A simple and economical method for unbiasedly quantifying the alveolar size of entire mouse lung tissue utilizing Hematoxylin and Eosin Staining.

Alveolar, the smallest structural and functional units within the respiratory system, play a crucial role in maintaining lung function. Alveolar damage is a typical pathological hallmark of respiratory diseases. Nevertheless, there is currently no simple, rapid, economical, and unbiased method for quantifying alveolar size for entire lung tissue. Here, firstly, we conducted lung sample slicing based on the size, shape, and distribution of airway branches of different lobes. Next, we performed HE staining on different slices. Then, we provided an unbiased quantification of alveolar size using free software ImageJ. Through this protocol, we demonstrated that C57Bl/6 mice exhibit varying alveolar sizes among different lobes. Collectively, we provided a simple and unbiased method for a more comprehensive quantification of alveolar size in mice, which holds promise for a broader range of respiratory research using mouse models.

Occurrence, bioaccumulation, fate, and risk assessment of emerging pollutants in aquatic environments: A review.

Significant concerns on a global scale have been raised in response to the potential adverse impacts of emerging pollutants (EPs) on aquatic creatures. We have carefully reviewed relevant research over the past 10 years. The study focuses on five typical EPs: pharmaceuticals and personal care products (PPCPs), per- and polyfluoroalkyl substances (PFASs), drinking water disinfection byproducts (DBPs), brominated flame retardants (BFRs), and microplastics (MPs). The presence of EPs in the global aquatic environment is source-dependent, with wastewater treatment plants being the main source of EPs. Multiple studies have consistently shown that the final destination of most EPs in the water environment is sludge and sediment. Simultaneously, a number of EPs, such as PFASs, MPs, and BFRs, have long-term environmental transport potential. Some EPs exhibit notable tendencies towards bioaccumulation and biomagnification, while others pose challenges in terms of their degradation within both biological and abiotic treatment processes. The results showed that, in most cases, the ecological risk of EPs in aquatic environments was low, possibly due to potential dilution and degradation. Future research topics should include adding EPs detection items for the aquatic environment, combining pollution, and updating prediction models.

First-line immunotherapy combinations for recurrent or metastatic nasopharyngeal carcinoma: An updated network meta-analysis and cost-effectiveness analysis.

OBJECTIVES: Recently updated results of randomized clinical trials (RCTs) have confirmed that toripalimab, camrelizumab, and tislelizumab plus chemotherapy (TOGP, CAGP, and TIGP) significantly prolonged survival compared to placebo plus chemotherapy (PLGP) in the first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). However, the high cost of immunotherapies imposes a huge financial burden on patients and health care systems. MATERIALS AND METHODS: RCTs estimating immunotherapies for R/M-NPC were searched. A Bayesian network meta-analysis (NMA) was carried out; the main outcomes were hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS). The cost and efficacy of four first-line therapies were evaluated using the Markov model. The main outcome in the cost-effectiveness analysis (CEA) was incremental cost-utility ratios (ICURs). The model robustness was assessed by one-way, three-way, and probabilistic sensitivity analyses. RESULTS: Three RCTs (JUPITER-02, CAPTAIN-1st, and RATIONALE-309) involving 815 patients were included in the NMA. Compared with PLGP, chemo-immunotherapies have significantly longer PFS and OS. Compared to the PLGP group, TOGP, CAGP, and TIGP groups resulted in additional costs of $48 339, $22 900, and $23 162, with additional 1.89, 0.73, and 0.960 QALYs, respectively, leading to the ICURs of $25 576/QALY, $31 370/QALY, and $31 729/QALY. Pairwise comparisons showed TOGP was the most cost-effective option among chemo-immunotherapy groups. CONCLUSION: From the Chinese payers' perspective, first-line immunotherapy combination therapies provided significant survival and cost-effectiveness superiority over chemotherapy alone for patients with R/M-NPC at the WTP of $38 029/QALY. Among the three chemo-immunotherapy groups, TOGP was the most cost-effective option.

