Glucose-oxygen coupling can serve as a biomarker for neuroinflammation-related genetic variants.

The single-nucleotide polymorphism rs3197999 in the macrophage-stimulating protein 1 gene is a missense variant. Studies have indicated that macrophage-stimulating protein 1 mediates neuronal loss and synaptic plasticity damage, and overexpression of the macrophage-stimulating protein 1 gene leads to the excessive activation of microglial cells, thereby resulting in an elevation of cerebral glucose metabolism. Traditional diagnostic models may be disrupted by neuroinflammation, making it difficult to predict the pathological status of patients solely based on single-modal images. We hypothesize that the macrophage-stimulating protein 1 rs3197999 single-nucleotide polymorphism may lead to imbalances in glucose and oxygen metabolism, thereby influencing cognitive resilience and the progression of Alzheimer's disease. In this study, we found that among 121 patients with mild cognitive impairment, carriers of the macrophage-stimulating protein 1 rs3197999 risk allele showed a significant reduction in the coupling of glucose and oxygen metabolism in the dorsolateral prefrontal cortex region. However, the rs3197999 variant did not induce significant differences in glucose metabolism and neuronal activity signals. Furthermore, the rs3197999 risk allele correlated with a higher rate of increase in clinical dementia score, mediated by the coupling of glucose and oxygen metabolism.

A novel EPID-based MLC QA method with log files achieving submillimeter accuracy.

The purpose of this study is to develop an electronic portal imaging device-based multi-leaf collimator calibration procedure using log files. Picket fence fields with 2-14 mm nominal strip widths were performed and normalized by open field. Normalized pixel intensity profiles along the direction of leaf motion for each leaf pair were taken. Three independent algorithms and an integration method derived from them were developed according to the valley value, valley area, full-width half-maximum (FWHM) of the profile, and the abutment width of the leaf pairs obtained from the log files. Three data processing schemes (Scheme A, Scheme B, and Scheme C) were performed based on different data processing methods. To test the usefulness and robustness of the algorithm, the known leaf position errors along the direction of perpendicular leaf motion via the treatment planning system were introduced in the picket fence field with nominal 5, 8, and 11 mm. Algorithm tests were performed every 2 weeks over 4 months. According to the log files, about 17.628% and 1.060% of the leaves had position errors beyond ± 0.1 and ± 0.2 mm, respectively. The absolute position errors of the algorithm tests for different data schemes were 0.062 ± 0.067 (Scheme A), 0.041 ± 0.045 (Scheme B), and 0.037 ± 0.043 (Scheme C). The absolute position errors of the algorithms developed by Scheme C were 0.054 ± 0.063 (valley depth method), 0.040 ± 0.038 (valley area method), 0.031 ± 0.031 (FWHM method), and 0.021 ± 0.024 (integrated method). For the efficiency and robustness test of the algorithm, the absolute position errors of the integration method of Scheme C were 0.020 ± 0.024 (5 mm), 0.024 ± 0.026 (8 mm), and 0.018 ± 0.024 (11 mm). Different data processing schemes could affect the accuracy of the developed algorithms. The integration method could integrate the benefits of each algorithm, which improved the level of robustness and accuracy of the algorithm. The integration method can perform multi-leaf collimator (MLC) quality assurance with an accuracy of 0.1 mm. This method is simple, effective, robust, quantitative, and can detect a wide range of MLC leaf position errors.

Hepatitis B antibody levels after different doses of hepatitis B vaccination: a retrospective study based on hospitalized children.

Many studies have investigated the positivity rate of hepatitis B surface antibody (HBsAb) after hepatitis B vaccine (HepB) immunization. However, the antibody level, assessed monthly or at more frequent intervals after each of the three doses, particularly within the first year after birth, has not been previously reported. To elucidate the level of antibody formation at various times after vaccination, the current study used the available detection data of HBsAb in hospitalized children to analyze the HBsAb level after immunization combined with their vaccination history. Both the positivity rate and geometric mean concentration (GMC) increased sequentially with immunization doses, reaching their peaks earlier after the third dose than after the first two doses, and the rate of HBsAb positivity was able to reach 100% between 11 and 90 days after completing the three doses of HepB. Within one year after receiving the three doses, the antibody positivity rate and GMC were maintained above 90% and 100 mIU/mL, respectively, and subsequently steadily declined, reaching the lowest value in the 9th and 10th years. The current findings reveal, in more detail, the level of antibody formation at different times following each dose of HepB in hospitalized children, particularly in the age group up to one year after vaccination. For the subjects of this study, we prefer to believe that the proportion of HBsAb non-response should be less than 5% after full immunization with HepB, provided that the appropriate time for blood collection is chosen.

