Phenylmethylsiloxanes in indoor dust from residential area of China: Source, occurrence, bioavailability and exposure assessment.

Phenylmethylsiloxanes, as modified products of dimethylsiloxanes, have been used in personal care products (PCPs) and household appliances, with indoor dust serving as one potential reservoir due to their particle-binding properties. This study measured six isomers of two phenylmethylsiloxanes (P3 and P4) in PCPs (99 %) intakes of phenylmethylsiloxanes for adults, while dust ingestion/adsorption (0.19 ng/d) may play important roles for toddlers/infants with little usage of phenylmethylsiloxanes-containing PCPs. Additionally, total daily intakes of PhMeSi(OH)2 (0.30-0.84 ng/d) via ingestion and dermal absorption of dust were higher than P3 (0.06-0.31 ng/d) and P4 (0.02-0.09 ng/d), suggesting exposure risk of degradation product of phenylmethylsiloxanes deserving attention.

Human health risk assessment of 6:2 Cl-PFESA through quantitative in vitro to in vivo extrapolation by integrating cell-based assays, an epigenetic key event, and physiologically based pharmacokinetic modeling.

Human health risk assessment of chemicals is essential but often relies on time-consuming and animal and labor-extensive procedures. Here, we develop a population-based, quantitative in vitro to in vivo extrapolation (QIVIVE) approach which depended on cellular effects monitored by in vitro assays, considered chemical internal concentration determined by LC-MS/MS, extrapolated into in vivo target tissue concentration through physiologically based pharmacokinetic (PBPK) modelling, and assessed populational health risk using in silico modelling. By applying this QIVIVE approach to 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), as a representative of the emerging pollutants, we find that 6:2 Cl-PFESA disturbed lipid homeostasis in HepG2 cells through enhancement of lipid accumulation and fatty acid ß-oxidation, during which miR-93-5p served as a key event towards toxicity and thus, could serve as an efficient toxicity marker for risk assessment; further, the disruption potency of lipid homeostasis of 6:2 Cl-PFESA for the most of studied populations in China might be of moderate concern. Together, our approach improved the reliability of QIVIVE during human health risk assessment, which can readily be used for other chemicals.

Binding, activity and risk assessment of bisphenols toward farnesoid X receptor pathway: In vitro and in silico study.

Bisphenols have been identified as emerging environmental pollutants of high concern with potential adverse effects through interactions with receptor-mediated pathways. However, their potential mechanism of action and health risks through the farnesoid X receptor (FXR) pathway remain poorly understood. In the present study, we aimed to explore the potential disruption mechanism of bisphenols through the FXR signalling pathway. Receptor binding assays showed that bisphenols bound to FXR directly, with tetrabromobisphenol A (TBBPA; 34-fold), tetrachlorobisphenol A (TCBPA; 8.7-fold), bisphenol AF (BPAF; 2.0-fold), and bisphenol B (BPB; 1.9-fold) showing a significantly stronger binding potency than bisphenol A (BPA). In receptor transcriptional activity assays, bisphenols showed agonistic activity toward FXR, with BPAF, BPB, and bisphenol F (BPF) exhibiting higher activity than BPA, but TBBPA and TCBPA showing significantly weaker activity than BPA. Molecular docking results indicated that the number of hydrogen bonds dictated their binding strength. Intracellular concentrations of bisphenols were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in receptor activity assays, and it was found that the intracellular concentrations of TBBPA and TCBPA were 40-fold lower than those of BPA. Using the bioactivity concentrations in the FXR receptor activity assay, the liver concentrations of bisphenols were estimated using physiologically-based pharmacokinetic (PBPK) models through their serum concentrations, and the hazard quotient (HQ) values were calculated. The results suggest a potentially high concern for the risk of activating the FXR pathway for some populations with high exposure. Overall, these results indicate that bisphenols can bind to and activate FXR receptors, and that the activation mechanism is dependent on cellular uptake and binding strength. This study provides important information regarding the exposure risk of bisphenols, which can promote the development of environmentally friendly bisphenols.

