Multitask deep learning for prediction of microvascular invasion and recurrence-free survival in hepatocellular carcinoma based on MRI images.

BACKGROUND AND AIMS: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence-free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. METHODS: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). RESULTS: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter-rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C-index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA-TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p < .001). CONCLUSIONS: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria.

Genetic variations of CYP3A4 on the metabolism of itraconazole in vitro.

Itraconazole is a triazole anti-infective drug that has been proven to prevent and treat a variety of fungal and viral infections and has been considered to be a potential therapeutic remedy for COVID-19 treatment. In this study, we aimed to completely evaluate the impacts of Cytochrome P450 3A4 (CYP3A4) variant proteins and drug interactions on the metabolism of itraconazole in recombinant insect microsomes, and to characterize the potential mechanism of substrate selectivity. Incubations with itraconazole (0.2-15 µM) in the presence/absence of lopinavir or darunavir were assessed by CYP3A4 variants, and the metabolite hydroxyitraconazole concentrations were measured by UPLC-MS/MS. Our data showed that when compared with CYP3A4.1, 4 variants (CYP3A4.9, .10, .28 and .34) displayed no significant differences, and 3 variants (CYP3A4.14, .15 and .19) exhibited increased intrinsic clearance (CLint), whereas the remaining 17 variant proteins showed decreased enzyme activities for the catalysis of itraconazole. Moreover, the inhibitory effects of lopinavir and darunavir on itraconazole metabolism varied in different degrees. Furthermore, different changed trend of the kinetic parameters in ten variants (CYP3A4.5, .9, .10, .16, .19, .24, .28, .29, .31, and .33) were observed, especially CYP3A4.5 and CYP3A4.16, and this may be related to the metabolic site-heme iron atom distance. In the present study, we functionally analyzed the effects of 25 CYP3A4 protein variants on itraconazole metabolism for the first time, and provided comprehensive data on itraconazole metabolism in vitro. This may help to better assess the metabolism and elimination of itraconazole in clinic to improve the safety and efficacy of its clinical treatment and also provide new possibilities for the treatment of COVID-19.

An ultrasound-based radiomics model for survival prediction in patients with endometrial cancer.

PURPOSE: To establish a nomogram integrating radiomics features based on ultrasound images and clinical parameters for predicting the prognosis of patients with endometrial cancer (EC). MATERIALS AND METHODS: A total of 175 eligible patients with ECs were enrolled in our study between January 2011 and April 2018. They were divided into a training cohort (n = 122) and a validation cohort (n = 53). Least absolute shrinkage and selection operator (LASSO) regression were applied for selection of key features, and a radiomics score (rad-score) was calculated. Patients were stratified into high risk and low-risk groups according to the rad-score. Univariate and multivariable COX regression analysis was used to select independent clinical parameters for disease-free survival (DFS). A combined model based on radiomics features and clinical parameters was ultimately established, and the performance was quantified with respect to discrimination and calibration. RESULTS: Nine features were selected from 1130 features using LASSO regression in the training cohort, which yielded an area under the curve (AUC) of 0.823 and 0.792 to predict DFS in the training and validation cohorts, respectively. Patients with a higher rad-score were significantly associated with worse DFS. The combined nomogram, which was composed of clinically significant variables and radiomics features, showed a calibration and favorable performance for DFS prediction (AUC 0.893 and 0.885 in the training and validation cohorts, respectively). CONCLUSION: The combined nomogram could be used as a tool in predicting DFS and may assist individualized decision making and clinical treatment.

Effect of MED-02 Containing Two Probiotic Strains, Limosilactobacillus fermentum MG4231 and MG4244, on Body Fat Reduction in Overweight or Obese Subjects: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Study.

