A nickel‐catalyzed three‐component reaction for the synthesis of difluoroalkylated compounds through tandem difluoroalkylation‐arylation of enamides has been developed. The reaction tolerates a ...variety of arylboronic acids and widely available difluoroalkyl bromides, and even the relatively inert substrate chlorodifluoroacetate. The significant advantages of this protocol are the low‐cost nickel catalyst, synthetic convenience, excellent functional‐group compatibility and high reaction efficiency.
All about efficiency: The title reaction tolerates a variety of arylboronic acids and widely available difluoroalkyl bromides, and even the relatively inert substrate chlorodifluoroacetate. The protocol provides a highly efficient method for the catalytic synthesis of difluoroalkylated compounds.
An efficient and general method for the synthesis of difluoroalkylated phenanthridine derivatives through palladium-catalyzed reaction of difluoroalkyl bromides with isocyanides is described. The ...reaction can also be extended to perfluoroalkyl iodides. Mechanistic studies reveal that a difluoroalkyl radical via a single-electron-transfer pathway is involved in the reaction.
An efficient palladium‐catalyzed Heck‐type reaction of fluoroalkyl halides, including perfluoroalkyl bromides, trifluoromethyl iodides, and difluoroalkyl bromides, has been developed. The reaction ...proceeds under mild reaction conditions with high efficiency and broad substrate scope, and provides a general and straightforward access to fluoroalkylated alkenes which are of interest in life and material sciences.
Simplicity is beauty: The title reaction features a broad substrate scope and excellent functional‐group compatibility. Mechanistic studies reveal that the free fluoroalkyl radicals initiated by Pd0Ln through a single‐electron transfer pathway is involved in the Heck‐type catalytic cycle.
Objectives
This study was conducted in order to establish and validate a radiomics model for predicting lymph node (LN) metastasis of intrahepatic cholangiocarcinoma (IHC) and to determine its ...prognostic value.
Methods
For this retrospective study, a radiomics model was developed in a primary cohort of 103 IHC patients who underwent curative-intent resection and lymphadenectomy. Radiomics features were extracted from arterial phase computed tomography (CT) scans. A radiomics signature was built based on highly reproducible features using the least absolute shrinkage and selection operator (LASSO) method. Multivariate logistic regression analysis was adopted to establish a radiomics model incorporating radiomics signature and other independent predictors. Model performance was determined by its discrimination, calibration, and clinical usefulness. The model was internally validated in 52 consecutive patients.
Results
The radiomics signature comprised eight LN-status–related features and showed significant association with LN metastasis in both cohorts (
p
< 0.001). A radiomics nomogram that incorporates radiomics signature and CA 19-9 level showed good calibration and discrimination in the primary cohort (AUC 0.8462) and validation cohort (AUC 0.8921). Promisingly, the radiomics nomogram yielded an AUC of 0.9224 in the CT-reported LN-negative subgroup. Decision curve analysis confirmed the clinical utility of this nomogram. High risk for metastasis portended significantly lower overall and recurrence-free survival than low risk for metastasis (both
p
< 0.001). The radiomics nomogram was an independent preoperative predictor of overall and recurrence-free survival.
Conclusions
Our radiomics model provided a robust diagnostic tool for prediction of LN metastasis, especially in CT-reported LN-negative IHC patients, that may facilitate clinical decision-making.
Key Points
• The radiomics nomogram showed good performance for prediction of LN metastasis in IHC patients, particularly in the CT-reported LN-negative subgroup.
• Prognosis of high-risk patients remains dismal after curative-intent resection.
• The radiomics model may facilitate clinical decision-making and define patient subsets benefiting most from surgery.
Current guidelines recommend surgical resection as the first-line option for patients with solitary hepatocellular carcinoma (HCC); unfortunately, postoperative recurrence rate remains high and there ...is no reliable prediction tool. We explored the potential of radiomics coupled with machine-learning algorithms to improve the predictive accuracy for HCC recurrence.
A total of 470 patients who underwent contrast-enhanced CT and curative resection for solitary HCC were recruited from 3 independent institutions. In the training phase of 210 patients from Institution 1, a radiomics-derived signature was generated based on 3384 engineered features extracted from primary tumor and its periphery using aggregated machine-learning framework. We employed Cox modeling to build predictive models. The models were then validated using an internal dataset of 107 patients and an external dataset of 153 patients from Institution 2 and 3.
Using the machine-learning framework, we identified a three-feature signature that demonstrated favorable prediction of HCC recurrence across all datasets, with C-index of 0.633–0.699. Serum alpha-fetoprotein, albumin-bilirubin grade, liver cirrhosis, tumor margin, and radiomics signature were selected for preoperative model; postoperative model incorporated satellite nodules into above-mentioned predictors. The two models showed superior prognostic performance, with C-index of 0.733–0.801 and integrated Brier score of 0.147–0.165, compared with rival models without radiomics and widely used staging systems (all P < 0.05); they also gave three risk strata for recurrence with distinct recurrence patterns.
