Thrombocytopenia and In-hospital Outcomes in Patients with Acute Ischemic Stroke Undergoing Intravenous Thrombolysis: Findings from a Nationwide Registry Study in China.

BACKGROUND AND OBJECTIVE: Our study aimed to evaluate the associations between platelet count (PC) and in-hospital outcomes for patients with stroke after rt-PA intravenous thrombolysis. METHODS: We identified patients who had been hospitalized with a primary diagnosis of stroke and had received rt-PA intravenous thrombolysis from June 2015 to July 2019 at participating hospitals in the Chinese Stroke Center Alliance. PC measured before intravenous thrombolysis was categorized into the following four groups: severe thrombocytopenia (PC<100 × 109/L), mild thrombocytopenia (100≤PC<150 × 109/L), normal PC (150≤PC≤450 × 109/L), and thrombocythemia (PC>450 × 109/L). Outcomes were determined from clinical data collected during hospitalization. The primary clinical outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes were mortality, bleeding events, gastrointestinal (GI) hemorrhage, and in-hospital stroke recurrence. We used multivariate logistic regression models to evaluate the associations between PC and outcomes. RESULTS: We included 44,882 individuals with a median age of 66 years, of whom 34.7% were female, 951 (2.1%) had severe thrombocytopenia, 7218 (16.1%) had mild thrombocytopenia, 36,522 (81.4%) had a normal PC, and 191 (0.4%) had thrombocythemia. Both severe and mild thrombocytopenia groups had higher risks of bleeding events (adjusted OR 1.30; 95% CI,1.01-1.67; p= 0.045; adjusted OR 1.32; 95% CI,1.19-1.46; p<0.001) and sICH (adjusted OR 1.48;95% CI,1.13-1.94; p=0.005; adjusted OR 1.43;95% CI,1.27-1.60; p<0.001) than the normal PC group. Patients with 100≤PC<150 × 109/L also had a higher risk of in-hospital stroke recurrence (adjusted OR 1.12; 95% CI,1.02-1.22; p=0.02). CONCLUSIONS: Intravenous thrombolysis brings a high risk of sICH given PC<150 × 109/L, especially PC<100 × 109/L. It indicated that PC<100 × 109/L is a reasonable contraindication to thrombolysis.

Enantioselective synthesis of chiral amides by carbene insertion into amide N-H bond.

Chiral amides are important structure in many natural products and pharmaceuticals, yet their efficient synthesis from simple amide feedstock remains challenge due to its weak Lewis basicity. Herein, we describe our study of the enantioselective synthesis of chiral amides by N-alkylation of primary amides taking advantage of an achiral rhodium and chiral squaramide co-catalyzed carbene N-H insertion reaction. This method features mild condition, rapid reaction rate (in all cases 1 min) and a wide substrate scope with high yield and excellent enantioselectivity. Further product transformations show the synthetic potential of this reaction. Mechanistic studies reveal that the non-covalent interactions between the catalyst and reaction intermediate play a critical role in enantiocontrol.

Multipolar condensates and multipolar Josephson effects.

When single-particle dynamics are suppressed in certain strongly correlated systems, dipoles arise as elementary carriers of quantum kinetics. These dipoles can further condense, providing physicists with a rich realm to study fracton phases of matter. Whereas recent theoretical discoveries have shown that an unconventional lattice model may host a dipole condensate as the ground state, we show that dipole condensates prevail in bosonic systems due to a self-proximity effect. Our findings allow experimentalists to manipulate the phase of a dipole condensate and deliver dipolar Josephson effects, where supercurrents of dipoles arise in the absence of particle flows. The self-proximity effects can also be utilized to produce a generic multipolar condensate. The kinetics of the n-th order multipoles unavoidably creates a condensate of the (n + 1)-th order multipoles, forming a hierarchy of multipolar condensates that will offer physicists a whole new class of macroscopic quantum phenomena.

Functional mouse hepatocytes derived from interspecies chimeric livers effectively mitigate chronic liver fibrosis.

