Assessment of the Added Value of Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging in Identifying Non-Diabetic Renal Disease in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Identification of non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus (T2DM) may help tailor treatment. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is a promising tool to evaluate renal function but its potential role in the clinical differentiation between diabetic nephropathy (DN) and NDRD remains unclear. PURPOSE: To investigate the added role of IVIM-DWI in the differential diagnosis between DN and NDRD in patients with T2DM. STUDY TYPE: Prospective. POPULATION: Sixty-three patients with T2DM (ages: 22-69 years, 17 females) confirmed by renal biopsy divided into two subgroups (28 DN and 35 NDRD). FIELD STRENGTH/SEQUENCE: 3 T/ T2 weighted imaging (T2WI), and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). ASSESSMENT: The parameters derived from IVIM-DWI (true diffusion coefficient [D], pseudo-diffusion coefficient [D*], and pseudo-diffusion fraction [f]) were calculated for the cortex and medulla, respectively. The clinical indexes related to renal function (eg cystatin C, etc.) and diabetes (eg diabetic retinopathy [DR], fasting blood glucose, etc.) were measured and calculated within 1 week before MRI scanning. The clinical model based on clinical indexes and the IVIM-based model based on IVIM parameters and clinical indexes were established and evaluated, respectively. STATISTICAL TESTS: Student's t-test; Mann-Whitney U test; Fisher's exact test; Chi-squared test; Intraclass correlation coefficient; Receiver operating characteristic analysis; Hosmer-Lemeshow test; DeLong's test. P < 0.05 was considered statistically significant. RESULTS: The cortex D*, DR, and cystatin C values were identified as independent predictors of NDRD in multivariable analysis. The IVIM-based model, comprising DR, cystatin C, and cortex D*, significantly outperformed the clinical model containing only DR, and cystatin C (AUC = 0.934, 0.845, respectively). DATA CONCLUSION: The IVIM parameters, especially the renal cortex D* value, might serve as novel indicators in the differential diagnosis between DN and NDRD in patients with T2DM. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging and Venous Tumor Thrombus Consistency in Renal Cell Carcinoma.

BACKGROUND: Venous tumor thrombus (VTT) consistency of renal cell carcinoma (RCC) is an important consideration in nephrectomy plus thrombectomy. However, evaluation of VTT consistency through preoperative MR imaging is lacking. PURPOSE: To evaluate VTT consistency of RCC through intravoxel incoherent motion-diffusion weighted imaging (IVIM-DWI) derived parameters (Dt , Dp , f, and ADC) and the apparent diffusion coefficient (ADC) value. STUDY TYPE: Retrospective. POPULATION: One hundred and nineteen patients (aged 55.8 ± 11.5 years, 85 male) with histologically-proven RCC and VTT who underwent radical resection. FIELD STRENGTH/SEQUENCES: 3.0-T; two-dimensional single-shot diffusion-weighted echo planar imaging sequence at 9 b-values (0-800 s/mm2 ). ASSESSMENT: IVIM parameters and ADC values of the primary tumor and the VTT were calculated. The VTT consistency (friable vs. solid) was determined through intraoperative findings of two urologists. The accuracy of VTT consistency classification based on the individual IVIM parameters of primary tumors and of VTT, and based on models combining parameters, was assessed. Type of operation, intra-operative blood loss, and operation length were recorded. STATISTICAL TESTS: Shapiro-Wilk test; Mann-Whitney U test; Student's t-test; Chi-square test; Receiver operating characteristic (ROC) analysis. Statistical significance level was P < 0.05. RESULTS: Of the enrolled 119 patients, 33 patients (27.7%) had friable VTT. Patients with friable VTT were significantly more likely to experience open surgery, have significantly more intraoperative blood loss, and significantly longer operative duration. The area under the ROC curve (AUC) values of Dt of the primary tumor and VTT in classifying VTT consistency were 0.758 (95% CI 0.671-0.832) and 0.712 (95% CI 0.622-0.792), respectively. The AUC value of the model combining Dp and Dt of VTT was 0.800 (95% CI 0.717-0.868). Furthermore, the AUC of the model combining Dp and Dt of VTT and Dt of the primary tumor was 0.886 (95% CI 0.814-0.937). CONCLUSION: IVIM-derived parameters had the potential to predict VTT consistency of RCC. EVIDENCE LEVEL: 3 Technical Efficacy: Stage 2.

