Progress in immune checkpoint inhibitor-based combined regimens in the treatment of metastatic urothelial carcinoma

Metastatic urothelial carcinoma （mUC） yields poor prognosis and is difficult to treat. Immunotherapy strategies have developed rapidly in recent years， and clinical prognosis of mUC patients has been significantly improved. However， immune checkpoint inhibitors （ICIs） alone have limited efficacy， and some ICIs monotherapy indications for mUC have also been withdrawn in recent years. Therefore， combined therapy based on ICIs has become a research hotspot in the treatment of mUC. At present， multiple clinical studies of ICIs combined with chemotherapy， antibody-drug conjugates， and dual immunotherapy for multiple lines of treatment of mUC have proved that combined therapy possesses promising development prospect. In this article， latest progress in ICI-based combined treatment for mUC was reviewed， aiming to provide reference for clinicians

Power Optimization of Wave Energy Converter (WEC) Arrray Based on Sea Conditions of a Wind Farm

[Introduction] In order to respond to the national initiative of intensive sea use, develop clean energy, and contribute to carbon neutralization, a preliminary analysis was conducted on the multi-energy integration mode of offshore wind power and wave energy devices, and the WEC was optimized to achieve higher power output. [Method] Based on potential flow theory, the floating fan platform - WEC array was simulated to analyze the influence of the dimension and the inherent period of the WEC on the output power of the WEC. [Result] The simulation results show that under the same inherent period, the flatter the WEC is, the greater the total power of the WEC array is, and the economic difference of the WEC is small. For sea conditions, the economic difference of WEC array under different inherent periods is great, so it should be considered comprehensively. [Conclusion] In the known sea conditions, the inherent period and the dimenson of WECs can be optimized to achieve higher power output and increase energy output per unit sea area

Clinical analysis and quality of life survey of hemophilia B patients in the central and western regions of China

ObjectiveTo study the current status of hemophilia B (HB) patients in the central and western regions of China.MethodsThis cross-sectional, multicenter study was conducted in seven provinces in the central and western regions of China from April 2019 to June 2023. Samples were collected for the factor IX activity, inhibitor screen, and gene mutation. Furthermore, the status of six index joints and quality of life (QoL) were assessed.ResultsA total of 185 HB patients (mild 15, moderate 75, and severe 95) with a median age of 12.17 years were enrolled. 30.3% (56/185) of patients had a family history of HB. 34.6% (64/185) of HB patients had diagnostic delay and 38.5% (69/179) experienced treatment delay. The incidence of inhibitors was 6.1% (11/179). We identified 123 genetic variants in this study, with missense mutations being the most common. 84.0% (89/106) of HB mothers were genetically identified as carriers, with 27.7% (13/47) of carriers having clotting factor levels less than 0.40 IU/ml. 71.4% (132/185) of HB patients had a history of joint hemorrhage, with a rate of target joint in these patients was 64.4% (85/132). Lower extremity joints were most often affected in patients. The Hemophilia Joint Health Score (HJHS) score was significantly positively correlated with the Hemophilia Early Arthropathy Detection with Ultrasound in China (HEAD-US-C) (r = 0.542, P < 0.001). Patients who received prevention treatment, inhibitor negative, without treatment delay, and without high-intensity replacement therapy showed a higher total score of the short form-36 health survey (SF-36).ConclusionsOne-third of HB patients had delay in diagnosis and treatment, and the incidence of inhibitors was 6.1%. Target joints were present in nearly half of HB patients. Missense was the main mutation type. 84.0% of mothers of HB patients in this study were found to be carriers. HEAD-US-C and HJHS can complement each other in the evaluation of joint status and give a valid basis for early clinical management. Early detection and preventive treatment, as well as reducing high-intensity replacement therapy and inhibitor generation, can effectively improve the QoL of patients

Enhanced sampling in molecular dynamics using metadynamics, replica-exchange, and temperature-acceleration

We review a selection of methods for performing enhanced sampling in molecular dynamics simulations. We consider methods based on collective variable biasing and on tempering, and offer both historical and contemporary perspectives. In collective-variable biasing, we first discuss methods stemming from thermodynamic integration that use mean force biasing, including the adaptive biasing force algorithm and temperature acceleration. We then turn to methods that use bias potentials, including umbrella sampling and metadynamics. We next consider parallel tempering and replica-exchange methods. We conclude with a brief presentation of some combination methods. \ua9 2013 by the author; licensee MDPI, Basel, Switzerland