Novel Multichannel Entropy Features and Machine Learning for Early Assessment of Pregnancy Progression Using Electrohysterography.

OBJECTIVE: Preterm birth is the leading cause of morbidity and mortality involving over 10% of infants. Tools for timely diagnosis of preterm birth are lacking and the underlying physiological mechanisms are unclear. The aim of the present study is to improve early assessment of pregnancy progression by combining and optimizing a large number of electrohysterography (EHG) features with a dedicated machine learning framework. METHODS: A set of reported EHG features are extracted. In addition, novel cross and multichannel entropy and mutual information are employed. The optimal feature set is selected using a wrapper method according to the accuracy of the leave-one-out cross validation. An annotated database of 74 EHG recordings in women with preterm contractions was employed to test the ability of the proposed method to recognize the onset of labor and the risk of preterm birth. Difference between using the contractile segments only and the whole EHG signal was compared. RESULTS: The proposed method produces an accuracy of 96.4% and 90.5% for labor and preterm prediction, respectively, much higher than that reported in previous studies. The best labor prediction was observed with the contraction segments and the best preterm prediction achieved with the whole EHG signal. Entropy features, particularly the newly-employed cross entropy contribute significantly to the optimal feature set for both labor and preterm prediction. SIGNIFICANCE: Our results suggest that changes in the EHG, particularly the regularity, might manifest early in pregnancy. Single-channel and cross entropy may therefore provide relevant prognostic opportunities for pregnancy monitoring.

Temporal and spatial variation, input fluxes and risk assessment of cyclic methylsiloxanes in Rivers-Bohai Sea System.

In the present study, the total concentrations of three cyclic methylsiloxanes (ΣCMSs), including octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6), in surface water and sediment samples of five main rivers draining into the Bohai Sea were in the range of 1.62-1.39 × 103 ng/L and 1.92-1.69 × 103 ng/g dw, respectively. Riverine input had great influence on the coastal distribution of siloxanes in the Bohai Sea. The concentrations of ΣCMSs in coastal sediments farthest away (40-50 Km) from the estuaries were only 4-33% of those close to the estuaries. But surprisingly, compared with those in coastal sediments (1.03-1.44 × 103 ng/g dw), the concentrations of CMSs (1.56-2.67 × 103 ng/g dw) in some deep-sea sediments were higher, and certain positive correlation existed between sediment ΣCMSs in this area with the total petroleum hydrocarbons concentration (R2 = 0.92, p < 0.05) suggested offshore oil exploitation as one important emission source of siloxanes. Overall, calculated based on their sediment concentrations, D4-D6 had negligible ecological risks to the benthic organisms in river-Bohai Sea system, i.e. HQs < 1. However, sediment-accumulation of siloxanes should be paid attention, especially for some deep-sea sediments nearby drilling platforms, where it will take only less than 1 year for D4 to reach its threshold.

Comparison of yield and relative costs of different screening algorithms for tuberculosis in active case-finding: a cross-section study.

