF treatment at 35 g/m3 for 4 h at >15 °C, the dose required for LCt99% (lethal concentration × time product required for 99% mortality of R. speratus), resulted in the complete control of R. speratus workers tested with rubber plants (Ficus benghalensis and F. retusa) and marble, 9% (w/v) and 60% (v/v) loading ratios, respectively. EF treatment did not adversely affect the leaf chlorophyll content, leaf color, and overall health of rubber plants or the visual appearance of the marble. Our results suggest that EF fumigation is a potential alternative to methyl bromide for the disinfestation of hitchhiking invasive termites and ants, including S. invicta, on imported rubber plants and stone products. [ABSTRACT FROM AUTHOR]

The impact of myosteatosis on septic patients has not been fully revealed. The aim of the study was to evaluate the impact of the myosteatosis area and percentage on the 28-day mortality in patients with septic shock. We conducted a single center, retrospective study from a prospectively collected registry of adult patients with septic shock who presented to the emergency department and performed abdominal computed tomography (CT) from May 2016 to May 2020. The myosteatosis area defined as the sum of low attenuation muscle area and intramuscular adipose tissue at the level of the third lumbar vertebra was measured by CT. Myosteatosis percentages were calculated by dividing the myosteatosis area by the total abdominal muscle area. Of the 896 patients, 28-day mortality was 16.3%, and the abnormal myosteatosis area was commonly detected (81.7%). Among variables of body compositions, non-survivors had relatively lower normal attenuation muscle area, higher low attenuation muscle area, and higher myosteatosis area and percentage than that of survivors. Trends of myosteatosis according to age group were different between the male and female groups. In subgroup analysis with male patients, the multivariate model showed that the myosteatosis percentage (adjusted OR 1.02 [95% CI 1.01–1.03]) was an independent risk factor for 28-day mortality. However, this association was not evident in the female group. Myosteatosis was common and high myosteatosis percentage was associated with short-term mortality in patients with septic shock. Our results implied that abnormal fatty disposition in muscle could impact on increased mortality, and this effect was more prominent in male patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Pheochromocytoma is regarded as a good human model for investigating the impact of sympathetic hyperactivity on various pathologic conditions. To determine the influence of catecholamine excess on human body composition, we compared computed tomography (CT)-based fat and skeletal muscle indices over time in a large patient population with histologically confirmed pheochromocytoma who underwent surgery. We observed considerable elevation in CT-measured visceral fat area and subcutaneous fat area, and the prevalence of visceral obesity after adrenalectomy in patients with pheochromocytoma. In contrast, there were no changes in skeletal muscle area, skeletal muscle index, and prevalence of sarcopenia. Furthermore, we observed that the severity of catecholamine excess was associated with a higher increase, especially in the subcutaneous fat area after surgery. These data provide important clinical evidence that sympathetic hyperactivity contributes to lipolysis in visceral and subcutaneous adipose tissues, whereas its impact on human skeletal muscle remains undetermined. Despite the potential biological importance of the sympathetic nervous system on fat and skeletal muscle metabolism in animal and in vitro studies, its relevance in humans remains undetermined. To clarify the influence of catecholamine excess on human body composition, we performed a retrospective longitudinal cohort study including 313 consecutive patients with histologically confirmed pheochromocytoma who underwent repeat abdominal computed tomography (CT) scans before and after adrenalectomy. Changes in CT-determined visceral fat area (VFA), subcutaneous fat area (SFA), skeletal muscle area (SMA), and skeletal muscle index (SMI) were measured at the level of the third lumbar vertebra. The mean age of all patients was 50.6 ± 13.6 years, and 171/313 (54.6%) were women. The median follow-up duration for repeat CTs was 25.0 months. VFA and SFA were 14.5% and 15.8% higher, respectively (both p < 0.001), after adrenalectomy, whereas SMA and SMI remained unchanged. Similarly, patients with visceral obesity significantly increased from 103 (32.9%) at baseline to 138 (44.1%) following surgery (p < 0.001); however, the prevalence of sarcopenia was unchanged. This study provides important clinical evidence that sympathetic hyperactivity can contribute to lipolysis in visceral and subcutaneous adipose tissues, but its impact on human skeletal muscle is unclear. [ABSTRACT FROM AUTHOR]

