Mean Apparent Propagator MRI: Quantitative Assessment of Tumor-Stroma Ratio in Invasive Ductal Breast Carcinoma.

Purpose To determine whether metrics from mean apparent propagator (MAP) MRI perform better than apparent diffusion coefficient (ADC) value in assessing the tumor-stroma ratio (TSR) status in breast carcinoma. Materials and Methods From August 2021 to October 2022, 271 participants were prospectively enrolled (ClinicalTrials.gov identifier: NCT05159323) and underwent breast diffusion spectral imaging and diffusion-weighted imaging. MAP MRI metrics and ADC were derived from the diffusion MRI data. All participants were divided into high-TSR (stromal component < 50%) and low-TSR (stromal component ≥ 50%) groups based on pathologic examination. Clinicopathologic characteristics were collected, and MRI findings were assessed. Logistic regression was used to determine the independent variables for distinguishing TSR status. The area under the receiver operating characteristic curve (AUC) and sensitivity, specificity, and accuracy were compared between the MAP MRI metrics, either alone or combined with clinicopathologic characteristics, and ADC, using the DeLong and McNemar test. Results A total of 181 female participants (mean age, 49 years ± 10 [SD]) were included. All diffusion MRI metrics differed between the high-TSR and low-TSR groups (P < .001 to P = .01). Radial non-Gaussianity from MAP MRI and lymphovascular invasion were significant independent variables for discriminating the two groups, with a higher AUC (0.81 [95% CI: 0.74, 0.87] vs 0.61 [95% CI: 0.53, 0.68], P < .001) and accuracy (138 of 181 [76%] vs 106 of 181 [59%], P < .001) than that of the ADC. Conclusion MAP MRI may serve as a better approach than conventional diffusion-weighted imaging in evaluating the TSR of breast carcinoma. Keywords: MR Diffusion-weighted Imaging, MR Imaging, Breast, Oncology ClinicalTrials.gov Identifier: NCT05159323 Supplemental material is available for this article. © RSNA, 2024.

Assessment of the Risk of Malnutrition or Frailty Among Patients Undergoing Liver Transplantation: A Hospital-Based Prospective Study.

Objective: We aimed to explore the status of nutritional and frailty in patients undergoing liver transplantation and the associated influencing factors. Methods: We conducted a follow-up analysis of 44 patients who underwent liver transplantation between 2021 and 2022. We followed up and recorded the nutritional status and risk of weakness at different time-points (days 1, 2, 3, 6, 9, and 12) postoperatively. Patient information regarding demographics, physical examination, medical history, and perioperative blood tests were collected. Binary logistic regression was applied to identify risk factors for weakness after liver transplantation. Results: The cohort comprised 44 liver transplant recipients, with a mean age of 47.66 years (standard deviation=9.49 years). Initial analysis revealed that, compared to the group without nutritional risks, the group with nutritional risks displayed elevated age and preoperative blood ammonia levels one week post-surgery. Moreover, this group had reduced levels of albumin and total bile acid preoperatively. Patients with preoperative nutritional risks were also prone to similar risks 2 weeks postoperatively. Further, a correlation was observed between preoperative pulmonary infections and increased frailty risk 6 days postoperatively. At both 9 and 12 days postoperatively, patients with frailty risk exhibited higher preoperative white blood cell counts and ammonia levels than those without. Multivariable analysis, controlling for confounding factors, indicated a significant association between preoperative nutritional status and nutritional risk 2 weeks postoperatively, as well as a link between preoperative white blood cell count and frailty risk at 12 days postoperatively. Conclusion: There was a significant correlation between preoperative nutritional status and nutritional risk 2 weeks after liver transplantation, and preoperative white blood cell count was an independent risk factor for weakness 12 days postoperatively. Preoperative nutritional management for patients could potentially mitigate the likelihood of adverse clinical outcomes.

Atom-ProteinQA: Atom-level protein model quality assessment through fine-grained joint learning.

