Critical assessment of missense variant effect predictors on disease-relevant variant data.

Regular, systematic, and independent assessment of computational tools used to predict the pathogenicity of missense variants is necessary to evaluate their clinical and research utility and suggest directions for future improvement. Here, as part of the sixth edition of the Critical Assessment of Genome Interpretation (CAGI) challenge, we assess missense variant effect predictors (or variant impact predictors) on an evaluation dataset of rare missense variants from disease-relevant databases. Our assessment evaluates predictors submitted to the CAGI6 Annotate-All-Missense challenge, predictors commonly used by the clinical genetics community, and recently developed deep learning methods for variant effect prediction. To explore a variety of settings that are relevant for different clinical and research applications, we assess performance within different subsets of the evaluation data and within high-specificity and high-sensitivity regimes. We find strong performance of many predictors across multiple settings. Meta-predictors tend to outperform their constituent individual predictors; however, several individual predictors have performance similar to that of commonly used meta-predictors. The relative performance of predictors differs in high-specificity and high-sensitivity regimes, suggesting that different methods may be best suited to different use cases. We also characterize two potential sources of bias. Predictors that incorporate allele frequency as a predictive feature tend to have reduced performance when distinguishing pathogenic variants from very rare benign variants, and predictors supervised on pathogenicity labels from curated variant databases often learn label imbalances within genes. Overall, we find notable advances over the oldest and most cited missense variant effect predictors and continued improvements among the most recently developed tools, and the CAGI Annotate-All-Missense challenge (also termed the Missense Marathon) will continue to assess state-of-the-art methods as the field progresses. Together, our results help illuminate the current clinical and research utility of missense variant effect predictors and identify potential areas for future development.

Assessment of radio-activation using spectroscopy in medical linear accelerators.

In radiotherapy, when photon energy exceeding 8 MV is utilized, photoneutrons can activate the components within the gantry of the linear accelerator (linac). At the end of the linac's lifecycle, radiation workers are tasked with its dismantling and disposal, potentially exposing them to unintentional radiation. This study aims to identify and measure the radioisotopes generated by this activation through spectroscopy, and to evaluate the effective dose rate. We selected nine medical linacs, considering various factors such as manufacturer (Siemens, Varian, and Elekta), model, energy, period of operation, and workload. We identified the radionuclides in the linac head by employing an in situ high-purity germanium (HPGe) detector. Spectroscopy and dose-rate measurements were conducted post-shutdown. We also measured the dose rates at the beam-exit window following irradiation with 10 MV and 15 MV photon beams. As a result of the spectroscopy, we identified approximately 20 nuclides including those with half-lives of 100 days or longer, such as 54Mn, 60Co, 65Zn, 122Sb, and 198Au. The dose rate measurements after 10 MV irradiation decreased to the background level in 10 min. By contrast, on 15 MV irradiation, the dose rate was 628 nSv/h after 10 min and decreased to 268 nSv/h after 1.5 hours. It was confirmed that the difference in the level of radiation and the type of nuclide depends on the period of use, energy, and workload. However, the type of nuclide does not differ significantly between the linacs. It is necessary to propose appropriate guidelines for the safety of workers, and disposal/move-install should be planned while taking into consideration the equipment's energy usage rate.

Automatic Assessment of Upper Extremity Function and Mobile Application for Self-Administered Stroke Rehabilitation.

Rehabilitation training is essential for a successful recovery of upper extremity function after stroke. Training programs are typically conducted in hospitals or rehabilitation centers, supervised by specialized medical professionals. However, frequent visits to hospitals can be burdensome for stroke patients with limited mobility. We consider a self-administered rehabilitation system based on a mobile application in which patients can periodically upload videos of themselves performing reach-to-grasp tasks to receive recommendations for self-managed exercises or progress reports. Sensing equipment aside from cameras is typically unavailable in the home environment. A key contribution of our work is to propose a deep learning-based assessment model trained only with video data. As all patients carry out identical tasks, a fine-grained assessment of task execution is required. Our model addresses this difficulty by learning RGB and optical flow data in a complementary manner. The correlation between the RGB and optical flow data is captured by a novel module for modality fusion using cross-attention with Transformers. Experiments showed that our model achieved higher accuracy in movement assessment than existing methods for action recognition. Based on the assessment model, we developed a patient-centered, solution-based mobile application for upper extremity exercises for hemiplegia, which can recommend 57 exercises with three levels of difficulty. A prototype of our application was evaluated by potential end-users and achieved a good quality score on the Mobile Application Rating Scale (MARS).