Ultrasonic Imaging Investigation of Tongue Movement Patterns of Cleft-Related Lateralized and Palatalized Misarticulation.

OBJECTIVES: To explore the tongue movement patterns on Mandarin speaking children with repaired cleft palate with lateralized and palatalized misarticulation (LPM) using ultrasound imaging technique. METHODS: A group of 20 subjects who were diagnosed with speech sound disorder after cleft palate repairment, and another group of 18 children with LPM were recruited. A group of 20 typical children were recruited as the control group. The ultrasonography was used to collect the articulation pattern of the 8 single vowels that are /a/, /o/, / ɘ/, /i/, /u/, /y/, /ɨ/, /ʉ/ in Mandarin Chinese. Various ultrasonic tongue parameters were analyzed from both sagittal and coronal planes. RESULTS: Compared with the control group, coronal height of peak point, coronal tongue dorsum constraint index, sagittal peak point offset distance, sagittal distance between tongue tip and peak point, and sagittal tongue dorsum constraint index of /ɘ/,/i/, /y/ and /ɨ/ were significantly smaller in the cleft-related lateralized and palatalized group (CLP) and noncleft-related lateralized and palatalized group (NLP) ( P   <  0.05). Compared with the noncleft-related later- alized and palatalized group and control group, sagittal peak point offset distance of the vowels /ɘ/ and /i/ was significant smaller in the cleft-related lateralized and palatalized group group ( P  < 0.05). CONCLUSIONS: The ultrasound images on the children with cleft palate showed a midline elevation of the tongue and a significant apical constriction. The children with LPM showed a midline elevation at the coronal plane and anterior movement of the tongue high point at the sagittal plane. The apical vowels were more informative and accurate in indicating the features of LPM than other vowels.

Estimating the accumulative dose uncertainty for intracavitary and interstitial brachytherapy.

BACKGROUND: Image-guided adaptive brachytherapy shows the ability to deliver high doses to tumors while sparing normal tissues. However, interfraction dose delivery introduces uncertainties to high dose estimation, which relates to normal tissue toxicity. The purpose of this study was to investigate the high-dose regions of two applicator approaches in brachytherapy. METHOD: For 32 cervical cancer patients, the CT images from each fraction were wrapped to a reference image, and the displacement vector field (DVF) was calculated with a hybrid intensity-based deformable registration algorithm. The fractional dose was then accumulated to calculate the position and the overlap of high dose (D2cc) during multiple fractions. RESULT: The overall Dice similarity coefficient (DSC) of the deformation algorithm for the bladder and the rectum was (0.97 and 0.91). No significant difference was observed between the two applicators. However, the location of the intracavitary brachytherapy (ICBT) high-dose region was relatively concentrated. The overlap volume of bladder and rectum D2cc was 0.42 and 0.71, respectively, which was higher than that of interstitial brachytherapy (ISBT) (0.26 and 0.31). The cumulative dose was overestimated in ISBT cases when using the GEC-recommended method. The ratio of bladder and rectum D2cc to the GEC method was 0.99 and 1, respectively, which was higher than that of the ISBT method (0.96 and 0.94). CONCLUSION: High-dose regions for brachytherapy based on different applicator types were different. The 3D-printed ICBT has better high-dose region consistency than freehand ISBT and hence is more predictable.

Sharp loss: a new loss function for radiotherapy dose prediction based on fully convolutional networks.