Distribution, sources, and risk assessment of polycyclic aromatic hydrocarbons (PAHs) in Kaokaowusu river sediments near a coal industrial zone.

This study systematically analyzed the contents, compositions, and sources of polycyclic aromatic hydrocarbons (PAHs) in river sediments near an important energy and chemical base in northwest China. In addition, their possible adverse effects on the ecology and human health were assessed. The PAH concentrations in this study area ranged from 2641.28 to 16783.72 (ng/g dw). PAHs of medium molecular weight (3-ring and 4-ring) showed the largest proportion, followed by PAHs of higher molecular weight (5-ring and 6-ring). The results of molecular diagnostic ratios and principal component analysis revealed that PAHs in the region have complex sources, with incomplete combustion of local fossil fuels and traffic exhaust factors being the main sources. The total toxic equivalent concentration of PAHs varied from 10.05 to 760.26 ng/g, and according to the sediment quality guidelines, PAHs have high potential ecological risk in the lower reaches of the river. The mean effect range-median quotient for the region was 0.46, and the combined ecological risk was at moderate to high levels (21% probability of toxicity). The lifetime carcinogenic risks for adults and children exposed to PAHs were 2.95 × 10-3 and 1.87 × 10-2, respectively, which are much higher than the limit of 10-4, indicating moderate to high potential cancer risks. Therefore, the local government should consider taking some environmental remediation measures. This study can provide theoretical support for pollution prevention measures and ecological restoration strategies for rivers in resource-rich areas.

Association of Insurance Type With Inpatient Surgery 30-Day Complications and Costs.

INTRODUCTION: Safety-net hospitals (SNHs) have higher postoperative complications and costs versus low-burden hospitals. Do low socioeconomic status/vulnerable patients receive care at lower-quality hospitals or are there factors beyond providers' control? We studied the association of private, Medicare, and vulnerable insurance type with complications/costs in a high-burden SNH. METHODS: Retrospective inpatient cohort study using National Surgical Quality Improvement Program (NSQIP) data (2013-2019) with cost data risk-adjusted by frailty, preoperative serious acute conditions (PASC), case status, and expanded operative stress score (OSS) to evaluate 30-day unplanned reoperations, any complication, Clavien-Dindo IV (CDIV) complications, and hospitalization variable costs. RESULTS: Cases (Private 1517; Medicare 1224; Vulnerable 3648) with patient mean age 52.3 y [standard deviation = 14.7] and 47.3% male. Adjusting for frailty and OSS, vulnerable patients had higher odds of PASC (aOR = 1.71, CI = 1.39-2.10, P < 0.001) versus private. Adjusting for frailty, PASC and OSS, Medicare (aOR = 1.27, CI = 1.06-1.53, P = 0.009), and vulnerable (aOR = 2.44, CI = 2.13-2.79, P < 0.001) patients were more likely to undergo urgent/emergent surgeries. Vulnerable patients had increased odds of reoperation and any complications versus private. Variable cost percentage change was similar between private and vulnerable after adjusting for case status. Urgent/emergent case status increased percentage change costs by 32.31%. We simulated "switching" numbers of private (3648) versus vulnerable (1517) cases resulting in an estimated variable cost of $49.275 million, a 25.2% decrease from the original $65.859 million. CONCLUSIONS: Increased presentation acuity (PASC and urgent/emergent surgeries) in vulnerable patients drive increased odds of complications and costs versus private, suggesting factors beyond providers' control. The greatest impact on outcomes may be from decreasing the incidence of urgent/emergent surgeries by improving access to care.

Retrospective cohort study comparing surgical inpatient charges, total costs, and variable costs as hospital cost savings measures.

