Over the past two decades, there have been major developments in transition metal–catalyzed aminations of aryl halides to form anilines, a common structure found in drug agents, natural product ...isolates, and fine chemicals. Many of these approaches have enabled highly efficient and selective coupling through the design of specialized ligands, which facilitate reductive elimination from a destabilized metal center. We postulated that a general and complementary method for carbon–nitrogen bond formation could be developed through the destabilization of a metal amido complex via photoredox catalysis, thus providing an alternative approach to the use of structurally complex ligand systems. Here, we report the development of a distinct mechanistic paradigm for aryl amination using ligand-free nickel(II) salts, in which facile reductive elimination from the nickel metal center is induced via a photoredox-catalyzed electron-transfer event.
A previous genetic study has suggested that schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) share common ...disease-associated genes. However, whether individuals with first-degree relatives (FDRs) with schizophrenia have a higher risk of these major psychiatric disorders requires further investigation. This study used Taiwan's National Health Insurance Research Database and identified 151 650 patients with schizophrenia and 227 967 individuals with FDRs with schizophrenia. The relative risks (RRs) of schizophrenia and other major psychiatric disorders were assessed in individuals with FDRs with schizophrenia. The individuals with FDRs with schizophrenia exhibited higher RRs (95% confidence interval) of major psychiatric disorders, namely schizophrenia (4.76, 4.65-4.88), bipolar disorder (3.23, 3.12-3.35), major depressive disorder (2.05, 2.00-2.10), ASD (2.55, 2.35-2.77) and ADHD (1.31, 1.25-1.37) than were found in the total population. Several sensitivity analyses were conducted to confirm these results. A dose-dependent relationship was observed between the risks of major psychiatric disorders and the numbers of FDRs with schizophrenia. The increased risks of major psychiatric disorders were consistent in different family relationships, namely among parents, offspring, siblings and twins. Our study supports the familial dose-dependent co-aggregation of schizophrenia, bipolar disorder, major depressive disorder, ASD and ADHD, and our results may prompt governmental public health departments and psychiatrists to focus on the mental health of individuals with FDRs with schizophrenia.
Teclistamab is a T-cell-redirecting bispecific antibody that targets both CD3 expressed on the surface of T cells and B-cell maturation antigen expressed on the surface of myeloma cells. In the phase ...1 dose-defining portion of the study, teclistamab showed promising efficacy in patients with relapsed or refractory multiple myeloma.
In this phase 1-2 study, we enrolled patients who had relapsed or refractory myeloma after at least three therapy lines, including triple-class exposure to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. Patients received a weekly subcutaneous injection of teclistamab (at a dose of 1.5 mg per kilogram of body weight) after receiving step-up doses of 0.06 mg and 0.3 mg per kilogram. The primary end point was the overall response (partial response or better).
Among 165 patients who received teclistamab, 77.6% had triple-class refractory disease (median, five previous therapy lines). With a median follow-up of 14.1 months, the overall response rate was 63.0%, with 65 patients (39.4%) having a complete response or better. A total of 44 patients (26.7%) were found to have no minimal residual disease (MRD); the MRD-negativity rate among the patients with a complete response or better was 46%. The median duration of response was 18.4 months (95% confidence interval CI, 14.9 to not estimable). The median duration of progression-free survival was 11.3 months (95% CI, 8.8 to 17.1). Common adverse events included cytokine release syndrome (in 72.1% of the patients; grade 3, 0.6%; no grade 4), neutropenia (in 70.9%; grade 3 or 4, 64.2%), anemia (in 52.1%; grade 3 or 4, 37.0%), and thrombocytopenia (in 40.0%; grade 3 or 4, 21.2%). Infections were frequent (in 76.4%; grade 3 or 4, 44.8%). Neurotoxic events occurred in 24 patients (14.5%), including immune effector cell-associated neurotoxicity syndrome in 5 patients (3.0%; all grade 1 or 2).