BACKGROUND: Neural-network methods have been widely used for the prediction of dose distributions in radiotherapy. However, the prediction accuracy of existing methods may be degraded by the problem of dose imbalance. In this work, a new loss function is proposed to alleviate the dose imbalance and achieve more accurate prediction results. The U-Net architecture was employed to build a prediction model. Our study involved a total of 110 patients with left-breast cancer, who were previously treated by volumetric-modulated arc radiotherapy. The patient dataset was divided into training and test subsets of 100 and 10 cases, respectively. We proposed a novel 'sharp loss' function, and a parameter γ was used to adjust the loss properties. The mean square error (MSE) loss and the sharp loss with different γ values were tested and compared using the Wilcoxon signed-rank test. RESULTS: The sharp loss achieved superior dose prediction results compared to those of the MSE loss. The best performance with the MSE loss and the sharp loss was obtained when the parameter γ was set to 100. Specifically, the mean absolute difference values for the planning target volume were 318.87 ± 30.23 for the MSE loss versus 144.15 ± 16.27 for the sharp loss with γ = 100 (p < 0.05). The corresponding values for the ipsilateral lung, the heart, the contralateral lung, and the spinal cord were 278.99 ± 51.68 versus 198.75 ± 61.38 (p < 0.05), 216.99 ± 44.13 versus 144.86 ± 43.98 (p < 0.05), 125.96 ± 66.76 versus 111.86 ± 47.19 (p > 0.05), and 194.30 ± 14.51 versus 168.58 ± 25.97 (p < 0.05), respectively. CONCLUSIONS: The sharp loss function could significantly improve the accuracy of radiotherapy dose prediction.

Radiotherapy dose distribution prediction for breast cancer using deformable image registration.

BACKGROUND: Radiotherapy treatment planning dose prediction can be used to ensure plan quality and guide automatic plan. One of the dose prediction methods is incorporating historical treatment planning data into algorithms to estimate the dose-volume histogram (DVH) of organ for new patients. Although DVH is used extensively in treatment plan quality and radiotherapy prognosis evaluation, three-dimensional dose distribution can describe the radiation effects more explicitly. The purpose of this retrospective study was to predict the dose distribution of breast cancer radiotherapy by means of deformable registration into atlas images with historical treatment planning data that were considered to achieve expert level. The atlas cohort comprised 20 patients with left-sided breast cancer, previously treated by volumetric-modulated arc radiotherapy. The registration-based prediction technique was applied to 20 patients outside the atlas cohort. This study evaluated and compared three different approaches: registration to the most similar image from a dataset of individual atlas images (SIM), registration to all images from a database of individual atlas images with the average method (WEI_A), and the weighted method (WEI_F). The dose prediction performance of each strategy was quantified using nine metrics, including the region of interest dose error, 80% and 100% prescription area dice similarity coefficients (DSCs), and γ metrics. A Friedman test and a nonparametric exact Wilcoxon signed rank test were performed to compare the differences among groups. The clinical doses of all cases served as the gold standard. RESULTS: The WEI_F method could achieve superior dose prediction results to those of WEI_A. WEI_F outperformed SIM in the organ-at-risk mean absolute difference (MAD). When using the WEI_F method, the MAD values for the ipsilateral lung, heart, and whole lung were 197.9 ± 42.9, 166 ± 55.1, 122.3 ± 25.5, and 55.3 ± 42.2 cGy, respectively. Moreover, SIM exhibited superior prediction in the DSC and γ metrics. When using the SIM method, the means of the 80% and 100% prescription area DSCs, 33γ metric, and 55γ metric were 0.85 ± 0.05, 0.84 ± 0.05, 0.64 ± 0.13, and 0.84 ± 0.10, respectively. The plan target volume and spinal cord MAD when using SIM and WEI were 235.6 ± 158.4 cGy versus 227.4 ± 144.0 cGy ([Formula: see text]) and 61.4 ± 44.9 cGy versus 55.3 ± 42.2 cGy ([Formula: see text]), respectively. CONCLUSIONS: A predicted dose distribution that approximated the clinical plan could be generated using the methods presented in this study.

Approach and assessment of automated stereotactic radiotherapy planning for early stage non-small-cell lung cancer.