We analyzed differences (charges, total, and variable costs) in estimating cost savings of quality improvement projects using reduction of serious/life-threatening complications (Clavien-Dindo Level IV) and insurance type (Private, Medicare, and Medicaid/Uninsured) to evaluate the cost measures. Multiple measures are used to analyze hospital costs and compare cost outcomes across health systems with differing patient compositions. We used National Surgical Quality Improvement Program inpatient (2013-2019) with charge and cost data in a hospital serving diverse socioeconomic status patients. Simulation was used to estimate variable costs and total costs at 3 proportions of fixed costs (FC). Cases (Private 1517; Medicare 1224; Medicaid/Uninsured 3648) with patient mean age 52.3 years (Standard Deviation = 14.7) and 47.3% male. Medicare (adjusted odds ratio = 1.55, 95% confidence interval = 1.16-2.09, P = .003) and Medicaid/Uninsured (adjusted odds ratio = 1.41, 95% confidence interval = 1.10-1.82, P = .008) had higher odds of complications versus Private. Medicaid/Uninsured had higher relative charges versus Private, while Medicaid/Uninsured and Medicare had higher relative variable and total costs versus Private. Targeting a 15% reduction in serious complications for robust patients undergoing moderate-stress procedures estimated variable cost savings of $286,392. Total cost saving estimates progressively increased with increasing proportions of FC; $443,943 (35% FC), $577,495 (50% FC), and $1184,403 (75% FC). In conclusion, charges did not identify increased costs for Medicare versus Private patients. Complications were associated with > 200% change in costs. Surgical hospitalizations for Medicare and Medicaid/Uninsured patients cost more than Private patients. Variable costs should be used to avoid overestimating potential cost savings of quality improvement interventions, as total costs include fixed costs that are difficult to change in the short term.

Cost-effectiveness analysis of metronomic capecitabine as adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma.

Background: Adding metronomic capecitabine to concurrent chemoradiotherapy (CCRT) brings failure-free survival (FFS) benefits to patients with locoregionally advanced nasopharyngeal carcinoma (NPC). This study assesses the cost-effectiveness of metronomic capecitabine in locoregionally advanced NPC. Methods: We created a Markov model to calculate the expense and health outcomes of metronomic capecitabine compared to those observed in locoregionally advanced NPC. Related costs, like life-years (LYs), quality-adjusted life years (QALYs), and incremental cost-effective ratios (ICERs) were measured at a willingness-to-pay (WTP) threshold of $33,585 per QALY. A combination of different sensitivity analyses was used to test for model robustness. Additionally, a subgroup analysis was also performed. Results: In contrast to what is observed in the locoregionally advanced NPC, adding the metronomic adjuvant capecitabine yielded an additional 1.11 QALYs with an incremental cost of $10,741.59, which obtained an ICER of $9,669.99 per QALY. The result of one-way sensitive analysis indicated that the utility of FFS, progression disease (PD), and the cost of follow-up were the most significant factors. The probability of metronomic capecitabine being cost-effective was 97.1% at a WTP of $33,585 per QALY. Conclusion: Metronomic capecitabine as adjuvant chemotherapy is a cost-effective strategy for locoregionally advanced NPC patients.

Factors Associated With Morbidity and Retreatment After Surgical Management of Nonacute Subdural Hematomas in Elderly Patients.

Background Preoperative identification of clinical, radiographic, and surgery-specific factors associated with nonacute subdural hematomas (SDHs) may enable clinicians to optimize the efficacy of the initial surgical intervention, improve outcomes, and decrease rates of surgical recurrence. Methods The authors identified patients aged ≥65 years who underwent surgical treatment of chronic, subacute, or mixed-density SDH at a level-1 trauma hospital over a ten-year period (2010-2019). Pre-and postoperative clinical, radiographic, and surgery-specific data were collected. Predictors of surgical recurrence as well as morbidity, mortality, and discharge disposition were analyzed. Results There were 268 nonacute SDHs treated surgically; 46 were chronic, 19 were subacute, and 203 were mixed density. Of these, 179 were treated with burr hole(s), 62 with miniature craniotomy, and 27 via a large craniotomy and removal of subdural membranes. Statin use was protective (OR 0.22; 95% CI 0.08, 0.60) against recurrence requiring reoperation. Preoperative use of antithrombotic agents was not significantly associated with increased recurrence requiring reoperation. Smaller preoperative hematoma thickness was associated with significantly lower mortality risk, whereas mixed-density hematomas, patient age, change in thickness after surgery, density, and presence of cisternal effacement were significantly associated with discharge disposition. Hematoma type was also associated with hospital and intensive care length of stay. Conclusions Our experience suggests that, in elderly patients, premorbid statin usage is associated with lower recurrence rates and preoperative antithrombotic use does not affect recurrence when appropriately reversed before surgery. Patient age, preoperative thickness, and hematoma type contribute to postoperative outcomes such as discharge disposition and length of stay.