Diagnostic Value of Clear Cell Likelihood Score v1.0 and v2.0 for Common Subtypes of Small Renal Masses: A Multicenter Comparative Study.

BACKGROUND: Clear cell likelihood score (ccLS) is reliable for diagnosing small renal masses (SRMs). However, the diagnostic value of Clear cell likelihood score version 1.0 (ccLS v1.0) and v2.0 for common subtypes of SRMs might be a potential score extension. PURPOSE: To compare the diagnostic performance and interobserver agreement of ccLS v1.0 and v2.0 for characterizing five common subtypes of SRMs. STUDY TYPE: Retrospective. POPULATION: 797 patients (563 males, 234 females; mean age, 53 ± 12 years) with 867 histologically proven renal masses. FIELD STRENGTH/SEQUENCES: 3.0 and 1.5 T/T2 weighted imaging, T1 weighted imaging, diffusion-weighted imaging, a dual-echo chemical shift (in- and opposed-phase) T1 weighted imaging, multiphase dynamic contrast-enhanced imaging. ASSESSMENT: Six abdominal radiologists were trained in the ccLS algorithm and independently scored each SRM using ccLS v1.0 and v2.0, respectively. All SRMs had definite pathological results. The pooled area under curve (AUC), accuracy, sensitivity, and specificity were calculated to evaluate the diagnostic performance of ccLS v1.0 and v2.0 for characterizing common subtypes of SRMs. The average κ values were calculated to evaluate the interobserver agreement of the two scoring versions. STATISTICAL TESTS: Random-effects logistic regression; Receiver operating characteristic analysis; DeLong test; Weighted Kappa test; Z test. The statistical significance level was P < 0.05. RESULTS: The pooled AUCs of clear cell likelihood score version 2.0 (ccLS v2.0) were statistically superior to those of ccLS v1.0 for diagnosing clear cell renal cell carcinoma (ccRCC) (0.907 vs. 0.851), papillary renal cell carcinoma (pRCC) (0.926 vs. 0.888), renal oncocytoma (RO) (0.745 vs. 0.679), and angiomyolipoma without visible fat (AMLwvf) (0.826 vs. 0.766). Interobserver agreement for SRMs between ccLS v1.0 and v2.0 is comparable and was not statistically significant (P = 0.993). CONCLUSION: The diagnostic performance of ccLS v2.0 surpasses that of ccLS v1.0 for characterizing ccRCC, pRCC, RO, and AMLwvf. Especially, the standardized algorithm has optimal performance for ccRCC and pRCC. ccLS has potential as a supportive clinical tool. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Kinetically Controlled Stereoselective Synthesis of 2-Oxo-2-aryl-1,3,2-dioxaphosphorinane Derivatives via a Palladium-Catalyzed Reaction.

Chiral phosphonate esters have been widely applied in the fields of organic chemistry, medicine, and photoelectric materials. However, it requires the challenging enantioselective synthesis of cyclic phosphonate esters with the desired chiral configuration. The two epimers of 2-oxo-2H-1,3,2-dioxaphosphorinane derivatives should have different reactivities in Pd-catalyzed coupling reactions, which could lead to an effective methodology for the asymmetric synthesis of 2-oxo-2-aryl-1,3,2-dioxaphosphorinane derivatives. A thorough investigation of the coupling reactions both computationally and experimentally led to the stereoselective synthesis of chiral cyclic phosphonate esters. The axial isomer of products can be obtained with both high diastereoselectivity and good chemical yields from the mixture of 2-oxo-2H-1,3,2-dioxaphosphorinane derivatives under kinetically controlled conditions.

Self-Assembly of Lanthanide-Aluminum Cluster-Organic Frameworks with Magnetocaloric Effect and Luminescence.