Novel crosslinked starch microspheres as adsorbents of Cu²⁺

A novel adsorbent, a crosslinked starch microsphere (CSM), was prepared from soluble starch and N,N'-methylenebisacrylamide. The microporous structure of the CSM was determined with scanning electron microscopy. The diameter distribution of the CSMs was quite uniform, and the average diameter of the microparticles was estimated to be 50 μm. Cu²⁺ was introduced into the CSM. The successful adsorption of Cu²⁺ in the CSM was confirmed with Fourier transform infrared spectroscopy. The crystal structure of the CSM was destroyed after the incorporation of Cu²⁺ . This was proven with X-ray diffraction. The thermal stability of the CSM was weakened with the introduction of Cu²⁺ during simultaneous thermal analysis.4 page(s

Modeling the morphology-dependent optical properties of single and dimer Pt nanodendrite structures

The optical properties of Pt nanodendrites prepared by the electrochemical method are investigated and modeled by the finite-element method (FEM). Experimentally, localized surface plasmon resonance (LSPR) peaks are observed. The three-dimensional (3D) calculations of the single Pt dendrite model demonstrate that the LSPR “hot spot” is localized at the branch-trunk junctions and turned out to be more pronounced with increasing longitudinal plasmon resonance mode, accompanied by a significant enhanced electric field induced by sharp morphology features. We find that the LSPR of the nanodendrites is inherently sensitive to dimensions and configuration, thus providing the guidelines for developing new LSPR dendritic materials

Achieving misalignment tolerance with hybrid topologies in electric vehicle wireless charging systems

With the rocketing progress of wireless power transfer (WPT) for electric vehicles (EVs), the issue of misalignment tolerance has become increasingly vital, a hybrid topology of the series–series (S–S) and inductor–capacitor–capacitor-parallel (LCC-P) is proposed in this paper to achieve misalignment tolerance. Both the S–S topology and the LCC-P topology have constant-current output, the difference is that the output power of S–S increases with the increasing misalignment, oppositely, the output power of LCC-P reduces with the increasing misalignment. A combination of these two topologies can enhance the anti-offset capability. The magnetic couplers utilize unipolar (Q) and bipolar (DD) coils as the two decoupled coils for power transfer. The mathematical model has been established and analyzed. The transfer efficiency and the output parameters’ expressions of current, voltage and power have been derived. The theoretical analysis has been verified in the simulation model of MATLAB/Simulink. The proposed hybrid topology has succeeded in achieving misalignment tolerance

Accuracy of Percutaneous Core Biopsy in the Diagnosis of Small Renal Masses (≤4.0 cm): A Meta-analysis

Objective To use meta-analysis to determine the accuracy of percutaneous core needle biopsy in the diagnosis of small renal masses (SMRs≤4.0 cm). Materials and Methods Studies were identified by searching PubMed, Embase, and the Cochrane Library database up to March 2013. Two of the authors independently assessed the study quality using QUADAS-2 tool and extracted data that met the inclusion criteria. The sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR) and also summary receiver operating characteristic (SROC) curve were investigated and draw. Deek’s funnel plot was used to evaluate the publication bias. Result A total of 9 studies with 788 patients (803 biopsies) were included. Failed biopsies without repeated or aborted from follow-up/surgery result were excluded (232 patients and 353 biopsies). For all cases, the pooled sensitivity was 94.0% (95% CI: 91.0%, 95.0%), the pooled positive likelihood was 22.57 (95% CI: 9.20-55.34), the pooled negative likelihood was 0.09 (95% CI: 0.06-0.13), the pooled DOR was 296.52(95% CI: 99. 42-884.38). The area under the curve of SROC analysis was 0.959±0.0254. Conclusion Imaging-guided percutaneous core needle biopsy of small renal masses (SMRs≤4.0 cm) is highly accurate to malignant tumor diagnosis with unknown metastatic status and could be offered to some patients after clinic judgment prior to surgical intervention consideration