BACKGROUND: Part of tuberculosis (TB) patients were missed if symptomatic screening was based on the main TB likely symptoms. This study conducted to compare the yield and relative costs of different TB screening algorithms in active case-finding in the whole population in China. METHODS: The study population was screened based on the TB likely symptoms through a face-to-face interview in selected 27 communities from 10 counties of 10 provinces in China. If the individuals had any of the enhanced TB likely symptoms, both chest X-ray and sputum tests were carried out for them furtherly. We used the McNemar test to analyze the difference in TB detection among four algorithms in active case-finding. Of four algorithms, two were from WHO recommendations including 1a/1c, one from China National Tuberculosis Program, and one from this study with the enhanced TB likely symptoms. Furthermore, a two-way ANOVA analysis was performed to analyze the cost difference in the performance of active case-finding adjusted by different demographic and health characteristics among different algorithms. RESULTS: Algorithm with the enhanced TB likely symptoms defined in this study could increase the yield of TB detection in active case-finding, compared with algorithms recommended by WHO (p < 0.01, Kappa 95% CI: 0. 93-0.99) and China NTP (p = 0.03, Kappa 95% CI: 0.96-1.00). There was a significant difference in the total costs among different three algorithms WHO 1c/2/3 (F = 59.13, p < 0.01). No significant difference in the average costs for one active TB case screened and diagnosed through the process among Algorithms 1c/2/3 was evident (F = 2.78, p = 0.07). The average costs for one bacteriological positive case through algorithm WHO 1a was about two times as much as the costs for one active TB case through algorithms WHO 1c/2/3. CONCLUSIONS: Active case-finding based on the enhanced symptom screening is meaningful for TB case-finding and it could identify more active TB cases in time. The findings indicated that this enhanced screening approach cost more compared to algorithms recommend by WHO and China NTP, but the increased yield resulted in comparative costs per patient. And it cost much more that only smear/bacteriological-positive TB cases are screened in active case-finding.

Generalized optical design and optimization of multipass cells with independent circle patterns based on the Monte Carlo and Nelder-Mead simplex algorithms.

In this paper, we propose an automatic approach to optimize the multipass cell (MPC) design with independent circle patterns. First, the Monte Carlo algorithm is performed to globally search for the characteristic values of the distance between two mirrors. Second, the Nelder-Mead simplex (NM) algorithm is applied to locally optimize the re-entry condition. In addition, we utilize the clustering method to select the independent circle patterns automatically. Three optimal MPCs with five, seven and nine independent circles are built and tested experimentally. We analyze the stability of the final point for the MPCs and optimize the quality of the output beam based on multi-ray tracing. This type of MPC shows the superior characteristics of compactness, high detection sensitivity, and affordability, has various applications, and can promote the development of portable gas sensors. The proposed approach is effective and efficient for automatically optimizing MPC design and can be further extended to versatile optical designs.

Deep learning-based automated left ventricular ejection fraction assessment using 2-D echocardiography.

Deep learning (DL) has been applied for automatic left ventricle (LV) ejection fraction (EF) measurement, but the diagnostic performance was rarely evaluated for various phenotypes of heart disease. This study aims to evaluate a new DL algorithm for automated LVEF measurement using two-dimensional echocardiography (2DE) images collected from three centers. The impact of three ultrasound machines and three phenotypes of heart diseases on the automatic LVEF measurement was evaluated. Using 36890 frames of 2DE from 340 patients, we developed a DL algorithm based on U-Net (DPS-Net) and the biplane Simpson's method was applied for LVEF calculation. Results showed a high performance in LV segmentation and LVEF measurement across phenotypes and echo systems by using DPS-Net. Good performance was obtained for LV segmentation when DPS-Net was tested on the CAMUS data set (Dice coefficient of 0.932 and 0.928 for ED and ES). Better performance of LV segmentation in study-wise evaluation was observed by comparing the DPS-Net v2 to the EchoNet-dynamic algorithm (P = 0.008). DPS-Net was associated with high correlations and good agreements for the LVEF measurement. High diagnostic performance was obtained that the area under receiver operator characteristic curve was 0.974, 0.948, 0.968, and 0.972 for normal hearts and disease phenotypes including atrial fibrillation, hypertrophic cardiomyopathy, dilated cardiomyopathy, respectively. High performance was obtained by using DPS-Net in LV detection and LVEF measurement for heart failure with several phenotypes. High performance was observed in a large-scale dataset, suggesting that the DPS-Net was highly adaptive across different echocardiographic systems.NEW & NOTEWORTHY A new strategy of feature extraction and fusion could enhance the accuracy of automatic LVEF assessment based on multiview 2-D echocardiographic sequences. High diagnostic performance for the determination of heart failure was obtained by using DPS-Net in cases with different phenotypes of heart diseases. High performance for left ventricle segmentation was obtained by using DPS-Net, suggesting the potential for a wider range of application in the interpretation of 2DE images.