Preclinical and dose-ranging assessment of hESC-derived dopaminergic progenitors for a clinical trial on Parkinson's disease.

Human embryonic stem cell (hESC)-derived midbrain dopaminergic (mDA) cell transplantation is a promising therapeutic strategy for Parkinson's disease (PD). Here, we present the derivation of high-purity mDA progenitors from clinical-grade hESCs on a large scale under rigorous good manufacturing practice (GMP) conditions. We also assessed the toxicity, biodistribution, and tumorigenicity of these cells in immunodeficient rats in good laboratory practice (GLP)-compliant facilities. Various doses of mDA progenitors were transplanted into hemi-parkinsonian rats, and a significant dose-dependent behavioral improvement was observed with a minimal effective dose range of 5,000-10,000 mDA progenitor cells. These results provided insights into determining a low cell dosage (3.15 million cells) for human clinical trials. Based on these results, approval for a phase 1/2a clinical trial for PD cell therapy was obtained from the Ministry of Food and Drug Safety in Korea, and a clinical trial for treating patients with PD has commenced.

Evaluating the Compliance, Efficacy, and Cost of Formulated Vitamins Versus Separate Supplements in Post-bariatric Surgery Patients.

OBJECTIVE: Micronutrient deficiencies are common complications after bariatric surgery as alterations to the gastrointestinal tract change absorption. Patients are recommended to take supplements including multivitamins, B complex, calcium, vitamin D, and iron after bariatric surgery, and can take these as specifically formulated vitamins for post-bariatric patients or separate vitamin supplements. We investigated the compliance, efficacy, and cost of specifically formulated vitamins for post-bariatric patients in comparison to separate vitamin supplements. METHODS: We surveyed 126 post-bariatric adult patients between February 1, 2022, and August 31, 2022, who had undergone bariatric surgery between 2014 and 2021 to assess the type of supplements taken, compliance, and cost. Demographics, type of bariatric surgery, and serum micronutrient levels were evaluated for all patients. RESULTS: There were 51 patients taking formulated vitamins and 75 patients taking separate vitamins. The formulated vitamin group demonstrated greater adherence to optimal vitamin dosage (formulated vitamin group, 76.5% vs. separate supplement group, 30.7%; p < 0.001) and higher compliance (formulated vitamin group, 90.2% vs. separate supplement group, 66.7%; p = 0.002). The costs associated with both groups were comparable. No significant difference was observed in the incidence of micronutrient deficiency between the groups. CONCLUSIONS: Our study shows that formulated vitamins do not offer significant difference in micronutrient levels or cost compared to separate standard vitamin supplements. However, formulated bariatric vitamins have improved compliance compared to separate vitamin supplements.

Cancer care patterns in South Korea: Types of hospital where patients receive care and outcomes using national health insurance claims data.

BACKGROUND: Although strengthening coverage has improved cancer care, there are concerns related to medical distortion. Previous studies have only examined whether patients visit a specific hospital, and not the continuum of patients with cancer, resulting in a lack of evidence in South Korea. This study aimed to investigate the patterns in hospital type for cancer care and analyze their association with outcomes. METHODS: The data for this study were obtained from the National Health Insurance Services Sampled Cohort database. This study included patients with four types of cancer (top four cancer incidence in 2020): gastric (3353), colorectal (2915), lung (1351), and thyroid (5158) cancer. The latent class mixed model was used to investigate cancer care patterns, and multiple regression or survival analysis was performed to examine medical cost, length of stay (LOS), and mortality. RESULTS: The patterns in each cancer type were classified into two to four classes, namely, mainly visited clinics or hospitals, mainly visited general hospitals, mainly visited tertiary hospitals (MT), and tertiary to general hospitals through trajectory modeling based on the utilization of cancer care. Compared to the MT pattern, other patterns were generally associated with higher cost, LOS, and mortality. CONCLUSION: The patterns found in this study may be a more realistic way of defining patients with cancer in South Korea compared to previous studies, and its association-related outcomes may be used as a basis to address problems in the healthcare system and prepare alternatives for patients with cancer. Future studies should review cancer care patterns related to other factors such as regional distribution.

