Safety and efficacy of baricitinib in steroid-resistant or relapsed immune thrombocytopenia: An open-label pilot study.

Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.

Predicting hepatocellular carcinoma: A new non-invasive model based on shear wave elastography.

BACKGROUND: Integrating conventional ultrasound features with 2D shear wave elastography (2D-SWE) can potentially enhance preoperative hepatocellular carcinoma (HCC) predictions. AIM: To develop a 2D-SWE-based predictive model for preoperative identification of HCC. METHODS: A retrospective analysis of 884 patients who underwent liver resection and pathology evaluation from February 2021 to August 2023 was conducted at the Oriental Hepatobiliary Surgery Hospital. The patients were divided into the modeling group (n = 720) and the control group (n = 164). The study included conventional ultrasound, 2D-SWE, and preoperative laboratory tests. Multiple logistic regression was used to identify independent predictive factors for malignant liver lesions, which were then depicted as nomograms. RESULTS: In the modeling group analysis, maximal elasticity (Emax) of tumors and their peripheries, platelet count, cirrhosis, and blood flow were independent risk indicators for malignancies. These factors yielded an area under the curve of 0.77 (95% confidence interval: 0.73-0.81) with 84% sensitivity and 61% specificity. The model demonstrated good calibration in both the construction and validation cohorts, as shown by the calibration graph and Hosmer-Lemeshow test (P = 0.683 and P = 0.658, respectively). Additionally, the mean elasticity (Emean) of the tumor periphery was identified as a risk factor for microvascular invasion (MVI) in malignant liver tumors (P = 0.003). Patients receiving antiviral treatment differed significantly in platelet count (P = 0.002), Emax of tumors (P = 0.033), Emean of tumors (P = 0.042), Emax at tumor periphery (P < 0.001), and Emean at tumor periphery (P = 0.003). CONCLUSION: 2D-SWE's hardness value serves as a valuable marker for enhancing the preoperative diagnosis of malignant liver lesions, correlating significantly with MVI and antiviral treatment efficacy.

Effect of COVID-19 on Thrombosis Incidence and Patient Prognosis in Kidney Transplant Recipients.

BACKGROUND Thrombosis poses a grave threat to patients undergoing kidney transplants, with a heightened risk of mortality. While previous studies have established a link between COVID-19 and thrombosis, the specific association between COVID-19 and thrombosis in this patient population remains unexplored. MATERIAL AND METHODS We conducted a retrospective analysis utilizing data from 394 individuals who underwent kidney transplantation within the period of September 1, 2015, to April 1, 2023. To evaluate overall survival, we employed Kaplan-Meier analysis and utilized a logistic regression model for risk analysis. Furthermore, we developed a prediction model and assessed its accuracy through calibration curves. RESULTS Out of the 394 patients included in our study, a total of 51 individuals experienced thrombosis, resulting in 2 deaths. Our analysis revealed that COVID-19 infection significantly increased the risk of thrombosis (odds ratio [OR] 8.60, 95% confidence interval 3.13-24.74, P<0.01). Additionally, the use of cyclosporine was found to elevate the risk of death (OR 20.86, 95% CI 7.93-59.24, P<0.01) according to multifactorial analysis. Logistic models were employed to screen variables, and predictive models were constructed based on the presence of COVID-19 infection and the usage of cyclosporine. A nomogram was developed, demonstrating promising accuracy in estimating the risk of thrombosis during internal validation, with a corrected C-index of 0.869. CONCLUSIONS Our study suggests that both COVID-19 infection and the use of cyclosporine can serve as reliable predictors of thrombosis risk in patients undergoing renal transplantation. Furthermore, we developed a mortality risk prediction model based on COVID-19 in assessing thrombosis.

Prognostic significance of dynamic changes in liver stiffness measurement in patients with chronic hepatitis B and compensated advanced chronic liver disease.