The objective of this study is to develop a mortality prediction model for patients undergoing gastric cancer surgery based on body morphometry, nutritional, and surgical information. Using a prospectively built gastric surgery registry from the Asan Medical Center (AMC), 621 gastric cancer patients, who were treated with surgery with no recurrence of cancer, were selected for the development of the prediction model. Input features (i.e., body morphometry, nutritional, surgical, and clinicopathologic information) were selected in the collected data based on the XGBoost analysis results and experts' opinions. A convolutional neural network (CNN) framework was developed to predict the mortality of patients undergoing gastric cancer surgery. Internal validation was performed in split datasets of the AMC, whereas external validation was performed in patients in the Ajou University Hospital. Fifteen features were selected for the prediction of survival probability based on the XGBoost analysis results and experts' suggestions. Accuracy, F1 score, and area under the curve of our CNN model were 0.900, 0.909, and 0.900 in the internal validation set and 0.879, 0.882, and 0.881 in the external validation set, respectively. Our developed CNN model was published on a website where anyone could predict mortality using individual patients' data. Our CNN model provides substantially good performance in predicting mortality in patients undergoing surgery for gastric cancer, mainly based on body morphometry, nutritional, and surgical information. Using the web application, clinicians and gastric cancer patients will be able to efficiently manage mortality risk factors. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the feasibility of a newly developed anticancer drug-releasing radiofrequency ablation (RFA) system in a porcine liver model. A 15-gauge drug-releasing cooled wet electrode (DRCWE) was newly developed to improve the RFA efficacy for creating a large ablation as well as for simultaneously delivering an anticancer drug to the tumor margin. Nine ablations in three pigs were performed by the DRCWE. The sectioned liver specimens were evaluated by measuring the ablation zone by a positron emission tomography/magnetic resonance imaging examination to investigate whether 18F-fluorodeoxyglucose was exactly diffused. Volumes of the ablation zones released drug injection volumes, circularity, retention rate defined as the ratio between an estimated and injection dose, and the standard uptake value were assessed. The drug-releasing RFA was technically successful without procedural-related complications. During the procedure, the color changes of the ablated zones of the liver were observed in all specimens. The mean drug injection volume was higher than the ablated volumes (17.21 ± 2.85 vs. 15.22 ± 2.30 cm3) and the circularity was 0.72 ± 0.08. Moreover, the retention rate was 72.89% ± 4.22% and the mean standard uptake value was 0.44 ± 0.05. The drug-releasing RFA system was feasible not only for local ablation but also for the delivery of anticancer drugs. The results of this study indicate that this novel strategy of localized RFA with a drug delivery system could be a promising option for the prevention of local recurrence rates. [ABSTRACT FROM AUTHOR]

In this work, experimental and numerical investigation on the deployment of solar panels with tape spring (TS) hinges showing complex nonlinear hysteresis behavior caused by the snap-through buckling was conducted. Subsequently, it was verified by comparing simulation results by multi-body dynamics (MBD) analysis with test results on ground-based deployment testing considering gravity compensation, termed zero-gravity (Zero-G) device. It has been difficult to predict the folding and unfolding behavior of TS hinges because their moment–rotation relationship showed a nonlinear hysteresis behavior. To realize this attribute, an algorithm that checks the sign of angular velocity of the revolute joints was used to distinguish folding from unfolding. The nonlinear hysteresis was implemented in terms of two path-dependent nonlinear moment–rotation curves with the aid of the expression function (a kind of user subroutine) in MBD software RecurDyn. Finally, it was found that the results of the deployment analysis were in excellent agreement with those of the test when the friction torques of the revolute joints were properly identified by an inverse analysis with the test frames, thus validating the MBD model. [ABSTRACT FROM AUTHOR]

A material density separator utilizes a high velocity channel of air with a ballistic trajectory to separate materials based on their different densities and sizes. Light materials are carried with the airflow, leaving behind the separated heavy materials. A vibrating bed is then used to collect both heavy and light plastic materials for further separation and recycling processes. The effectiveness of the separation process mainly depends on the ballistic trajectory of the air stream and the slanting position of the vibrating bed. In this study, flow characteristics inside the density separation system were investigated to optimize the ballistic trajectory of air and the slanting position of the vibrating bed to improve the separation process. Various inlet air velocities, duct shapes, and the slanting angles of the mechanical separators were used to study their effects on flow properties (velocity magnitude, pressure, shear stress, and vorticity). Results show that the ballistic trajectory of air strongly depends on the diameter and shape of the duct hole, the inclination angle of the vibrating bed, and the air inlet velocity. The selection of the suitable values of these parameters is necessary to improve the plastic separation process. [ABSTRACT FROM AUTHOR]

Our meta-analysis aimed to evaluate the diagnostic performance of surveillance magnetic resonance imaging (sMRI) for detecting hepatocellular carcinoma (HCC), and to compare the diagnostic performance of sMRI between different protocols. Original articles about the diagnostic accuracy of sMRI for detecting HCC were found in major databases. The meta-analytic pooled sensitivity and specificity of sMRI for detecting HCC were determined using a bivariate random effects model. The pooled sensitivity and specificity of full MRI and abbreviated MRI protocols were compared using bivariate meta-regression. In the total seven included studies (1830 patients), the pooled sensitivity of sMRI for any-stage HCC and very early-stage HCC were 85% (95% confidence interval, 79–90%; I2 = 0%) and 77% (66–85%; I2 = 32%), respectively. The pooled specificity for any-stage HCC and very early-stage HCC were 94% (90–97%; I2 = 94%) and 94% (88–97%; I2 = 96%), respectively. The pooled sensitivity and specificity of abbreviated MRI protocols were 87% (80–94%) and 94% (90–98%), values that were comparable with those of full MRI protocols (84% [76–91%] and 94% [89–99%]; p = 0.83). In conclusion, sMRI had good sensitivity for detecting HCC, particularly very early-stage HCC. Abbreviated MRI protocols for HCC surveillance had comparable diagnostic performance to full MRI protocols. [ABSTRACT FROM AUTHOR]