The self-assembly of the lanthanide metal-organic frameworks presents a formidable challenge but profound significance. Compared with the metal-organic frameworks based on 4f-3d ions, the chemistry of 4f-3p metal-organic frameworks has not been fully explored so far. In this study, two lanthanide-aluminum-based clusters [Ln6Al(IN)10(µ3-OH)5(µ3-O)3(H2O)8]·xH2O (x = 2, Ln = Gd, abbreviated as Gd6Al; x = 2.5, Ln = Eu, abbreviated as Eu6Al; HIN = isonicotinic acid) have been meticulously designed and obtained by hydrothermal reaction at low pH. The crystallographic study revealed that both Gd6Al and Eu6Al clusters exhibit an unprecedented sandwiched metal-organic framework holding a highly ordered honeycomb network. To our knowledge, it is the first case of Ln-Al-based cluster-organic frameworks. Furthermore, magnetic investigation of Gd6Al manifests a decent magnetic entropy change of -ΔSmmax = 28.8 J kg-1 K-1 at 2 K for ΔH = 7.0 T. Significantly, the introduction of AlIII ions into the lanthanide metal-organic frameworks displays excellent solid-state luminescent capability with a lifetime of 371.6 µs and quantum yield of 6.64%. The construction and investigation of these two Ln-Al clusters represent great progress in the 4f-3p metal-organic framework.

Analyzing the photoassociation spectrum of ultracold 85Rb 133Cs molecule in (3)3Σ+ state.

We establish a theoretical model to analyze the photoassociative spectroscopy of 85Rb 133Cs molecules in the (3)3Σ+ state. The vibrational energy, spin-spin coupling constant, and hyperfine interaction constant of the (3)3Σ+ state are determined based on nine observed vibrational levels. Consequently, the Rydberg-Klein-Rees potential energy curve of the (3)3Σ+ state is obtained and compared with the ab initial potential energy curve. Our model can be adopted to analyze the photoassociative spectroscopy of other heteronuclear alkali-metal diatomic molecules in the (3)3Σ+ state.

An NMPC-Based Integrated Longitudinal and Lateral Vehicle Stability Control Based on the Double-Layer Torque Distribution.

With the ongoing promotion and adoption of electric vehicles, intelligent and connected technologies have been continuously advancing. Electrical control systems implemented in electric vehicles have emerged as a critical research direction. Various drive-by-wire chassis systems, including drive-by-wire driving and braking systems and steer-by-wire systems, are extensively employed in vehicles. Concurrently, unavoidable issues such as conflicting control system objectives and execution system interference emerge, positioning integrated chassis control as an effective solution to these challenges. This paper proposes a model predictive control-based longitudinal dynamics integrated chassis control system for pure electric commercial vehicles equipped with electro-mechanical brake (EMB) systems, centralized drive, and distributed braking. This system integrates acceleration slip regulation (ASR), a braking force distribution system, an anti-lock braking system (ABS), and a direct yaw moment control system (DYC). This paper first analyzes and models the key components of the vehicle. Then, based on model predictive control (MPC), it develops a controller model for integrated stability with double-layer torque distribution. The required driving and braking torque for each wheel are calculated according to the actual and desired motion states of the vehicle and applied to the corresponding actuators. Finally, the effectiveness of this strategy is verified through simulation results from Matlab/Simulink. The simulation shows that the braking deceleration of the braking condition is increased by 32% on average, and the braking distance is reduced by 15%. The driving condition can enter the smooth driving faster, and the time is reduced by 1.5 s~5 s. The lateral stability parameters are also very much improved compared with the uncontrolled vehicles.

Whole-Transcriptome Profiling and Functional Prediction of Long Non-Coding RNAs Associated with Cold Tolerance in Japonica Rice Varieties.

Low-temperature chilling is a major abiotic stress leading to reduced rice yield and is a significant environmental threat to food security. Low-temperature chilling studies have focused on physiological changes or coding genes. However, the competitive endogenous RNA mechanism in rice at low temperatures has not been reported. Therefore, in this study, antioxidant physiological indices were combined with whole-transcriptome data through weighted correlation network analysis, which found that the gene modules had the highest correlation with the key antioxidant enzymes superoxide dismutase and peroxidase. The hub genes of the superoxide dismutase-related module included the UDP-glucosyltransferase family protein, sesquiterpene synthase and indole-3-glycerophosphatase gene. The hub genes of the peroxidase-related module included the WRKY transcription factor, abscisic acid signal transduction pathway-related gene plasma membrane hydrogen-ATPase and receptor-like kinase. Therefore, we selected the modular hub genes and significantly enriched the metabolic pathway genes to construct the key competitive endogenous RNA networks, resulting in three competitive endogenous RNA networks of seven long non-coding RNAs regulating three co-expressed messenger RNAs via four microRNAs. Finally, the negative regulatory function of the WRKY transcription factor OsWRKY61 was determined via subcellular localization and validation of the physiological indices in the mutant.