Liver disease is a major global health challenge. There is a shortage of liver donors worldwide, and hepatocyte transplantation (HT) may be an effective treatment to overcome this problem. However, the present approaches for generation of hepatocytes are associated with challenges, and interspecies chimera-derived hepatocytes produced by interspecies blastocyst complementation (IBC) may be promising donor hepatocytes because of their more comprehensive hepatic functions. In this study, we isolated mouse hepatocytes from mouse-rat chimeric livers using IBC and found that interspecies chimera-derived hepatocytes exhibited mature hepatic functions in terms of lipid accumulation, glycogen storage, and urea synthesis. Meanwhile, they were more similar to endogenous hepatocytes than hepatocytes derived in vitro. Interspecies chimera-derived hepatocytes could relieve chronic liver fibrosis and reside in the injured liver after transplantation. Our results suggest that interspecies chimera-derived hepatocytes are a potentially reliable source of hepatocytes and can be applied as a therapeutic approach for HT.

Redox-neutral electrochemical decontamination of hypersaline wastewater with high technology readiness level.

Industrial hypersaline wastewaters contain diverse pollutants that harm the environment. Recovering clean water, alkali and acid from these wastewaters can promote circular economy and environmental protection. However, current electrochemical and advanced oxidation processes, which rely on hydroxyl radicals to degrade organic compounds, are inefficient and energy intensive. Here we report a flow-through redox-neutral electrochemical reactor (FRER) that effectively removes organic contaminants from hypersaline wastewaters via the chlorination-dehalogenation-hydroxylation route involving radical-radical cross-coupling. Bench-scale experiments demonstrate that the FRER achieves over 75% removal of total organic carbon across various compounds, and it maintains decontamination performance for over 360 h and continuously treats real hypersaline wastewaters for two months without corrosion. Integrating the FRER with electrodialysis reduces operating costs by 63.3% and CO2 emissions by 82.6% when compared with traditional multi-effect evaporation-crystallization techniques, placing our system at technology readiness levels of 7-8. The desalinated water, high-purity NaOH (>95%) and acid produced offset industrial production activities and thus support global sustainable development objectives.

Eye movements as predictor of cognitive improvement after cognitive remediation therapy in patients with schizophrenia.

Aim: Baseline cognitive functions of patients predicted the efficacy of cognitive remediation therapy (CRT), but results are mixed. Eye movement is a more objective and advanced assessment of cognitive functions than neuropsychological testing. We aimed to investigate the applicability of eye movements in predicting cognitive improvement after patients with schizophrenia were treated with CRT. Methods: We recruited 79 patients with schizophrenia to complete 8 weeks of CRT and assessed their cognitive improvement outcomes. Eye movements were assessed by prosaccades, antisaccades, and free-viewing tasks at baseline, and neuropsychological tests in four cognitive domains were assessed before and after treatment to calculate treatment outcomes. Predictors of demographic information, clinical characteristics, and eye movement measures at baseline on cognitive improvement outcomes were analyzed using logistic regression analysis. We further compared the predictive performance between eye movement measurements and neuropsychological test regarding the effect of CRT on cognitive improvement, and explored factors that could be affect the treatment outcomes in different cognitive domains. Results: As operationally defined, 33 patients showed improved in cognition (improved group) and 46 patients did not (non-improved group) after CRT. Patients with schizophrenia being employed, lower directional error rate in antisaccade task, and lower the gap effect (i.e., the difference in saccadic latency between the gap condition and overlap condition) in prosaccade task at baseline predicted cognitive improvement in CRT. However, performance in the free-viewing task not associated with cognitive improvement in patients in CRT. Our results show that eye-movement prediction model predicted the effect of CRT on cognitive improvement in patients with schizophrenia better than neuropsychological prediction model in CRT. In addition, baseline eye-movements, cognitive reserve, antipsychotic medication dose, anticholinergic cognitive burden change, and number of training sessions were associated with improvements in four cognitive domains. Conclusion: Eye movements as a non-invasiveness, objective, and sensitive method of evaluating cognitive function, and combined saccadic measurements in pro- and anti-saccades tasks could be more beneficial than free-viewing task in predicting the effect of CRT on cognitive improvement in patients with schizophrenia.

Tailoring the Holocellulose Fiber/Acrylic Resin Composite Interface with Hydrophobic Carboxymethyl Cellulose to Enhance Optical and Mechanical Properties.

