LiverRisk score: An accurate, cost-effective tool to predict fibrosis, liver-related, and diabetes-related mortality in the general population.

BACKGROUND: Noninvasive and early assessment of liver fibrosis is of great significance and is challenging. We aimed to evaluate the predictive performance and cost-effectiveness of the LiverRisk score for liver fibrosis and liver-related and diabetes-related mortality in the general population. METHODS: The general population from the NHANES 2017-March 2020, NHANES 1999-2018, and UK Biobank 2006-2010 were included in the cross-sectional cohort (n = 3,770), along with the NHANES follow-up cohort (n = 25,317) and the UK Biobank follow-up cohort (n = 17,259). The cost-effectiveness analysis was performed using TreeAge Pro software. Liver stiffness measurements ≥10 kPa were defined as compensated advanced chronic liver disease (cACLD). FINDINGS: Compared to conventional scores, the LiverRisk score had significantly better accuracy and calibration in predicting liver fibrosis, with an area under the receiver operating characteristic curve (AUC) of 0.76 (0.72-0.79) for cACLD. According to the updated thresholds of LiverRisk score (6 and 10), we reclassified the population into three groups: low, medium, and high risk. The AUCs of LiverRisk score for predicting liver-related and diabetes-related mortality at 5, 10, and 15 years were all above 0.8, with better performance than the Fibrosis-4 score. Furthermore, compared to the low-risk group, the medium-risk and high-risk groups in the two follow-up cohorts had a significantly higher risk of liver-related and diabetes-related mortality. Finally, the cost-effectiveness analysis showed that the incremental cost-effectiveness ratio for LiverRisk score compared to FIB-4 was USD $18,170 per additional quality-adjusted life-year (QALY) gained, below the willingness-to-pay threshold of $50,000/QALY. CONCLUSIONS: The LiverRisk score is an accurate, cost-effective tool to predict liver fibrosis and liver-related and diabetes-related mortality in the general population. FUNDING: The National Natural Science Foundation of China (nos. 82330060, 92059202, and 92359304); the Key Research and Development Program of Jiangsu Province (BE2023767a); the Fundamental Research Fund of Southeast University (3290002303A2); Changjiang Scholars Talent Cultivation Project of Zhongda Hospital of Southeast University (2023YJXYYRCPY03); and the Research Personnel Cultivation Program of Zhongda Hospital Southeast University (CZXM-GSP-RC125).

Assessment of Calf Skeletal Muscle in Male Type 2 Diabetes Mellitus Patients With Different Courses Using T1ρ Mapping.

CONTEXT: The current clinical methods for detecting skeletal muscle complications of type 2 diabetes mellitus (T2DM) are invasive and insensitive. There is an urgent need for noninvasive assessment of skeletal muscle microstructure changes during the disease progression and treatment to assist the clinical management. OBJECTIVE: This work aimed to investigate the T2DM caused changes in the fast-twitch tibialis anterior (TA) and slow-twitch soleus (SOL) skeletal muscles using T1ρ magnetic resonance imaging (MRI). METHODS: This cross-sectional study took place from December 2014 to December 2020 at Zhongda Hospital Southeast University. A total of 26 new-onset and 15 long-term T2DM patients were enrolled, with the addition of 20 young and 13 older healthy volunteers as age-matched controls. T1ρ relaxation times of SOL and TA muscles in different groups were measured. Parametric and nonparametric tests were used to analyze the relationship between the T1ρ values in SOL and TA muscles and the length of illness, level of fasting blood glucose, and status of homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: T1ρ relaxation times of SOL and TA muscles both of new-onset and long-term T2DM patients were significantly higher than those of the young (P < .01, P < .05) and older healthy controls (P < .05, P < .01). Positive correlations were observed between the T1ρ relaxation times of the TA or SOL and the duration of T2DM (R2 = 0.420, R2 = 0.326), the level of fasting blood glucose (R2 = 0.253, R2 = 0.071) and HOMA-IR (R2 = 0.232, R2 = 0.414). CONCLUSION: Quantitative MRI measurement of T1ρ provides a noninvasive tool to assess T2DM-induced changes in the skeletal muscles of T2DM patients.

In vivo Monitoring and Assessment of Exogenous Mesenchymal Stem Cell-Derived Exosomes in Mice with Ischemic Stroke by Molecular Imaging.