Proportion of malignancy in Bosniak classification of cystic renal masses version 2019 (v2019) classes: systematic review and meta-analysis.

OBJECTIVES: Determine the proportion of malignancy within Bosniak v2019 classes. METHODS: MEDLINE and EMBASE were searched. Eligible studies contained patients with cystic renal masses undergoing CT or MRI renal protocol examinations with pathology confirmation, applying Bosniak v2019. Proportion of malignancy was estimated within Bosniak v2019 class. Risk of bias was assessed using QUADAS-2. RESULTS: We included 471 patients with 480 cystic renal masses. No class I malignant masses were observed. Pooled proportion of malignancy were class II, 12% (6/51, 95% CI 5-24%); class IIF, 46% (37/85, 95% CI 28-66%); class III, 79% (138/173, 95% CI 68-88%); and class IV, 84% (114/135, 95% CI 77-90%). Proportion of malignancy differed between Bosniak v2019 II-IV classes (p = 0.004). Four studies reported the proportion of malignancy by wall/septa feature. The pooled proportion of malignancy with 95% CI were class III thick smooth wall/septa, 77% (41/56, 95% CI 53-91%); class III obtuse protrusion ≤ 3 mm (irregularity), 83% (97/117, 95% CI 75-89%); and class IV nodule with acute angulation, 86% (50/58, 95% CI 75-93%) or obtuse angulation ≥ 4 mm, 83%, (64/77, 95% CI 73-90%). Subgroup analysis by wall/septa feature was limited by sample size; however, no differences were found comparing class III masses with irregularity to class IV masses (p = 0.74) or between class IV masses by acute versus obtuse angles (p = 0.62). CONCLUSION: Preliminary data suggest Bosniak v2019 class IIF masses have higher proportion of malignancy compared to the original classification, controlling for pathologic reference standard. There are no differences in proportion of malignancy comparing class III masses with irregularities to class IV masses with acute or obtuse nodules. KEY POINTS: • The proportion of malignancy in Bosniak v2019 class IIF cystic masses is 46% (37 malignant/85 total IIF masses, 95% confidence intervals (CI) 28-66%). • The proportion of malignancy in Bosniak v2019 class III cystic masses is 79% (138/173, 95% CI 68-88%) and in Bosniak v2019 class IV cystic masses is 84% (114/135, 95% CI 77-90%). • Class III cystic masses with irregularities had similar proportion of malignancy (83%, 97/117, 95% CI 75-89%) compared to Bosniak class IV masses (84%, 114/135, 95% CI 77-90%) overall (p = 0.74) with no difference within class IV masses by acute versus obtuse angulation (p = 0.62).

Design, synthesis, and pharmacological evaluation of quinazoline derivatives as novel and potent pan-JAK inhibitors.

Janus kinases (JAKs) play a critical role in modulating the function and expression of inflammatory cytokines related to rheumatoid arthritis (RA). Herein, we report the design, synthesis, and structure-activity relationships (SARs) of a series of novel quinazoline derivatives as JAK inhibitors. Among these inhibitors, compound 11n showed high potency against JAKs (JAK1/JAK2/JAK3/TYK2, IC50 = 0.40, 0.83, 2.10, 1.95 nM), desirable metabolic characters, and excellent pharmacokinetic properties. In collagen-induced arthritis (CIA) models, compound 11n exhibited significant reduction in joint swelling with good safety, which could be served as a potential therapeutic candidate for the treatment of inflammatory diseases.

Predicting Breast Cancer Subtypes Using Magnetic Resonance Imaging Based Radiomics With Automatic Segmentation.