Immune checkpoint inhibition in first-line treatment for recurrent or metastatic nasopharyngeal carcinoma: A CAPTAIN-1st and JUPITER-02 trial-based cost-effectiveness analysis.

OBJECTIVES: This study was aimed to evaluate the cost-effectiveness of the recently approved first-line treatments, toripalimab or camrelizumab combined with gemcitabine plus cisplatin2 (GP) and GP alone for patients with recurrent or metastatic nasopharyngeal carcinoma3 (RM-NPC) from the Chinese payers' perspective. MATERIALS AND METHODS: We established a Markov model to estimate the cost and effectiveness of currently first-line therapies for RM-NPC. Survival data were derived from the CAPTAIN-1st and JUPITER-02 trials. Direct medical costs and utilities were collected from the published literature and standard fee database. Main outcomes were total costs, quality-adjusted life-year4 (QALY), and incremental cost-effectiveness ratios (ICER) at a willingness-to-pay5 (WTP) of $34 066/QALY. The robustness of the model was assessed by performing one-way and probability sensitivity analyses. RESULTS: Compared with the GP chemotherapy, toripalimab or camrelizumab plus GP chemotherapy as first-line therapy for RM-NPC provided an incremental cost of $6 026 and $43 138 with additional 0.90 QALYs and 0.78 QALYs, respectively, resulting in an ICER of 6 696 $/QALY and 55 305 $/QALY. In the pairwise comparison between the two immunotherapy-related groups, toripalimab plus GP was the dominant strategy with lower costs and higher efficiency than the camrelizumab plus GP group. CONCLUSION: In our analysis, compared with GP chemotherapy alone, toripalimab plus GP was more cost-effective, while camrelizumab plus GP chemotherapy was not cost-effective. In the pairwise comparison between the two immunotherapy-related groups, toripalimab plus GP would be more cost-effective than camrelizumab plus GP chemotherapy.

Pembrolizumab with or without chemotherapy versus cetuximab plus chemotherapy to treat recurrent or metastatic head and neck squamous cell carcinoma: An updated KEYNOTE-048 based cost-effectiveness analysis.

OBJECTIVES: Recently, updated data from KEYNOTE-048 revealed that pembrolizumab with or without chemotherapy could improve progression-free survival (PFS)2 compared with cetuximab plus chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: A Markov structure was conducted to evaluate the cost and effectiveness of pembrolizumab monotherapy or pembrolizumab plus chemotherapy vs. cetuximab plus chemotherapy in the first-line treatment of recurrent or metastatic HNSCC from the United States payer's perspective. Total cost, health outcomes, and incremental cost-effective ratios (ICERs) were estimated. Additional analyses were conducted in the total population and in two different programmed cell death 1 ligand 1 (PD-L1) combined positive scores (CPSs) (≥1 and ≥ 20) population. Sensitivity analysis were used to test the stability of the model. RESULTS: When compared with cetuximab plus chemotherapy, the pembrolizumab monotherapy strategy was dominated by lower cost and better efficacy in all three populations. The incremental costs and quality adjusted life years (QALYs) yielded by pembrolizumab plus chemotherapy compared with cetuximab plus chemotherapy were $16016.88 and 0.11 in the total population, and $24467.47 and 0.18 and $30448.46 and 0.20 in the populations with a PD-L1 CPS ≥ 1 and CPS ≥ 20, respectively, leading to ICERs of $147876.14, $134237.84, and $153660.78 per QALY, respectively. CONCLUSION: First-line treatment with pembrolizumab or pembrolizumab plus chemotherapy are cost-effective strategies compared with cetuximab plus chemotherapy when the value of willingness-to-pay (WTP) was $150000 per QALY for the total and PD-L1 CPS ≥ 1 populations with recurrent or metastatic HNSCC.