Heterogeneity Assessment of Kenaf Breeding Field through Spatial Dependence Analysis on Crop Growth Status Map Derived by Unmanned Aerial Vehicle.

The investigation of quantitative phenotypic traits resulting from the interaction between targeted genotypic traits and environmental factors is essential for breeding selection. Therefore, plot-wise controlled environmental factors must be invariable for accurate identification of phenotypes. However, the assumption of homogeneous variables within the open-field is not always accepted, and requires a spatial dependence analysis to determine whether site-specific environmental factors exist. In this study, spatial dependence within the kenaf breeding field was assessed in a geo-tagged height map derived from an unmanned aerial vehicle (UAV). Local indicators of spatial autocorrelation (LISA) were applied to the height map using Geoda software, and the LISA map was generated in order to recognize the existence of kenaf height status clusters. The spatial dependence of the breeding field used in this study appeared in a specific region. The cluster pattern was similar to the terrain elevation pattern of this field and highly correlated with drainage capacity. The cluster pattern could be utilized to design random blocks based on regions that have similar spatial dependence. We confirmed the potential of spatial dependence analysis on a crop growth status map, derived by UAV, for breeding strategy design with a tight budget.

Decision-tree-based ion-specific dosing algorithm for enhancing closed hydroponic efficiency and reducing carbon emissions.

The maintenance of ion balance in closed hydroponic solutions is essential to improve the crop quality and recycling efficiency of nutrient solutions. However, the absence of robust ion sensors for key ions such as P and Mg and the coupling of ions in fertilizer salts render it difficult to effectively manage ion-specific nutrient solutions. Although ion-specific dosing algorithms have been established, their effectiveness has been inadequately explored. In this study, a decision-tree-based dosing algorithm was developed to calculate the optimal volumes of individual nutrient stock solutions to be supplied for five major nutrient ions, i.e., NO3, K, Ca, P, and Mg, based on the concentrations of NO3, K, and Ca and remaining volume of the recycled nutrient solution. In the performance assessment based on five nutrient solution samples encompassing the typical concentration ranges for leafy vegetable cultivation, the ion-selective electrode array demonstrated feasible accuracies, with root mean square errors of 29.5, 10.1, and 6.1 mg·L-1 for NO3, K, and Ca, respectively. In a five-step replenishment test involving varying target concentrations and nutrient solution volumes, the system formulated nutrient solutions according to the specified targets, exhibiting average relative errors of 10.6 ± 8.0%, 7.9 ± 2.1%, 8.0 ± 11.0%, and 4.2 ± 3.7% for the Ca, K, and NO3 concentrations and volume of the nutrient solution, respectively. Furthermore, the decision tree method helped reduce the total fertilizer injections and carbon emissions by 12.8% and 20.6% in the stepwise test, respectively. The findings demonstrate that the decision-tree-based dosing algorithm not only enables more efficient reuse of nutrient solution compared to the existing simplex method but also confirms the potential for reducing carbon emissions, indicating the possibility of sustainable agricultural development.

Does fragmented cancer care affect survival? Analysis of gastric cancer patients using national insurance claim data.

BACKGROUND: We aimed to investigate the association between fragmented cancer care in the early phase after cancer diagnosis and patient outcomes using national insurance claim data. METHODS: From a nationwide sampled cohort database, we identified National Health Insurance beneficiaries diagnosed with gastric cancer (ICD-10: C16) in South Korea during 2005-2013. We analyzed the results of a multiple logistic regression analysis using the generalized estimated equation model to investigate which patient and institution characteristics affected fragmented cancer care during the first year after diagnosis. Then, survival analysis using the Cox proportional hazard model was conducted to investigate the association between fragmented cancer care and five-year mortality. RESULTS: Of 2879 gastric cancer patients, 11.9% received fragmented cancer care by changing their most visited medical institution during the first year after diagnosis. We found that patients with fragmented cancer care had a higher risk of five-year mortality (HR: 1.310, 95% CI: 1.023-1.677). This association was evident among patients who only received chemotherapy or radiotherapy (HR: 1.633, 95% CI: 1.005-2.654). CONCLUSIONS: Fragmented cancer care was associated with increased risk of five-year mortality. Additionally, changes in the most visited medical institution occurred more frequently in either patients with severe conditions or patients who mainly visited smaller medical institutions. Further study is warranted to confirm these findings and examine a causal relationship between fragmented cancer care and survival.