BACKGROUND AND AIM: Liver stiffness measurements (LSMs) are promising for monitoring disease progression or regression. We assessed the prognostic significance of dynamic changes in LSM over time on liver-related events (LREs) and death in patients with chronic hepatitis B (CHB) and compensated advanced chronic liver disease (cACLD). METHODS: This retrospective study included 1272 patients with CHB and cACLD who underwent at least two measurements, including LSM and fibrosis score based on four factors (FIB-4). ΔLSM was defined as [(follow-up LSM - baseline LSM)/baseline LSM × 100]. We recorded LREs and all-cause mortality during a median follow-up time of 46 months. Hazard ratios (HRs) and confidence intervals (CIs) for outcomes were calculated using Cox regression. RESULTS: Baseline FIB-4, baseline LSM, ΔFIB-4, ΔLSM, and ΔLSM/year were independently and simultaneously associated with LREs (adjusted HR, 1.04, 95% CI, 1.00-1.07; 1.02, 95% CI, 1.01-1.03; 1.06, 95% CI, 1.03-1.09; 1.96, 95% CI, 1.63-2.35, 1.02, 95% CI, 1.01-1.04, respectively). The baseline LSM combined with the ΔLSM achieved the highest Harrell's C (0.751), integrated AUC (0.776), and time-dependent AUC (0.737) for LREs. Using baseline LSM and ΔLSM, we proposed a risk stratification method to improve clinical applications. The risk proposed stratification based on LSM performed well in terms of prognosis: low risk (n = 390; reference), intermediate risk (n = 446; HR = 3.38), high risk (n = 272; HR = 5.64), and extremely high risk (n = 164; HR = 11.11). CONCLUSIONS: Baseline and repeated noninvasive tests measurement allow risk stratification of patients with CHB and cACLD. Combining baseline and dynamic changes in the LSM improves prognostic prediction.

A Review of Design Strategies in SiO/C Composite Anodes for Rechargeable Lithium-Ion Batteries.

Lithium-ion batteries (LIBs) are widely used in electric vehicles, portable electronic devices, clean energy storage, and other fields due to their long service life, high energy density, and low self-discharge rate, which also puts forward higher requirements for the performance of lithium-ion batteries. As an anode for lithium-ion batteries, SiO materials have garnered significant attention from researchers due to its high specific capacity (2400 mAh·g-1), abundance of raw materials, and simple preparation. However, its large volume change (~ 200%) and poor electrical conductivity hinder its large-scale commercial application. Researchers employ various methods to reduce the volume change of SiO during lithium intercalation and improve its structural stability during cycling. This work mainly reviews the chemical structure and lithium storage mechanism of SiO, as well as the latest research progress on the preparation methods of SiO/C anode materials, focusing on summarizing the following preparation strategies: chemical vapor deposition, mechanical ball milling, spray drying, and in-situ reduction/oxidation methods. The obtained SiO-based anode materials' structural characteristics and electrochemical properties are compared and summarized. Finally, this review discusses the advantages and disadvantages of the current preparation methods, the future research directions, and the development prospects of SiO-based anode materials.

Characteristics of deformation and damage of surrounding rock along the top roadway in the working face of an isolated island and its evolution law.

This study investigates the deformation and damage characteristics of the surrounding rock along the top return mining roadway of an isolated island working face at different stages and reveals its damage mechanism and evolution law. Utilizing a mine in Yangquan City, Shanxi Province, China, as the engineering background, this research employs FLAC 3D numerical simulation and on-site measurements. The findings suggest that the evolution of the plastic zone along the top roadway of the 15,106 island face is largely similar during both the excavation and mining periods. The plastic zones on either side of the roadway are expanding asymmetrically and gradually merging into the plastic zone of the coal pillar. In the destructive stage, the sub-gangs of the roadway are penetrated, indicating the progression into the plastic zone. The investigation points to extensive damage on the larger side of the roadway, the development of fissures, and the significant depth of damage as primary causes of roadway deformation. Moreover, the extent of the plastic zones on both sides of the roadway correlates positively with their relative distance. Continuous monitoring reveals an ongoing increase in roadway displacement, consistent with general observations in coal mining. The results provide valuable insights for optimizing support structures in similar mining environments.

A universal AC electrokinetics-based strategy toward surface antifouling of underwater optics.

The practical applications of underwater optical devices, such as cameras or sensors, often suffer from widespread surface biofouling. Current antifouling techniques are primarily hindered by low efficiency, poor compatibility, as well as environmental pollution issues. This paper presents a transparent electrode coating as antifouling system of underwater optics as potential substitute for alternating current electrokinetic (ACEK)-based systems. A strong-coupling model is established to predict the Joule heating induced fluid flows and the negative dielectrophoretic (nDEP) effect for mobilizing organisms or deposited sediments on optic surfaces. The performance of the proposed antifouling system is numerically evaluated through simulations of electrostatic, fluid and temperature fields as well as trajectories of submicron particles, which is then experimentally verified and found to be in good agreement. A parametric study revealed that the degree of electrodes asymmetry is the key factor affecting the flow pattern and therefore the overall performance of the system. This ACEK-based universal strategy is expected to shed light on designing high performance and non-toxic platforms toward energy-efficient surface antifouling applications of underwater optics.