Interface engineering is essential for cellulosic fiber-reinforced polymer composites to achieve high strength and toughness. In this study, carboxymethyl cellulose (CMC) functionalized with hydrophobic quaternary ammonium ions (QAs) were utilized to modify the interface between holocellulose fibers (HF) and acrylic resin. The wet HF/CMC papers were prepared by vacuum filtration, akin to papermaking, followed by cationic ion exchange with different hydrophobic QAs. Subsequently, the modified papers were dried, impregnated with an acrylic resin monomer, and cured to produce transparent composite films. The effect of the hydrophobic QA moieties on the structure and optical and mechanical properties of the HF/CMC/acrylic resin composites were investigated. The composite film with cetyltrimethylammonium (CTA)-functionalized CMC showed high optical transmittance (87%) with low haze (43%), while the composite film with phenyltrimethylammonium (PTMA)-functionalized CMC demonstrated high Young's modulus of 7.6 GPa and high tensile strength of 180 MPa. These properties are higher than those of the composites prepared through covalent interfacial modification strategies. The results highlighted the crucial role of hydrophobic functionalized CMCs in facilitating homogeneous resin impregnation in the HF fiber network, producing a composite with enhanced interfacial adhesion strength, increased optical transparency, and mechanical strength. This facile use of hydrophobic CMCs as interfacial compatibilizers provides an energy-efficient route for preparing transparent, thin, and flexible composite films favorable in optoelectronic applications.

Recombinant linear multiple epitopes of σB protein protect Muscovy ducks against novel duck reovirus infection.

Infection by the novel duck reovirus (NDRV) in ducklings causes high mortality, which leads to substantial economic losses in the duck industry in China. To date, no commercial vaccine is available for this disease. In this study, linear B cell epitopes of the σB protein of the NDRV were predicted and recombinant multiple linear B cell epitopes (MLBEs) were constructed through linkers. The recombinant MLBEs were then expressed and purified. One-day-old Muscovy ducklings were immunized with different doses of MLBEs and challenged with 5 × 104 ELD50 of the virulent CHY strain of NDRV 14 days after immunization. The ducklings vaccinated with 20 and 40 µg of MLBE performed no clinical signs or gross or histopathological lesions, indicating 100% protection against infection. The viral load in the liver and spleens of these birds was significantly lower than that in the control group. Additionally, these ducklings exhibited positive seroconversion at 7 days after vaccination on enzyme-linked immunosorbent assay. These results indicate that MLBE of σB could be used as a candidate for developing vaccines against NDRV infection.

The ratio of high aspartate aminotransferase to alanine aminotransferase: an independent risk factor associated with poor prognosis in IgA nephropathy.

OBJECTIVE: To investigate the relationship between the aspartate aminotransferase to alanine aminotransferase ratio (AAR) and the prognosis of IgA nephropathy (IgAN). METHODS: Clinical, pathological and follow-up data of 271 patients with IgAN from January 1, 2013, to July 31, 2023, were collected. A 50% decrease in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD) was used as renal composite end point events. A receiver operating characteristic (ROC) curve was plotted to predict the composite end point events by AAR. The optimal cutoff value of 1.24 was determined, and patients were allocated to high AAR and low AAR groups. Kaplan‒Meier (K‒M) curves and Cox proportional hazard models were used to evaluate the predictive effect of AAR on renal composite end point events. RESULTS: After a mean follow-up of 29 months, 39 patients achieved renal composite end point events. Among them, 9 and 30 patients in the low and high AAR groups achieved renal composite end point events, respectively, with a significant difference (P < 0.001). After adjustment for confounding factors, AAR was found to be an independent prognostic factor for renal composite end point events (HR = 3.283, 95% CI: 1.489-7.238, P = 0.003). Kaplan‒Meier analysis showed that high AAR was associated with achieving renal composite end point events in patients with IgAN. Moreover, the clinical features in the high AAR group were more severe. Further subgroup analysis showed that high AAR had a better predictive effect in patients with more severe clinicopathological manifestations. CONCLUSION: AAR is an independent prognostic factor in patients with IgAN.

Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer.

BACKGROUND: The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. METHODS: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS). RESULTS: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)]. CONCLUSIONS: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. TRIAL REGISTRATION: NCT03534453. Registered at May 23, 2018.

Influence of continuous 4C nursing on quality of life and self-care ability of patients with diabetes retinopathy: An observational study.