Previous studies on changes in body composition of pancreatic cancer patients have only focused on short-term survivors. We studied longitudinal body composition changes and factors affecting them in long-term survivors by analyzing many abdominal computed tomography images using artificial intelligence technology. Of 302 patients who survived for >36 months after surgery were analyzed. Multivariate logistic regression analysis for factors affecting body composition changes and repeated-measures analysis of variance to observe differences in the course of change according to each factor were performed. In logistic analysis, preoperative sarcopenia and recurrence were the main factors influencing body composition changes at 1 and 3 years after surgery, respectively. In changes of longitudinal body composition, the decrease in body composition was the greatest at 3–6 months postoperatively, and the preoperative status did not recover even 3 years after surgery. Especially, males showed a greater reduction in skeletal muscle (SKM) after surgery than females (p < 0.01). In addition, SKM (p < 0.001) and subcutaneous adipose tissue (p < 0.05) mass rapidly decreased in case of recurrence. In conclusion, long-term survivors of pancreatic cancer did not recover their preoperative body composition status, and preoperative sarcopenia and recurrence influenced body composition changes. [ABSTRACT FROM AUTHOR]

Simple Summary: The average human life expectancy is increasing worldwide, which is leading to increases in the proportion of elderly patients (≥80 years) with gastric cancer. Endoscopic submucosal dissection (ESD) is widely regarded as a safe and effective treatment for early gastric cancer (EGC), even in aged or high-risk patients. We investigated the oncologic outcomes in elderly patients who underwent endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) by focusing on the impact of comorbidities, sarcopenia, and nutritional status. Over a median follow-up period of 70.5 months, the 3- and 5-year overall survival (OS) rates were 89.5% and 77.1%, respectively; of the114 patients who died, only four (3.5%) were due to gastric cancer. A total of 173 (61.8%) had sarcopenia, and they had lower rates of 3-year (88.4% vs. 91.4%) and 5-year (73.1% vs. 84.0%; p = 0.046) OS than did those without sarcopenia. In multivariable analyses, prognostic nutritional index (hazard ratio [HR], 0.93; 95% confidence interval [CI]: 0.90–0.98; p = 0.002) and Charlson comorbidity index (HR 1.19; 95% CI: 1.03–1.37; p = 0.018) showed that ESD was a feasible and safe therapeutic method to use in elderly patients, whose long-term survival was significantly associated with nutritional status and comorbidities. Background/Aim: We investigated the oncologic outcomes in elderly patients who underwent endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) by focusing on the impact of comorbidities, sarcopenia, and nutritional status. Methods: Between 2005 and 2016, 280 patients aged ≥ 80 years with 289 EGCs underwent ESD at a tertiary care center. The short- and long-term survival outcomes were assessed. Cox regression analysis was used to identify factors associated with survival, including clinicopathologic factors and abdominal muscle area measured by computed tomography. Results: The rates of en bloc, R0, and, curative resection were 99.3%, 90.0%, and 69.2%, respectively. The rates of post-ESD bleeding and perforation rates were 2.1% and 3.1%, respectively, and no cases showed significant life-threatening adverse events. Over a median follow-up period of 70.5 months, the 3- and 5-year overall survival (OS) rates were 89.5% and 77.1%, respectively; of the114 patients who died, only four (3.5%) were due to gastric cancer. A total of 173 (61.8%) had sarcopenia, and they had lower rates of 3-year (88.4% vs. 91.4%) and 5-year (73.1% vs. 84.0%; p = 0.046) OS than did those without sarcopenia. In multivariable analyses, prognostic nutritional index (hazard ratio [HR], 0.93; 95% confidence interval [CI]: 0.90–0.98; p = 0.002) and Charlson comorbidity index (HR 1.19; 95% CI: 1.03–1.37; p = 0.018) were significant factors associated with overall survival. Conclusions: ESD was a feasible and safe therapeutic method to use in elderly patients, whose long-term survival was significantly associated with nutritional status and comorbidities. These results suggest the need for a possible extension of the curative criteria for ESD in elderly patients with EGC. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia contributes to increased morbidity and mortality in patients undergoing surgery for abdominal aortic aneurysms (AAA). However, few reports have demonstrated whether sarcopenia would affect the development of postoperative acute kidney injury (AKI) in these patients. This study aimed to examine whether sarcopenia is associated with AKI and morbidity and mortality after infrarenal AAA operation. Methods: We retrospectively analysed 379 patients who underwent infrarenal AAA surgery. The diagnosis of sarcopenia was performed using the skeletal muscle index, which was calculated from axial computed tomography at the level of L3. The patients were separated into those with sarcopenia (n = 104) and those without sarcopenia (n = 275). We applied multivariable and Cox regression analyses to evaluate the risk factors for AKI and overall mortality. A propensity score matching (PSM) evaluation was done to assess the postoperative results. Results: The incidence of AKI was greater in sarcopenia than non-sarcopenia group before (34.6% vs. 15.3%; p < 0.001) and after the PSM analysis (34.6% vs. 15.4%; p = 0.002). Multivariable analysis revealed sarcopenia to be associated with AKI before (p = 0.010) and after PSM (p = 0.016). Sarcopenia was also associated with overall mortality before (p = 0.048) and after PSM (p = 0.032). A Kaplan–Meier analysis revealed that overall mortality was elevated patients with sarcopenia before and after PSM than in those without (log-rank test, p < 0.001, p = 0.022). Conclusions: Sarcopenia was associated with increased postoperative AKI incidence and overall mortality among individuals who underwent infrarenal AAA operation. [ABSTRACT FROM AUTHOR]