OBJECTIVE: The aim of the study is to demonstrate whether radiomics based on an automatic segmentation method is feasible for predicting molecular subtypes. METHODS: This retrospective study included 516 patients with confirmed breast cancer. An automatic segmentation-3-dimensional UNet-based Convolutional Neural Networks, trained on our in-house data set-was applied to segment the regions of interest. A set of 1316 radiomics features per region of interest was extracted. Eighteen cross-combination radiomics methods-with 6 feature selection methods and 3 classifiers-were used for model selection. Model classification performance was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RESULTS: The average dice similarity coefficient value of the automatic segmentation was 0.89. The radiomics models were predictive of 4 molecular subtypes with the best average: AUC = 0.8623, accuracy = 0.6596, sensitivity = 0.6383, and specificity = 0.8775. For luminal versus nonluminal subtypes, AUC = 0.8788 (95% confidence interval [CI], 0.8505-0.9071), accuracy = 0.7756, sensitivity = 0.7973, and specificity = 0.7466. For human epidermal growth factor receptor 2 (HER2)-enriched versus non-HER2-enriched subtypes, AUC = 0.8676 (95% CI, 0.8370-0.8982), accuracy = 0.7737, sensitivity = 0.8859, and specificity = 0.7283. For triple-negative breast cancer versus non-triple-negative breast cancer subtypes, AUC = 0.9335 (95% CI, 0.9027-0.9643), accuracy = 0.9110, sensitivity = 0.4444, and specificity = 0.9865. CONCLUSIONS: Radiomics based on automatic segmentation of magnetic resonance imaging can predict breast cancer of 4 molecular subtypes noninvasively and is potentially applicable in large samples.

CTH/H2S Regulates LPS-Induced Inflammation through IL-8 Signaling in MAC-T Cells.

Hydrogen sulfide (H2S), as an endogenous gaseous signaling molecule, plays an important role in the inflammatory process. Our previous study found that Cystathionine-γ-lyase (CTH) and H2S are correlated with the occurrence and development of Clinical Mastitis (CM) in Holstein cows. However, the functions and regulatory mechanisms of CTH/H2S are still unknown. In this study, the inflammatory mammary cell model based on the MAC-T cell line was established by Lipopolysaccharide (LPS)-induced manner to further explore the function and regulatory mechanism of CTH/H2S in cows with CM. In the inflammatory MAC-T cell, the CTH expression and H2S production were both repressed in an LPS-dose dependent manner, which demonstrated that CTH/H2S is related to the progression of inflammation. The inhibition of CTH/H2S using a selective CTH inhibitor, ß-cyano-l-Alanine (BCA), promoted LPS-induced inflammation response and the expression of inflammatory cytokines. However, this was reversed by the H2S donor NaHS, demonstrating that H2S can protect cells from inflammatory damage. Intriguingly, interleukin-8 (IL-8) showed an inverse expression pattern correlated with the H2S-mediated cell protection effect during the inflammation process, and the inhibition test using a selective IL-8 receptor antagonist, SB225002, showed that IL-8 signaling plays a critical role in mediating endogenous H2S synthesis, and CTH/H2S exerts its anti-inflammation via IL-8-mediated signaling. This study provided support for the prevention and treatment of CM and the development of a novel anti-inflammatory strategy.

Toll-like Receptor 2 Is Associated with the Immune Response, Apoptosis, and Angiogenesis in the Mammary Glands of Dairy Cows with Clinical Mastitis.

Toll-like receptor 2 (TLR2) plays a crucial role in bacterial recognition and the host immune response during infection. However, its function and downstream biological processes (BPs) in the mammary glands (MGs) of Holstein cows with clinical mastitis (CM) are not fully understood. This study aimed to comprehensively identify the BPs and differentially expressed proteins (DEPs) associated with the bacterial response and TLR2 using data-independent acquisition (DIA) proteomic data. A possible mechanism for the action of TLR2 was proposed, and the results suggested that the expression levels of TLR2 and caspase 8 (CASP8) were positively correlated with the apoptosis of MGs. The expression patterns of TLR2 and TEK receptor tyrosine kinase 2 (Tie2) were negatively correlated with angiogenesis. These results indicated that TLR2 might promote apoptosis in mammary epithelial cells (MECs) and vascular endothelial cells (VECs) via upregulation of CASP8 expression, and inhibition of angiogenesis in VECs via downregulation of Tie2 expression in dairy cows with CM. In conclusion, TLR2 is associated with inflammation, apoptosis, and angiogenesis in the MGs of dairy cows with bacteria-induced mastitis. These results contribute to a deeper understanding of the pathogenic mechanisms and provide the knowledge needed for developing the prevention and treatment of dairy mastitis.