This study aims to investigate the impact of continuous 4C nursing on patients with diabetes retinopathy (DR) and its influence on self-care ability. A total of 100 DR patients admitted to our hospital from October 2020 to October 2022 were randomly divided into a control group and an observation group, with 50 cases in each group. The control group received routine care, while the observation group received continuous 4C care. The nursing effects of both groups were compared. After nursing, the observation group showed a lower self-rating anxiety scale score and a higher self-care ability scale score compared to the control group (P < .05). The SQQL-VI scores for all social activities were also higher in the observation group (P < .05). Additionally, the observation group had lower levels of fasting blood glucose, 2-hour postprandial blood glucose, and glycated hemoglobin than the control group (P < .05). Moreover, the observation group had higher visual acuity and lower intraocular pressure than the control group (P < .05). The visual impairment rate was lower and the overall compliance rate was higher in the observation group compared to the control group (P < .05). After nursing, both groups showed improvements in symptoms, visual function, physical function, psychological and social activity scores, visual acuity, and patient satisfaction scores. The observation group showed greater improvements compared to the control group (P < .05). The application of continuous 4C nursing in DR patients has shown positive effects, including improved patient compliance and satisfaction, enhanced patient quality of life and visual acuity. These findings suggest that continuous 4C nursing should be widely promoted and applied in clinical practice.

The FAITHS2 Model Predicts Functional Disability in Patients With Acute Ischemic Stroke.

The present study aimed to develop a model to predict functional disability at 3 months in patients with acute ischemic stroke (AIS) (n = 5,406). The primary outcome was functional disability (modified Rankin Scale [mRS] >2) at 3 months. A prediction model including blood biomarkers was developed based on a multivariable logistic regression model, which was internally validated by the 100-time bootstrap method. A nomogram and a web-based calculator were developed for usage in clinical practice. At 3 months, 11% (638/5,406) of the patients had functional disability. Seven independent predictors of functional disability at 3 months were incorporated into the FAITHS2 model (fasting plasma glucose, age, interleukin-6, stroke history, National Institute of Health Stroke Scale [NIHSS] at admission, sex, and systolic blood pressure). The Area Under Curves (AUCs) were 0.814 (95% confidence interval [CI] 0.796-0.832) and 0.808 (95% CI 0.806-0.810), and the Brier scores were 0.088 ± 0.214 and 0.089 ± 0.003 for the derivation cohort and internal validation, respectively, showing optimal performance of the model. The FAITHS2 model has excellent potential to be a dependable application for individualized clinical decision making.

Preparation of a Nanosheeted Uranyl-Organic Framework for Enhanced Photocatalytic Oxidation of Toluene.

Preparation of ultrathin metal-organic framework (MOF) nanosheets is an effective way to improve the catalytic efficiency of MOF photocatalysts owing to their superiority in reducing the recombination rate of photogenerated electrons and holes and enhancing charge transfer. Herein, a light-sensitive two-dimensional uranyl-organic framework named HNU-68 was synthesized. Due to its interlayer stacking structure, the corresponding ultrathin nanosheets with a thickness of 4.4 nm (HNU-68-N) can be obtained through ultrasonic exfoliation. HNU-68-N exhibited an enhanced ability to selectively oxidize toluene to benzaldehyde, with the value of turnover frequency being approximately three times higher than that of the bulk HNU-68. This enhancement is attributed to the smaller size and interface resistance of the layered HNU-68-N nanosheets, which facilitate more thorough substrate contact and faster charge transfer, leading to an improvement in the photocatalytic efficiency. This work provides a potential candidate for the application of ultrathin uranyl-based nanosheets.

Efficacy and safety of Ferrous iron on the prevention of Vascular cOgnitive impaiRment among patients with cerebral Infarction/TIA (FAVORITE): rationale and design of a multicentre randomised trial.

BACKGROUND: The incidence of vascular cognitive impairment (VCI) is high in patients suffering from ischaemic stroke or transient ischaemic attack (TIA) or with vascular risk factors. Effective prevention strategies for VCI remain limited. Anaemia or low haemoglobin was found as an independent risk factor for adverse outcomes after acute stroke. Anaemia or low haemoglobin was possibly associated with an increased risk of poststroke cognitive impairment. Whether supplement of ferrous iron to correct anaemia reduces the risk of VCI and improves adverse outcomes in patients with ischaemic cerebrovascular disease remains uncertain. AIM: We aim to introduce the design and rationale of the safety and efficacy of Ferrous iron on the prevention of Vascular cOgnitive impaiRment in patients with cerebral Infarction or TIA (FAVORITE) trial. DESIGN: FAVORITE is a randomised, placebo-controlled, double-blind, multicentre trial that compares supplement of ferrous iron with placebo for recent minor stroke/TIA patients complicated with mild anaemia or iron deficiency: Ferrous succinate sustained-release tablet 0.2 g (corresponding to 70 mg of elemental iron) once daily after or during breakfast for 12 weeks or placebo with much the same colour, smell and size as ferrous iron once daily during or after breakfast for 12 weeks. All paticipants will be followed within the next year. STUDY OUTCOMES: The primary effective outcome is the incidence of VCI at 3 months after randomisation and the primary safety outcome includes any gastrointestinal adverse event during 3 months. DISCUSSION: The FAVORITE trial will clarify whether supplement of ferrous iron to correct low haemoglobin reduces the risk of VCI in patients with recent ischaemic stroke or TIA complicated with mild anaemia or iron deficiency compared with placebo. TRIAL REGISTRATION NUMBER: NCT03891277.

