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.

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.

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.

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.

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.

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.

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.

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.

Investigate Non-EPI Vaccination Recommendation Practice from a Socio-Ecological Perspective: A Mixed-Methods Study in China.

The uptake of non-EPI vaccines, such as influenza and pneumonia vaccines, are very low in China compared to other countries. In China, immunization services are provided by dedicated vaccination service providers (VSPs), and their recommendation is the key to improve vaccine uptake. This study explores VSP recommendation practices for non-EPI vaccines from a socio-ecological perspective. A mixed-methods study, combining a questionnaire survey and key informant interviews, was conducted in Anhui, Shaanxi, and Guangdong provinces. 555 VSPs completed the valid questionnaire, and 49 VSPs participated in in-depth interviews. Among the surveyed VSPs, 51.54% stated that they always or often recommended non-EPI vaccines in work, and the remaining half reported that they sometimes or never recommended non-EPI vaccines. Most VSPs interviewed communicated about non-EPI vaccines with the public in an informed style, not a presumptive one, and provided the public with all the decision-making latitude. The infrequent recommendation of non-EPI vaccines was widely prevalent among Chinese VSPs regardless of their individual characteristics, and was mainly driven by the interpersonal relationship, institutional arrangement, and public policy. Firstly, the VSPs were concerned about conflicts arising from the recommendation of self-paid vaccines and the risk of adverse reactions following vaccination. Secondly, high workloads left them insufficient time to communicate about non-EPI vaccines. Thirdly, there was no performance assessment or financial incentive for VSPs to recommend non-EPI vaccination, and their main responsibility was around EPI vaccination. Therefore, multi-level socio-ecological systems around non-EPI vaccination should be improved to optimize the communication between VSPs and the public, which include a better system of legal redress to resolve potential misunderstandings between the VSPs and the public, more effective workload management through whole-process health information system and strengthening public health workforce, and the introduction of performance assessment and appropriate incentives on non-EPI vaccination.

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.

Immunogenicity and safety of concomitant administration of the chinese inactivated poliovirus vaccine with the diphtheria-tetanus-acellular pertussis (DTaP) vaccine in children: A multicenter, randomized, non-inferiority, controlled trial.

Key point: Considering that vaccination with the sIPV and DTaP overlap at the ages of 3 and 4 months in China, to reduce the burden of treatment on parents and increase vaccination coverage rates, we designed a postmarket clinical study of co-administration. Background: The Sabin-strain-based inactivated poliovirus vaccine (sIPV) and the diphtheria-tetanus-acellular pertussis vaccine (DTaP) have been licensed in China for many years. To conduct a clinical study on the safety and immunogenicity of the sIPV when administered concomitantly with the DTaP. Methods: The study population was divided into three groups: group 1 was the sIPV+ DTaP concomitant administration group, group 2 was the sIPV inoculation group, and group 3 was the DTaP inoculation group. Blood samples were collected prevaccination and 30 days postvaccination, and serum antibody levels were detected. Results: This study showed that the seropositive and seroconversion rates of type 1, 2 and 3 poliovirus in group 1 were higher than those in group 2, with no statistically significant difference after vaccination (P>0.05). Groups 1 and 3 also showed similar responses for all vaccine antigens except anti-FHA (97.65 (94.09-99.36) vs. 100 (97.89-100)). The geometric mean titers (GMTs) for the DTaP and sIPV among the groups were comparable, and the non-inferiority t test result was P<0.001. The number of local adverse events (AEs) reported in group 1 (29.91%) were larger than those in group 2 (12.39%) and group 3 (21.93%), among which the most common was redness. Similarly, the most common systemic AE was fever. All 5 severe AE (SAE) cases were determined by experts to be unrelated to the vaccines during the study. Conclusions: The evidence of similar seroconversion and safety with co-administered DTaP and sIPV supports the co-administration supports the introduction of a strategy of simultaneous administration of both vaccines into routine infant immunization, and it could increase vaccination coverage and protect more infants from morbidity and mortality from these related diseases. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04054882?term=NCT04054882&cntry=CN&draw=2&rank=1, identifier NCT04054882.

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.

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.

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.

Comparing of two dimensional and three dimensional fully convolutional networks for radiotherapy dose prediction in left-sided breast cancer.