MOTIVATION: Protein model quality assessment (ProteinQA) is a fundamental task that is essential for biologically relevant applications, i.e., protein structure refinement, protein design, etc. Previous works aimed to conduct ProteinQA only on the global structure or per-residue level, ignoring potentially usable and precise cues from a fine-grained per-atom perspective. In this study, we propose an atom-level ProteinQA model, named Atom-ProteinQA, in which two innovative modules are designed to extract geometric and topological atom-level relationships respectively. Specifically, on the one hand, a geometric perception module exploits 3D sparse convolution to capture the geometric features of the input protein, generating fine-grained atom-level predictions. On the other hand, natural chemical bonds are utilized to construct an atom-level graph, then message passing from a topological perception module is applied to output residue-level predictions in parallel. Eventually, through a cross-model aggregation module, features from different modules mutually interact, enhancing performance on both the atom and residue levels. RESULTS: Extensive experiments show that our proposed Atom-ProteinQA outperforms previous methods by a large margin, regardless of residue-level or atom-level assessment. Concretely, we achieved state-of-the-art performance on CATH-2084, Decoy-8000, public benchmarks CASP13 & CASP14, and the CAMEO. AVAILABILITY: The repository of this project is released on: https://github.com/luyfcandy/Atom_ProteinQA.

Improved anaerobic sludge fermentation mediated by a tryptophan-degrading consortium: Effectiveness assessment and mechanism deciphering.

The hydrolysis of extracellular polymeric substances (EPS) represents a critical bottleneck in the anaerobic fermentation of waste activated sludge (WAS), while tryptophan is identified as an underestimated constituent of EPS. Herein, we harnessed a tryptophan-degrading microbial consortium (TDC) to enhance the hydrolysis efficiency of WAS. At TDC dosages of 5%, 10%, and 20%, a notable increase in SCOD was observed by factors of 1.13, 1.39, and 1.88, respectively. The introduction of TDC improved both the yield and quality of short chain fatty acids (SCFAs), the maximum SCFA yield increased from 590.6 to 1820.2, 1957.9 and 2194.9 mg COD/L, whilst the acetate ratio within SCFAs was raised from 34.1% to 61.2-70.9%. Furthermore, as TDC dosage increased, the relative activity of protease exhibited significant increments, reaching 116.3%, 168.0%, and 266.1%, respectively. This enhancement facilitated WAS solubilization and the release of organic substances from bound EPS into soluble EPS. Microbial analysis identified Tetrasphaera and Soehngenia as key participants in WAS solubilization and the breakdown of protein fraction. Metabolic analysis revealed that TDC triggered the secretion of enzymes associated with amino acid metabolism and fatty acid biosynthesis, thereby fostering the decomposition of proteins and production of SCFAs.

Dimethylsiloxanes in dust from nine indoor microenvironments of Henan Province: Occurrence and human exposure assessment.

Dimethylsiloxanes (MSs) are widely used in daily life and industry, with indoors being the main release site. Detecting the levels of MSs in indoor dust is essential for assessing the risks of human exposure. In this study, the content of MSs (D3-D8 and L3-L16) was quantified in indoor dust samples from nine microenvironments of Henan Province. The detection frequency of the targets ranged from 5.00 % to 100 %. The sum concentration of dimethylsiloxanes (TSi) was in a range of 463-3.32 × 104 ng·g-1 (median: 1.92 × 103 ng·g-1). The sum concentration of linear dimethylsiloxanes (TLSi) from all microenvironments was higher than the sum concentration of cyclic dimethylsiloxanes (TCSi), which was consistent with previously reported results. D7 and D8 were the main cyclic dimethylsiloxane, which had similar sources based on Spearman correlation analysis (p < 0.001). Moreover, D8 was detected with high levels in indoor dust for the first time, which warrants further exploration. L8-L16 were the main linear dimethylsiloxanes, which may have been due to their widespread use in electronic equipment and office equipment. The Spearman analysis found that total organic carbon (TOC) in indoor dust had weak effect on MSs. Additionally, relatively high MS levels were recorded in high people-flow working microenvironments. Accordingly, the exposure doses of MSs via indoor dust intake were estimated for different age groups using the model of worst-case exposure and median concentration. Toddlers had the highest EDIs (95th percentile concentration, 90.7 ng·kg-1-bw·d-1) to MSs.