MED-02 is a complex supplement containing two probiotic strains, Limosilactobacillus fermentum MG4231 and MG4244, isolated from humans. The anti-obesity effects and safety profile of MED-02 were assessed in overweight and obese subjects. In this randomized, double-blinded, placebo-controlled, multicenter study, 100 healthy obese and overweight subjects aged 19-65 years with a body mass index (BMI) between 25 and 31.9 kg/m2 were recruited and randomized to receive a placebo or MED-02 (5 × 109 CFU/day). After 12 weeks of consumption, body fat mass (-1166.82 g vs. -382.08 g; p = 0.024) and body fat percentage (-0.85% vs. -0.11%; p = 0.030), as evaluated by dual-energy X-ray absorptiometry (DEXA) and body weight (-2.06 kg vs. -1.22 kg; p = 0.041), were significantly reduced in the MED-02 group compared to the placebo group. The safety profile did not differ among the groups. No serious adverse effects were observed in either group. These results suggest that MED-02 is a safe and beneficial probiotics that reduces body fat and body weight in overweight or obese individuals.

Bio-inspired Superwettable Surface for the Detection of Cancer Biomarker: A Mini Review.

Inspired by nature, superwettable material-based biosensors have aroused wide interests due to their potential in cancer biomarker detection. This mini review mainly summarized the superwettable materials as novel biosensing substrates for the development of evaporation-induced enrichment-based signal amplification and visual biosensing method. Biosensing applications based on the superhydrophobic surfaces, superwettable micropatterned surfaces, and slippery lubricant-infused porous surfaces for various cancer biomarker detections were described in detail. Finally, an insight of remaining challenges and perspectives of superwettable biosensor is proposed.

Current Status of Physical Activity in South Korea.

The health benefits of physical activity have been well established. However, more than a quarter of the adult population in the world is insufficiently active (not performing at least 150 minutes of moderate-intensity physical activity per week, 75 minutes of vigorous-intensity physical activity per week, or any equivalent combination of the two), and there has been little improvement since 2001. In South Korea, the prevalence of insufficient physical activity was 54.4% in adults and 94.1% in adolescents in 2020. There was continuous decrease in the prevalence of sufficient aerobic physical activity, from 58.3% in 2014 to 45.6% in 2020. However, daily duration of sedentary behavior increased from 7.5 to 8.6 hours in the same period. Interventions to promote physical activity are necessary in various fields including clinical and policy approaches. As physical activity has decreased during the coronavirus disease 2019 pandemic, safer and more effective strategies to promote physical activity are required.

Analysis of Continuity of Care and Its Related Factors in Diabetic Patients: A Cross-Sectional Study.

BACKGROUND: Continuity of care in primary care settings is crucial for managing diabetes. We aimed to statistically define and analyze continuity factors associated with demographics, clinical workforce, and geographical relationships. METHODS: We used 2014-2015 National Health Insurance Service claims data from the Korean registry, with 39,096 eligible outpatient attendance. We applied multivariable logistic regression to analyze factors that may affect the continuity of care indices for each patient: the most frequent provider continuity index (MFPCI), modified-modified continuity index (MMCI), and continuity of care index (COCI). RESULTS: The mean continuity of care indices were 0.90, 0.96, and 0.85 for MFPCI, MMCI and COCI, respectively. Among patient factors, old age >80 years (MFPCI: odds ratio [OR], 0.81; 95% confidence interval [CI], 0.74-0.89; MMCI: OR, 0.84; 95% CI, 0.76-0.92; and COCI: OR, 0.81; 95% CI, 0.74-0.89) and mild disability were strongly associated with lower continuity of care. Another significant factor was the residential area: the farther the patients lived from their primary care clinic, the lower the continuity of diabetes care (MFPCI: OR, 0.74; 95% CI, 0.70-0.78; MMCI: OR, 0.70; 95% CI, 0.66-0.73; and COCI: OR, 0.74; 95% CI, 0.70-0.78). CONCLUSION: The geographical proximity of patients' residential areas and clinic locations showed the strongest correlation as a continuity factor. Further efforts are needed to improve continuity of care to address the geographical imbalance in diabetic care.

Superwettable Biosensor for Disease Biomarker Detection.