CT-based visual grading system for assessment of hepatic steatosis: diagnostic performance and interobserver agreement.

BACKGROUND: Hepatic steatosis (HS) can be comprehensively assessed by visually comparing the hepatic and vessel attenuation on unenhanced computed tomography (CT). We aimed to evaluate the reliability and reproducibility of a CT-based visual grading system (VGS) for comprehensive assessment of HS. METHODS: In this retrospective study, a four-point VGS based on the visual comparison of liver and hepatic vessels was validated by six reviewers with diverse clinical experience using the unenhanced CT images of 717 potential liver donors. The diagnostic performance of VGS and quantitative indices (difference and ratio of the hepatic and splenic attenuation) to diagnose HS were evaluated using multi-reader multi-case receiver operating characteristics (ROC) analysis (reference: pathology). The interobserver agreement was assessed using Fleiss κ statistics. RESULTS: Using the VGS, all six reviewers showed areas under the ROC curves (AUROCs) higher than 0.9 for diagnosing total steatosis (TS) ≥ 30%, macrovesicular steatosis (MaS) ≥ 30%, and MaS ≥ 10%. No difference was noted between the AUROCs of the VGS and quantitative indices (p ≥ 0.1). The reviewers showed substantial agreement (Fleiss κ, 0.61). Most discrepancies occurred between the two lowest grades of VGS (81.5%; 233/283), in which most subjects (97.0%; 226/233) had a MaS < 10%. The average-reader sensitivity and specificity of the VGS were 0.80 and 0.94 to detect TS ≥ 30% and 0.93 and 0.81 to detect MaS ≥ 10%. CONCLUSION: VGS was reliable and reproducible in assessing HS. It may be useful as a non-invasive and simple tool for comprehensive HS assessment.

Geriatric assessment predicts nonfatal toxicities and survival for intensively treated older adults with AML.

Given that there are only a few prospective studies with conflicting results, we investigated the prognostic value of multiparameter geriatric assessment (GA) domains on tolerance and outcomes after intensive chemotherapy in older adults with acute myeloid leukemia (AML). In all, 105 newly diagnosed patients with AML who were older than age 60 years and who received intensive chemotherapy consisting of cytarabine and idarubicin were enrolled prospectively. Pretreatment GA included evaluations for social and nutritional support, cognition, depression, distress, and physical function. The median age was 64 years (range, 60-75 years), and 93% had an Eastern Cooperative Oncology Group performance score <2. Between 32.4% and 69.5% of patients met the criteria for impairment for each domain of GA. Physical impairment by the Short Physical Performance Battery (SPPB) and cognitive dysfunction by the Mini-Mental State Examination in the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Assessment Packet (MMSE-KC) were significantly associated with nonfatal toxicities, including grade 3 to 4 infections (SPPB, P = .024; MMSE-KC, P = .044), acute renal failure (SPPB, P = .013), and/or prolonged hospitalization (≥40 days) during induction chemotherapy (MMSE-KC, P = .005). Reduced physical function by SPPB and depressive symptoms by the Korean version of the short form of geriatric depression scales (SGDS-K) were significantly associated with inferior survival (SPPB, P = .027; SGDS-K, P = .048). Gait speed and sit-and-stand speed were the most powerful measurements for predicting survival outcomes. Notably, the addition of SPPB and SGDS-K, gait speed and SGDS-K, or sit-and-stand speed and SGDS-K significantly improved the power of existing survival prediction models. In conclusion, GA improved risk stratification for treatment decisions and may inform interventions to improve outcomes for older adults with AML. This study was registered at the Clinical Research Information Service as #KCT0002172.

Diagnostic performance of liver fibrosis assessment by quantification of liver surface nodularity on computed tomography and magnetic resonance imaging: systematic review and meta-analysis.