Exploring the influencing factors of carbon neutralization in Chinese manufacturing enterprises.

One of the key issues facing the government in achieving carbon neutrality is what methods can be used to effectively reduce carbon emissions. Taking manufacturing enterprises as an example, this paper studies the carbon emission reduction effects of green technology innovation subsidy (GIS), carbon tax (CT), and carbon emission trading (CET). Under the background of social welfare and carbon emission reduction efficiency, we get the results of optimal carbon emission reduction measures in different environments. The results are as follows: (1) In the initial and mature stage of green technology innovation, GIS is the best choice to improve the degree of green manufacturing and maximize social welfare. CT and CET are the best choice to obtain the highest SE (carbon emission reduction efficiency). (2) In the transitional stage, CET and CT can promote the maturity of green technology. However, with the maturity of green technology, the promotion of green technology has weakened. CT is the best choice to achieve the highest SE. (3) When the carbon tax or carbon trading price is at a high or low level, raising the tax rate or carbon trading price can increase the income of enterprises. Therefore, the government should take measures according to the objectives of different stages. When the goal is to maximize social benefits, GIS is the best choice in the initial stage and transition stage, and CET or CT is the best choice in the transition stage. In the initial stage and fertilization stage, when the highest SE, CT, or CET is the best choice, while in the transition stage, CT is the best choice.

Efficient and economical production of polyhydroxyalkanoate from sustainable rubber wood hydrolysate and xylose as co-substrate by mixed microbial cultures.

Using co-substrate to accumulate polyhydroxyalkanoate (PHA) is an efficient approach to reduce production cost and improve yield of PHA. In the study, PHA was biosynthesized under full aerobic mode by using rubber wood hydrolysate and xylose co-substrate as the carbon source. The effects of co-substrate on PHA production, microbial community and carbon conversion were explored. The results showed that proper addition of xylose was beneficial for the synthesis of PHA and monomer 3-hydroxyvalerate (3HV). Higher conversion yield of substrate-to-PHA (YPHA/S) of 0.933 g COD PHA/g COD S and PHA content of 43.6 g PHA/100 g VSS were gained at co-substrate ratio of 1:1. Likewise, under this condition, PHA production also reached the highest value of 1849 mg COD/L (1088 mg/L). Moreover, the addition of xylose created a favorable screening of PHA dominant strains, improved the conversion of carbon source, and saved 72.3% of feedstock consumption.

A multicenter study to evaluate the disease burden and health economics of inpatients with multiple sclerosis in China.

OBJECTIVE: To assess the disease burden and health economics of inpatients with multiple sclerosis (MS) in China by evaluating the direct, indirect, and intangible costs. METHODS: A total of 863 patients were included for a cross-sectional retrospective study in 50 centers. The direct economic burden was measured by the cost of hospitalization and out-of-hospital application drugs, and the indirect economic burden was measured by the human capital method. The disability-adjusted life year (DALY) was used to express the intangible economic burden. Cost-utility analysis (CUA) using DALYs as indicators of health benefits was performed by calculating the incremental cost-utility ratio. RESULTS: The mean direct economic burden/year, daily medication expenses/year, DALY, indirect economic burden, and indirect economic burden/year were 27,655.57 Yuan, 17,944.97 Yuan, 10.89 Yuan, 512,041.7 Yuan, and 11,299.85 Yuan, respectively. For the study period of two years, the direct economic burden, daily medication expense, and indirect economic burden were 48.6%, 31.5%, and 19.85% of the total economic burden, respectively. Disease burden and the number of episodes of remission were not statistically significant (p>0.001). The direct economic burden and total economic burden of the disease-modifying therapy (DMT) group were higher than those of the non-DMT group, but DALYs had no statistical significance (p>0.001). CUA showed that inpatients with MS in the DMT group received a DALY every time compared with the non-DMT group. CONCLUSION: The DALY losses are concentrated in young and middle-aged Chinese people. In this two-year study, CUA prompted the application of DMT drugs to increase the economic burden and DALYs. However, follow-up time is still short, and further follow-up observation is required.