BACKGROUND: Intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) are standard physical technologies of stereotactic body radiotherapy (SBRT) that are used for patients with non-small-cell lung cancer (NSCLC). The treatment plan quality depends on the experience of the planner and is limited by planning time. An automated planning process can save time and ensure a high-quality plan. This study aimed to introduce and demonstrate an automated planning procedure for SBRT for patients with NSCLC based on machine-learning algorithms. The automated planning was conducted in two steps: (1) determining patient-specific optimized beam orientations; (2) calculating the organs at risk (OAR) dose achievable for a given patient and setting these dosimetric parameters as optimization objectives. A model was developed using data of historical expertise plans based on support vector regression. The study cohort comprised patients with NSCLC who were treated using SBRT. A training cohort (N = 125) was used to calculate the beam orientations and dosimetric parameters for the lung as functions of the geometrical feature of each case. These plan-geometry relationships were used in a validation cohort (N = 30) to automatically establish the SBRT plan. The automatically generated plans were compared with clinical plans established by an experienced planner. RESULTS: All 30 automated plans (100%) fulfilled the dose criteria for OARs and planning target volume (PTV) coverage, and were deemed acceptable according to evaluation by experienced radiation oncologists. An automated plan increased the mean maximum dose for ribs (31.6 ± 19.9 Gy vs. 36.6 ± 18.1 Gy, P < 0.05). The minimum, maximum, and mean dose; homogeneity index; conformation index to PTV; doses to other organs; and the total monitor units showed no significant differences between manual plans established by experts and automated plans (P > 0.05). The hands-on planning time was reduced from 40-60 min to 10-15 min. CONCLUSION: An automated planning method using machine learning was proposed for NSCLC SBRT. Validation results showed that the proposed method decreased planning time without compromising plan quality. Plans generated by this method were acceptable for clinical use.

Au@Ag core-shell nanocubes: epitaxial growth synthesis and surface-enhanced Raman scattering performance.

Novel Au@Ag core-shell nanocubes (NCs) were successfully prepared by the controlled epitaxial growth of Ag shells onto Au nanoellipsoids (NEs) in the presence of surfactants. The growth mechanism of the Au@Ag core-shell NCs was systematically investigated by analyzing their morphology, optical properties, and crystallography. The localized surface plasmon resonance (LSPR) characteristics and the electric field distribution of the Au@Ag core-shell NCs were studied using the finite element method (FEM) based on the plasmon hybridization theory. Compared with pure Ag NCs, the absorption spectrum of the Au@Ag core-shell NCs exhibits a red shift and a weak shoulder near 550 nm, and the notable enhancement of electric field occurs around the corners along the long-axis of the Au ellipsoidal core because of plasmonic resonant coupling. Surface-enhanced Raman scattering (SERS) of the Au@Ag core-shell NCs labeled with 4-mercaptobenzoic acid molecules reveals that the bimetallic core-shell NCs possess efficient SERS activity with an enhancement factor EF = 2.27 × 10(6), thus confirming the possibility of using the Au@Ag core-shell NCs as a stable probe for SERS-based biosensing applications.

Controllable synthesis and SERS characteristics of hollow sea-urchin gold nanoparticles.

Hollow sea-urchin gold nanoparticles (HSU-GNPs) were successfully prepared through a novel one-step galvanic replacement strategy, and their corresponding optical properties was studied in detail. During the synthesis process, the sizes of the interior hollows of the HSU-GNPs could be changed by adjusting the amount of silver nitrate added into hydrogen tetrachloroaurate trihydrate solution. The absorption spectra of the HSU-GNPs showed that the localized surface plasmon resonance (LSPR) peaks were red-shifted with increasing size of the interior hollows in the HSU-GNPs. When the added amount of silver nitrate was up to 6 µl, the LSPR peak of the synthesized HSU-GNP reached 726 nm as a maximum red-shift. Furthermore, the absorption spectra of the HSU-GNPs with different morphologies were theoretically simulated by the finite element method, which was consistent with the experimental results and explained the origin of the red-shift of the LSPR peaks. In addition, the surface-enhanced Raman scattering (SERS) of the sea urchin gold nanoparticles were also investigated using 4-mercaptobenzoic acid as a Raman reporter molecule. Both the experimental and calculated results showed that the HSU-GNPs had stronger SERS enhancement than the solid sea-urchin gold nanoparticles. In particular, the HSU-GNPs prepared by adding 6 µl silver nitrate exhibited a maximum SERS enhancement factor, EF = 1.1 × 10(9), due to the LSPR peak at 726 nm which is near to the excitation wavelength, 785 nm. This feature is significant for designing a biosensor with a super-high sensitivity based on the morphology of the HSU-GNPs.

A Review of Artificial Intelligence Application for Radiotherapy.