High-Efficiency Photo-Fenton-like Catalyst of FeOOH/g-C3N4 for the Degradation of PNP: Characterization, Catalytic Performance and Mechanism Exploration.

The composite photocatalyst FeOOH/g-C3N4 was prepared through thermal polycondensation and co-precipitation methods, followed by XRD, SEM and UV-vis characterization. The stability of FeOOH/g-C3N4 was explored by the recycling test. The active species in the reaction system were investigated by the capture experiment. The results indicated that the optimal preparation condition for g-C3N4 involved calcination at 600 °C for 4 h. XRD analysis revealed that g-C3N4 exhibits a high-purity phase, and Fe in FeOOH/g-C3N4 exists in a highly dispersed amorphous state. SEM analysis showed that FeOOH/g-C3N4 has a rough surface with an irregular layered structure. Element composition analysis confirmed that the content of elements in the prepared catalyst is consistent with the theoretical calculation. FeOOH/g-C3N4 possesses the largest specific surface area of 143.2 m2/g and a suitable pore distribution. UV-vis DRS analysis showed that the absorption intensity of FeOOH/g-C3N4 is stronger than that of g-C3N4. When the catalyst dosage was 1.0 g/L, the H2O2 dosage was 4 mmol/L, the PNP initial concentration was 10 mg/L and the initial pH value was 5, the PNP removal could reach 92% in 120 min. Even after 5 cycles, the efficiency of PNP removal by FeOOH/g-C3N4 remains nearly 80%. The capture experiment indicated that both •OH and •O2- play roles in the photocatalytic degradation of PNP, with •OH being more significant. These findings affirm that FeOOH has been successfully incorporated into g-C3N4, resulting in a conspicuous catalytic effect on the degradation of PNP in the visible light-assisted Fenton-like reaction.

A SAR Ship Detection Method Based on Adversarial Training.

SAR (synthetic aperture radar) ship detection is a hot topic due to the breadth of its application. However, limited by the volume of the SAR image, the generalization ability of the detector is low, which makes it difficult to adapt to new scenes. Although many data augmentation methods-for example, clipping, pasting, and mixing-are used, the accuracy is improved little. In order to solve this problem, the adversarial training is used for data generation in this paper. Perturbation is added to the SAR image to generate new samples for training, and it can make the detector learn more abundant features and promote the robustness of the detector. By separating batch normalization between clean samples and disturbed images, the performance degradation on clean samples is avoided. By simultaneously perturbing and selecting large losses of classification and location, it can keep the detector adaptable to more confrontational samples. The optimization efficiency and results are improved through K-step average perturbation and one-step gradient descent. The experiments on different detectors show that the proposed method achieves 8%, 10%, and 17% AP (Average Precision) improvement on the SSDD, SAR-Ship-Dataset, and AIR-SARShip, compared to the traditional data augmentation methods.

Dendritic morphology of developing hippocampal neurons in Cyp11a1 null mice.

INTRODUCTION: Neurosteroids have a variety of neurological functions, such as neurite growth, neuroprotection, myelination, and neurogenesis. P450scc, encoded by CYP11A1 gene, is the cholesterol side chain cleavage enzyme that catalyzes the first and rate limiting step in the steroidogenesis. In this study, we examine the dendritic morphology in developing hippocampal neurons of Cyp11a1 null mice at P15, a critical period for synapse formation and maturation. METHODS: Knockout mice were maintained until P15 with hormone administration. The Golgi-Cox method stained CA1 and CA3 pyramidal neurons in the hippocampus to reveal dendritic morphology. RESULTS: We demonstrated that Cyp11a1 null mice usually die within 7 days after birth and thus collected brain samples at postnatal day 5 (P5) for examination. There were significant shrinkage of dendrite size and diminishment of dendritic branching in CA1 and CA3 pyramidal neurons in the hippocampus of Cyp11a1 null mice, suggesting a developmental delay. We wonder if this delay may catch up later in life. Since the age of P15 is a critical period for synapse formation and maturation, the Cyp11a1 null mice were rescued by receiving hormone administration until P15 that the dendritic morphology in the developing hippocampal neurons could be examined. The results indicated that the total dendritic length, number of dendritic branches, as well as dendritic arborization in the CA1 and CA3 pyramidal neurons are significantly decreased in P15 knockout mice when compared to the wild type. The spine densities were also significantly decreased. In addition, the western blot analysis revealed decrease PSD-95 expression levels in the knockout mice compared to the wild type at P15. CONCLUSION: These results suggested that Cyp11a1 deficiency impairs the dendritic structures in the developing hippocampal pyramidal neurons.