Preoperative nutritional evaluation of prostate cancer patients undergoing laparoscopic radical prostatectomy.

BACKGROUND AND OBJECTIVE: Prostate cancer (PCa) is one of the most common malignant tumors in men. Geriatric Nutritional Risk Index (GNRI) is an objective index for evaluating nutritional status of elderly people over 65 years old. The aim of the current study was to explore the correlation and predictive value between GNRI and postoperative recovery and complications in PCa patients undergoing laparoscopic radical prostatectomy (LRP). METHODS: Taking 98 as the GNRI boundary value, 96 PCa patients (aged≥65 y) undergoing LRP in the Department of Urology, Affiliated Hospital of North Sichuan Medical College from January 2018 to December 2020 were grouped into malnutrition group (MNg, 34 patients, 35.4%) and normal nutrition group (NNg, 62 patients, 64.6%). Basic information, laboratory examination indexes, operation conditions, postoperative complications and postoperative recovery indexes of patients were recorded and retrospectively analyzed. Clavien-Dindo Classification System (CDCS) was used to assess postoperative complications. T-test was used to analyze differences between the two groups. ROC curve was generated to determine the predictive value of GNRI for postoperative complications. RESULTS: Percentage of complications was significantly higher in MNg group compared with that in NNg group (P < 0.01). The average grade based on CDCS was significantly lower in NNg group compared with that in MNg group (P < 0.01). Body weight, Body Mass Index (BMI), preoperative hemoglobin value (HGB), serum albumin (ALB) values of MNg and NNg were significantly positively correlated with GNRI (P<0.01). Incidence and severity of postoperative complications of MNg patients were significantly higher compared with those of NNg patients (P<0.05). Average hospitalization cost of MNg patients was higher in MNg patients compared with that of NNg patients (P<0.05). Duration of post-anesthesia care unit (PACU), duration of antibiotic use and duration of indwelling drainage tube were longer in MNg patients compared with those in NNg patients (P<0.05). Furthermore, volume of indwelling drainage tube was higher in MNg patients compared with that in NNg patients (P<0.05). CONCLUSION: GNRI is an effective and reliable tool for evaluation of preoperative nutritional status of prostate cancer patients. The findings showed that GNRI is correlated with postoperative recovery and complications, and is an effective predictive marker.

Characterization and exposure assessment of household fine particulate matter pollution in China.

Household fine particulate matter (PM2.5 ) pollution greatly impacts residents' health. To explore the current national situation of household PM2.5 pollution in China, a study was conducted based on literature published from 1998 to 2018. After extracting data from the literature in conformity with the requirements, the nationwide household-weighted mean concentration of household PM2.5 (HPL) was calculated. Subgroup analyses of spatial, geographic, and temporal differences were also done. The estimated overall HPL in China was 132.2 ± 117.7 µg/m3 . HPL in the rural area (164.3 ± 104.5 µg/m3 ) was higher than that in the urban area (123.9 ± 122.3 µg/m3 ). For HPLs of indoor sampling sites, the kitchen was the highest, followed by the bedroom and living room. There were significant differences of geographic distributions. The HPLs in the South were higher than the North in four seasons. The inhaled dose of household PM2.5 among school-age children differed from provinces with the highest dose up to 5.9 µg/(kg·d). Countermeasures should be carried out to reduce indoor pollution and safeguard health urgently.