Development of genic SSR marker resources from RNA-seq data in Camellia japonica and their application in the genus Camellia.

Camellia is a genus of flowering plants in the family Theaceae, and several species in this genus have economic importance. Although a great deal of molecular makers has been developed for molecular assisted breeding in genus Camellia in the past decade, the number of simple sequence repeats (SSRs) publicly available for plants in this genus is insufficient. In this study, a total of 28,854 potential SSRs were identified with a frequency of 4.63 kb. A total of 172 primer pairs were synthesized and preliminarily screened in 10 C. japonica accessions, and of these primer pairs, 111 were found to be polymorphic. Fifty-one polymorphic SSR markers were randomly selected to perform further analysis of the genetic relationships of 89 accessions across the genus Camellia. Cluster analysis revealed major clusters corresponding to those based on taxonomic classification and geographic origin. Furthermore, all the genotypes of C. japonica separated and consistently grouped well in the genetic structure analysis. The results of the present study provide high-quality SSR resources for molecular genetic breeding studies in camellia plants.

Bioavailability Evaluation of Perchlorate in Different Foods In Vivo: Comparison with In Vitro Assays and Implications for Human Health Risk Assessment.

Perchlorate in various foods continuously arouses public health concern. Bioavailability is a critical parameter to better estimate perchlorate exposure from diets. In this study, perchlorate bioavailability in five foods was determined in an in vivo mouse model and compared with in vitro bioaccessibility/bioavailability. The estimated in vivo perchlorate bioavailability for different foods ranged from 18.01 ± 4.53% to 45.60 ± 7.11%, with the order lettuce > pork > rice > milk powder > soybean. Moisture, fiber, and fat in foods were identified as critical factors affecting perchlorate bioavailability (correlation r = 0.71, 0.52, and -0.67, respectively). Linear regression analysis revealed that the in vitro perchlorate bioavailability determined using the Caco-2 cell model has the potential to estimate the in vivo perchlorate bioavailability in foods (R2 = 0.67, slope = 1.33, and y intercept = 4.99). These findings provide insights into the effects of the food matrices on perchlorate bioavailability and could contribute to decrease the uncertainty regarding perchlorate dietary exposure risk assessment.

Social and Behavioral Determinants of Health in the Era of Artificial Intelligence with Electronic Health Records: A Scoping Review.

Background. There is growing evidence that social and behavioral determinants of health (SBDH) play a substantial effect in a wide range of health outcomes. Electronic health records (EHRs) have been widely employed to conduct observational studies in the age of artificial intelligence (AI). However, there has been limited review into how to make the most of SBDH information from EHRs using AI approaches.Methods. A systematic search was conducted in six databases to find relevant peer-reviewed publications that had recently been published. Relevance was determined by screening and evaluating the articles. Based on selected relevant studies, a methodological analysis of AI algorithms leveraging SBDH information in EHR data was provided.Results. Our synthesis was driven by an analysis of SBDH categories, the relationship between SBDH and healthcare-related statuses, natural language processing (NLP) approaches for extracting SBDH from clinical notes, and predictive models using SBDH for health outcomes.Discussion. The associations between SBDH and health outcomes are complicated and diverse; several pathways may be involved. Using NLP technology to support the extraction of SBDH and other clinical ideas simplifies the identification and extraction of essential concepts from clinical data, efficiently unlocks unstructured data, and aids in the resolution of unstructured data-related issues.Conclusion. Despite known associations between SBDH and diseases, SBDH factors are rarely investigated as interventions to improve patient outcomes. Gaining knowledge about SBDH and how SBDH data can be collected from EHRs using NLP approaches and predictive models improves the chances of influencing health policy change for patient wellness, ultimately promoting health and health equity.

Phenylmethylsiloxanes and trifluoropropylmethylsiloxanes in municipal sludges from wastewater treatment plants in China: Their distribution, degradation and risk assessment.

