Multimode Ultrasound Model for Predicting the Early Treatment Response of Anti-VEGF Agents Plus Anti-PD-1 Antibody in Patients with Unresectable Hepatocellular Carcinoma.

OBJECTIVE: The purpose of the study described was to establish prediction models to initially screen the beneficiary patients with unresectable hepatocellular carcinoma (HCC) in the treatment of anti-vascular endothelial growth factor (VEGF) agents plus anti-programmed cell death-1 (PD-1) antibody. METHODS: A total of 62 patients were enrolled in this study. All patients underwent ultrasound (US), color ddoppler flowing imaging (CDFI), contrast-enhanced ultrasound (CEUS) and laboratory examinations within 2 wk before the treatment. Tumor response was assessed according to mRECIST criteria. Univariate and multivariate analyses were used to select the independent predictors. US + CDFI, CEUS and FULL models were established. Three models were displayed by nomography. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the predictive ability of models. Decision curve analysis (DCA) was used to assess the clinical utility of models. RESULTS: On univariate and multivariate analysis, the US boundary (p = 0.037), halo (p = 0.002) and CDFI (p = 0.024) were included in the US + CDFI model. CEUS boundary (p = 0.001) and washout time (p < 0.001) were included in the CEUS model. The number of lesions (p = 0.104), halo on US (p = 0.014), CDFI (p = 0.057) and washout time on CEUS (p = 0.015) were incorporated into the FULL model. The C indices of the US + CDFI, CEUS and FULL models were 0.918, 0.920 and 0.973. CEUS and FULL models yielded a good net benefit for almost all threshold probabilities. CONCLUSION: Nomograms based on US, CDFI, CEUS and clinical characteristics could help to non-invasively predict the response to treatment with anti-PD-1 antibodies plus anti-VEGF agents.

Analyzing the Trends and Causes of Birth Defects - Jinan City, Shandong Province, China, 2005-2022.

What is already known about this topic?: Numerous studies conducted in China have reported on the prevalence of birth defects (BDs). However, the limited surveillance periods in select studies curtail comprehensive trends and cause evaluation. Accordingly, the surveillance duration of BDs is extended, and a comprehensive analysis of their prevailing trends is conducted to provide a basis for government intervention and policy implementation. What is added by this report?: There is a distinct increase in the incidence of BDs observed in Jinan. In rural areas, a pronounced upward trend was observed, and the increase was more rapid than in urban areas. BD prevalence among mothers over 35 years old and under 20 years old was substantially higher than BD prevalence rates in other maternal age brackets. Specifically, the period from 2005 to 2022 saw the prevalence of congenital heart disease surge, the fastest average annual growth rate among all birth defects. What are the implications for public health practice?: It's essential to prioritize pregnant women in rural areas and those at both ends of the maternal age spectrum. Implementing comprehensive initiatives is crucial to address the high prevalence of congenital heart disease.

[Environmental impact differences in Qingtian rice-fish culture system at different management scales in the context of land transfer: An empirical study with the carbon footprint method.] / åœŸåœ°æµè½¬èƒŒæ™¯ä¸‹ä¸åŒç»è¥è§„æ¨¡é’ç”°ç¨»é±¼å ±ç”Ÿç³»ç»Ÿçš„çŽ¯å¢ƒå½±å“å·®å¼‚­­åŸºäºŽç¢³è¶³è¿¹çš„å®žè¯ç ”ç©¶.

Under rapid industrialization and urbanization, the conservation and management of agricultural heritage systems is facing many threats and challenges, such as the massive outflow of working labor, land abandonment, and the difficulty in maintaining traditional knowledge systems. Promoting land transfer and carrying out moderate-scale management play an active role in the conservation of agricultural heritage systems. While land transfer brings economic benefits to heritage sites, its environmental impacts to heritage sites are worthy of attention. However, empirical studies are scarce. This study took Qingtian rice-fish culture system in Zhejiang Province as an example, which was designated as Globally Important Agricultural Heritage Systems (GIAHS) in 2005. Small farmer management model and land scale management model were distinguished, while the life cycle method was used to calculate the carbon footprints of two models. The results showed that the carbon footprints of small farmer management model and land scale management model were 6510.80 and 5917.00 kg CO2-eq·hm-2, respectively, while the carbon footprints per unit output were 0.13 and 0.10 kg CO2-eq·yuan-1, respectively. Compared with small farmer management model, land scale management model had lower greenhouse gas emission and lower environmental impact of per unit output. As farmers expanded the scale of land management, local greenhouse gas emissions had been reduced by 4097.20 kg CO2-eq. Furthermore, the accumulation of CH4 in agricultural production accounted for the largest proportion of carbon footprint. The input of compound fertilizer among agricultural production materials was next to CH4 accumulation, becoming the second largest source of greenhouse gas emission. Corn and wheat being used as fish feed also had a significant impact on greenhouse gas emission in small farmer management model. Therefore, the promotion of moderate scale land management is conducive to the win-win of economic and environmental benefits of traditional agricultural systems and plays an important role in the conservation of agricultural heritage systems.

Comb-assisted, Pound-Drever-Hall locked cavity ring-down spectrometer for high-performance retrieval of transition parameters.