Cross-cultural adaptation and validation of the First-Time Fathers Questionnaire in China.

OBJECTIVE: The study aimed to cross-culturally adapt and validate the First-Time Fathers Questionnaire (FTFQ) in the cultural context of China. DESIGN: Prospective validation study. SETTING: The study was conducted in four public hospitals in Hangzhou, a southeast coastal city of China. PARTICIPANTS: Four hundred and nineteen first-time fathers (mean age=30.45 years, SD=3.44, range 22-46) whose partners had given birth between July 20 and October 10, 2019. METHODS: The instrument "First Time Fathers Questionnaire (FTFQ)" was translated and culturally adapted to the Chinese context according to the methodological criteria of the International Society for Pharmacoeconomic and Outcomes Research. The construct-related validity of the instrument was tested through EFA and CFA. Content validity was evaluated with an analysis of the expert judgment. Reliability was assessed based on the internal consistency. RESULTS: Four domains were identified: "Worry", "Information", "Emotional Support", and "Acceptance", with 19 items and adequate internal reliability (0.86, 0.80, 0.86, and 0.72, respectively) and a total variance of 64.65%. The CFA model showed there is a good fit for the data: X2/df =1.20; RMSA = 0.03; CFI = 0.99; and NFI = 0.93. Additionally, each item achieved an I-CVI ≧0.83, and the S-CVI/Ave = 0.90. KEY CONCLUSIONS: The Chinese version of the FTFQ is a valid and reliable instrument to assess first-time fathers' experience of childbirth in China. IMPLICATIONS FOR PRACTICE: This study provides a validated questionnaire that is suitable for the Chinese cultural context. It contributes to the knowledge of first-time fathers' experience of childbirth and facilitate further actions to improve paternal satisfaction and behavior as labour companion.

Long-Term Clinical Outcomes and Pain Assessment after Posterior Lumbar Interbody Fusion for Recurrent Lumbar Disc Herniation.

OBJECTIVES: The aim of this study was to investigate the long term effects of posterior lumbar interbody fusion (PLIF), applied after recurrent lumbar disc herniation (rLDH), on pain relief and clinical outcome improvement. METHODS: The current study is a retrospective study. We observed 22 cases from 85 patients that had undergone PLIF during February 2003 to October 2012 and all patients were followed for at least 5 years. The average age of those patients were 53 years, among them there were eight men and 14 women. Plain radiography and dynamic plain films were obtained, pre-operation, for every patient. Magnetic resonance imaging (MRI) or computed tomography (CT) was conducted to confirm the diagnosis of rLDH before the operation. All surgeries were performed from posterior approach by the same surgeon using PLIF. Quality of life (QOL) and clinical outcomes were assessed by Numerical Rating Scale (NRS), Japanese Orthopaedic Association (JOA) scoring system, and Oswestry Disability Index (ODI) before revision surgery and at 1 week, 3 months, 12 months, and 24 months postoperative. These were also examined every time they came back to the hospital for a review. RESULTS: All patients were discharged and no serious comorbidities occurred. Three cases with wound infections and one case with dural laceration were cured and discharged. The end point of follow-up was August 2018 and the mean follow-up after revision surgery was 85 months. There were significant differences in NRS. It decreased from 7.32 ± 1.17 to 2.77 ± 1.31 (P < 0.05). The mean postoperative NRS score was 2.27 ± 1.48 (P < 0.05), 1.90 ± 1.51 (P < 0.05), and 2.36 ± 1.36 (P < 0.05) at 3, 12, and 24 months after surgery. There were no statistically significant differences (P > 0.05) in ODI scores. The average JOA score improved from 5.00 ± 1.08 to 8.18 ± 1.59 (P < 0.05) 1 week after revision surgery. RR was between 50% and 70%. Overall satisfaction rates were beyond 80%. Only one patient required subsequent lumber surgery during the follow-up period. CONCLUSION: If surgical indications are mastered, undergoing PLIF after rLDH may induce efficient pain relief and major improvements in clinical outcome scores, as well as quality of life scores.