When integrated with clinical data sources, our three-feature radiomics signature promises to accurately predict individual recurrence risk that may facilitate personalized HCC management.
Display omitted
•We identified a three-feature fusion signature using machine-learning framework.•The signature coupled with clinical sources accurately predicted HCC recurrence.•This signature may serve as an early detector of aggressive disease.•We highlight the complementary nature of radiomics and existing variables.
An ortho‐selective CF bond borylation between N‐heterocycle‐substituted polyfluoroarenes and Bpin‐Bpin with simple and commercially available Rh(cod)2BF4 as a catalyst is now reported. The reaction ...proceeds under mild reaction conditions with high efficiency and broad substrate scope, even toward monofluoroarene, thus providing a facile access to a wide range of borylated fluoroarenes that are useful for photoelectronic materials. Preliminary mechanistic studies reveal that a RhIII/V catalytic cycle via a key intermediate rhodium(III) hydride complex (H)RhIIILn(Bpin) may be involved in the reaction.
RhIII/V for borylation: The significant features of the title reaction are the simple catalytic system, the broad substrate scope, and the efficient synthesis of photoelectronic materials. A RhIII/V catalytic cycle is proposed for the reaction, which involves a rhodium(III) hydride complex as a key intermediate.
The subthalamic nucleus (STN) controls basal ganglia outputs via the substantia nigra pars reticulata (SNr) and the globus pallidus internus (GPi). However, the synaptic properties of these ...projections and their roles in motor control remain unclear. We show that the STN-SNr and STN-GPi projections differ markedly in magnitude and activity-dependent plasticity despite the existence of collateral STN neurons projecting to both the SNr and GPi. Stimulation of either STN projection reduces locomotion; in contrast, inhibition of either the STN-SNr projection or collateral STN neurons facilitates locomotion. In 6-OHDA-hemiparkinsonian mice, the STN-SNr projection is dramatically attenuated, but the STN-GPi projection is robustly enhanced; apomorphine inhibition of the STN-GPi projection through D2 receptors is significantly augmented and improves locomotion. Optogenetic inhibition of either the STN-SNr or STN-GPi projection improves parkinsonian bradykinesia. These results suggest that the STN-GPi and STN-SNr projections are differentially involved in motor control in physiological and parkinsonian conditions.
Display omitted
•Subthalamic neurons differentially control nigral and pallidal neurons and movement•Subthalamonigral and subthalamopallidal pathways are modified in parkinsonian mice•Inhibition of subthalamic projections restores parkinsonian locomotor deficit
Ji et al. report that subthalamic neurons project to two basal ganglia output nuclei with different strength and activity dependence. These projections differ in movement control in normal mice and are subjected to opposite modifications and different dopamine-receptor-agonist-modulation in parkinsonian mice. Inhibition of these projections restores parkinsonian bradykinesia.
The connection between vitamin D to non-alcoholic fatty liver disease (NAFLD) is still unclear. Herein, the relationship of vitamin D with NAFLD and liver fibrosis (LF) detected by vibration ...controlled transient elastography was investigated in US adults.
The National Health and Nutrition Examination Survey of 2017-2018 was employed for our analysis. Participants were categorized as having either vitamin D deficiency (<50 nmol/L) or vitamin D sufficiency (≥50 nmol/L). A controlled attenuation parameter score of ≥ 263 dB/m was employed to define NAFLD. Significant LF was identified by the liver stiffness measurement value of ≥ 7.9 kPa. Multivariate logistic regression was adopted to explore the relationships.
Among the 3407 participants, the prevalence of NAFLD and LF was 49.63% and 15.93% respectively. Compared to participants without NAFLD, no significant difference in serum vitamin D was observed in NALFD participants (74.26 vs. 72.24 nmol/L; p = 0.21). Using multivariate logistic regression analysis, no obvious connection of vitamin D status to NAFLD (sufficiency vs. deficiency, OR 0.89, 95%CI 0.70-1.13) was discovered. However, among NAFLD participants, the sufficiency of vitamin D represents a lower LF risk (OR 0.56, 95%CI 0.38-0.83). When evaluated in quartiles, in comparison to the lowest quartile, high vitamin D represents low LF risk in a dose-dependent manner (Q2 vs. Q1, OR 0.65, 95%CI 0.37-1.14; Q3 vs. Q1, OR 0.64, 95%CI 0.41-1.00; Q4 vs. Q1, OR 0.49, 95%CI 0.30-0.79).
No relationship was found between vitamin D and CAP-defined NAFLD. However, a positive connection of the high serum vitamin D to the reduced LF risk was found among NAFLD subjects.
Key messages:
Our study found no relationship between vitamin D and CAP-defined NAFLD in US adults.
High serum vitamin D was inversely associated with liver fibrosis in a dose-dependent manner among NAFLD participants.