Teclistamab resulted in a high rate of deep and durable response in patients with triple-class-exposed relapsed or refractory multiple myeloma. Cytopenias and infections were common; toxic effects that were consistent with T-cell redirection were mostly grade 1 or 2. (Funded by Janssen Research and Development; MajesTEC-1 ClinicalTrials.gov numbers, NCT03145181 and NCT04557098.).
The effects of solution composition and temperature on the microstructure and corrosion resistance of stannate conversion coatings on AZ61 magnesium alloys were investigated. The conversion coating ...consisted of a porous layer as under layer intimately contacted with the magnesium plate and a hemispherical particle layer as major overlay formed right on top of the porous layer. During the coalescence of the hemispherical particles to form a complete coating on the magnesium alloy, some sites of discontinuity inevitably left and determined the corrosion resistance of the coating evaluated using a salt spray test. Increasing bath stannate ion concentration and lowering bath pH increased the population density of the hemispherical particles whose size was accordingly reduced. The corrosion resistance of the conversion coating was improved with finer particles, which were preferably formed at less alkaline solution with higher stannate ion contents. Furthermore, the conditions favoring the formation of finer particles also reduced the immersion time necessary for producing the conversion coating with optimal corrosion resistance.
Objective
Electroconvulsive therapy (ECT) is commonly used to treat patients with treatment‐resistant depression. We aimed to investigate whether combining an antidepressant agent with ECT might ...enhance therapeutic efficacy and prevent early relapse.
Method
During the acute ECT phase, patients (N = 97) with treatment‐resistant depression were randomized to receive ECT plus agomelatine 50 mg/day (n = 48) or ECT plus placebo (n = 49). Symptom severity measures, including the 17‐item Hamilton Depression Rating Scale (HAMD‐17) and other scales, functional impairment, quality of life, neuropsychological tests, adverse events and attitudes toward ECT, were assessed regularly. Remission was defined as a HAMD‐17 score ≤7. If patients achieved post‐ECT remission, they were prescribed agomelatine 50 mg/day and participated in a 12‐week follow‐up trial. HAMD‐17 was rated at 4‐week intervals. Relapse was defined as a HAMD‐17 score ≥14, or rehospitalization for a psychiatric reason.
Results
The two treatment groups were comparable at (i) baseline variables; (ii) score changes in all symptom measures, functional impairment, quality of life, and neuropsychological tests; (iii) frequency of adverse events and attitudes toward ECT; and (iv) post‐ECT response/remission rates. There were no statistically significant differences following ECT in relapse rates and time to relapse between these two groups.
Conclusion
Adding agomelatine to ECT yielded comparable response/remission rates to ECT without agomelatine in the acute ECT phase. Starting agomelatine in combination with ECT did not seem to be more efficacious in preventing relapse than starting agomelatine after the acute ECT course. More research is needed to guide clinical recommendations.
There is insufficient evidence to assess the risk for hypertension in patients with sleep disorders (SDs) in a large population-based cohort study. The aim of this study was to examine the risk of ...hypertension in groups both with and without SDs. Taiwan's National Health Insurance Research Database (NHIRD) data from 2005 to 2010 were used in a retrospective cohort study. A Cox proportional hazard regression analysis was used to evaluate the effects of SDs on hypertension risk. The overall incidence of hypertension was 120.7 per 1000 person-years for patients with SDs, which was significantly higher than that of the non-SD comparison cohort (76.4 per 1000 person-years). Overall, patients with SDs had a higher risk of hypertension compared with comparison cohort (adjusted hazard ratio (HR)=1.58, 95% confidence interval (CI)=1.26-1.79). Among patients aged <40 years, patients with SDs had a higher risk for hypertension than the comparison cohort (adjusted HR, 2.90 (95% CI, 2.46-3.14)). Compared with the cohort without insomnia, patients with insomnia had a 21% higher risk for hypertension (adjusted HR, 1.21 (95% CI, 1.01-1.76)). Compared with non-SD comparison cohort, patients with SDs had a higher risk for developing hypertension, particularly pronounced among those who were younger adults (age ⩽40 years) and who had insomnia. We suggest that possible persisting exposure to sleep problems was correlated with a greater risk of hypertension.
