PD-1 inhibitor-augmented HAIC-TKI therapy in hepatocellular carcinoma with portal vein tumor thrombosis: real-world survival benefits, safety, and subgroup-specific efficacy

BackgroundPD-1/PD-L1 inhibitors have shown efficacy in improving the prognosis of patients with hepatocellular carcinoma (HCC) accompanied by portal vein tumor thrombosis (PVTT) in pivotal clinical trials including the landmark IMbrave150 study. However, not all the patients benefit from the PD-1/PD-L1 blockade immunotherapy. This study aimed to improve the identification of PVTT-associated HCC patients who may benefit from the combination of PD-1 inhibitor and hepatic arterial infusion chemotherapy (HAIC) and tyrosine kinase inhibitor (TKI) treatment under real-world conditions.MethodsFrom 377 HCC-PVTT patients receiving HAIC-TKI ± PD-1 inhibitors (2016-2023), we compared 76 dual-therapy (HT) and 175 triple-therapy (HTP) cases. Median follow-up period was 34.8 months in the HT group and 33.4 months in the HTP group (P=0.175). Propensity score matching (1:1 caliper=0.2) was used to balance baseline characteristics. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were evaluated in both groups. Specific subgroups including Vp4 type PVTT, extrahepatic metastases, and patients over 60 years old, were analyzed.ResultsTriple therapy significantly improved median OS (24.6 vs. 13.5 months; HR=0.58, 95%CI:0.42–0.80; P=0.001) and PFS (11.1 vs. 6.4 months; HR=0.56, P<0.001), with a 15% absolute ORR increase (66.3% vs. 51.3%, P=0.034). In subgroup analysis, for patients with Vp4 type PVTT, the addition of PD-1 inhibitor prolonged overall survival by 6.0 months (P=0.04). For patients aged 60 years and above, the addition of PD-1 inhibitor prolonged overall survival by 1.9 months (P=0.363). For patients with extrahepatic metastasis, the addition of PD-1 inhibitor prolonged overall survival by 3.0 months (P=0.913). Grade 3–4 adverse events were comparable (30.9% vs. 19.7%, P=0.09), but two patients experienced immune treatment-related fatalities in the HTP group.ConclusionThe triple therapy (HAIC-TKI-PD-1) demonstrated superior efficacy over HAIC-TKI dual therapy in HCC patients with PVTT, achieving significant improvements in ORR, mOS, and mPFS, with an acceptable safety profile. However, PD-1 inhibitors showed minimal survival benefits in patients aged >60 or with extrahepatic metastases

Ultra-small topological spin textures with size of 1.3nm at above room temperature in Fe78Si9B13 amorphous alloy

Topologically protected spin textures, such as skyrmions1,2 and vortices3,4, are robust against perturbations, serving as the building blocks for a range of topological devices5-9. In order to implement these topological devices, it is necessary to find ultra-small topological spin textures at room temperature, because small size implies the higher topological charge density, stronger signal of topological transport10,11 and the higher memory density or integration for topological quantum devices5-9. However, finding ultra-small topological spin textures at high temperatures is still a great challenge up to now. Here we find ultra-small topological spin textures in Fe78Si9B13 amorphous alloy. We measured a large topological Hall effect (THE) up to above room temperature, indicating the existence of highly densed and ultra-small topological spin textures in the samples. Further measurements by small-angle neutron scattering (SANS) reveal that the average size of ultra-small magnetic texture is around 1.3nm. Our Monte Carlo simulations show that such ultra-small spin texture is topologically equivalent to skyrmions, which originate from competing frustration and Dzyaloshinskii-Moriya interaction12,13 coming from amorphous structure14-17. Taking a single topological spin texture as one bit and ignoring the distance between them, we evaluated the ideal memory density of Fe78Si9B13, which reaches up to 4.44*104 gigabits (43.4 TB) per in2 and is 2 times of the value of GdRu2Si218 at 5K. More important, such high memory density can be obtained at above room temperature, which is 4 orders of magnitude larger than the value of other materials at the same temperature. These findings provide a unique candidate for magnetic memory devices with ultra-high density.Comment: 26 pages, 4 figure

The Role of Eye Gaze in Security and Privacy Applications: Survey and Future HCI Research Directions

For the past 20 years, researchers have investigated the use of eye tracking in security applications. We present a holistic view on gaze-based security applications. In particular, we canvassed the literature and classify the utility of gaze in security applications into a) authentication, b) privacy protection, and c) gaze monitoring during security critical tasks. This allows us to chart several research directions, most importantly 1) conducting field studies of implicit and explicit gaze-based authentication due to recent advances in eye tracking, 2) research on gaze-based privacy protection and gaze monitoring in security critical tasks which are under-investigated yet very promising areas, and 3) understanding the privacy implications of pervasive eye tracking. We discuss the most promising opportunities and most pressing challenges of eye tracking for security that will shape research in gaze-based security applications for the next decade

Large-Scale Self-Assembly of the Nitrogen-Doped Graphene with High Electrocatalytic Activity for Oxygen Reduction

Abstract not Available.</jats:p

Laboratory Model Test and Field In Situ Test of Distributed Optical Fiber Monitoring of Seepage in a Karst Depression Reservoir Basin

Karst depressions are ideal places for building reservoirs and stacking wastes, but karst depressions are mostly located in areas with strong karst development, and there is a problem of karst leakage. The study of karst depression monitoring methods can provide technical support for the construction of reservoirs in karst depressions, and leakage monitoring technology based on distributed temperature sensing (DTS) has the clear advantages of a large measurement range, high precision, continuity, wide distribution, large area, etc. In this paper, a temperature-sensing optical cable is first used to conduct leakage monitoring tests in different soil media, and the temperature change curve in different media is obtained, which verifies the feasibility of the heatable temperature-sensing optical cable to identify leakage in soil media with different moisture contents. Then, for the heatable distributed temperature-sensing optical cable, the variation law of the temperature eigenvalues of the sensing optical cable under different seepage velocities is studied using the layout method wrapped with saturated medium-coarse sand, and the relationship between the seepage rate and the temperature eigenvalues was analyzed. A regression formula for quantitative analysis of leakage velocity was established; finally, the manganese slag silo project in Songtao County in Guizhou Province, China, was used to simulate different leakage conditions on site for testing, and the data were compared and analyzed to obtain the route under different conditions. The temperature distribution law of the seepage section verifies the feasibility of the application of heatable temperature-sensing optical cables in the seepage monitoring of karst depressions