Organellophagy regulates cell death:A potential therapeutic target for inflammatory diseases.

BACKGROUND: Dysregulated alterations in organelle structure and function have a significant connection with cell death, as well as the occurrence and development of inflammatory diseases. Maintaining cell viability and inhibiting the release of inflammatory cytokines are essential measures to treat inflammatory diseases. Recently, many studies have showed that autophagy selectively targets dysfunctional organelles, thereby sustaining the functional stability of organelles, alleviating the release of multiple cytokines, and maintaining organismal homeostasis. Organellophagy dysfunction is critically engaged in different kinds of cell death and inflammatory diseases. AIM OF REVIEW: We summarized the current knowledge of organellophagy (e.g., mitophagy, reticulophagy, golgiphagy, lysophagy, pexophagy, nucleophagy, and ribophagy) and the underlying mechanisms by which organellophagy regulates cell death. KEY SCIENTIFIC CONCEPTS OF REVIEW: We outlined the potential role of organellophagy in the modulation of cell fate during the inflammatory response to develop an intervention strategy for the organelle quality control in inflammatory diseases.

Significantly Enhanced Nitrate and Phosphorus Removal by Pyrite/Sawdust Composite-Driven Mixotrophic Denitrification with Boosted Electron Transfer: Comprehensive Evaluation of Water-Gas-Biofilm Phases during a Long-Term Study.

Further reducing total nitrogen (TN) and total phosphorus (TP) in the secondary effluent needs to be realized effectively and in an eco-friendly manner. Herein, four pyrite/sawdust composite-based biofilters were established to treat simulated secondary effluent for 304 days. The results demonstrated that effluent TN and TP concentrations from biofilters under the optimal hydraulic retention time (HRT) of 3.5 h were stable at <2.0 and 0.1 mg/L, respectively, and no significant differences were observed between inoculated sludge sources. The pyrite/sawdust composite-based biofilters had low N2O, CH4, and CO2 emissions, and the effluent's DOM was mainly composed of five fluorescence components. Moreover, mixotrophic denitrifiers (Thiothrix) and sulfate-reducing bacteria (Desulfosporosinus) contributing to microbial nitrogen and sulfur cycles were enriched in the biofilm. Co-occurrence network analysis deciphered that Chlorobaculum and Desulfobacterales were key genera, which formed an obvious sulfur cycle process that strengthened the denitrification capacity. The higher abundances of genes encoding extracellular electron transport (EET) chains/mediators revealed that pyrite not only functioned as an electron conduit to stimulate direct interspecies electron transfer by flagella but also facilitated EET-associated enzymes for denitrification. This study comprehensively evaluates the water-gas-biofilm phases of pyrite/sawdust composite-based biofilters during a long-term study, providing an in-depth understanding of boosted electron transfer in pyrite-based mixotrophic denitrification systems.

Heterogeneity of immune cells and their communications unveiled by transcriptome profiling in acute inflammatory lung injury.