OBJECTIVES: To determine the diagnostic performance of the liver surface nodularity (LSN) score for assessment of hepatic fibrosis. METHODS: Major databases were searched to identify studies reporting the diagnostic performance of the LSN score published from January 2011 to April 2021. The pooled sensitivity and specificity of the LSN score in the diagnosis of significant fibrosis (F2-4), advanced fibrosis (F3-4), and liver cirrhosis (F4) were calculated using a bivariate random-effects model, and the summary areas under the hierarchical summary receiver operating characteristics curve (AUC) for each were calculated. Subgroup analysis was performed to explore the causes of study heterogeneity. RESULTS: Of 168 screened studies, six were included in the analysis. The pooled sensitivity, specificity, and AUC of the LSN score were 68% (95% confidence interval [CI], 45-84%), 89% (95% CI, 83-93%), and 0.90 (95% CI, 0.87-0.92), respectively, for the diagnosis of significant fibrosis; 88% (95% CI, 60-97%), 78% (95% CI, 57-90%), and 0.89 (95% CI, 0.86-0.91), respectively, for the diagnosis of advanced fibrosis; and 83% (95% CI, 71-91%), 80% (95% CI, 72-85%), and 0.87 (95% CI, 0.83-0.89), respectively, for the diagnosis of liver cirrhosis. Cutoff values of the LSN score affected study heterogeneity in the diagnosis of advanced fibrosis (p = 0.03) and liver cirrhosis (p = 0.01). Imaging modality (p = 0.01) and reference standard (p = 0.01) affected study heterogeneity in the diagnosis of liver cirrhosis. CONCLUSIONS: The LSN score showed good diagnostic performance in assessing the hepatic fibrosis stage. Additional investigations are needed to improve and standardize the LSN score. Key Points • The liver surface nodularity (LSN) score showed overall good diagnostic performance in assessing hepatic fibrosis. • The pooled sensitivity of the LSN score was highest in the diagnosis of advanced fibrosis (88%; 95% confidence interval [CI], 60-97%), and the pooled specificity was highest in the diagnosis of significant fibrosis (89%; 95% CI, 83-93%). • The diagnostic performance of the LSN score differed according to the cutoff value, imaging modality, and reference standard.

Comparison of 3-month cytogenetic and molecular assays for early assessment of long-term clinical impact after BCR-ABL1 tyrosine kinase inhibitor treatment in chronic myeloid leukemia.

To compare the clinical significance of 3-month cytogenetic and molecular monitoring, we analyzed 1,410 paired cytogenetic and molecular data from 705 chronic-phase chronic myeloid leukemia patients. Based on early cytogenetic response (ECyR, Ph+≤35 %) and molecular response (EMR, BCR-ABL1IS≤10 %) at 3 months, the patients were divided into four groups (group 1: ECyR + EMR, n = 560; group 2: no ECyR + EMR, n = 27; group 3: ECyR + no EMR, n = 55; group 4: no ECyR + no EMR, n = 63). By 10 years, major molecular response (MMR), deep molecular response (MR4.5), overall survival (OS), and progression-free survival (PFS) rates were significantly high in group 1 (P < 0.001). Comparing groups 2 and 3, the MMR (P = 0.096), MR4.5 (P = 0.945), OS (P = 0.832), and PFS (P = 0.627) rates tended to be higher in group 2, although not significantly. Thus, the cytogenetic assay can not only be useful but its addition may also provide a more precise prediction of MR4.5.

Integration of rotatable tandem applicator to conventional ovoid applicator toward complete framework of intensity modulated brachytherapy (IMBT) for cervical cancer.

A new tandem applicator with tungsten shield for Ir-192 radiation source used in intra-cavitary brachytherapy (ICBT) enabled intensity modulated brachytherapy (IMBT) in cervical cancer treatment through fluence-modulation by rotating shield. Our previous work employed group-wise and element-wise sparsity constraints for plan optimization of tandem applicator to minimizes the number of activated angles and source dwell points for delivery efficiency. It, however, did not incorporate the ovoid applicators into the optimizing process, which is generally used to prevent cancer recurrence. To integrate ovoid applicators to the new tandem applicator, this work proposed a comprehensive framework that modifies 1) dose deposition matrix for inverse planning, and 2) plan optimizing algorithm. The dose deposition matrix was newly formulated by the Monte-Carlo simulated dose distribution for 10 positions of ovoid applicators, followed by combining those with tandem-associated dose deposition matrix. The plan optimizing algorithm decomposed entire elements into tandem and ovoid applicators, which were governed by different constraints adaptive to specified plan objectives. The integrated framework was compared against conventional ICBT, and IMBT with tandem only for three patients with asymmetric dose distributions. Integrated IMBT framework resulted in the most optimal plans. Including fluence-modulation by rotating-shield outperformed conventional ICBT in dose sparing to critical organs. Adopting ovoid applicators to the optimization yielded more conformal dose distribution around inferior, laterally expanded region of target volume. The resulting plans reduced D5cc and D2cc by 30.9% and 27.8% for critical organs over conventional ICBT, and by 20.6% and 21.5% for target volume over IMBT with tandem only.