Background and Purpose: Artificial intelligence (AI) is a technique which tries to think like humans and mimic human behaviors. It has been considered as an alternative in a lot of human-dependent steps in radiotherapy (RT), since the human participation is a principal uncertainty source in RT. The aim of this work is to provide a systematic summary of the current literature on AI application for RT, and to clarify its role for RT practice in terms of clinical views. Materials and Methods: A systematic literature search of PubMed and Google Scholar was performed to identify original articles involving the AI applications in RT from the inception to 2022. Studies were included if they reported original data and explored the clinical applications of AI in RT. Results: The selected studies were categorized into three aspects of RT: organ and lesion segmentation, treatment planning and quality assurance. For each aspect, this review discussed how these AI tools could be involved in the RT protocol. Conclusions: Our study revealed that AI was a potential alternative for the human-dependent steps in the complex process of RT.

Novel Alzheimer's disease subtypes based on functional brain connectivity in human connectome project.

The pathogenesis of Alzheimer's disease (AD) remains unclear, but revealing individual differences in functional connectivity (FC) may provide insights and improve diagnostic precision. A hierarchical clustering-based autoencoder with functional connectivity was proposed to categorize 82 AD patients from the Alzheimer's Disease Neuroimaging Initiative. Compared to directly performing clustering, using an autoencoder to reduce the dimensionality of the matrix can effectively eliminate noise and redundant information in the data, extract key features, and optimize clustering performance. Subsequently, subtype differences in clinical and graph theoretical metrics were assessed. Results indicate a significant inter-subject heterogeneity in the degree of FC disruption among AD patients. We have identified two neurophysiological subtypes: subtype I exhibits widespread functional impairment across the entire brain, while subtype II shows mild impairment in the Limbic System region. What is worth noting is that we also observed significant differences between subtypes in terms of neurocognitive assessment scores associations with network functionality, and graph theory metrics. Our method can accurately identify different functional disruptions in subtypes of AD, facilitating personalized treatment and early diagnosis, ultimately improving patient outcomes.

A hybrid multimodal machine learning model for Detecting Alzheimer's disease.

Alzheimer's disease (AD) diagnosis utilizing single modality neuroimaging data has limitations. Multimodal fusion of complementary biomarkers may improve diagnostic performance. This study proposes a multimodal machine learning framework integrating magnetic resonance imaging (MRI), positron emission tomography (PET) and cerebrospinal fluid (CSF) assays for enhanced AD characterization. The model incorporates a hybrid algorithm combining enhanced Harris Hawks Optimization (HHO) algorithm referred to as ILHHO, with Kernel Extreme Learning Machine (KELM) classifier for simultaneous feature selection and classification. ILHHO enhances HHO's search efficiency by integrating iterative mapping (IM) to improve population diversity and local escaping operator (LEO) to balance exploration-exploitation. Comparative analysis with other improved HHO algorithms, classic meta-heuristic algorithms (MHAs), and state-of-the-art MHAs on IEEE CEC2014 benchmark functions indicates that ILHHO achieves superior optimization performance compared to other comparative algorithms. The synergistic ILHHO-KELM model is evaluated on 202 AD Neuroimaging Initiative (ADNI) subjects. Results demonstrate superior multimodal classification accuracy over single modalities, validating the importance of fusing heterogeneous biomarkers. MRI + PET + CSF achieves 99.2 % accuracy for AD vs. normal control (NC), outperforming conventional and proposed methods. Discriminative feature analysis provides further insights into differential AD-related neurodegeneration patterns detected by MRI and PET. The differential PET and MRI features demonstrate how the two modalities provide complementary biomarkers. The neuroanatomical relevance of selected features supports ILHHO-KELM's potential for extracting sensitive AD imaging signatures. Overall, the study showcases the advantages of capitalizing on complementary multimodal data through advanced feature learning techniques for improving AD diagnosis.

Epidemiological Characteristics of Varicella in Anhui Province, China, 2012-2021: Surveillance Study.