Assessment of the Bioavailability of Mercury Sulfides in Paddy Soils Using Sodium Thiosulfate Extraction - Results from Microcosm Experiments.

Mercury sulfides (HgS), one of the largest Hg sinks in the lithosphere, has long been considered to be highly inert. Recently, several HgS speciation (e.g., nano- or micro-sized HgS particles) in paddy soils have been found to be reactive and bioavailable, increasing the possibility of methylation and bioaccumulation and posing a potential risk to humans. However, a simple and uniform method for investigating HgS bioavailability is still lacking. To address this issue, we extracted dissolved Hg from HgS particles by sodium thiosulfate (Na2S2O3) in paddy soils and analyzed the correlation between extracted Hg and soil methylmercury (MeHg). Results showed that the amounts of Hg extracted by Na2S2O3 had a strong positive correlation with the levels of soil MeHg (R 2 adj = 0.893, p < 0.05). It is suggested that Na2S2O3 extraction may be a good method of predicting Hg bioavailability in paddy soils. Our results would help to give clues in better predicting Hg risk in natural environments.

Aromatic Heterocycles as Productive Dienophiles in the Inverse Electron-Demand Diels-Alder Reactions of 1,3,5-Triazines.

Heterocycles are often found as the structural nucleus in natural products and biological active compounds. Consequently, research toward the discovery and development of novel and efficient synthetic methodologies is of constant interest to organic chemists. Diels-Alder reactions are powerful at forming multiple bonds simultaneously, often with stereoselectivity, and thus are one of the most widely used synthetic methodologies in organic syntheses. Inverse electron-demand Diels-Alder (IEDDA) reactions, a subclass of Diels-Alder reactions, have been developed for the efficient synthesis of various heterocycles, with 1,3,5-triazines used as azadienes. The initial 1,3,5-triazine IEDDA reactions mostly included nonaromatic, electron-rich species such as vinyl ethers, enamines, ynamines, and amidines as dienophiles, producing in high yields pyrimidine derivatives with excellent regioselectivity. We hypothesized that some electron-rich aromatic heterocycles could be studied as potential dienophiles for 1,3,5-triazine IEDDA reactions; 5-aminopyrazoles proved to be productive dienophiles leading to high yields of pyrazolopyrimidines. Subsequently, many studies were reported to investigate the mechanism and scope of this new type of IEDDA reaction. Mechanistically, this new type of IEDDA reaction is quite interesting since it entails two aromatic compounds proceeding through a perceived high energy nonaromatic transition state, leading to a new aromatic compound, a counterintuitive process. Both theoretical and experimental studies provide key insights to this reaction mechanism, with learnings from these studies possibly stimulating unconventional thinking in other areas. Theoretical calculations of these cascade reactions of amino-substituted heterocycles with 1,3,5-triazines indicate that the reactions occur in a stepwise fashion via a highly polar zwitterionic intermediate; elimination of ammonia from IEDDA adducts and subsequent retro Diels-Alder reaction drive the reaction toward the fully aromatized IEDDA products. This amino substituent is critical in determining the regioselectivity and driving the cascade reactions to completion. With regard to reaction scope, many amino-heterocycles such as pyrroles, imidazoles, furans, thiophenes, and indoles all proved to be productive dienophiles for this new IEDDA reaction, leading to various fused-pyrimidines in a single step with moderate to high yields and high regioselectivity. Application of this new IEDDA reaction with 1,3,5-triazines was reported to lead to interesting heterocyclic compounds such as nucleoside natural product nebularine and analogues, as well as fluorine-containing fused pyrimidines with potential for biological activities.Herein, the scope of various aromatic heterocycles as dienophiles in the 1,3,5-triazine IEDDA reaction is reviewed. Moreover, both experimental and theoretical studies of the mechanisms for this interesting cascade IEDDA reaction are discussed. Finally, applications of this new type (aromatic heterocycles as dienophiles with 1,3,5-triazines as azadienes) of IEDDA reaction are also covered.

MRI radiomics-based nomogram for individualised prediction of synchronous distant metastasis in patients with clear cell renal cell carcinoma.