ADGRA1 negatively regulates energy expenditure and thermogenesis through both sympathetic nervous system and hypothalamus-pituitary-thyroid axis in male mice.

Adhesion G protein-coupled receptor A1 (ADGRA1, also known as GPR123) belongs to the G protein-coupled receptors (GPCRs) family and is well conserved in the vertebrate lineage. However, the structure of ADGRA1 is unique and its physiological function remains unknown. Previous studies have shown that Adgra1 is predominantly expressed in the central nervous system (CNS), indicating its important role in the transduction of neural signals. The aim of this study is to investigate the central function of Adgra1 in vivo and clarify its physiological significance by establishing an Adgra1-deficient mouse (Adgra1-/-) model. The results show that Adgra1-/- male mice exhibit decreased body weight with normal food intake and locomotion, shrinkage of body mass, increased lipolysis, and hypermetabolic activity. Meanwhile, mutant male mice present elevated core temperature coupled with resistance to hypothermia upon cold stimulus. Further studies show that tyrosine hydroxylase (TH) and ß3-adrenergic receptor (ß3-AR), indicators of sympathetic nerve excitability, are activated as well as their downstream molecules including uncoupling protein 1 (UCP1), coactivator 1 alpha (PGC1-α) in brown adipose tissue (BAT), and hormone-sensitive lipase (HSL) in white adipose tissue (WAT). In addition, mutant male mice have higher levels of serum T3, T4, accompanied by increased mRNAs of hypothalamus-pituitary-thyroid axis. Finally, Adgra1-/- male mice present abnormal activation of PI3K/AKT/GSK3ß and MEK/ERK pathways in hypothalamus. Overexpression of ADGRA1 in Neuro2A cell line appears to suppress these two signaling pathways. In contrast, Adgra1-/- female mice show comparable body weight along with normal metabolic process to their sex-matched controls. Collectively, ADGRA1 is a negative regulator of sympathetic nervous system (SNS) and hypothalamus-pituitary-thyroid axis by regulating PI3K/AKT/GSK3ß and MEK/ERK pathways in hypothalamus of male mice, suggesting an important role of ADGRA1 in maintaining metabolic homeostasis including energy expenditure and thermogenic balance.

Association of Socioeconomic Area Deprivation Index with Hospital Readmissions After Colon and Rectal Surgery.

BACKGROUND: Risk adjustment for reimbursement and quality measures omits social risk factors despite adversely affecting health outcomes. Social risk factors are not usually available in electronic health records (EHR) or administrative data. Socioeconomic status can be assessed by using US Census data. Distressed Communities Index (DCI) is based upon zip codes, and the Area Deprivation Index (ADI) provides more granular estimates at the block group level. We examined the association of neighborhood disadvantage using the ADI, DCI, and patient-level insurance status on 30-day readmission risk after colorectal surgery. METHODS: Our 677 patient cohort was derived from the 2013-2017 National Surgical Quality Improvement Program at a safety net hospital augmented with EHR data to determine insurance status and 30-day readmissions. Patients' home addresses were linked to the ADI and DCI. RESULTS: Our cohort consisted of 53.9% males and 63.8% Hispanics with a 22.9% 30-day readmission rate from the date of discharge; > 50% lived in highly deprived neighborhoods. Controlling for medical comorbidities and complications, ADI was associated with increased risk of 30 days from the date of discharge readmissions among patients living in medium (OR = 2.15, p = .02) or high (OR = 1.88, p = .03) deprived areas compared to less-deprived neighborhoods, but not insurance status or DCI. CONCLUSIONS: The ADI identified patients living in deprived communities with increased readmission risk. Our results show that block-group level ADI can potentially be used in risk adjustment, to identify high-risk patients and to design better care pathways that improve health outcomes.

Trends and Disparities of Energy Intake and Macronutrient Composition in China: A Series of National Surveys, 1982-2012.