Bioinspired superwettable materials have aroused wide interests in recent years for their promising application fields from service life to industry. As one kind of emerging application, the superwettable surfaces used to fabricate biosensors for the detection of disease biomarkers, especially tumor biomarkers, have been extensively studied. In this mini review, we briefly summarized the sensing strategy for disease biomarker detection based on superwettable biosensors, including fluorescence, electrochemistry, surface-enhanced Raman scattering, and visual assays. Finally, the challenges and direction for future development of superwettable biosensors are also discussed.

An MRI-based radiomics signature and clinical characteristics for survival prediction in early-stage cervical cancer.

OBJECTIVES: To investigate the prognostic role of magnetic resonance imaging (MRI)-based radiomics signature and clinical characteristics for overall survival (OS) and disease-free survival (DFS) in the early-stage cervical cancer. METHODS: A total of 207 cervical cancer patients (training cohort: n = 144; validation cohort: n = 63) were enrolled. 792 radiomics features were extracted from T2W and diffusion-weighted imaging (DWI). 19 clinicopathological parameters were collected from the electronic medical record system. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to select significant features to construct prognostic model for OS and DFS. Kaplan-Meier (KM) analysis and log-rank test were applied to identify the association between the radiomics score (Rad-score) and survival time. Nomogram discrimination and calibration were evaluated as well. Associations between radiomics features and clinical parameters were investigated by heatmaps. RESULTS: A radiomics signature derived from joint T2W and DWI images showed better prognostic performance than that from either T2W or DWI image alone. Higher Rad-score was associated with worse OS (p < 0.05) and DFS (p < 0.05) in the training and validation set. The joint models outperformed both radiomics model and clinicopathological model alone for 3-year OS and DFS estimation. The calibration curves reached an agreement. Heatmap analysis demonstrated significant associations between radiomics features and clinical characteristics. CONCLUSIONS: The MRI-based radiomics nomogram showed a good performance on survival prediction for the OS and DFS in the early-stage cervical cancer. The prediction of the prognostic models could be improved by combining with clinical characteristics, suggesting its potential for clinical application. ADVANCES IN KNOWLEDGE: This is the first study to build the radiomics-derived models based on T2W and DWI images for the prediction of survival outcomes on the early-stage cervical cancer patients, and further construct a combined risk scoring system incorporating the clinical features.

Predicting intraventricular hemorrhage growth with a machine learning-based, radiomics-clinical model.

We constructed a radiomics-clinical model to predict intraventricular hemorrhage (IVH) growth after spontaneous intracerebral hematoma. The model was developed using a training cohort (N=626) and validated with an independent testing cohort (N=270). Radiomics features and clinical predictors were selected using the least absolute shrinkage and selection operator (LASSO) method and multivariate analysis. The radiomics score (Rad-score) was calculated through linear combination of selected features multiplied by their respective LASSO coefficients. The support vector machine (SVM) method was used to construct the model. IVH growth was experienced by 13.4% and 13.7% of patients in the training and testing cohorts, respectively. The Rad-score was associated with severe IVH and poor outcome. Independent predictors of IVH growth included hypercholesterolemia (odds ratio [OR], 0.12 [95%CI, 0.02-0.90]; p=0.039), baseline Graeb score (OR, 1.26 [95%CI, 1.16-1.36]; p<0.001), time to initial CT (OR, 0.70 [95%CI, 0.58-0.86]; p<0.001), international normalized ratio (OR, 4.27 [95%CI, 1.40, 13.0]; p=0.011), and Rad-score (OR, 2.3 [95%CI, 1.6-3.3]; p<0.001). In the training cohort, the model achieved an AUC of 0.78, sensitivity of 0.83, and specificity of 0.66. In the testing cohort, AUC, sensitivity, and specificity were 0.71, 0.81, and 0.64, respectively. This radiomics-clinical model thus has the potential to predict IVH growth.

Analysis of the Comprehensiveness of Primary Care Clinics in Korea.