OBJECTIVE: To evaluate the performance of a multiparametric MRI radiomics-based nomogram for the individualised prediction of synchronous distant metastasis (SDM) in patients with clear cell renal cell carcinoma (ccRCC). METHODS: Two-hundred and one patients (training cohort: n = 126; internal validation cohort: n = 39; external validation cohort: n = 36) with ccRCC were retrospectively enrolled between January 2013 and June 2019. In the training cohort, the optimal MRI radiomics features were selected and combined to calculate the radiomics score (Rad-score). Incorporating Rad-score and SDM-related clinicoradiologic characteristics, the radiomics-based nomogram was established by multivariable logistic regression analysis, then the performance of the nomogram (discrimination and clinical usefulness) was evaluated and validated subsequently. Moreover, the prediction efficacy for SDM in ccRCC subgroups of different sizes was also assessed. RESULTS: Incorporating Rad-score derived from 9 optimal MR radiomics features (age, pseudocapsule and regional lymph node), the radiomics-based nomogram was capable of predicting SDM in the training cohort (area under the ROC curve (AUC) = 0.914) and validated in both the internal and external cohorts (AUC = 0.854 and 0.816, respectively) and also showed a convincing predictive power in ccRCC subgroups of different sizes (≤ 4 cm, AUC = 0.875; 4-7 cm, AUC = 0.891; 7-10 cm, 0.908; > 10 cm, AUC = 0.881). Decision curve analysis indicated that the radiomics-based nomogram is of clinical usefulness. CONCLUSIONS: The multiparametric MRI radiomics-based nomogram could achieve precise individualised prediction of SDM in patients with ccRCC, potentially improving the management of ccRCC. KEY POINTS: • Radiomics features derived from multiparametric magnetic resonance images showed relevant association with synchronous distant metastasis in clear cell renal cell carcinoma. • MRI radiomics-based nomogram may serve as a potential tool for the risk prediction of synchronous distant metastasis in clear cell renal cell carcinoma.

MALDI-TOF-MS and XAS analysis of complexes formed by metallothionein with mercury and/or selenium.

Mercury (Hg) is highly toxic while selenium (Se) has been found to antagonize Hg. Both Hg and Se have been found to induce metallothioneins (MTs). In this study, the complexes formed by metallothionein-1 (MT-1) with HgCl2 and/or Na2SeO3 was studied using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and X-ray absorption spectrometry (XAS). MALDI-TOF-MS and XAS indicated the formation of Hg-S bond or Se-S bond when MT-1 reacted with HgCl2 or Na2SeO3, respectively. The bond lengths of Hg-S and coordination number in MT-Hg are 2.41 ± 0.02 Å and 3.10 and in MT-Se are 2.50 ± 0.03 Å and 2.69. A MT-Se-Hg complex was formed when MT-1 reacted with both HgCl2 and Na2SeO3, in which the neighboring atom of Hg is Se, while the neighboring atoms of Se are S and Hg. Our study is an important step towards a better understanding of the interaction of HgCl2 and/or Na2SeO3 with proteins like MT-1.

Treatment of Optic Canal Decompression Combined with Umbilical Cord Mesenchymal Stem (Stromal) Cells for Indirect Traumatic Optic Neuropathy: A Phase 1 Clinical Trial.

PURPOSE: This study was aimed to investigate the safety and feasibility of umbilical cord-derived mesenchymal stem cell (MSC) transplantation in patients with traumatic optic neuropathy (TON). METHODS: This is a single-center, prospective, open-labeled phase 1 study that enrolled 20 patients with TON. Patients consecutively underwent either optic canal decompression combined with MSC local implantation treatment (group 1) or only optic canal decompression (group 2). Patients were evaluated on the first day, seventh day, first month, third month, and sixth month postoperatively. Adverse events, such as fever, urticarial lesions, nasal infection, and death, were recorded at each visit. The primary outcome was changes in best-corrected visual acuity. The secondary outcomes were changes in color vision, relative afferent pupillary defect, and flash visual evoked potential. RESULTS: All 20 patients completed the 6-month follow-up. None of them had any systemic or ocular complications. The change in best-corrected visual acuity at follow-up was not significantly different between group 1 and group 2 (p > 0.05); however, group 1 showed better visual outcome than group 2. Both groups showed significant improvements in vision compared with the baseline (p < 0.05); however, there were no statistically significant differences between the groups (p > 0.05). In addition, no adverse events related to local transplantation were observed in the patients. CONCLUSIONS: A single, local MSC transplantation in the optic nerve is safe for patients with TON.