PURPOSE: Mesenchymal stem cell-derived exosomes (MSC-exos) are considered an important restorative treatment for ischemic stroke. However, the migration ability and survival of exogenous MSC-exos remain unclear. Here, we investigated whether MSC-exos migrate into the ischemic brain and play a protective role against ischemic stroke. METHODS: MSC-exos labeled with DiR were injected intravenously into mice with ischemic stroke. Near-infrared fluorescence (NIRF) images were obtained on days 0, 1, 3, 5, 7, 10, and 14, and magnetic resonance (MR) images were obtained on days 1, 7 and 14. On day 14, the functional outcomes, angiogenesis, neurogenesis, and white matter remodeling were assessed, and Western blot assays were performed. RESULTS: Fluorescence signals from the MSC-exos appeared in the injured brain from day 1 and peaked on day 3. The immunofluorescence staining of the brain samples revealed that the MSC-exos were localized in neurons. The behavioral scores and T2-weighted imaging indicated that the MSC-exos improved neurological functional recovery after stroke. In addition, the in vivo MR-diffusion tensor imaging (DTI) indicated that the exogenous MSC-exos increased the fractional anisotropy (FA) value, fiber length, and fiber number ratio. Furthermore, in the mice with ischemic stroke treated with MSC-exos, angiogenesis and neurogenesis were significantly improved, and the expression of IL-1ß was reduced. CONCLUSION: MSC-exos can migrate into the brains of mice with ischemic stroke and exert therapeutic effects against ischemic stroke; therefore, MSC-exos may have broad clinical applications in the future.

Functional magnetic resonance imaging-based assessment of terlipressin vs. octreotide on renal function in cirrhotic patients with acute variceal bleeding (CHESS1903): study protocol of a multicenter randomized controlled trial.

BACKGROUND: Acute variceal bleeding is one of the critical complications in patients with liver cirrhosis. Severe renal vasoconstriction in consequence of low peripheral vascular resistance triggers the reduction of glomerular filtration rate (GFR), and thus induces acute kidney injury (AKI)/hepato-renal syndrome (HRS). Terlipressin and octreotide have been used in the management of cirrhotic patients with variceal bleeding. Also, terlipressin has been recommended as the international first-line pharmacological therapy for the treatment of HRS. In addition, the use of renal functional magnetic resonance imaging (fMRI) has become increasingly prevalent in research and clinical applications. However, the renal function-protective effect of terlipressin and octreotide and the value of fMRI in monitoring renal function remains unclear in patients with cirrhosis undergoing acute variceal bleeding. METHODS: This is a multicenter, randomized controlled trial (RCT). Participants will be 1:1 assigned randomly into either terlipressin or octreotide groups. Sixty participants with clinically and/or pathologically diagnosed cirrhosis and active gastroesophageal variceal bleeding (GVB) will be recruited in several sites in China. Participants will receive either the treatment of terlipressin or octreotide after assigned into each group. The primary end point for the trial is the renal function. The secondary end points are (I) renal perfusion; (II) renal blood oxygenation; (III) failure to control bleeding; (IV) intra-hospital rebleeding; (V) intra-hospital mortality; (VI) adverse events (AE); (VII) overall survival. Statistical analysis including multivariate Cox regression, Kaplan-Meier analysis with log-rank test, etc. will be conducted. DISCUSSION: The study will provide new insight into the protection of renal function in the process of the treatment of variceal bleeding in patients with cirrhosis. TRIAL REGISTRATION NUMBER: NCT04028323.

Diabetes risk assessment with imaging: a radiomics study of abdominal CT.

OBJECTIVES: To identify CT markers for screening of early type 2 diabetes and assessment of the risk of incident diabetes using a radiomics method. METHODS: The medical records of 26,947 inpatients were reviewed. A total of 690 patients were selected and allocated to a primary cohort, a validation cohort, and a prediction cohort and used to build prediction models for diabetes. Three radiomics signatures were constructed using CT image features extracted from three regions of interest, i.e., in the pancreas, liver, and psoas major muscle. By incorporating radiomics signatures and other markers, we built a radiomics nomogram that could be used to screen for early diabetes and predict future diabetes. RESULTS: Of the three abdominal organs for which radiomics signature were constructed, that of the pancreas showed the best discriminatory power for early diabetes screening and prediction (C-statistics of 0.833, 0.846, and 0.899 for the primary cohort, validation cohort, and prediction cohort, respectively). The sensitivity and specificity of the nomogram for prediction of 3-year incident diabetes were 0.827 and 0.807, respectively. CONCLUSIONS: This study presents alternative radiomics markers that have potential for use in screening for undiagnosed type 2 diabetes and prediction of 3-year incident diabetes. KEY POINTS: • CT images may provide useful information to evaluate the risk of developing diabetes. • Radiomics score for diabetes prediction is based on subtle changes of abdominal organs detected by CT. • The radiomics signature of pancreas, a combination of five features of CT images, is efficient for early diabetes screening and prediction of future diabetes (AUC > 0.8).

Thermal Boundary Conductance Across Heteroepitaxial ZnO/GaN Interfaces: Assessment of the Phonon Gas Model.

We present experimental measurements of the thermal boundary conductance (TBC) from 78-500 K across isolated heteroepitaxially grown ZnO films on GaN substrates. This data provides an assessment of the underlying assumptions driving phonon gas-based models, such as the diffuse mismatch model (DMM), and atomistic Green's function (AGF) formalisms used to predict TBC. Our measurements, when compared to previous experimental data, suggest that TBC can be influenced by long wavelength, zone center modes in a material on one side of the interface as opposed to the '"vibrational mismatch"' concept assumed in the DMM; this disagreement is pronounced at high temperatures. At room temperature, we measure the ZnO/GaN TBC as 490[+150,-110] MW m-2 K-1. The disagreement among the DMM and AGF, and the experimental data at elevated temperatures, suggests a non-negligible contribution from other types of modes that are not accounted for in the fundamental assumptions of these harmonic based formalisms, which may rely on anharmonicity. Given the high quality of these ZnO/GaN interfaces, these results provide an invaluable, critical, and quantitative assessment of the accuracy of assumptions in the current state of the art computational approaches used to predict phonon TBC across interfaces.