P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are regulatory small non-coding RNAs that participate in transposon inactivation, chromatin regulation, and endogenous gene regulation. Numerous genetic and epigenetic factors regulate cell proliferation and tumor metastasis. PIWI proteins and piRNAs have been revealed to function in regulating upstream or downstream of oncogenes or tumor-suppressor genes in cancer tissues. In the present review, we summarize major recent findings in uncovering the regulation and role of PIWI proteins and piRNAs in tumorigenesis and highlight some of the promising applications of specific piRNAs in cancer therapeutics and as cancer biomarkers. [ABSTRACT FROM AUTHOR]

We evaluated the incidence of pseudoprogression and indeterminate response (IR) in patients with lymphoma treated with immune checkpoint inhibitors (ICIs). A systematic search of PubMed and EMBASE was performed up to 6 February 2021, using the keywords "lymphoma," "immunotherapy," and "pseudoprogression." Random-effects models were used to calculate both pooled incidence of pseudoprogression patients with lymphoma and an IR according to LYRIC criteria, while the Higgins inconsistency index (I2) test and Cochran's Q test were used for heterogeneity. Eight original articles were included, in which the number of patients ranged from 7 to 243. Among the lymphoma patients with ICIs, the pooled incidence of pseudoprogression was 10% (95% confidence interval [CI]: 0.06–0.17). There was no publication bias in Begg's test (p = 0.14). Three articles were analyzed to determine the pooled incidence of pseudoprogression in patients with IR according to LYRIC criteria in a subgroup analysis, which was shown to be 19% (95% CI: 0.08–0.40). A significant proportion (10%) of patients with lymphoma treated with ICIs showed pseudoprogression, and 19% of patients with an IR response showed pseudoprogression and a delayed response. Immune-related response criteria such as LYRIC may be used for patients with lymphoma treated with ICIs. [ABSTRACT FROM AUTHOR]

Simple Summary: The number of colorectal cancer survivors is increasing due to improvements in oncologic outcomes. Therefore, the risks of metachronous cancer and second cancer are also increased, as well as recurrences. The influence of muscle mass measured as sarcopenia on long-term survival has been studied recently in colorectal cancer patients. Sarcopenia is a factor controllable by lifestyle modification and has gained interest more recently. This study showed an influence of changes in sarcopenia on long-term oncologic outcomes in colorectal cancer and suggests a basis for further investigation of body composition factors, including sarcopenia. The effect of perioperative sarcopenic changes on prognosis remains unclear. We conducted a retrospective cohort study with 2333 non-metastatic colorectal cancer patients treated between January 2009 and December 2012 at the Asan Medical Center. The body composition at diagnosis was measured via abdominopelvic computed tomography (CT) using Asan-J software. Patients underwent CT scans preoperatively, as well as at 6 months–1 year and 2–3 years postoperatively. The primary outcome was the association between perioperative sarcopenic changes and survival. According to sarcopenic criteria, 1155 (49.5%), 890 (38.2%), and 893 (38.3%) patients had sarcopenia preoperatively, 6 months–1 year, and 2–3 years postoperatively, respectively. The 5-year overall survival (OS) (95.8% vs. 92.1%, hazard ratio (HR) = 2.234, p < 0.001) and 5-year recurrence-free survival (RFS) (93.2% vs. 86.2%, HR = 2.251, p < 0.001) rates were significantly lower in patients with preoperative sarcopenia. Both OS and RFS were lower in patients with persistent sarcopenia 2–3 years postoperatively than in those who recovered (OS: 96.2% vs. 90.2%, p = 0.001; RFS: 91.1% vs. 83.9%, p = 0.002). In multivariate analysis, postoperative sarcopenia was confirmed as an independent factor associated with decreased OS and RFS. Pre- and postoperative sarcopenia and changes in the condition during surveillance were associated with oncological outcomes. [ABSTRACT FROM AUTHOR]

Exposure to high oxygen concentrations leads to generation of excessive reactive oxygen species, causing cellular injury and multiple organ dysfunctions and is associated with a high mortality rate. Clusterin (CLU) is a heterodimeric glycoprotein that mediates several intracellular signaling pathways, including cell death and inflammation. However, the role of CLU in the pathogenesis of hyperoxic acute lung injury (HALI) is unknown. Wild-type (WT) and CLU-deficient mice and cultured human airway epithelial cells were used. Changes in cell death- and inflammation-related molecules with or without hyperoxia exposure in cells and animals were determined. Hyperoxia induced an increase in CLU expression in mouse lungs and human airway epithelial cells. Mice lacking CLU had increased HALI and mortality rate compared with WT mice. In vitro, CLU-disrupted cells showed enhanced release of cytochrome c, Bax translocation, cell death and inflammatory cytokine expression. However, treatment with recombinant CLU attenuated hyperoxia-induced apoptosis. Moreover, the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed metabolic pathways, hematopoietic cell lineage, response to stress and localization and regulation of immune system that were differentially regulated between WT and CLU−/− mice. These results demonstrate that prolonged hyperoxia-induced lung injury is associated with CLU expression and that CLU replenishment may alleviate hyperoxia-induced cell death. [ABSTRACT FROM AUTHOR]