Distribution characteristics and noncarcinogenic risk assessment of culturable airborne bacteria and fungi during winter in Xinxiang, China.

Bioaerosols are an important component of particulate matter in the atmosphere and are harmful to human health. In this study, the concentration, size distribution, and factors influencing culturable airborne bacteria and fungi in the atmosphere were investigated using a six-stage impactor device in the city of Xinxiang, China, during the winter season. The results revealed that the concentration of culturable airborne bacteria and fungi varied significantly during the sampling period: 4595 ± 3410 and 6358 ± 5032 CFU/m3, respectively. The particle sizes of the bioaerosols were mainly within stage V (1.1-2.1 µm), and fine particulate matter accounted for 45.9% ± 18.9% of airborne bacteria and 52.0% ± 18.5% of airborne fungi, respectively. With the deterioration of air quality, the concentration of airborne fungi gradually increased, and that of airborne bacteria increased when the air quality index was lower than 200 and decreased when it was higher than 200. With respect to the diurnal variation pattern of bioaerosol concentration, the highest and lowest concentrations were registered at night and noon, respectively, probably because of changes in ultraviolet radiation intensity. Bioaerosol concentration positively correlated with humidity, concentration of PM2.5, PM10, SO2, and NO2 and negatively correlated with O3 concentration. The risk of exposure of humans to the airborne bacteria was primarily associated with the respiratory inhalation pathway, and the risk of skin exposure was negligible. These results should improve our understanding of the threat of bioaerosols to public health.

Homogeneity assessment for pivotal medical device clinical studies.

A question that routinely arises in medical device clinical studies is the homogeneity across demographic subgroups, geographical regions, or investigational sites of the enrolled patients in terms of treatment effects or outcome variables. The main objective of this paper is to discuss statistical concepts and methods for the assessment of such homogeneity and to provide the practitioner a statistical framework and points to consider in conducting homogeneity assessment. Demographic subgroups, geographical regions, and investigational sites are discussed separately as each has its unique issues. Specific considerations are also given to randomized controlled trials, non-randomized comparative studies, and single-arm studies. We point out that judicious use of statistical methods, in conjunction with sound clinical judgment, is essential in handling the issue of homogeneity of treatment effect in medical device clinical studies.

Three-dimensional nitrogen-doped mesoporous carbon nanomaterials derived from plant biomass: Cost-effective construction of label-free electrochemical aptasensor for sensitively detecting alpha-fetoprotein.

We synthesized three kinds of nitrogen-doped nanoporous carbon nanomaterials (represented by N-mC) through a cost-effective method, that is, pyrolysis of plant biomasses (grass, flower, and peanut shells). We further explored their potential as sensitive bioplatforms for electrochemical label-free aptasensors to facilitate the early detection of alpha-fetoprotein (AFP). Chemical structure characterizations revealed that rich functional groups coexisted in as-synthesized N-mC nanomaterials, such as C-C, C-O, C=O, C-N, and COOH. Among the three kinds of N-mC nanomaterials, the one derived from grass (N-mCg) exhibited the lowest carbon defect degree, the highest ID/IG ratio in the Raman spectra, and the largest specific surface area (186.2 m2 g-1). Consequently, N-mCg displayed excellent electrochemical activity and strong affinity toward aptamer strands, further endowing the corresponding aptasensor with sensitive detection ability for AFP. Electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) were used to investigate the whole detection procedure for AFP. The EIS and DPV results showed that the fabricated N-mCg-based aptasensor possessed an extremely low limit of detection of 60.8 and 61.8 fg·mL-1 (s/n = 3), respectively, for detecting AFP within a wide linear range from 0.1 pg mL-1 to 100 ng mL-1. Moreover, the aptasensor displayed acceptable selectivity and applicability, high reproducibility, and excellent stability in serum samples of cancer patients. Therefore, the proposed cost-effective and label-free strategy based on the nitrogen-doped nanoporous carbon derived from plant biomass is a promising approach for the early detection of various tumor markers.