BACKGROUND: China's diet transition might offer guidance to undeveloped countries on the way to prosperity. This report describes the trends and disparities in energy and macronutrient composition among Chinese adults, and between subpopulations. METHODS: Data for the current study were obtained from the 1982, 1992, 2002, and 2010-2012 China National Nutrition Survey (CNNS) rounds, which were nationally representative cross-sectional surveys. We applied 24-h dietary recall and food weighing to assess dietary intake. RESULTS: There were 204,877 participants aged 20 years or older included in the current analysis. From 1982 to 2012, the estimated energy intake declined from 2614.7 kcal to 2063.9 kcal. The trend in the estimated percentage of energy intake from fat showed a spike. It increased from 16.3% to 33.1% (1992 vs. 1982 difference, 7.6%; 95% CI 7.4% to 7.7%; 2002 vs. 1992 difference, 7.7%; 95% CI 7.6% to 7.9%; 2012 vs. 2002 difference, 1.6%; 95% CI 1.4% to 1.7%; p < 0.01 for trend). The trends coincided in all the subgroups (all p < 0.01 for trend) except for the subgroup of those educated over 15 years, whose percentage of energy intake from fat declined from 37.4% to 36.6% (2012 vs. 2002 difference, -0.8%; 95% CI -1.6% to 0.0%). The estimated percentage of energy intake from carbohydrates declined from 74.0% to 55.0%. The ranges of the estimated percentage of energy intake from fat, within population subgroups stratified by education level, area and Gross national product (GNP) level, were narrowed. CONCLUSIONS: Quick improvements in society and the economy effectively curbed undernutrition, but easily triggered overnutrition. Disparities persistently existed between different subpopulations, while the gaps would narrow if comprehensive efforts were made. Education might be a promising way to prevent overnutrition during prosperous progress. The low-social profile populations require specific interventions so as to avoid further disease burdens.

Assessment of angiogenesis in rabbit orthotropic liver tumors using three-dimensional dynamic contrast-enhanced ultrasound compared with two-dimensional DCE-US.

OBJECTIVES: To evaluate quantitative three-dimensional (3D) dynamic contrast-enhanced ultrasound (DCE-US) in the assessment of tumor angiogenesis using an orthotropic liver tumor model. METHODS: Nine New Zealand white rabbits with liver orthotropic VX2 tumors were established and imaged by two-dimensional (2D) and 3D DCE-US after SonoVue® bolus injections. The intraclass correlation coefficients of perfusion parameters, including peak intensity (PI), mean transit time, time to peak, and area under the curve, were calculated based on time-intensity curve. The percentage area of microvascular (PAMV) and the expression of vascular endothelial growth factor (VEGF) were both evaluated by immunohistochemical analysis and weighted by the tumor activity area ratio. Correlations between quantitative and histologic parameters were analyzed. RESULTS: The reproducibility of 3D DCE-US quantitative parameters was excellent (ICC 0.91-0.99); but only PI showed high reproducibility (ICC 0.97) in 2D. None of the parameters of quantitative 2D DCE-US were significantly correlated with weighted PAMV or VEGF. For 3D DCE-US, there was a positive correlation between PI and weighted PAMV (r = 0.74, P = 0.04) as well as VEGF (r = 0.79, P = 0.02). CONCLUSION: Quantitative parameters of 3D DCE-US show feasibility, higher reproducibility and accuracy for the assessment of tumor angiogenesis using an orthotropic liver tumor model compared with 2D DCE-US.

Development of a novel and economical agar-based non-adherent three-dimensional culture method for enrichment of cancer stem-like cells.