Embedding Single Pd Atoms on NiGa Intermetallic Surfaces for Efficient and Selective Alkyne Semi-hydrogenation.

Catalytic removal of alkynes is essential in industry for producing polymer-grade alkenes from steam cracking processes. Non-noble Ni-based catalysts hold promise as effective alternatives to industrial Pd-based catalysts but suffer from low activity. Here we report embedding of single-atom Pd onto the NiGa intermetallic surface with replacing Ga atoms via a well-defined synthesis strategy to design Pd1-NiGa catalyst for alkyne semi-hydrogenation. The fabricated Pd1Ni2Ga1 ensemble sites deliver remarkably higher specific mass activity under superb alkene selectivity of >96% than the state-of-the-art catalysts under industry-relevant conditions. Integrated experimental and computational studies reveal that the single-atom Pd located synergizes with the neighbouring Ni sites to facilitate the σ-adsorption of alkyne and dissociation of hydrogen while suppress the alkene adsorption. Such synergistic effects confer the single-atom Pd on the NiGa intermetallic with a Midas touch for alkyne semi-hydrogenation, providing an effective strategy for stimulating low active Ni-based catalysts for other selective hydrogenations in industry.

Cytology or Multiparameter Flow Cytometry Positivity in the Cerebrospinal Fluid Before Transplantation is Predictive of Poor Outcomes After Allotransplantation in Acute Myeloid Leukemia Patients.

INTRODUCTION: Central nervous system leukemia (CNSL) remains a serious complication in patients with acute myeloid leukemia (AML) and an ambiguous prognostic factor for those receiving allo-geneic hematopoiesis stem cell transplantation (allo-HSCT). It is unknown whether using more sensitive tools, such as multiparameter flow cytometry (MFC), to detect blasts in the cerebrospinal fluid (CSF) would have an impact on outcome. METHODS: We retrospectively analyzed the clinical outcomes of 1472 AML patients with or without cytology or MFC positivity in the CSF before transplantation. Abnormal CSF (CSF+) was detected via conventional cytology and MFC in 44 patients at any time after diagnosis. A control group of 175 CSF-normal (CSF-) patients was generated via propensity score matching (PSM) analyses according to sex, age at transplant, and white blood cell count at diagnosis. RESULTS: Compared to those in the CSF-negative group, the conventional cytology positive and MFC+ groups had comparable 8-year nonrelapse mortality (NRM) (4%, 4%, and 6%, p = 0.82), higher cumulative incidence of relapse (CIR) (14%, 31%, and 32%, p = 0.007), lower leukemia-free survival (LFS) (79%, 63%, and 64%, p = 0.024), and overall survival (OS) (83%, 63%, and 68%, p = 0.021), with no significant differences between the conventional cytology positive and MFC+ groups. Furthermore, multivariate analysis confirmed that CSF involvement was an independent factor affecting OS and LFS. CONCLUSION: Our results indicate that pretransplant CSF abnormalities are adverse factors independently affecting OS and LFS after allotransplantation in AML patients.

Measurable residual disease testing by next generation sequencing is more accurate compared with multiparameter flow cytometry in adults with B-cell acute lymphoblastic leukemia.

Results of measurable residual disease (MRD)-testing by next-generation sequencing (NGS) correlate with relapse risk in adults with B-cell acute lymphoblastic leukemia (ALL) receiving chemotherapy or an allotransplant from a human leukocyte antigen (HLA)-identical relative or HLA-matched unrelated donor. We studied cumulative incidence of relapse (CIR) and survival prediction accuracy using a NGS-based MRD-assay targeting immunoglobulin genes after 2 courses of consolidation chemotherapy cycles in 93 adults with B-cell ALL most receiving HLA-haplotype-matched related transplants. Prediction accuracy was compared with MRD-testing using multi-parameter flow cytometry (MPFC). NGS-based MRD-testing detected residual leukemia in 28 of 65 subjects with a negative MPFC-based MRD-test. In Cox regression multi-variable analyses subjects with a positive NGS-based MRD-test had a higher 3-year CIR (Hazard Ratio [HR] = 3.37; 95 % Confidence Interval [CI], 1.34-8.5; P = 0.01) and worse survival (HR = 4.87 [1.53-15.53]; P = 0.007). Some data suggest a lower CIR and better survival in NGS-MRD-test-positive transplant recipients but allocation to transplant was not random. Our data indicate MRD-testing by NGS is more accurate compared with testing by MPFC in adults with B-cell ALL in predicting CIR and survival. (Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTROPC-14005546]).