To assess the additional value of 2-deoxy-2-[18F] fluoro-d-glucose ([18F]FDG) positron emission tomography (PET) or PET/CT over conventional morphological imaging techniques in the treatment response assessment of gastrointestinal stromal tumor (GIST) to molecular targeted therapy (MTT), we performed a meta-analysis of all the available studies to compare the predictive value of [18F]FDG PET or PET/CT and conventional imaging techniques for assessing the response to MTT in GIST. We determined the sensitivities and specificities across studies, we calculated the positive and negative likelihood ratios (LR) and made summary receiver operating characteristic curves (SROC) using hierarchical regression models. Pooled analysis included 4 studies comprising 88 patients. The performance characteristics in [18F]FDG PET or PET/CT and CT were as follows: sensitivity, 89% (95% confidence interval (CI) 78, 95), 52% (39, 64); specificity, 65% (44, 83), 92% (75, 99); diagnostic odds ratios (DOR), 5.8 (2.0, 16.8 4.9 (1.5, 16.1); positive LR, 1.9 (1.1, 3.4), 3.0 (1.1, 8.1); and negative LR, 0.23 (0.03, 1.6), 0.66 (0.42, 1.0), respectively. In SROC curves, the area under the curve (AUC) was 0.81 (SE, 0.11) and 0.71 (SE, 0.13) and the Q* index was 0.74 and 0.66, respectively. [18F]FDG PET/CT had higher sensitivity, while DOR and SROC curves showed better diagnostic performance in [18F]FDG PET and PET/CT studies as compared to CT. [ABSTRACT FROM AUTHOR]

Simple Summary: It is controversial whether iRECIST has a significant impact over RECIST 1.1 in evaluating the efficacy of immune checkpoint inhibitor treatment. We aimed to evaluate the impact of iRECIST on assessing treatment efficacy of immune checkpoint inhibitors over RECIST 1.1 through a systematic review and meta-analysis. Compared to RECIST 1.1, iRECIST had no impact on the overall response rate and disease control rate but detected 3.9% of patients with discordance in the date of progressive disease determination due to pseudoprogression and prolonged restricted mean progression-free survival time by 0.46 months. Therefore, the application of iRECIST had no impact on the response-related endpoints but had a minor impact on the survival endpoint, compared to RECIST 1.1. Such a modest benefit of iRECIST should be considered when we design a clinical trial for immune checkpoint inhibitors. Despite wide recognition of iRECIST, evidence regarding the impact of iRECIST over RECIST 1.1 is lacking. We aimed to evaluate the impact of iRECIST on assessing treatment efficacy of immune checkpoint inhibitors (ICIs) over RECIST 1.1. Articles that evaluated the treatment response and outcome based on both RECIST 1.1 and iRECIST were eligible. Data regarding overall response rates (ORR) and disease control rate (DCR) based on RECIST 1.1 and iRECIST, and data required to estimate individual patient data of progression-free survival (PFS) were extracted. Estimates were compared using meta-regression and pooled incidence rate ratios. The pooled difference of restricted mean survival time (RMST) of PFS between two criteria were calculated. Eleven studies with 6210 patients were analyzed. The application of iRECIST had no impact on the response-related endpoint by showing no significantly different ORR and DCR from RECIST 1.1 (pooled ORR, 23.6% and 24.7% [p = 0.72]; pooled DCR, 45.3% and 48.7% [p = 0.56] for iRECIST and RECIST 1.1, respectively) and had a minor impact on a survival endpoint by showing longer RMST of PFS than RECIST 1.1 (pooled difference, 0.46 months; 95% CI, 0.10–0.82 months; p = 0.01). Such a modest benefit of iRECIST should be considered when we design a clinical trial for immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Due to the spread of COVID-19 worldwide in 2020, the tourism industry is facing a calamitous crisis as migration and travel between the countries has been restricted. The purpose of this study is to explore changes in Korean tourism behavior after COVID-19. Korean social media data was collected from the World Health Organization's declaration of a public health emergency of international concern, in January 2020, to August 2020, the summer vacation season. Keywords were extracted via text mining, and the current perspectives of Koreans concerning tourism that manifest content analysis were investigated. In addition, UCINET 6 was used to visualize related words by conducting centrality analysis, CONCOR (CONvergent CORrelation) analysis, and semantic system network analysis. The analysis showed that Korean tourists have increased their preference for domestic travel, and showed interest in government subsidies. Korean tourists also showed greater interest in eco-trips and gourmet trips. Although this study is limited to Korea, it can be used as a regional strategy. [ABSTRACT FROM AUTHOR]

This study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of cuprizone-induced demyelination as detected using in vivo 7 T proton magnetic resonance spectroscopy. Nineteen Sprague Dawley rats were randomly divided into two groups and fed a normal chow diet or cuprizone (0.2%, w/w) for 7 weeks. Demyelinated hippocampal lesions were quantitatively measured using a 7 T magnetic resonance imaging scanner. All proton spectra were quantified for metabolite concentrations and relative ratios. Compared to those in the controls, the cuprizone-induced rats had significantly higher concentrations of glutamate (p = 0.001), gamma-aminobutyric acid (p = 0.019), and glutamate + glutamine (p = 0.001); however, creatine + phosphocreatine (p = 0.006) and myo-inositol (p = 0.001) concentrations were lower. In addition, we found that the glutamine and glutamate complex/total creatine (p < 0.001), glutamate/total creatine (p < 0.001), and GABA/total creatine (p = 0.002) ratios were significantly higher in cuprizone-treated rats than in control rats. Our results showed that cuprizone-induced neuronal demyelination may influence the severe abnormal metabolism in hippocampal lesions, and these responses could be caused by microglial activation, mitochondrial dysfunction, and astrocytic necrosis. [ABSTRACT FROM AUTHOR]