Fully convolutional networks were developed for predicting optimal dose distributions for patients with left-sided breast cancer and compared the prediction accuracy between two-dimensional and three-dimensional networks. Sixty cases treated with volumetric modulated arc radiotherapy were analyzed. Among them, 50 cases were randomly chosen to conform the training set, and the remaining 10 were to construct the test set. Two U-Net fully convolutional networks predicted the dose distributions, with two-dimensional and three-dimensional convolution kernels, respectively. Computed tomography images, delineated regions of interest, or their combination were considered as input data. The accuracy of predicted results was evaluated against the clinical dose. Most types of input data retrieved a similar dose to the ground truth for organs at risk (p > 0.05). Overall, the two-dimensional model had higher performance than the three-dimensional model (p < 0.05). Moreover, the two-dimensional region of interest input provided the best prediction results regarding the planning target volume mean percentage difference (2.40 ± 0.18%), heart mean percentage difference (4.28 ± 2.02%), and the gamma index at 80% of the prescription dose are with tolerances of 3 mm and 3% (0.85 ± 0.03), whereas the two-dimensional combined input provided the best prediction regarding ipsilateral lung mean percentage difference (4.16 ± 1.48%), lung mean percentage difference (2.41 ± 0.95%), spinal cord mean percentage difference (0.67 ± 0.40%), and 80% Dice similarity coefficient (0.94 ± 0.01). Statistically, the two-dimensional combined inputs achieved higher prediction accuracy regarding 80% Dice similarity coefficient than the two-dimensional region of interest input (0.94 ± 0.01 vs 0.92 ± 0.01, p < 0.05). The two-dimensional data model retrieves higher performance than its three-dimensional counterpart for dose prediction, especially when using region of interest and combined inputs.

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.

Safety of measles-containing vaccines in post-marketing surveillance in Anhui, China.

The safety of measles vaccination is of great interest and importance to public health practice and the general society. We have analyzed the adverse events following immunization (AEFIs) of currently used measles-containing vaccines (including live attenuated measles vaccine, live attenuated measles and rubella combined vaccine, live attenuated measles and mumps combined vaccine, live attenuated Measles, Mumps and Rubella Combined Vaccine) in Anhui Province, China. From 2009 to 2014, 9.9 million doses of measles-containing vaccines were administrated and 1893 AEFIs were found (191.4 per million doses), of which, 33 serious AEFIs (3.3 per million vaccine doses) were reported. 59.4% (1124 cases) were male cases, and 85.1% (1611 cases) occurred in persons aged < 1 year. 93.3% (1766 cases) occurred at the first dose of vaccination and 95.9% (1815 cases) were found within 3 days after vaccination. This study presents up-to-date data and suggests that the measles-containing vaccines used in Anhui Province of China are safe.

Comparison of dual influenza and pneumococcal polysaccharide vaccination with influenza vaccination alone for preventing pneumonia and reducing mortality among the elderly: A meta-analysis.

The purpose of this study was to perform a meta-analysis comparing the effectiveness of influenza vaccination alone versus influenza plus pneumococcal dual vaccination for the prevention of pneumonia and mortality in adults ≥ 65 years of age. Medline, Cochrane, CENTRAL, EMBASE, and Google Scholar databases were searched. Inclusion criteria were: 1) Randomized controlled trials (RCTs), 2-arm prospective studies, or retrospective cohort studies; 2) Patients were ≥ 65 years of age with or without chronic respiratory disease; 3) Patients received the influenza vaccine alone or dual pneumococcal and influenza vaccination; 4) Results included incidence of recurrent respiratory tract infections, length of hospital stay, and overall mortality rate. The outcomes were pneumonia and all-cause mortality rates. Of 142 studies identified in the database searches, 6 were ultimately included in the systematic review, and 5 were included in meta-analysis. The number of patients that received the influenza vaccination alone ranged from 211 to 29,346 (total = 53,107), and the number that received influenza+pneumococcal vaccination ranged from 246 to 72,107 (total = 102,068). Influenza+pneumococcal vaccination was associated with a significantly lower pneumonia rate than influenza vaccination alone (relative risk [RR] = 0.835, 95% confidence interval [CI]: 0.718-0.971, P = 0.019), and with a significantly lower all-cause mortality rate than influenza vaccination alone (relative risk [RR] = 0.771, 95% confidence interval [CI]: 0.707-0.842, P = 0.001). In conclusion, the results of this study support concomitant pneumococcal and influenza vaccination of the elderly as a dual vaccination strategy is associated with lower pneumonia and all-cause mortality rates.