BACKGROUND: Varicella is a mild, self-limited disease caused by varicella-zoster virus (VZV) infection. Recently, the disease burden of varicella has been gradually increasing in China; however, the epidemiological characteristics of varicella have not been reported for Anhui Province. OBJECTIVE: The aim of this study was to analyze the epidemiology of varicella in Anhui from 2012 to 2021, which can provide a basis for the future study and formulation of varicella prevention and control policies in the province. METHODS: Surveillance data were used to characterize the epidemiology of varicella in Anhui from 2012 to 2021 in terms of population, time, and space. Spatial autocorrelation of varicella was explored using the Moran index (Moran I). The Kulldorff space-time scan statistic was used to analyze the spatiotemporal aggregation of varicella. RESULTS: A total of 276,115 cases of varicella were reported from 2012 to 2021 in Anhui, with an average annual incidence of 44.8 per 100,000, and the highest incidence was 81.2 per 100,000 in 2019. The male-to-female ratio of cases was approximately 1.26, which has been gradually decreasing in recent years. The population aged 5-14 years comprised the high-incidence group, although the incidence in the population 30 years and older has gradually increased. Students accounted for the majority of cases, and the proportion of cases in both home-reared children (aged 0-7 years who are not sent to nurseries, daycare centers, or school) and kindergarten children (aged 3-6 years) has changed slightly in recent years. There were two peaks of varicella incidence annually, except for 2020, and the incidence was typically higher in the winter peak than in summer. The incidence of varicella in southern Anhui was higher than that in northern Anhui. The average annual incidence at the county level ranged from 6.61 to 152.14 per 100,000, and the varicella epidemics in 2018-2021 were relatively severe. The spatial and temporal distribution of varicella in Anhui was not random, with a positive spatial autocorrelation found at the county level (Moran I=0.412). There were 11 districts or counties with high-high clusters, mainly distributed in the south of Anhui, and 3 districts or counties with high-low or low-high clusters. Space-time scan analysis identified five possible clusters of areas, and the most likely cluster was distributed in the southeastern region of Anhui. CONCLUSIONS: This study comprehensively describes the epidemiology and changing trend of varicella in Anhui from 2012 to 2021. In the future, preventive and control measures should be strengthened for the key populations and regions of varicella.

Radioactive 125I Seed Inhibits Cell Migration and Invasion and Promotes Apoptosis by Inactivating the VEGFR2 Signaling Pathway in Cholangiocarcinoma.

Objectives: To investigate the potential mechanisms of 125I seed implantation therapeutic treatment on inactivating the VEGFR2/PI3K/AKT pathway in cholangiocarcinoma. Methods: The human cholangiocarcinoma cell lines HCCC-9810 and HuCCT1 were purchased for in vitro studies. The BALB/c nude mice were obtained for in vivo studies. The proliferation of cells was detected by CCK-8, colony formation, and BrdU staining. The migration and invasion of cells were determined by wound healing assay and Transwell assay, respectively. Hematoxylin and eosin staining was utilized for histological evaluation. Protein expression was determined by western blotting and immunohistochemistry. Results: Compared with the control group, .6 mCi group and .8 mCi group inhibited cholangiocarcinoma cells proliferation, invasion, migration, and promoted apoptosis, the protein expression of p-VEGFR2, VEGFR2, PI3K, p-AKT/AKT, cyclin B1, cyclin A, CDK1, and Bcl-2 was decreased. Similar results were obtained from in vitro experiments. However, when VEGF is overexpressed, the inhibitory effect of .8 mCi was partially significantly reversed on cholangiocarcinoma cells. The in vivo studies further confirmed the inhibitory effects of .6 mCi group and .8 mCi group on cholangiocarcinoma. Conclusion: 125I seed irradiation could inhibit cholangiocarcinoma cells proliferation, migration, and invasion and promote apoptosis through inactivation of the VEGFR2/PI3K/AKT signaling pathway.

An integrated solution of deep reinforcement learning for automatic IMRT treatment planning in non-small-cell lung cancer.

Purpose: To develop and evaluate an integrated solution for automatic intensity-modulated radiation therapy (IMRT) planning in non-small-cell lung cancer (NSCLC) cases. Methods: A novel algorithm named as multi-objectives adjustment policy network (MOAPN) was proposed and trained to learn how to adjust multiple optimization objectives in commercial Eclipse treatment planning system (TPS), based on the multi-agent deep reinforcement learning (DRL) scheme. Furthermore, a three-dimensional (3D) dose prediction module was developed to generate the patient-specific initial optimization objectives to reduce the overall exploration space during MOAPN training. 114 previously treated NSCLC cases suitable for stereotactic body radiotherapy (SBRT) were selected from the clinical database. 87 cases were used for the model training, and the remaining 27 cases for evaluating the feasibility and effectiveness of MOAPN in automatic treatment planning. Results: For all tested cases, the average number of adjustment steps was 21 ± 5.9 (mean ± 1 standard deviation). Compared with the MOAPN initial plans, the actual dose of chest wall, spinal cord, heart, lung (affected side), esophagus and bronchus in the MOAPN final plans reduced by 14.5%, 11.6%, 4.7%, 16.7%, 1.6% and 7.7%, respectively. The dose result of OARs in the MOAPN final plans was similar to those in the clinical plans. The complete automatic treatment plan for a new case was generated based on the integrated solution, with about 5-6 min. Conclusion: We successfully developed an integrated solution for automatic treatment planning. Using the 3D dose prediction module to obtain the patient-specific optimization objectives, MOAPN formed action-value policy can simultaneously adjust multiple objectives to obtain a high-quality plan in a shorter time. This integrated solution contributes to improving the efficiency of the overall planning workflow and reducing the variation of plan quality in different regions and treatment centers. Although improvement is warranted, this proof-of-concept study has demonstrated the feasibility of this integrated solution in automatic treatment planning based on the Eclipse TPS.