MDTS: automatic complex materials design using Monte Carlo tree search.

Complex materials design is often represented as a black-box combinatorial optimization problem. In this paper, we present a novel python library called MDTS (Materials Design using Tree Search). Our algorithm employs a Monte Carlo tree search approach, which has shown exceptional performance in computer Go game. Unlike evolutionary algorithms that require user intervention to set parameters appropriately, MDTS has no tuning parameters and works autonomously in various problems. In comparison to a Bayesian optimization package, our algorithm showed competitive search efficiency and superior scalability. We succeeded in designing large Silicon-Germanium (Si-Ge) alloy structures that Bayesian optimization could not deal with due to excessive computational cost. MDTS is available at https://github.com/tsudalab/MDTS.

Noninvasive assessment of age, gender, and exercise effects on skeletal muscle: Initial experience with T1 ρ MRI of calf muscle.

PURPOSE: To prospectively investigate age- and gender-related changes in the fast-twitch (tibialis anterior, TA) and slow-twitch (soleus, SOL) skeletal muscle of healthy rats and volunteers and to compare the exercise-related difference in health volunteers with T1 ρ magnetic resonance imaging (MRI). MATERIALS AND METHODS: In all, 18 rats and 70 humans were involved in this study. For the animal study, T1 ρ relaxation times were measured in the TA and SOL rat muscle with a 3.0T MRI scanner and compared to histological data. For the human study, three groups (young, middle-aged, and elderly) of volunteers underwent T1 ρ MRI scans (3.0T) of their calves. To further differentiate the human scans, 18 volunteers were recruited, half of them (n = 9) routinely trained with high-intensity sports, while the other half (n = 9) with no physical training. Statistical analysis was performed via paired t-test, independent-sample t-test, and analysis of variance (ANOVA). Correlations between T1 ρ and age/gender/physical endurance were calculated. RESULTS: The average T1 ρ relaxation times of the TA and SOL of female rats were higher than that of male rats (P < 0.001). The T1 ρ relaxation time of TA was significantly lower compared to SOL (P < 0.001). A significant linear correlation was observed between T1 ρ and the type I slow-twitch fiber proportion (%) in SOL (R2 = 0.837, P < 0.001). Similarly, in human studies the average T1 ρ relaxation times of TA were significantly lower than SOL for all age groups (P < 0.001). The higher T1 ρ relaxation times of TA and SOL in the elderly volunteers (P < 0.001) and in the females (P < 0.05) indicated significant age- and gender-dependent differences. In high-intensity sports groups, the higher T1 ρ in SOL (P < 0.01) and lower in TA (P < 0.05) were observed compared with the control group. CONCLUSION: This study demonstrated that T1 ρ MRI can be used to display the differences in fast- and slow-twitch skeletal muscle as well as potentially age-, gender-, and exercise-related differences. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:61-70.

Value of CT and clinical criteria in assessment of patients with acute pancreatitis.

OBJECTIVE: To re-assess the value of CT and clinical criteria as prognostic and severity indicators in acute pancreatitis and the correlation between them. METHODS: Sixty-five cases with acute pancreatitis (AP) were included in the study. The hospitalization days, fevering days and overall complications were regarded as clinical endpoints for the patient group. CT criteria used for AP evaluation included Balthazar's plain CT scan score, CT severity index (CTSI) and London's pancreatic size index (PSI) score. Clinical criteria was Ranson score. The correlations between each criterion and the clinical endpoints, and the relation between CT and clinical criteria were analyzed. The power of each criterion and combination of CT and clinical criteria in predicting overall complications of AP were assessed and compared by using a receiver operative characteristic curve (ROC) analysis. RESULTS: The mean scores of PSI, Ranson among the three groups classified according to overall complications were significantly different. Except Balthazar's plain CT scan criterion, each criterion's mean score in-groups with local complications was significantly higher than that in-group without. The overall complications were significantly more in severe group than that in mild group classified according to each criterion except plain CT scan criterion. Mean days of hospital stay and fevering were significantly longer in severe group with Ranson score than that in mild group. PSI and Ranson score had a linear correlation with fevering days, and Ranson score had a linear correlation with hospitalization days. In CT criteria, only PSI had a linear correlation with Ranson score. The findings of plain CT scan was found to be some laggard compared with that of clinic. ROC analysis showed the largest A(Z) of Ranson score, and there was no A(Z) increase when CT criteria were added to clinical criteria. CONCLUSION: The predictive values of Ranson and PSI score in AP patients are superior to that of other criteria. CT criteria are superior to clinical criterion in predicting local complications, and short-term CT follow-up examination is important in the evaluation of AP.