MRI-based Bosniak Classification of Cystic Renal Masses, Version 2019: Interobserver Agreement, Impact of Readers' Experience, and Diagnostic Performance.

Background The 2019 Bosniak classification (version 2019) of cystic renal masses (CRMs) provides a systematic update to the currently used 2005 Bosniak classification (version 2005). Further validation is required before widespread application. Purpose To evaluate the interobserver agreement of MRI criteria, the impact of readers' experience, and the diagnostic performance between version 2019 and version 2005. Materials and Methods From January 2009 to December 2018, consecutive patients with CRM who had undergone renal MRI and surgical-pathologic examination were included in this retrospective study. On the basis of version 2019 and version 2005, all CRMs were independently classified by eight radiologists with different levels of experience. By using multirater κ statistics, interobserver agreement was evaluated with comparisons between classifications and between senior and junior radiologists. Diagnostic performance between classifications by dichotomizing classes I-IV into lower (I-IIF) and higher (III-IV) classes was compared by using the McNemar test. P < .05 was considered to indicate a statistically significant difference. Results A total of 207 patients (mean age ± standard deviation, 49 years ± 12; 139 male and 68 female patients) with CRMs were included. Overall, interobserver agreement was higher with version 2019 than version 2005 (weighted κ = 0.64 vs 0.50, respectively; P < .001). Interobserver agreement between senior and junior radiologists did not differ between version 2019 (weighted κ = 0.65 vs 0.64, respectively; P = .71) and version 2005 (weighted κ = 0.54 vs 0.46; P < .001). Diagnostic specificity for malignancy was higher with version 2019 than with version 2005 (83% [92 of 111] vs 68% [75 of 111], respectively; P < .001), without any difference in sensitivity (89% [85 of 96] vs 84% [81 of 96]; P = .34). Conclusion In the updated Bosniak classification, interobserver agreement improved and was unaffected by observers' experience. The diagnostic performance with version 2019 was superior to that with version 2005, with higher specificity. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Choyke in this issue.

Multiparametric MRI Radiomic Model for Preoperative Predicting WHO/ISUP Nuclear Grade of Clear Cell Renal Cell Carcinoma.

BACKGROUND: Nuclear grade is of importance for treatment selection and prognosis in patients with clear cell renal cell carcinoma (ccRCC). PURPOSE: To develop and validate an MRI-based radiomic model for preoperative predicting WHO/ISUP nuclear grade in ccRCC. STUDY TYPE: Retrospective. POPULATION: In all, 379 patients with histologically confirmed ccRCC. Training cohort (n = 252) and validation cohort (n = 127) were randomly assigned. FIELD STRENGTH/SEQUENCE: Pretreatment 3.0T renal MRI. Imaging sequences were fat-suppressed T2 WI, contrast-enhanced T1 WI, and diffusion weighted imaging. ASSESSMENT: Three prediction models were developed using selected radiomic features, radiomic and clinicoradiologic characteristics, and a model containing only clinicoradiologic characteristics. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to assess the predictive performance of these models in predicting high-grade ccRCC. STATISTICAL TESTS: The least absolute shrinkage and selection operator (LASSO) and minimum redundancy maximum relevance (mRMR) method were used for the selection of radiomic features and clinicoradiologic characteristics, respectively. Multivariable logistic regression analysis was used to develop the radiomic signature of radiomic features and clinicoradiologic model of clinicoradiologic characteristics. RESULTS: The radiomic signature showed good performance in discriminating high-grade (grades 3 and 4) from low-grade (grades 1 and 2) ccRCC, with sensitivity, specificity, and AUC of 77.3%, 80.0%, and 0.842, respectively, in the validation cohort. The radiomic model, combining radiomic signature and clinicoradiologic characteristics, displayed good predictive ability for high-grade with sensitivity, specificity, and accuracy of 63.6%, 93.3%, and 88.2%, respectively, in the validation cohort. The radiomic model showed a significantly better performance than the clinicoradiologic model (P < 0.05). DATA CONCLUSION: Multiparametric MRI-based radiomic model can predict WHO/ISUP grade in patients with ccRCC with satisfying performance, and thus could help the physician to improve treatment decisions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.