Perceptual Pattern of Cleft-Related Speech: A Task-fMRI Study on Typical Mandarin-Speaking Adults.

Congenital cleft lip and palate is one of the common deformities in the craniomaxillofacial region. The current study aimed to explore the perceptual pattern of cleft-related speech produced by Mandarin-speaking patients with repaired cleft palate using the task-based functional magnetic resonance imaging (task-fMRI) technique. Three blocks of speech stimuli, including hypernasal speech, the glottal stop, and typical speech, were played to 30 typical adult listeners with no history of cleft palate speech exploration. Using a randomized block design paradigm, the participants were instructed to assess the intelligibility of the stimuli. Simultaneously, fMRI data were collected. Brain activation was compared among the three types of speech stimuli. Results revealed that greater blood-oxygen-level-dependent (BOLD) responses to the cleft-related glottal stop than to typical speech were localized in the right fusiform gyrus and the left inferior occipital gyrus. The regions responding to the contrast between the glottal stop and cleft-related hypernasal speech were located in the right fusiform gyrus. More significant BOLD responses to hypernasal speech than to the glottal stop were localized in the left orbital part of the inferior frontal gyrus and middle temporal gyrus. More significant BOLD responses to typical speech than to the glottal stop were localized in the left inferior temporal gyrus, left superior temporal gyrus, left medial superior frontal gyrus, and right angular gyrus. Furthermore, there was no significant difference between hypernasal speech and typical speech. In conclusion, the typical listener would initiate different neural processes to perceive cleft-related speech. Our findings lay a foundation for exploring the perceptual pattern of patients with repaired cleft palate.

Safety of primary immunization using inactivated SARS-CoV-2 vaccine (CoronaVac®) among population aged 3 years and older in a large-scale use: A multi-center open-label study in China.

OBJECTIVE: To evaluate the safety of primary immunization using CoronaVac® among population aged 3 years and above in a large-scale use. METHOD: A multi-center open-label study was carried out in 11 provinces of China. Individuals aged 3 years and older who had no history of COVID-19 vaccination or had received only one dose of CoronaVac® were enrolled in this study. Adults and elderly with or without underlying medical conditions(UMCs) were also recruited. Eligible participants received one or two doses of CoronaVac® with an interval of 28 days. Demographic information, vaccination and the occurrence of adverse events were recorded by participants or guardians using data collection system designed for this study. All adverse events occurred within 6 months after the second dose of vaccination were collected. The incidence of adverse events that cannot be ruled out as being caused by the vaccine were calculated to assess the safety of CoronaVac®. This study is registered with ClinicalTrials. Gov (NCT04911790 and NCT04992208). RESULTS: A total of 162,691 participants have been included in this study and 89.50 % had finished primary immunization. Among adults and elderly, people with UMCs accounted for 25.85 %, with the top five disease being hypertension, diabetes, chronic gastritis, coronary heart disease(CHD) and kidney stone. The overall incidence of adverse reactions (ARs) within 6 months after the second vaccination was 2.70 %, with incidence for children and adolescents, adults, and elderly being 2.03 %, 3.46 %, and 1.90 %, respectively. Most ARs were mild (grade 1). Pain at the injection sites, fatigue, induration/swelling, and headache were the most common symptoms, occurring in 1.64 %, 0.46 %, 0.31 % and 0.24 %, respectively. No serious adverse events related to vaccines were reported. No adverse events of special interest (AESIs) were identified. For children and adolescents, children aged 3-5 years had the highest incidence of ARs of 3.29 %. The incidence of ARs among those aged 18 years and older with and without UMCs were 2.81 % and 2.99 %, respectively, with no statistical significance between two groups(P = 0.089). And people with coronary heart disease had higher AR incidence compared to those with other UMCs, but the most common symptoms was pain at the injection site. CONCLUSION: CoronaVac® is safe in a large-scale use and shows well-tolerance for children and adolescents and people with underlying medical conditions. Further studies need to be conducted to explore the relation of ARs incidence to age or different kinds of UMCs.