Background: Acute Respiratory Distress Syndrome (ARDS) or its earlier stage Acute lung injury (ALI), is a worldwide health concern that jeopardizes human well-being. Currently, the treatment strategies to mitigate the incidence and mortality of ARDS are severely restricted. This limitation can be attributed, at least in part, to the substantial variations in immunity observed in individuals with this syndrome. Methods: Bulk and single cell RNA sequencing from ALI mice and single cell RNA sequencing from ARDS patients were analyzed. We utilized the Seurat program package in R and cellmarker 2.0 to cluster and annotate the data. The differential, enrichment, protein interaction, and cell-cell communication analysis were conducted. Results: The mice with ALI caused by pulmonary and extrapulmonary factors demonstrated differential expression including Clec4e, Retnlg, S100a9, Coro1a, and Lars2. We have determined that inflammatory factors have a greater significance in extrapulmonary ALI, while multiple pathways collaborate in the development of pulmonary ALI. Clustering analysis revealed significant heterogeneity in the relative abundance of immune cells in different ALI models. The autocrine action of neutrophils plays a crucial role in pulmonary ALI. Additionally, there was a significant increase in signaling intensity between B cells and M1 macrophages, NKT cells and M1 macrophages in extrapulmonary ALI. The CXCL, CSF3 and MIF, TGFß signaling pathways play a vital role in pulmonary and extrapulmonary ALI, respectively. Moreover, the analysis of human single-cell revealed DCs signaling to monocytes and neutrophils in COVID-19-associated ARDS is stronger compared to sepsis-related ARDS. In sepsis-related ARDS, CD8+ T and Th cells exhibit more prominent signaling to B-cell nucleated DCs. Meanwhile, both MIF and CXCL signaling pathways are specific to sepsis-related ARDS. Conclusion: This study has identified specific gene signatures and signaling pathways in animal models and human samples that facilitate the interaction between immune cells, which could be targeted therapeutically in ARDS patients of various etiologies.

Niraparib maintenance therapy using an individualised starting dose in patients with platinum-sensitive recurrent ovarian cancer (NORA): final overall survival analysis of a phase 3 randomised, placebo-controlled trial.

Background: Niraparib significantly prolonged progression-free survival versus placebo in patients with platinum-sensitive, recurrent ovarian cancer (PSROC), regardless of germline BRCA mutation (gBRCAm) status, in NORA. This analysis reports final data on overall survival (OS). Methods: This randomised, double-blind, placebo-controlled, phase 3 trial enrolled patients across 30 centres in China between 26 September 2017 and 2 February 2019 (clinicaltrials.gov, NCT03705156). Eligible patients had histologically confirmed, recurrent, (predominantly) high-grade serous epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma (no histological restrictions for those with gBRCAm) and had received ≥2 prior lines of platinum-based chemotherapy. Patients were randomised (2:1) to receive niraparib or placebo, with stratification by gBRCAm status, time to recurrence following penultimate platinum-based chemotherapy, and response to last platinum-based chemotherapy. Following a protocol amendment, the starting dose was individualised: 200 mg/day for patients with bodyweight <77 kg and/or platelet count <150 × 103/µL at baseline and 300 mg/day otherwise. OS was a secondary endpoint. Findings: Totally, 265 patients were randomised to receive niraparib (n = 177) or placebo (n = 88), and 249 (94.0%) received an individualised starting dose. As of 14 August 2023, median follow-up for OS was 57.9 months (IQR, 54.8-61.6). Median OS (95% CI) with niraparib versus placebo was 51.5 (41.4-58.9) versus 47.6 (33.3-not evaluable [NE]) months, with hazard ratio [HR] of 0.86 (95% CI, 0.60-1.23), in the overall population; 56.0 (36.1-NE) versus 47.6 (31.6-NE) months, with HR of 0.86 (95% CI, 0.46-1.58), in patients with gBRCAm; and 46.5 (41.0-NE) versus 46.9 (31.8-NE) months, with HR of 0.87 (95% CI, 0.56-1.35), in those without. No new safety signals were identified, and myelodysplastic syndromes/acute myeloid leukaemia occurred in three (1.7%) niraparib-treated patients. Interpretation: Niraparib maintenance therapy with an individualised starting dose demonstrated a favourable OS trend versus placebo in PSROC patients, regardless of gBRCAm status. Funding: Zai Lab (Shanghai) Co., Ltd; National Major Scientific and Technological Special Project for "Significant New Drugs Development" in 2018, China [grant number 2018ZX09736019].

Dinuclear ytterbium(III) benzamidinate complexes with bridging S32-, Se22- and Te22- ligands: synthesis, structure and magnetic properties.

Treatment of Yb(II) complex [L2Yb(THF)2] (L = PhC(NSiMe3)2) with elemental sulfur, selenium or tellurium resulted in the isolation of a series of dinuclear Yb(III) complexes featuring side-on bound S32- (1), Se22- (2) or Te22- (3) moieties, respectively. Magnetic study on these complexes revealed that 3 is a rare lanthanide telluride single-molecule magnet (SMM).