Based on wastewater and raw/digested sludge samples from 29 wastewater treatment plants in 25 Chinese cities, the nationwide profiles of cis- and trans- isomers of phenylmethylsiloxanes (P3 and P4) and trifluoropropylmethylsiloxanes (D3F and D4F) were investigated. Calculated with paired influents/sludges positive for these compounds, majority (93% at mean) of them were found accumulating in raw sludges [

Monte Carlo sensitivity analysis of vehicle suspension energy harvesting in frequency domain.

Regenerative shock absorbers (RSAs) have still not entered production lines despite the promising potentials in energy efficiency and emission reduction. Vibration energy harvesting from vehicle dampers has been replicating the dynamics of passive viscous dampers. An accurate frequency-based analysis of the harvestable energy and dynamics for vehicle suspensions under typical operating conditions is essentially needed for designing functional Vibratory Regenerative Dampers (VRDs). This paper proposes frequency-based parametrical bandwidth sensitivity analyses of both the vehicular suspension dynamics and energy harvesting potentiality in accordance with the Monte Carlo sensitivity simulations. This provides insights into which suspension parameter could highly broaden the harvestable power magnitude, which contributes positively to conceptualizing an efficient design of a wide broad-banded energy harvesting damper leading to improved harvesting efficiencies in different road conditions. The conducted sensitivity analysis included the change in both frequency and amplitude bandwidth of the dissipative damping power, body acceleration, dynamic tire load, and suspension deflection. During the sensitivity simulations, a 2-DOFs (degrees-of-freedom) quarter-car model is considered, being excited by harmonic excitations. The selected suspension parameters were normally randomized according to the Gaussian probability distribution based on their nominal values and a 30% SD (standard deviation) with respect to the uniformly randomized excitation frequency. The results inferred higher sensitivity change in the harvestable power bandwidth versus the excitation parameters, damping rate, and tire properties. Conversely, the harvestable power hardly broadened with respect to the body and wheel masses and the spring stiffness.

Tumor neoantigenicity assessment with CSiN score incorporates clonality and immunogenicity to predict immunotherapy outcomes.

Lack of responsiveness to checkpoint inhibitors is a central problem in the modern era of cancer immunotherapy. Tumor neoantigens are critical targets of the host antitumor immune response, and their presence correlates with the efficacy of immunotherapy treatment. Many studies involving assessment of tumor neoantigens principally focus on total neoantigen load, which simplistically treats all neoantigens equally. Neoantigen load has been linked with treatment response and prognosis in some studies but not others. We developed a Cauchy-Schwarz index of Neoantigens (CSiN) score to better account for the degree of concentration of immunogenic neoantigens in truncal mutations. Unlike total neoantigen load determinations, CSiN incorporates the effect of both clonality and MHC binding affinity of neoantigens when characterizing tumor neoantigen profiles. By analyzing the clinical responses in 501 treated patients with cancer (with most receiving checkpoint inhibitors) and the overall survival of 1978 patients with cancer at baseline, we showed that CSiN scores predict treatment response to checkpoint inhibitors and prognosis in patients with melanoma, lung cancer, and kidney cancer. CSiN score substantially outperformed prior genetics-based prediction methods of responsiveness and fills an important gap in research involving assessment of tumor neoantigen burden.

Tourism, Transportation and Low-Carbon City System Coupling Coordination Degree：A Case Study in Chongqing Municipality, China.

Tourism and transportation have extremely complex interactions. Tourism developments have expanded demand and stimulated transportation development, which has consequently affected the environment of cities striving towards low-carbon sustainable development. Therefore, there has been an increased research focus on the coordinated binary development of the tourism and transportation industries to ensure sustainable low-carbon cities. To this end also this paper first developed a comprehensive evaluation index system with three subsystems, seven aspects, and 31 indicators. Then, entropy weight and gray correlation were combined to determine the index weights and a physics coupling concept employed to build a tourism, transportation and low-carbon city (TTLC) coupling coordination degree model, which was then applied to quantitatively analyze the coupling and evolutionary trends in Chongqing's TTLC efforts from 2008 to 2017. It was found that the overall coupling coordination was volatile and rising, and that industry scale, industry performance, and energy consumption had the most significant impact on the coupled systems, indicating that these key factors must be considered in macro decision-making. In general, it was shown that the combination of the coupling coordination degree model and entropy weight gray correlation was able to effectively evaluate dynamic coupling relationships.