Immunogenicity and safety of concomitant administration of the sabin-strain-based inactivated poliovirus vaccine, the diphtheria-tetanus-acellular pertussis vaccine, and measles-mumps-rubella vaccine to healthy infants aged 18 months in China.

OBJECTIVES: During the COVID-19 pandemic, there was a decline in vaccine coverage, and the implementation of combined vaccines and co-administration strategies emerged as potential solutions to alleviate this predicament. Our objective is to delve into the concurrent administration of the sabin-strain-based inactivated poliovirus vaccine (sIPV), the diphtheria-tetanus-acellular pertussis vaccine (DTaP), and measles-mumps-rubella vaccine (MMR), with the intention of bridging the evidentiary gap pertaining to vaccine co-administration in Chinese infants, and to ensure a safe and effective vaccination strategy, ultimately leading to an augmentation in immunization coverage. METHODS: This study was a follow-up trial of the "Immunogenicity and safety of concomitant administration of the sIPV with the DTaP vaccine in children: a multicenter, randomized, non-inferiority, controlled trial." Blood samples were collected on day 0 and day 30, and serum antibody levels were detected to measure antibody responses to each of the antigens. Local and systemic adverse events were monitored and compared among groups. This study is the first to fill the knowledge gap in China regarding the safe and effective combined vaccination of sIPV, DTaP, and MMR vaccines. RESULTS: The geometric mean titer of the poliovirus types I, II, and III neutralizing antibodies were 1060.22 (95% CI: 865.73-1298.39), 1537.06 (95% CI: 1324.27-1784.05), and 1539.10 (95% CI: 1296.37-1827.29) in group I on day 30; geometric mean titer of antibodies against DTaP and MMR in the simultaneous vaccination group was non-inferior to those in the DTaP alone and MMR alone group. Reporting rates of local and systemic adverse reactions were similar between groups and no serious adverse events were reported throughout the clinical study period. CONCLUSION: Co-administration of the sIPV, DTaP, and MMR was safe and did not impact immunogenicity, which would help to mitigate administrative costs and enhance vaccine coverage rates.

Epidemiological investigation and prevention and control strategies of rubella in Anhui province, China, from 2012 to 2021.

Background: Rubella is a highly contagious viral infection with mild manifestations that occurs most often in children and young adults. Infection during pregnancy, especially during the first trimester, can result in an infant born with congenital rubella syndrome (CRS). The purpose of this paper is to analyze the characteristics of rubella epidemics in Anhui province from 2012 to 2021 and explore the prevention and control strategies of rubella. Methods: A descriptive epidemiological approach was used to examine the epidemiological characteristics of rubella in Anhui Province between 2012 and 2021. Results: From 2012 to 2021, a total of 4,987 cases of rubella were reported in Anhui province, with an average annual incidence of 8.11 per million, demonstrating an overall downward trend (χ2 trend =3141.06, P < 0.01). The average yearly incidence of rubella in southern Anhui, central Anhui, and northern Anhui were 9.99 per million, 11.47 per million, and 4.50 per million, respectively, with statistically significant differences (χ2 =792.50, P < 0.01). The male to female incidence ratio was 1.67:1, and the male incidence rate was higher than the female incidence rate. Most cases occurred among students, accounting for 56.59% of all cases, and the 10-34 age group accounted for ~73.71% of all cases. Regarding immunization history, 3.57% of cases had two doses or more, 6.62% had one dose, 16.40% had none, and the remainder were uncertain. Conclusion: The incidence of rubella in Anhui province from 2012 to 2021 continued to decline, with regional variations observed. The 10-34-year-old population without a history of rubella vaccination is at high risk for the disease. It is suggested to carry out rubella vaccination and congenital rubella syndrome monitoring according to the actual situation.