BACKGROUND: In the Republic of Korea, which medical specialties should take the responsibility for primary care and what the role of primary care should be are still unclear. In this study, we focused on the comprehensiveness of primary care to identify related factors. METHODS: The National Health Insurance Service (NHIS)-National Sample Cohort is a population-based cohort, sampled in the 2002 NHIS database and followed up until 2015. We used data collected from January 2014 to December 2015, including 20,423,832 outpatient visits in 19,557 office-based clinics. The Korean government has designated 52 simple or minor disease groups (SMDGs) to enhance the experience of patients who attend primary care for managing those diseases. We assessed comprehensiveness for each clinic as the number of SMDGs treated in each clinic for 2 years. We also identified the factors related to higher comprehensiveness, using logistic regression for analysis. RESULTS: The clinics included in the study had provided treatment for an average of 14 SMDGs during a 2-year period. Compared to general practitioners, internal medicine physicians presented higher comprehensiveness with an odds ratio (OR) of 2.29 (95% confidence interval [CI], 2.03-2.59), and family medicine physicians illustrated higher comprehensiveness (OR, 4.96; 95% CI, 3.59-6.83). Other specialties showed lower comprehensiveness than general practitioners. Clinics located in the capital city and metropolitan area tended to have lower comprehensiveness. Clinics hiring more doctors and having hospitalization facility showed higher comprehensiveness. CONCLUSION: General physician, internal medicine, and family medicine are the fields providing comprehensive medical care in Korea. Clinics located in metropolitan area and capital city show lower comprehensiveness. The number of physicians is related to higher comprehensiveness of clinics.

Radiomics-based model for accurately distinguishing between severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) and influenza A infected pneumonia.

Clinicians have been faced with the challenge of differentiating between severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) infected pneumonia (NCP) and influenza A infected pneumonia (IAP), a seasonal disease that coincided with the outbreak. We aim to develop a machine-learning algorithm based on radiomics to distinguish NCP from IAP by texture analysis based on computed tomography (CT) imaging. Forty-one NCP and 37 IAP patients admitted from January to February 6, 2019 admitted to two hospitals in Wenzhou, China. All patients had undergone chest CT examination and blood routine tests prior to receiving medical treatment. NCP was diagnosed by real-time RT-PCR assays. Eight of 56 radiomic features extracted by LIFEx were selected by least absolute shrinkage and selection operator regression to develop a radiomics score and subsequently constructed into a nomogram to predict NCP with area under the operating characteristics curve of 0.87 (95% confidence interval: 0.77-0.93). The nomogram also showed excellent calibration with Hosmer-Lemeshow test yielding a nonsignificant statistic (P = .904). The novel nomogram may efficiently distinguish between NCP and IAP patients. The nomogram may be incorporated to existing diagnostic algorithm to effectively stratify suspected patients for SARS-CoV-2 pneumonia.

Penumbra-based radiomics signature as prognostic biomarkers for thrombolysis of acute ischemic stroke patients: a multicenter cohort study.

BACKGROUND AND PURPOSE: This study aimed at developing a radiomics signature (R score) as prognostic biomarkers based on penumbra quantification and to validate the radiomics nomogram to predict the clinical outcomes for thrombolysis for acute ischemic stroke (AIS) patients. METHODS: In total, 168 patients collected from seven centers were retrospectively included. A score of mismatch was defined as MIS. Based on a short-term clinical label, 456 radiomics features were evaluated with feature selection methods. R score was constructed with the selected features. To compare the predictive capabilities of the clinical factors, MIS, and R score, three nomograms were developed and evaluated, according to the short-term clinical assessment on day 7. Finally, the radiomics nomogram was validated by predicting the 3-month clinical outcomes of AIS patients, in an external cohort. RESULTS: R scores were found to be significantly higher in patients with favorable clinical outcomes in both training and validation datasets. The predictive value of the radiomics nomogram estimating favorable clinical outcomes was modest, with a concordance index (C-index) of 0.695 [95% confidence interval (CI) 0.667-0.723) in an external validation dataset. In addition, the area under curve (AUC) of the radiomics nomogram predicting favorable clinical outcome reached 0.886 (95% CI 0.809-0.963) on day 7 and 0.777 (95% CI 0.666-0.888) at 3 months. CONCLUSIONS: The radiomics signature is an independent biomarker for estimating the clinical outcomes in AIS patients. By improving the individualized prediction of the clinical outcome for AIS patients 3 months after onset, the radiomics nomogram adds more value to the current clinical decision-making process.