Development of a fully automatic deep learning system for L3 selection and body composition assessment on computed tomography.

As sarcopenia research has been gaining emphasis, the need for quantification of abdominal muscle on computed tomography (CT) is increasing. Thus, a fully automated system to select L3 slice and segment muscle in an end-to-end manner is demanded. We aimed to develop a deep learning model (DLM) to select the L3 slice with consideration of anatomic variations and to segment cross-sectional areas (CSAs) of abdominal muscle and fat. Our DLM, named L3SEG-net, was composed of a YOLOv3-based algorithm for selecting the L3 slice and a fully convolutional network (FCN)-based algorithm for segmentation. The YOLOv3-based algorithm was developed via supervised learning using a training dataset (n = 922), and the FCN-based algorithm was transferred from prior work. Our L3SEG-net was validated with internal (n = 496) and external validation (n = 586) datasets. Ground truth L3 level CT slice and anatomic variation were identified by a board-certified radiologist. L3 slice selection accuracy was evaluated by the distance difference between ground truths and DLM-derived results. Technical success for L3 slice selection was defined when the distance difference was < 10 mm. Overall segmentation accuracy was evaluated by CSA error and DSC value. The influence of anatomic variations on DLM performance was evaluated. In the internal and external validation datasets, the accuracy of automatic L3 slice selection was high, with mean distance differences of 3.7 ± 8.4 mm and 4.1 ± 8.3 mm, respectively, and with technical success rates of 93.1% and 92.3%, respectively. However, in the subgroup analysis of anatomic variations, the L3 slice selection accuracy decreased, with distance differences of 12.4 ± 15.4 mm and 12.1 ± 14.6 mm, respectively, and with technical success rates of 67.2% and 67.9%, respectively. The overall segmentation accuracy of abdominal muscle areas was excellent regardless of anatomic variation, with CSA errors of 1.38-3.10 cm2. A fully automatic system was developed for the selection of an exact axial CT slice at the L3 vertebral level and the segmentation of abdominal muscle areas.

Assessment of Myosteatosis on Computed Tomography by Automatic Generation of a Muscle Quality Map Using a Web-Based Toolkit: Feasibility Study.

BACKGROUND: Muscle quality is associated with fatty degeneration or infiltration of the muscle, which may be associated with decreased muscle function and increased disability. OBJECTIVE: The aim of this study is to evaluate the feasibility of automated quantitative measurements of the skeletal muscle on computed tomography (CT) images to assess normal-attenuation muscle and myosteatosis. METHODS: We developed a web-based toolkit to generate a muscle quality map by categorizing muscle components. First, automatic segmentation of the total abdominal muscle area (TAMA), visceral fat area, and subcutaneous fat area was performed using a predeveloped deep learning model on a single axial CT image at the L3 vertebral level. Second, the Hounsfield unit of each pixel in the TAMA was measured and categorized into 3 components: normal-attenuation muscle area (NAMA), low-attenuation muscle area (LAMA), and inter/intramuscular adipose tissue (IMAT) area. The myosteatosis area was derived by adding the LAMA and IMAT area. We tested the feasibility of the toolkit using randomly selected healthy participants, comprising 6 different age groups (20 to 79 years). With stratification by sex, these indices were compared between age groups using 1-way analysis of variance (ANOVA). Correlations between the myosteatosis area or muscle densities and fat areas were analyzed using Pearson correlation coefficient r. RESULTS: A total of 240 healthy participants (135 men and 105 women) with 40 participants per age group were included in the study. In the 1-way ANOVA, the NAMA, LAMA, and IMAT were significantly different between the age groups in both male and female participants (P≤.004), whereas the TAMA showed a significant difference only in male participants (male, P<.001; female, P=.88). The myosteatosis area had a strong negative correlation with muscle densities (r=-0.833 to -0.894), a moderate positive correlation with visceral fat areas (r=0.607 to 0.669), and a weak positive correlation with the subcutaneous fat areas (r=0.305 to 0.441). CONCLUSIONS: The automated web-based toolkit is feasible and enables quantitative CT assessment of myosteatosis, which can be a potential quantitative biomarker for evaluating structural and functional changes brought on by aging in the skeletal muscle.

Assessment of dosimetric leaf gap correction factor in Mobius3D commissioning affected by couch top.