Photonic Nanochains for Continuous Glucose Monitoring in Physiological Environment.

Diabetes is a common disease that seriously endangers human health. Continuous glucose monitoring (CGM) is important for the prevention and treatment of diabetes. Glucose-sensing photonic nanochains (PNCs) have the advantages of naked-eye colorimetric readouts, short response time and noninvasive detection of diabetes, showing immense potential in CGM systems. However, the developed PNCs cannot disperse in physiological environment at the pH of 7.4 because of their poor hydrophilicity. In this study, we report a new kind of PNCs that can continuously and reversibly detect the concentration of glucose (Cg) in physiological environment at the pH of 7.4. Polyacrylic acid (PAA) added to the preparation of PNCs forms hydrogen bonds with polyvinylpyrrolidone (PVP) in Fe3O4@PVP colloidal nanoparticles and the hydrophilic monomer N-2-hydroxyethyl acrylamide (HEAAm), which increases the content of PHEAAm in the polymer shell of prepared PNCs. Moreover, 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylboronic acid (AFPBA), with a relatively low pKa value, is used as the glucose-sensing monomer to further improve the hydrophilicity and glucose-sensing performances of PNCs. The obtained Fe3O4@(PVP-PAA)@poly(AFPBA-co-HEAAm) PNCs disperse in artificial serum and change color from yellow-green to red when Cg increases from 3.9 mM to 11.4 mM, showing application potential for straightforward CGM.

Target Identification and Mechanistic Characterization of Indole Terpenoid Mimics: Proper Spindle Microtubule Assembly Is Essential for Cdh1-Mediated Proteolysis of CENP-A.

Centromere protein A (CENP-A), a histone H3 variant specific to centromeres, is crucial for kinetochore positioning and chromosome segregation. However, its regulatory mechanism in human cells remains incompletely understood. A structure-activity relationship (SAR) study of the cell-cycle-arresting indole terpenoid mimic JP18 leads to the discovery of two more potent analogs, (+)-6-Br-JP18 and (+)-6-Cl-JP18. Tubulin is identified as a potential cellular target of these halogenated analogs by using the drug affinity responsive target stability (DARTS) based method. X-ray crystallography analysis reveals that both molecules bind to the colchicine-binding site of ß-tubulin. Treatment of human cells with microtubule-targeting agents (MTAs), including these two compounds, results in CENP-A accumulation by destabilizing Cdh1, a co-activator of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. This study establishes a link between microtubule dynamics and CENP-A accumulation using small-molecule tools and highlights the role of Cdh1 in CENP-A proteolysis.

Proton pump inhibitor use is associated with increased liver steatosis.

Despite proton pump inhibitors (PPIs) being generally safe, there are questions about their potential long-term complications. The present study aimed to investigate the association between PPI therapy and the incidence of hepatic steatosis and liver fibrosis in the outpatient population of the United States. The present study included 7,395 individuals aged ≥20 years who underwent hepatic vibration-controlled transient elastography (VCTE) examination. The data were obtained from the January 2017 to March 2020 pre-pandemic National Health and Nutrition Examination Survey. Among the 7,395 adults who were included (mean age, 50.59 years; 3,656 male), 9.8% were prescribed PPIs. Following multivariable adjustment, the use of PPIs was significantly associated with hepatic steatosis [odds ratio (OR), 1.25; 95% confidence interval (CI), 1.02-1.53]. Prolonged use of PPIs was found to increase the risk of developing hepatic steatosis over time (P=0.006). Sensitivity analyses using different definitions of hepatic steatosis, such as a controlled attenuation parameter ≥285 dB/m (OR, 1.19; CI, 1.01-1.40), non-alcoholic fatty liver disease (OR, 1.50; 95% CI, 1.16-1.93) and metabolic dysfunction-associated steatotic liver disease (OR, 1.26; 95% CI, 1.05-1.52), consistently demonstrated an association between PPI prescription and hepatic steatosis. The administration of PPI therapy was linked with hepatic steatosis in US adults, although no significant association was observed with liver stiffness, as determined by VCTE.