An Overview of Current Physical Activity Recommendations in Primary Care.

Primary care physicians should encourage their patients to engage in adequate physical activity. Current recommendations for physical activity in adults are as follows: at least 150-300 minutes per week of moderate-intensity, 75-150 minutes per week of vigorous-intensity aerobic physical activity, or an equivalent combination of moderate- and vigorous-intensity aerobic activity. Adults should also perform muscle-strengthening activities of moderate intensity or higher that involve all major muscle groups for 2 or more days per week. The elderly should perform additional balance training and fall prevention exercises more than 3 times a week. Children and adolescents should perform at least 1 hour of moderate-to-vigorous physical activity daily, which includes vigorous aerobic activity at least 3 days per week. As part of their 60 minutes or more of daily physical activity, resistance training and bone strengthening exercise should be done at least 3 days per week. According to new evidence, one bout of any exercises can be shorter than 10 minutes. Previously, physical activities were recommended for more than 10 minutes. For patients with diabetes, it is advisable to perform resistance exercise or short-distance running before aerobic exercise to prevent hypoglycemia. New evidence shows that dynamic resistance training is safe and effective in patients with hypertension provided the load is not too heavy. Exercise reduces pain and improves quality of life and physical function in patients with osteoarthritis,. Therefore, the treatment guidelines for osteoarthritis have been changed recently from not recommending exercise to highly recommending it.

Comparative Decellularization and Recellularization of Normal Versus Streptozotocin-Induced Diabetes Mellitus Rat Pancreas.

Decellularized (DC) organs/tissues offer a promising scaffold for regenerative bioengineering. However, it is not clear whether the diabetic mellitus (DM) pancreas can be used in decellularized and recellularized bioengineering. For assessment of these questions, murine pancreatic scaffolds of normal, type 1DM (T1DM) and type 2 DM (T2DM) pancreas were generated using a perfusion decellularization technique and assessed by histology, scanning electron microscopy, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). The capacity of DC pancreatic scaffolds to support attachment and proliferation of human umbilical vein endothelial cells (HUVECs) and MIN-6 ß cells was also assessed. Our results showed that DC pancreatic scaffolds were successfully produced from T1DM and T2DM pancreas and maintained their extracellular matrix (ECM) composition, 3D ultrastructure, and various cytokines. All of the pancreatic scaffolds were sufficiently cytocompatible and were able to support proliferation and adhesion of HUVECs and MIN-6 ß cells. The preliminary results support the biological utility of diabetes mellitus pancreatic scaffolds and pave the way for further investigations to assess the potential ability of using diabetes mellitus pancreas as scaffolds for recellularization and eventual medical applications.

Development and validation of a penumbra-based predictive model for thrombolysis outcome in acute ischemic stroke patients.

The use of thrombolysis in acute ischemic stroke is restricted to a small proportion of patients because of the rigid 4·5-h window. With advanced imaging-based patient selection strategy, rescuing penumbra is critical to improving clinical outcomes. In this study, we included 155 acute ischemic stroke patients (84 patients in training dataset, age from 43 to 80, 59 males; 71 patients in validation dataset, age from 36 to 80, 45 males) who underwent MR scan within the first 9-h after onset, from 7 independent centers. Based on the mismatch concept, penumbra and core area were identified and quantitatively analyzed. Moreover, predictive models were developed and validated to provide an approach for identifying patients who may benefit from thrombolytic therapy. Predictive models were constructed, and corresponding areas under the curve (AUC) were calculated to explore their performances in predicting clinical outcomes. Additionally, the models were validated using an independent dataset both on Day-7 and Day-90. Significant correlations were detected between the mismatch ratio and clinical assessments in both the training and validation datasets. Treatment option, baseline systolic blood pressure, National Institutes of Health Stroke Scale score, mismatch ratio, and three regional radiological parameters were selected as biomarkers in the combined model to predict clinical outcomes of acute ischemic stroke patients. With the external validation, this predictive model reached AUCs of 0·863 as short-term validation and 0·778 as long-term validation. This model has the potential to provide quantitative biomarkers that aid patient selection for thrombolysis either within or beyond the current time window.