Background: Glutamate-weighted chemical exchange saturation transfer (GluCEST) is a useful imaging tool that can be used to detect changes in glutamate levels in vivo and could also be helpful in the diagnosis of brain myelin changes. We investigated glutamate level changes in the cerebral white matter of a rat model of cuprizone-administered demyelination and remyelination using GluCEST. Method: We used a 7 T pre-clinical magnetic resonance imaging (MRI) system. The rats were divided into the normal control (CTRL), cuprizone-administered demyelination (CPZDM), and remyelination (CPZRM) groups. GluCEST data were analyzed using the conventional magnetization transfer ratio asymmetry in the corpus callosum. Immunohistochemistry and transmission electron microscopy analyses were also performed to investigate the myelinated axon changes in each group. Results: The quantified GluCEST signals differed significantly between the CPZDM and CTRL groups (−7.25 ± 1.42% vs. −2.84 ± 1.30%; p = 0.001). The increased GluCEST signals in the CPZDM group decreased after remyelination (−6.52 ± 1.95% in CPZRM) to levels that did not differ significantly from those in the CTRL group (p = 0.734). Conclusion: The apparent temporal signal changes in GluCEST imaging during demyelination and remyelination demonstrated the potential usefulness of GluCEST imaging as a tool to monitor the myelination process. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the radiologic response and adverse event rates of immune checkpoint inhibitor (ICI) therapy with or without radiotherapy for the treatment of non-small cell lung cancer (NSCLC) brain metastases. A systematic literature search was performed up to January 3, 2020. Studies evaluating the intracranial objective response rates (ORR) and/or disease control rates (DCR) of ICI with or without radiotherapy for treating NSCLC brain metastases were included. Consequently, twelve studies satisfied inclusion criteria. ICI combined with radiotherapy (pooled ORR, 95%; DCR, 97%) showed better local efficacy compared to ICI monotherapy (pooled ORR, 24%; DCR, 44%; p < 0.01 for both ORR and DCR). Grade 3 or 4 central nervous system (CNS)-related adverse event rates were not different (5% vs. 4%; p = 0.93). In conclusion, ICI combined with radiotherapy showed better intracranial efficacy than ICI monotherapy for treating NSCLC brain metastases. CNS-related grade 3 or 4 adverse event rate was not statistically different between the two groups. Several prospective trials are needed to compare the efficacy of ICI combined with radiotherapy and ICI monotherapy. [ABSTRACT FROM AUTHOR]

In children with concomitant food allergy and atopic dermatitis (AD), uncovering the causative food allergen is more arduous. We evaluated the basophil activation test (BAT) for its diagnostic value in children, including those with AD, for milk or egg allergy. We simultaneously measured serum-specific immunoglobulin E (sIgE) levels and performed BATs for cow's milk and egg white. We compared their overall diagnostic performance using the area under the receiver operating characteristic curve (AUC) with the Delong method and compared them in children with AD. Analyses were completed for 75 children for milk allergy and for 85 children for egg allergy. The sIgE and percentage of basophils with the expression of CD63 were correlated for both milk (r = 0.384, p < 0.001) and egg (r = 0.557, p < 0.001). The AUC of sIgE (0.701) for milk allergy was significantly increased when combined with the BAT (0.805; p = 0.029). In children with AD, the AUC of the BAT (0.924) for milk allergy was significantly larger than that of sIgE (0.701; p = 0.017). The BAT is a potentially useful diagnostic tool for milk allergy in children when combined with sIgE. Moreover, it may be a surrogate marker for milk allergy in children with AD. [ABSTRACT FROM AUTHOR]

Purpose: To investigate glutamate signal distributions in multiple brain regions of a healthy rat brain using glutamate-weighted chemical exchange saturation transfer (GluCEST) imaging. Method: The GluCEST data were obtained using a 7.0 T magnetic resonance imaging (MRI) scanner, and all data were analyzed using conventional magnetization transfer ratio asymmetry in eight brain regions (cortex, hippocampus, corpus callosum, and rest of midbrain in each hemisphere). GluCEST data acquisition was performed again one month later in five randomly selected rats to evaluate the stability of the GluCEST signal. To evaluate glutamate level changes calculated by GluCEST data, we compared the results with the concentration of glutamate acquired from 1H magnetic resonance spectroscopy (1H MRS) data in the cortex and hippocampus. Results: GluCEST signals showed significant differences (all p ≤ 0.001) between the corpus callosum (−1.71 ± 1.04%; white matter) and other brain regions (3.59 ± 0.41%, cortex; 5.47 ± 0.61%, hippocampus; 4.49 ± 1.11%, rest of midbrain; gray matter). The stability test of GluCEST findings for each brain region was not significantly different (all p ≥ 0.263). In line with the GluCEST results, glutamate concentrations measured by 1H MRS also appeared higher in the hippocampus (7.30 ± 0.16 μmol/g) than the cortex (6.89 ± 0.72 μmol/g). Conclusion: Mapping of GluCEST signals in the healthy rat brain clearly visualize glutamate distributions. These findings may yield a valuable database and insights for comparing glutamate signal changes in pre-clinical brain diseases. [ABSTRACT FROM AUTHOR]

Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor that mediates numerous biological processes in all living cells. Multiple NAD+ biosynthetic enzymes and NAD+-consuming enzymes are involved in neuroprotection and axon regeneration. The nematode Caenorhabditis elegans has served as a model to study the neuronal role of NAD+ because many molecular components regulating NAD+ are highly conserved. This review focuses on recent findings using C. elegans models of neuronal damage pertaining to the neuronal functions of NAD+ and its precursors, including a neuroprotective role against excitotoxicity and axon degeneration as well as an inhibitory role in axon regeneration. The regulation of NAD+ levels could be a promising therapeutic strategy to counter many neurodegenerative diseases, as well as neurotoxin-induced and traumatic neuronal damage. [ABSTRACT FROM AUTHOR]

Recently, biocompatible energy harvesting devices have received a great deal of attention for biomedical applications. Among various biomaterials, viruses are expected to be very promising biomaterials for the fabrication of functional devices due to their unique characteristics. While other natural biomaterials have limitations in mass-production, low piezoelectric properties, and surface modification, M13 bacteriophages (phages), which is one type of virus, are likely to overcome these issues with their mass-amplification, self-assembled structure, and genetic modification. Based on these advantages, many researchers have started to develop virus-based energy harvesting devices exhibiting superior properties to previous biomaterial-based devices. To enhance the power of these devices, researchers have tried to modify the surface properties of M13 phages, form biomimetic hierarchical structures, control the dipole alignments, and more. These methods for fabricating virus-based energy harvesting devices can form a powerful strategy to develop high-performance biocompatible energy devices for a wide range of practical applications in the future. In this review, we discuss all these issues in detail. [ABSTRACT FROM AUTHOR]

Mercury is a cumulative neurotoxic agent, exposure to high levels of which may increase the risk of psychiatric symptoms. The purpose of this study was to examine the associations between blood mercury and depression risk in Korean adults. We analyzed the Korean National Health and Nutrition Examination Survey (KNHANES) with 11,754 participants (male: 5834 female: 5920) aged ≥19 years from 2008 to 2013. The associations of blood mercury with risk of depression were estimated using multivariate logistic regression after adjustment for potential confounders. We found a significantly increased risk of depression in the highest quintile for blood mercury (multivariate OR = 2.05; 95% CI = 1.20–3.48; p trend = 0.03) among female, but not male. A stratification analysis by fish intake showed that the association between depression and blood mercury was strengthened (OR = 4.00; 95% CI = 1.51–10.6; p trend = 0.015) among females with the lowest tertile of fish intake. The results of this study suggest that higher levels of blood mercury, especially in cases of lower fish intake, are positively associated with the risk of depression in Korean women. [ABSTRACT FROM AUTHOR]

Continuous renal replacement therapy (CRRT) has been used as an important intervention in critically ill children. Our center has the only specialized CRRT team (SCT) for children in Korea, which consists of pediatric intensivists, a pediatric nephrologist and CRRT-specialized-nurses. This study was a retrospective single-center analysis, including all pediatric patients admitted to the intensive care unit (ICU) of Severance hospital in Korea and received CRRT between 2003 and 2016, grouped as before SCT (group A, n = 51) and after SCT (group B, n = 212). We obtained the data for sex, age, weight, diagnosis, blood flow rate or type of CRRT machine used, administration of inotropic agents or anticoagulants, and ICU duration before CRRT (hours). A total of 263 patients were included. The age was significantly younger (p < 0.001) and blood flow rate was lower (p = 0.001) in group B than group A. Vasopressors (p < 0.001), continuous veno-venous hemodiafiltration (CVVHDF) (p < 0.001), nafamostat mesilate (p < 0.001), and extracorporeal membrane oxygenation (ECMO)-CRRT (p = 0.004) were more frequently used in group B. Based on our 14-year experience, we conclude that SCT operation could have played an important role in increasing the amount of CRRT utilization. [ABSTRACT FROM AUTHOR]

The effects of an intermittent fasting diet (IFD) in the general population are still controversial. In this study, we aimed to systematically evaluate the effectiveness of an IFD to reduce body mass index and glucose metabolism in the general population without diabetes mellitus. Cochrane, PubMed, and Embase databases were searched to identify randomized controlled trials and controlled clinical trials that compared an IFD with a regular diet or a continuous calorie restriction diet. The effectiveness of an IFD was estimated by the weighted mean difference (WMD) for several variables associated with glucometabolic parameters including body mass index (BMI) and fasting glucose. The pooled mean differences of outcomes were calculated using a random effects model. From 2814 studies identified through a literature search, we finally selected 12 articles (545 participants). Compared with a control diet, an IFD was associated with a significant decline in BMI (WMD, −0.75 kg/m2; 95% CI, −1.44 to −0.06), fasting glucose level (WMD, −4.16 mg/dL; 95% CI, −6.92 to −1.40), and homeostatic model assessment of insulin resistance (WMD, −0.54; 95% CI, −1.05 to −0.03). Fat mass (WMD, −0.98 kg; 95% CI, −2.32 to 0.36) tended to decrease in the IFD group with a significant increase in adiponectin (WMD, 1008.9 ng/mL; 95% CI, 140.5 to 1877.3) and a decrease in leptin (WMD, −0.51 ng/mL; 95% CI, −0.77 to −0.24) levels. An IFD may provide a significant metabolic benefit by improving glycemic control, insulin resistance, and adipokine concentration with a reduction of BMI in adults. [ABSTRACT FROM AUTHOR]