Socioeconomic support, quality of life, and prognosis of frailty among the older adults.

Background: Although socioeconomic support is recommended for frailty management, its association with the prognosis of frailty is unclear. Methods: Using data from participants aged ≥65 years in the Chinese Longitudinal Healthy Longevity Survey (2008-2018), the associations between socioeconomic support (source of income, medical insurance, community support, living status), onset of prefrailty/frailty, and worsening of prefrailty, were analyzed using multinominal logistic regression models. The associations between self-reported low quality of life (QoL) and reversion of prefrailty/frailty were analyzed using multivariate logistic regression models. Associations with mortality risk were analyzed using Cox proportional hazard regression models. Results: A total of 13,859 participants (mean age: 85.8 ± 11.1 years) containing 2056 centenarians were included. Financial dependence was a risk factor for low QoL among prefrail/frail individuals, but not among robust individuals. Having commercial or other insurance, and receiving social support from the community were protective factors for low QoL among prefrail/frail individuals and for the worsening of prefrailty. Continuing to work was a risk factor for low QoL, but a protective factor for worsening of prefrailty. A negative association between continuing to work and mortality existed in prefrail individuals aged <85 years and ≥85 years. Living alone was a risk factor for low QoL, but was not significantly associated with frailty prognosis. Conclusions: Prefrail and frail individuals were vulnerable to changes in socioeconomic support and more sensitive to it compared with robust individuals. Preferential policies regarding financial support, social support, and medical insurance should be developed for individuals with frailty.

Finotonlimab with chemotherapy in recurrent or metastatic head and neck cancer: a randomized phase 3 trial.

Immunotherapy combined with chemotherapy regimen has been shown to be effective in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, due to the small number of patients, its efficacy remains controversial in Asian populations, particularly in mainland China. Here a randomized, double-blind phase 3 trial evaluated the efficacy and safety of finotonlimab (SCT-I10A), a programmed cell death 1 (PD-1) monoclonal antibody, combined with cisplatin plus 5-fluorouracil (C5F) for the first-line treatment of R/M HNSCC. Eligible patients (n = 370) were randomly 2:1 assigned to receive finotonlimab plus C5F (n = 247) or placebo plus C5F (n = 123). The primary endpoint was overall survival (OS). In the finotonlimab plus C5F group, OS was 14.1 months (95% confidence interval (CI) 11.1-16.4), compared with 10.5 months (95% CI 8.1-11.8) in the placebo plus C5F group. The hazard ratio was 0.73 (95% CI 0.57-0.95, P = 0.0165), meeting the predefined superiority criteria for the primary endpoint. Finotonlimab plus C5F showed significant OS superiority compared with C5F alone and acceptable safety profile with R/M HNSCC, supporting its use as a first-line treatment option for R/M HNSCC. These results validate the efficacy and safety of the combination of finotonlimab and C5F in Asian patients with R/M HNSCC. ClinicalTrials.gov identifier: NCT04146402 .

In Vitro Toxicity and Modeling Reveal Nanoplastic Effects on Marine Bivalves.

Nanoplastics (NPs) represent a growing concern for global environmental health, particularly in marine ecosystems where they predominantly accumulate. The impact of NPs on marine benthic organisms, such as bivalves, raises critical questions regarding ecological integrity and food safety. Traditional methods for assessing NP toxicity are often limited by their time-intensive nature and ethical considerations. Herein, we explore the toxicological effects of NPs on the marine bivalve Ruditapes philippinarum, employing a combination of in vitro cellular assays and advanced modeling techniques. Results indicate a range of adverse effects at the organismal level, including growth inhibition (69.5-108%), oxidative stress, lipid peroxidation, and DNA damage in bivalves, following exposure to NPs at concentrations in the range of 1.6 × 109-1.6 × 1011 particles/mL (p/mL). Interestingly, the growth inhibition predicted by models (54.7-104%), based on in vitro cellular proliferation assays, shows strong agreement with the in vivo outcomes of NP exposure. Furthermore, we establish a clear correlation between cytotoxicity observed in vitro and the toxicological responses at the organismal level. Taken together, this work suggests that the integration of computational modeling with in vitro toxicity assays can predict the detrimental effects of NPs on bivalves, offering insightful references for assessing the environmental risk assessment of NPs in marine benthic ecosystems.