Effect of high-dose ginsenoside complex (UG0712) supplementation on physical performance of healthy adults during a 12-week supervised exercise program: A randomized placebo-controlled clinical trial.

BACKGROUND: Ginseng has been used as an ergogenic agent, although evidence for its effectiveness is weak. A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the effect of a ginsenoside complex (UG0712) on changes in exercise performance. METHODS: Sedentary individuals (n = 117) were randomly assigned into one of three groups: low-dose ginsenoside supplementation (100 mg/d, n = 39), high-dose ginsenoside supplementation (500 mg/d, n = 39), or a placebo group (500 mg/d, n = 39). All participants underwent a supervised 12-wk aerobic and resistance exercise training course. To assess the effects of supplementation on physical performance, maximal oxygen consumption (VO2max), anaerobic threshold (AT), lactic acid, and muscle strength of the dominant knee were measured at baseline, every visit, and after the training program. RESULTS: Both ginsenoside groups showed significant increases in VO2max and muscular strength during exercise training. There were no definite changes in AT and lactic acid levels over time. After exercise training, there were definite differences in the VO2max (28.64.9 to 33.7 ± 4.9 ml/kg/min in high-dose group vs. 30.4 ± 6.7 to 32.8 ± 6.6 ml/kg/min in placebo, p = 0.029) and AT (19.3 ± 4.2 to 20.9 ± 3.5 ml/kg/min in high-dose group vs. 20.0 ± 5.1 to 20.0 ± 4.9 ml/kg/min in placebo, p = 0.038) between the high-dose ginsenoside and placebo groups. However, there was no difference in VO2max between the low-dose ginsenoside and placebo groups (p = 0.254). There were no differences in muscular strength during exercise training among the three groups. CONCLUSION: High-dose ginsenoside supplementation (UG0712) augmented the improvement of aerobic capacity by exercise training.

Elderly population have a decreased aneurysmal subarachnoid hemorrhage incidence rate than Middle aged population: a descriptive analysis of 8,144 cases in mainland China.

PURPOSE: Rupture of an intracranial aneurysm is a life-threatening acute cerebrovascular event. The purpose of this study was to investigate whether aneurysmal subarachnoid haemorrhage (SAH) incidence rate is higher or lower in elderly population than in middle aged population. MATERIALS AND METHODS: Aneurysmal SAH cases were collected retrospectively from the archives of 21 hospitals in Mainland China. All the cases were collected from September 2016 and backward consecutively for a period of time up to 8 years. SAH was initially diagnosed by brain computed tomography (CT). CT angiography (CTA) or digital subtraction angiography (DSA) was followed and SAH was confirmed to be due to cerebral aneurysm rupture. For cases when multiple bleeding occurred, the age of the first SAH was used in this study. The total incidence from all hospitals at each age group were summed together for females and males respectively; then adjusted by the total population number at each age group for females and males which was from the 2010 population census of the People's Republic of China. RESULTS: In total there were 8,144 cases of intracranial aneurysmal SAH, with 4,861 females and 3,283 males. For females the relative aneurysmal SAH incidence rate started to decrease after around 65 years old, while for males the relative aneurysmal SAH incidence rate started to decrease after around 53 years old. CONCLUSION: Our data tentatively suggest elderly patients may be at a reduced risk of rupture compared with patients who are younger while have similar other risk factors.