Aims To evaluate the clinical inference of serum alpha-fetoprotein (AFP) response in hepatocellular carcinoma (HCC) patients undergoing percutaneous radiofrequency ablation (RFA). Materials and ...methods Three hundred and thirteen previously untreated HCC patients were enrolled in the study. The optimal AFP response was defined as >20% decrease from baseline after 1 month of RFA for those with a baseline AFP level of ≥100 ng/ml. The impact of AFP response on prognosis was analysed and prognostic factors were assessed. Results After a median follow-up of 26.7 ± 19.1 months, 49 patients died and 264 patients were alive. The cumulative 5 year survival rates were 75.3 and 57.4% in patients with an initial AFP of <100 ng/ml and ≥100 ng/ml, respectively ( p = 0.003). In the 58 patients with a baseline AFP of ≥100 ng/ml and initial completed tumour necrosis after RFA, the cumulative 5 year survival rates were 62.4 and 25.7% in optimal and non-optimal AFP responders, respectively ( p = 0.001). By multivariate analysis, the prothrombin time international normalized ratio >1.1 ( p = 0.009), non-optimal AFP response ( p = 0.023), and creatinine >1.5 mg/dl ( p = 0.021) were independent risk factors predictive of poor overall survival. Besides, the cumulative 5 year recurrence rates were 83.4 and 100% in optimal and non-optimal AFP responders, respectively ( p < 0.001). Multivariate analysis demonstrated platelet count ≤105 /mm3 ( p = 0.048), tumour size >2 cm ( p = 0.027), and non-optimal AFP response ( p < 0.001) were independent risk factors associated with tumour recurrence after RFA. Conclusions Serum AFP response may be a useful marker for predicting prognosis in HCC patients undergoing RFA.
Phytochemicals have been used as potential chemopreventive or chemotherapeutic agents. However, there are data suggesting a mutagenic effect of some phytochemicals. We hypothesized that safrole would ...have anticancer effects on human oral squamous cell carcinoma HSC-3 cells. Safrole decreased the percentage of viable HSC-3 cells via induction of apoptosis by an increased level of cytosolic Ca2+ and a reduction in the mitochondrial membrane potential (ΔΨ
m
). Changes in the membrane potential were associated with changes in the Bax, release of cytochrome c from mitochondria, and activation of downstream caspases-9 and -3, resulting in apoptotic cell death. In vivo studies also showed that safrole reduced the size and volume of an HSC-3 solid tumor on a xenograft athymic nu/nu mouse model. Western blotting and flow cytometric analysis studies confirmed that safrole-mediated apoptotic cell death of HSC-3 cells is regulated by cytosolic Ca2+ and by mitochondria- and Fas-dependent pathways.
An innovative wet‐treatment with Na2S transforms two indium metal‐organic frameworks (MOFs) into a series of porous inorganic sorbents. These MOF‐templated materials display remarkable affinity for ...heavy metals with saturation occurring in less than 1 h. The saturation capacity for Hg(II) exceeds 2 g g‐1, more than doubling the best thiol‐functionalized sorbents in the literature.
Sulfonic acid based mesostructures (SAMs) have been developed in recent years and have important catalytic applications. The primary applications of these materials are in various organic synthesis ...reactions, such as multicomponent reactions, carbon–carbon bond couplings, protection reactions, and Fries and Beckman rearrangements. This review aims to provide an overview of the recent developments in the field of SAMs with a particular emphasis on the reaction scope and advantages of heterogeneous solid acid catalysts.
Sulfur lining: Sulfonic acid‐based mesostructures (SAMs) have been developed in recent years and have important catalytic applications. The primary applications of these materials are in various organic synthesis reactions such as multicomponent reactions, carbon–carbon bond couplings, protection reactions, and Fries and Beckman rearrangements. This Review aims to provide an overview of the recent developments in the field of SAMs with a particular emphasis on the reaction scope and advantages of heterogeneous solid acid catalysts.
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