BACKGROUND: Non-adherent or ultra-low attachment three-dimensional (3D) culture, also called sphere formation assay, has been widely used to assess the malignant phenotype and stemness potential of transformed or cancer cells. This method is also popularly used to isolate the cancer stem-like cells (CSCs) or tumor-initiating cells based on their unique anchorage-independent growth or anoikis-resistant capacity. Different non-adhesive coating agents, such as poly-2-hydroxyethyl methacrylate (poly-HEMA) and synthetic hydrogels, have been used in this non-adherent 3D culture. However, preparation of non-adherent culture-ware is labor-intensive and technically demanding, and also costs of commercial non-adherent culture-ware prepared with various coating agents are relatively expensive and the culture-ware cannot be used repeatedly. METHODS: In this study, we developed a non-adherent 3D culture method based on agar coating for growing tumor spheres derived from various cancer cell lines and primary prostate cancer tissues under a non-adherent and serum-free condition. The tumor spheres generated by this 3D culture method were analyzed on their expression profiles of CSC-associated markers by reverse transcription quantitative polymerase chain reaction, presence and relative proportion of CSCs by fluorescence-activated cell sorting (CD133+/CD44+ cell sorting) and also a CSC-visualizing reporter system responsive to OCT4 and SOX2 (SORE6), and in vivo tumorigenicity. The repeated use of agar-coated plates for serial passages of tumor spheres was also evaluated. RESULTS: Our results validated that the multicellular tumor spheres generated by this culture method were enriched of CSCs, as evidenced by their enhanced expression profiles of CSC markers, presence of CD133+/CD44+ or SORE6+ cells, enhanced self-renewal capacity, and in vivo tumorigenicity, indicating its usefulness in isolation and enrichment of CSCs. The agar-coated plates could be used multiple times in serial passages of tumor spheres. CONCLUSIONS: The described agar-based 3D culture method offers several advantages as compared with other methods in isolation of CSCs, including its simplicity and low-cost and repeated use of agar-coated plates for continuous passages of CSC-enriched spheres.

Exposure Assessment of Sb2O3 in PET Food Contact Materials.

This study was conducted to do exposure assessment of the possible migration of antimony trioxide (Sb2O3) from Polyethylene terephthalate (PET) food contact materials (FCM). Consumption Factor (CF) and Food-type Distribution Factor (fT) were calculated from survey data with reference to the US FDA method. The most conservative migration conditions were obtained by testing Sb migration from PET FCM based on the Chinese national standard of GB/T 5009.101-2003[1]. Migration levels of Sb from PET FCM were tested and migration levels of Sb2O3 were obtained through molecular weight conversion between Sb and Sb2O3. Exposure assessment of Sb2O3 was undertaken. The Chinese Estimated Daily Intake (EDI) of Sb2O3 resulted from PET FCM was 90.7 ng p-1d-1.

High Levels of Antibiotic Resistance Genes and Their Correlations with Bacterial Community and Mobile Genetic Elements in Pharmaceutical Wastewater Treatment Bioreactors.

To understand the diversity and abundance of antibiotic resistance genes (ARGs) in pharmaceutical wastewater treatment bioreactors, the ARGs in sludge from two full-scale pharmaceutical wastewater treatment plants (PWWTPs) were investigated and compared with sludge samples from three sewage treatment plants (STPs) using metagenomic approach. The results showed that the ARG abundances in PWWTP sludge ranged from 54.7 to 585.0 ppm, which were higher than those in STP sludge (27.2 to 86.4 ppm). Moreover, the diversity of ARGs in PWWTP aerobic sludge (153 subtypes) was higher than that in STP aerobic sludge (118 subtypes). In addition, it was found that the profiles of ARGs in PWWTP aerobic sludge were similar to those in STP aerobic sludge but different from those in PWWTP anaerobic sludge, suggesting that dissolve oxygen (DO) could be one of the important factors affecting the profiles of ARGs. In PWWTP aerobic sludge, aminoglycoside, sulfonamide and multidrug resistance genes were frequently detected. While, tetracycline, macrolide-lincosamide-streptogramin and polypeptide resistance genes were abundantly present in PWWTP anaerobic sludge. Furthermore, we investigated the microbial community and the correlation between microbial community and ARGs in PWWTP sludge. And, significant correlations between ARG types and seven bacterial genera were found. In addition, the mobile genetic elements (MGEs) were also examined and correlations between the ARGs and MGEs in PWWTP sludge were observed. Collectively, our results suggested that the microbial community and MGEs, which could be affected by DO, might be the main factors shaping the profiles of ARGs in PWWTP sludge.