Rapid analysis of the Tanreqing injection by near-infrared spectroscopy combined with least squares support vector machine and Gaussian process modeling techniques.

Near-infrared spectroscopy (NIRS) combined with chemometrics was used to analyze the main active ingredients including chlorogenic acid, caffeic acid, luteoloside, baicalin, ursodesoxycholic acid, and chenodeoxycholic acid in the Tanreqing injection. In this paper, first, two hundred samples collected in the product line were divided into the calibration set and prediction set, and the reference values were determined by the High Performance Liquid Chromatography- Diode Array Detector/Evaporative Light Scattering Detector (HPLC-DAD/ELSD) method. Partial least squares (PLS) analysis was implemented as a linear method for models calibrated with different preprocessing means. Wavelet transformation (WT) was introduced as a variable selection technique by means of multiscale decomposition, and wavelet coefficients were employed as the input for modeling. Furthermore, two nonlinear approaches, least squares support vector machine (LS-SVM) and Gaussian process (GP), were applied to exploit the complicated relationship between the spectra and active ingredients. The optimal models for each ingredient were obtained by LS-SVM and GP methods. The performance of the final models was evaluated by the root mean square error of calibration (RMSEC), root mean square error of cross-validation (RMSECV), root mean square error of prediction (RMSEP) and correlation coefficient (R). All of the models in the paper give a good calibration ability with an R value above 0.92, and the prediction ability is also satisfactory, with an R value higher than 0.85. The overall results demonstrate that nonlinear models are more stable and predictable than linear ones, and they will be more suitable for the CHM system when high accuracy analysis is required. It can be concluded that NIRS with the LS-SVM and GP modeling methods is promising for the implementation of process analytical technology (PAT) in the pharmaceutical industry of Chinese herbal injections (CHIs).

[Emission Inventory of Greenhouse Gas from Urban Wastewater Treatment Plants and Its Temporal and Spatial Distribution in China].

Urban wastewater treatment plants are considered important greenhouse gas resources with massive emissions of carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) during operation. Based on the emission factor approach of pollutant reduction, the 2014 emission inventory of greenhouse gases (CO2, CH4, and N2O) from urban wastewater treatment plants in China was established. In addition, the temporal and spatial distribution and influencing factors of greenhouse gas emissions were analyzed in this study. The results showed that total emissions of greenhouse gas from urban wastewater treatment plants in China was 7348.60 Gg (CO2-eq) in 2014, which included CO2, CH4, and N2O emissions of 6054.57 Gg, 27.47 Gg (769.08 Gg, CO2-eq), and 1.98 Gg (524.95 Gg, CO2-eq), respectively. The difference in greenhouse gas emissions among provinces was significant:high emissions appeared in the eastern areas of China, low emissions were observed in the northwest, and hardly any emissions were found in Xizang. From 2005 to 2014, annual greenhouse gas emissions from urban sewage treatment plants in China increased by 229.4%, and the rates of CO2, CH4, and N2O increased by 217.9%, 217.9%, and 520.3%, respectively. The regional economic development level and number of wastewater treatment plants were correlated the most with the emissions of greenhouse gasses, and the per-capita protein supply was closely related with the N2O emission.

Optimization of a Coupling Process for Insulin Degludec According to a Quality by Design (QbD) Paradigm.