Abnormalities in body composition are associated with poor prognosis in cancer patients. We investigated the association between body composition and 90-day mortality in cancer patients who developed septic shock. We included consecutive septic shock patients with active cancer from 2010 to 2017. The muscle area at the level of the third lumbar vertebra was measured by computed tomography upon emergency department admission and adjusted by height squared, yielding the Skeletal Muscle Index (SMI). Hazard ratios (HRs) and 95% confidence intervals (CIs) for 90-day mortality were estimated using a Cox proportional hazards model. Among 478 patients, the prevalence of muscle depletion was 87.7%. Among markers of body composition, the SMI only differed significantly between non-survivors and survivors (mean, 35.48 vs. 33.32 cm2/m2; P = 0.002) and was independently associated with lower 90-day mortality (adjusted HR, 0.970; P = 0.001). The multivariable-adjusted HRs (95% CI) for 90-day mortality comparing quartiles 2, 3, and 4 of the SMI to the lowest quartile were 0.646 (0.916–1.307), 0.620 (0.424–0.909), and 0.529 (0.355–0.788), respectively. The associations were evident in male patients, but not in female patients. The SMI was independently associated with 90-day mortality in cancer patients with septic shock. The graded association between the SMI and 90-day mortality was observed in male patients. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the prognostic value of variables used in the 2017 PRE-Treatment EXTent of tumor (PRETEXT) system and the Children's Hepatic tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) system in pediatric patients with hepatoblastoma. A retrospective analysis of data from the pediatric hepatoblastoma registry of a tertiary referral center was conducted to evaluate the clinical and imaging variables (annotation factors) of the PRETEXT staging system. The primary outcome was event-free survival (EFS). Data from 84 patients (mean age: 2.9 ± 3.5 years) identified between 1998 and 2017 were included. Univariable Cox proportional hazards analysis revealed that PRETEXT annotation factors P (portal vein involvement), F (multifocality of tumor), and M (distant metastasis) showed a significant negative association with EFS. Multivariable Cox proportional hazard analysis showed that factor F was the strongest predictor (HR (hazard ratio), 2.908; 95% CI (confidence interval), 1.061–7.972; p = 0.038), whereas factor M showed borderline significance (HR, 2.416; 95% CI, 0.918–6.354; p = 0.074). The prediction model based on F and M (F + M) showed good performance to predict EFS (C-statistic, 0.734; 95% CI, 0.612–0.854). In conclusion, the PRETEXT annotation factor F was the strongest predictor of EFS, and the F + M model showed good performance to predict EFS in pediatric patients with hepatoblastoma. [ABSTRACT FROM AUTHOR]

We performed a systematic review and meta-analysis of the treatment efficacy of immune checkpoint inhibitors (ICIs) in advanced/metastatic neuroendocrine neoplasms (NENs). MEDLINE and EMBASE were searched to identify studies that provide data on treatment response and/or survival outcomes of advanced/metastatic NEN patients treated with ICIs. The overall response rate (ORR) was pooled using a random-effects model. Meta-regression was performed to explore factors influencing the ORR. Individual patient data (IPD) meta-analysis of survival was performed using stratified Cox regression. Ten studies (464 patients) were included. The overall pooled ORR was 15.5% (95% confidence interval (CI), 9.5-24.3%), and it varied according to the primary site (thoracic, 24.7%; gastro-entero-pancreatic, 9.5%), tumor differentiation (poorly differentiated, 22.7%; well-differentiated, 10.4%), and drug regimen (combination, 25.3%; monotherapy, 10.1%). All these variables significantly influenced the ORR. Tumor differentiation was associated with both overall survival and progression-free survival (hazard ratio of poorly differentiated tumors, 4.2 (95% CI, 2.0-8.7) and 2.6 (95% CI, 1.6-4.4), respectively). Thus, the treatment efficacy of ICIs for advanced/metastatic NENs varied according to primary site, tumor differentiation, and drug regimen. Poorly differentiated NENs showed a better ORR than well-differentiated NENs but had a negative impact on survival.

Nicotinamide adenine dinucleotide (NAD + ) is an essential cofactor that mediates numerous biological processes in all living cells. Multiple NAD + biosynthetic enzymes and NAD + -consuming enzymes are involved in neuroprotection and axon regeneration. The nematode Caenorhabditis elegans has served as a model to study the neuronal role of NAD + because many molecular components regulating NAD + are highly conserved. This review focuses on recent findings using C. elegans models of neuronal damage pertaining to the neuronal functions of NAD + and its precursors, including a neuroprotective role against excitotoxicity and axon degeneration as well as an inhibitory role in axon regeneration. The regulation of NAD + levels could be a promising therapeutic strategy to counter many neurodegenerative diseases, as well as neurotoxin-induced and traumatic neuronal damage.