Assessment of liver fibrosis in chronic hepatitis B using acoustic structure quantification: quantitative morphological ultrasound.

OBJECTIVES: To prospectively investigate the usefulness of acoustic structure quantification (ASQ) for noninvasive assessment of liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: Consecutive patients with CHB scheduled for liver biopsy or partial liver resection underwent standardized ASQ examinations. The ASQ parameter, named focal disturbance (FD) ratio, were compared with METAVIR scores. The analysis was based on receiver operating characteristic (ROC) curves and multiple regression analysis. RESULTS: A total of 114 patients were enrolled in the final analysis. The area under the ROC curve for the FD ratio was 0.84 for significant fibrosis (≥ F2), 0.86 for severe fibrosis (≥ F3), and 0.83 for cirrhosis (= F4). The optimal cutoff values for the FD ratio were 0.25, 0.30 and 0.50 for fibrosis stages ≥ F2, ≥ F3 and = F4, respectively. The prevalence of a difference of at least two stages between the FD ratio and the histological stage was 12.3 % (14 of 114). The fibrosis stage (P < 0.001), degree of steatosis (P < 0.001) were independent factors associated with the FD ratio. CONCLUSIONS: FD ratio should be an effective noninvasive imaging biomarker for the assessment of liver fibrosis in patients with CHB. KEY POINTS: • Focal disturbance (FD) ratio increased with the increasing histological fibrosis stages. • FD ratio showed promising diagnostic accuracy in assessing liver fibrosis. • Degree of fibrosis and steatosis were independent factors associated with FD ratio.

Variable selection for zero-inflated and overdispersed data with application to health care demand in Germany.

In health services and outcome research, count outcomes are frequently encountered and often have a large proportion of zeros. The zero-inflated negative binomial (ZINB) regression model has important applications for this type of data. With many possible candidate risk factors, this paper proposes new variable selection methods for the ZINB model. We consider maximum likelihood function plus a penalty including the least absolute shrinkage and selection operator (LASSO), smoothly clipped absolute deviation (SCAD), and minimax concave penalty (MCP). An EM (expectation-maximization) algorithm is proposed for estimating the model parameters and conducting variable selection simultaneously. This algorithm consists of estimating penalized weighted negative binomial models and penalized logistic models via the coordinated descent algorithm. Furthermore, statistical properties including the standard error formulae are provided. A simulation study shows that the new algorithm not only has more accurate or at least comparable estimation, but also is more robust than the traditional stepwise variable selection. The proposed methods are applied to analyze the health care demand in Germany using the open-source R package mpath.

[The validation of the effect of correcting spectral background changes based on floating reference method by simulation].

There are some challenges in near-infrared non-invasive blood glucose measurement, such as the low signal to noise ratio of instrument, the unstable measurement conditions, the unpredictable and irregular changes of the measured object, and etc. Therefore, it is difficult to extract the information of blood glucose concentrations from the complicated signals accurately. Reference measurement method is usually considered to be used to eliminate the effect of background changes. But there is no reference substance which changes synchronously with the anylate. After many years of research, our research group has proposed the floating reference method, which is succeeded in eliminating the spectral effects induced by the instrument drifts and the measured object's background variations. But our studies indicate that the reference-point will changes following the changing of measurement location and wavelength. Therefore, the effects of floating reference method should be verified comprehensively. In this paper, keeping things simple, the Monte Carlo simulation employing Intralipid solution with the concentrations of 5% and 10% is performed to verify the effect of floating reference method used into eliminating the consequences of the light source drift. And the light source drift is introduced through varying the incident photon number. The effectiveness of the floating reference method with corresponding reference-points at different wavelengths in eliminating the variations of the light source drift is estimated. The comparison of the prediction abilities of the calibration models with and without using this method shows that the RMSEPs of the method are decreased by about 98.57% (5%Intralipid)and 99.36% (10% Intralipid)for different Intralipid. The results indicate that the floating reference method has obvious effect in eliminating the background changes.