Fast and high-performance cavity ring-down spectrometer (CRDS) is highly desired to precisely extract spectral parameters. In this paper, we present our comb-assisted Pound-Drever-Hall (PDH) locked CRDS setup, aiming to retrieve molecular parameters. In the setup, a dynamic feedback is used to keep the tight PDH locking even under strong absorption in the spectral measurement. PDH light and probing light enter the ring-down cavity simultaneously under orthogonal polarization, which enables a fast acquisition of ring-down events without interrupting PDH locking. Ultra-stable cavity temperature is realized, which has an accuracy below 0.5 mK in 27 minutes. The optical frequency comb (OFC) system is developed to rapidly and automatically measure the frequency axis with a relatively wide beat-note range. The minimum detectable absorption coefficient and noise-equivalent absorption coefficient (NEA) are 7.6×10-12cm-1 and 5.3×10-12cm-1Hz-1/2, respectively. The spectrometer is implemented to measure CO2 transition and extract line parameters. The uncertainty for line position is evaluated to be 120 kHz. An accuracy of 0.31% for line intensity is beneficial to the precise determination of CO2 content for the purpose of environment protection and other applications.

QM/MM free energy Simulations of an efficient Gluten Hydrolase (Kuma030) Implicate for a Reactant-State Based Protein-Design Strategy for General Acid/Base Catalysis.

It is a grand attraction for contemporary biochemists to computationally design enzymes for novel chemical transformation or improved catalytic efficiency. Rosetta by Baker et al. is no doubt the leading software in the protein design society. Generally, optimization of the transition state (TS) is part of the Rosetta's protocol to enhance the catalytic efficiency of target enzymes, since TS stabilization is the determining factor for catalytic efficiency based on the TS theory (TST). However, it is confusing that optimization of the reactant state (RS) also results in significant improvement of catalytic efficiency in some cases, such as design of gluten hydrolase (Kuma030). Therefore, it is interesting to uncover underlying reason why a better binding in the RS leading to an increased k cat . In this study, the combined quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) and free energy (PMF) simulations, pK a calculation, and the statistical analysis such as the ANOVA test were carried out to shed light on the interesting but elusive question. By integration of our computational results and general acid/base theory, we answered the question why optimization of RS stabilization leads to a better TS stabilization in the general acid/base catalysis. In addition, a new and simplified protein-design strategy is proposed for the general acid/base catalysis. The idea, that application of traditional well-defined enzyme mechanism to protein design strategy, would be a great help for methodology development of protein design.

Therapeutic effects of 5-fluorouracil sustained-release particles in 81 malignant pericardial effusion patients.

This study aimed to investigate the clinical application value of the 5-fluorouracil (5-FU) sustained-release particles implanted along the cardiac tangent direction into malignant pericardial effusion (MPCE). A total of 81 MPCE patients underwent pericardiocentesis, and were implanted with 5-FU sustained-release particles into the pericardial cavity under ultrasound guidance. The puncturing path was along the cardiac tangent direction. Ultrasound examinations were performed every week, and the efficacy was evaluated 4 weeks after treatment. The 45 patients who were treated with pericardial catheter drainage and simultaneous intracavitary chemotherapy were used as the control group. The success rate of pericardiocentesis was 100%. Ultrasound reviews performed 4 weeks after treatment showed that 71 cases achieved complete remission and eight cases achieved partial remission, while treatment was completely ineffective in two cases. The total remission rate was 97.53%, which was significantly higher than that of the control group (77.78%, p < 0.01). The implantation of 5-FU sustained-release particles along the cardiac tangent direction was safe, and demonstrated good efficacy and fewer adverse reactions. Thus, this method could be ideal for the treatment of MPCE.

Level set segmentation of medical images based on local region statistics and maximum a posteriori probability.

This paper presents a variational level set method for simultaneous segmentation and bias field estimation of medical images with intensity inhomogeneity. In our model, the statistics of image intensities belonging to each different tissue in local regions are characterized by Gaussian distributions with different means and variances. According to maximum a posteriori probability (MAP) and Bayes' rule, we first derive a local objective function for image intensities in a neighborhood around each pixel. Then this local objective function is integrated with respect to the neighborhood center over the entire image domain to give a global criterion. In level set framework, this global criterion defines an energy in terms of the level set functions that represent a partition of the image domain and a bias field that accounts for the intensity inhomogeneity of the image. Therefore, image segmentation and bias field estimation are simultaneously achieved via a level set evolution process. Experimental results for synthetic and real images show desirable performances of our method.

Localized FCM Clustering with Spatial Information for Medical Image Segmentation and Bias Field Estimation.

This paper presents a novel fuzzy energy minimization method for simultaneous segmentation and bias field estimation of medical images. We first define an objective function based on a localized fuzzy c-means (FCM) clustering for the image intensities in a neighborhood around each point. Then, this objective function is integrated with respect to the neighborhood center over the entire image domain to formulate a global fuzzy energy, which depends on membership functions, a bias field that accounts for the intensity inhomogeneity, and the constants that approximate the true intensities of the corresponding tissues. Therefore, segmentation and bias field estimation are simultaneously achieved by minimizing the global fuzzy energy. Besides, to reduce the impact of noise, the proposed algorithm incorporates spatial information into the membership function using the spatial function which is the summation of the membership functions in the neighborhood of each pixel under consideration. Experimental results on synthetic and real images are given to demonstrate the desirable performance of the proposed algorithm.