Prostate cancer with bone metastasis in Beijing: an observational study of prevalence, hospital visits and treatment costs using data from an administrative claims database.

OBJECTIVES: To estimate the prevalence of prostate cancer with bone metastasis in Beijing, and to estimate hospital visits and direct treatment costs among male urban employees with the disease in Beijing. DESIGN: Cross-sectional observational study. SETTING AND PARTICIPANTS: Patients with prostate cancer and bone metastasis from the Urban Employee Basic Medical Insurance database covering the employed population of Beijing, China, from 2011 to 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence, treatment costs and healthcare visits of patients with prostate cancer and bone metastasis. RESULTS: A total of 1672 individuals were identified as having prostate cancer. Of these, 737 (44.1%) had bone metastasis, and among these, this was already present at the time of initial prostate cancer diagnosis in 27.0% (199/737). Mean age was 74.6 years (SD ±9.1). Prevalence of prostate cancer with bone metastasis increased from 5.3 per 100 000 males in 2011 to 8.3 per 100 000 males in 2014. The total annual health expenditure per patient (in 2014 American dollars) during the study period was $15 772.1 (SD=$16 942.6) ~$18 206.3 (SD=$18 700.2); 88% of these costs were reimbursed by insurance. Medication accounted for around 50% of total healthcare costs. Western drugs accounted for over 80% of medical costs with endocrine therapy being the most commonly prescribed treatment. There was an average 6.7% increase in expenditure related to diagnostical and therapeutical procedures over study years. CONCLUSIONS: The increase in the prevalence of prostate cancer with bone metastasis and associated healthcare costs in China reveals the growing clinical and economical burden of this disease. The high prevalence of bone metastasis among patients with prostate cancer seen in our study suggests that efforts may be needed to improve symptoms awareness and promote early help-seeking behaviour among the Chinese population.

Evaluation of the diagnostic performance of the simple method of computed tomography in the assessment of patients with shoulder instability: a prospective cohort study.

BACKGROUND: Physical examinations may reveal the instability of a glenohumeral joint but cannot diagnose the bony Bankart lesions. Soft tissue Bankart lesion cannot be visualized on traditional radiogram. Magnetic resonance images have high cost and availability issues. The purpose of the study was to access the diagnostic performance of the Computed Tomography (CT) in the assessment of patients with shoulder instability and to diagnose the Bankart and bony Bankart lesions. METHODS: A total of 145 patients with shoulder instability were included in the study. Patients were subjected to clinical examination tests, traditional radiography, and CT. Two orthopedic surgeons, two engineers (trained in musculoskeletal imaging), and two physiotherapists have analyzed the radiological images, CT scans, and the clinical examination tests respectively. The Chi-square test or one-way ANOVA/ Dunnett Multiple comparisons test was performed at 99% of confidence level. RESULTS: Sensitivity (0.972 ± 0.18 vs. 1, p = 0.11) and accuracy (0.942 ± 0.17 vs. 1, p < 0.0001, q = 3.88) for the clinical examination tests combining the traditional radiological images were same to CT. However, the clinical examination tests combining the traditional radiological images had more inconclusive results (5 vs. 1), false-positive results (6 vs. 5), and false negative results (4 vs. 1) than CT. The area that detects the Bankart and bony Bankart lesions at least one time for CT was higher than that of the clinical examination tests combining the traditional radiological images. CONCLUSION: CT should be considered for evaluation in patients with shoulder instability and suspected Bankart and bony Bankart lesions. TRIAL REGISTRATION: Researchregistry3990 dated 15 December 2014 ( www.researchregistry.com ).