This study assesses the dosimetric leaf gap (DLG) correction factor in Mobius3D commissioning affected by a couch top platform and calculates the optimal DLG value according to the point dose difference function. DLG optimizations were performed for 3 LINAC machines and a total of 30 patient volumetric modulated arc therapy plans (i.e., 10 plans per each LINAC). Point dose calculations were performed using an automatic dose calculation system in Mobius3D as well as Mobis3D calculation using a Mobius Verification Phantom (MVP)-based quality assurance plan with a carbon fiber couch top. Subsequently, the results were compared with measurement data. The averaged point dose measured for the MVP with a couch top decreased by approximately 2% relative to that without the couch top. The average of the optimal DLG factors increased by 1.153 mm due to the couch top effect for a dose decrease of 2% at the measured point. In the procedure of Mobius beam commissioning, users should adjust the DLG correction factor using a specific phantom (including MVP) with a couch top structure. If the DLG optimization were performed by using MVP automatic dose calculation system, the factor should be increased by approximately 1.2 mm per 2% dose difference considering user's couch top effect.

Does Diabetes Increase the Risk of Contracting COVID-19? A Population-Based Study in Korea.

BACKGROUND: This study aimed to determine the infection risk of coronavirus disease 2019 (COVID-19) in patients with diabetes (according to treatment method). METHODS: Claimed subjects to the Korean National Health Insurance claims database diagnosed with COVID-19 were included. Ten thousand sixty-nine patients with COVID-19 between January 28 and April 5, 2020, were included. Stratified random sampling of 1:5 was used to select the control group of COVID-19 patients. In total 50,587 subjects were selected as the control group. After deleting the missing values, 60,656 subjects were included. RESULTS: Adjusted odds ratio (OR) indicated that diabetic insulin users had a higher risk of COVID-19 than subjects without diabetes (OR, 1.25; 95% confidence interval [CI], 1.03 to 1.53; P=0.0278). In the subgroup analysis, infection risk was higher among diabetes male insulin users (OR, 1.42; 95% CI, 1.07 to 1.89), those between 40 and 59 years (OR, 1.66; 95% CI, 1.13 to 2.44). The infection risk was higher in diabetic insulin users with 2 to 4 years of morbidity (OR, 1.744; 95% CI, 1.003 to 3.044). CONCLUSION: Some diabetic patients with certain conditions would be associated with a higher risk of acquiring COVID-19, highlighting their need for special attention. Efforts are warranted to ensure that diabetic patients have minimal exposure to the virus. It is important to establish proactive care and screening tests for diabetic patients suspected with COVID-19 for timely disease diagnosis and management.

Trends in Hyperglycemic Crisis Hospitalizations and in- and out-of-Hospital Mortality in the Last Decade Based on Korean National Health Insurance Claims Data.

BACKGROUND: Hyperglycemic crisis is a metabolic emergency associated with diabetes mellitus. However, accurate epidemiologic information on cases of hyperglycemic crisis in Korea remains scarce. We evaluated trends in hyperglycemic crisis hospitalizations and in- and out-of-hospital mortality in Korea. We also predicted future trends. METHODS: We extracted claims data with hyperglycemic crisis as the principal diagnosis from the National Health Insurance Service database in Korea from January 2004 to December 2013. We investigated the numbers of claims with hyperglycemic crisis and identified trends in hyperglycemic crisis based on those claims data. We predicted future trends by statistical estimation. RESULTS: The total annual number of claims of hyperglycemic crisis increased from 2,674 in 2004 to 5,540 in 2013. Statistical analysis revealed an increasing trend in hyperglycemic crisis hospitalizations (P for trend <0.01). In contrast, the hospitalization rate per 1,000 diabetes cases showed a decreasing trend (P for trend <0.01) during this period. The mortality rate per 1,000 diabetes cases also showed a decreasing trend (P for trend <0.0001). However, no distinct linear trend in the case-related fatality rate at <60 days over the last decade was observed. The predicted number of annual claims of hyperglycemic crisis will increase by 2030. CONCLUSION: The number of hyperglycemic crisis hospitalizations in Korea increased in the last decade, although the hospitalization rate per 1,000 diabetes cases and mortality rate decreased. Also, the predicted number of annual claims will increase in the future. Thus, it is necessary to establish long-term healthcare policies to prevent hyperglycemic crisis.