This case study described a successful application of the quality by design (QbD) principles to a coupling process development of insulin degludec. Failure mode effects analysis (FMEA) risk analysis was first used to recognize critical process parameters (CPPs). Five CPPs, including coupling temperature (Temp), pH of desB30 solution (pH), reaction time (Time), desB30 concentration (Conc), and molar equivalent of ester per mole of desB30 insulin (MolE), were then investigated using a fractional factorial design. The curvature effect was found significant, indicating the requirement of second-order models. Afterwards, a central composite design was built with an augmented star and center points study. Regression models were developed for the CPPs to predict the purity and yield of predegludec using above experimental data. The R2 and adjusted R2 were higher than 96 and 93% for the two models respectively. The Q2 values were more than 80% indicating a good predictive ability of models. MolE was found to be the most significant factor affecting both yield and purity of predegludec. Temp, pH, and Conc were also significant for predegludec purity, while Time appeared to remarkably influence the yield model. The multi-dimensional design space and normal operating region (NOR) with a robust setpoint were determined using a probability-based Monte-Carlo simulation method. The verified experimental results showed that the design space was reliable and effective. This study enriches the understanding of acetylation process and is instructional to other complicated operations in biopharmaceutical engineering.

Assessment of Microvascular Invasion of Hepatocellular Carcinoma with Diffusion Kurtosis Imaging.

Purpose To evaluate the potential role of diffusion kurtosis imaging and conventional magnetic resonance (MR) imaging findings including standard monoexponential model of diffusion-weighted imaging and morphologic features for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC). Materials and Methods Institutional review board approval and written informed consent were obtained. Between September 2015 and November 2016, 84 patients (median age, 54 years; range, 29-79 years) with 92 histopathologically confirmed HCCs (40 MVI-positive lesions and 52 MVI-negative lesions) were analyzed. Preoperative MR imaging examinations including diffusion kurtosis imaging (b values: 0, 200, 500, 1000, 1500, and 2000 sec/mm2) were performed and kurtosis, diffusivity, and apparent diffusion coefficient maps were calculated. Morphologic features of conventional MR images were also evaluated. Univariate and multivariate logistic regression analyses were used to evaluate the relative value of these parameters as potential predictors of MVI. Results Features significantly related to MVI of HCC at univariate analysis were increased mean kurtosis value (P < .001), decreased mean diffusivity value (P = .033) and apparent diffusion coefficient value (P = .011), and presence of infiltrative border with irregular shape (P = .005) and irregular circumferential enhancement (P = .026). At multivariate analysis, mean kurtosis value (odds ratio, 6.25; P = .001), as well as irregular circumferential enhancement (odds ratio, 6.92; P = .046), were independent risk factors for MVI of HCC. The mean kurtosis value for MVI of HCC showed an area under the receiver operating characteristic curve of 0.784 (optimal cutoff value was 0.917). Conclusion Higher mean kurtosis values in combination with irregular circumferential enhancement are potential predictive biomarkers for MVI of HCC. © RSNA, 2017.

Effect of myelin water exchange on DTI-derived parameters in diffusion MRI: Elucidation of TE dependence.

PURPOSE: Water exchange exists between different neuronal compartments of brain tissue but is often ignored in most diffusion models. The goal of the current study was to demonstrate the dependence of diffusion measurements on echo time (TE) in the human brain and to investigate the underlying effects of myelin water exchange. METHODS: Five healthy subjects were examined with single-shot pulsed-gradient spin-echo echo-planar imaging with fixed duration (δ) and separation (Δ) of diffusion gradient pulses and a set of varying TEs. The effects of water exchange and intrinsic T2 difference in cellular environments were investigated with Monte Carlo simulations. RESULTS: Both in vivo measurements and simulations showed that fractional anisotropy (FA) and axial diffusivity (AD) had positive correlations with TE, while radial diffusivity (RD) showed a negative correlation, which is consistent with a previous study. The simulation results further indicated the sensitivity of TE dependence to the change of g-ratio. CONCLUSION: The exchange between myelin and intra/extra-axonal water pools often plays a non-negligible role in the observed TE dependence of diffusion parameters, which may accompany or alter the effect of intrinsic T2 in causing such dependence. The TE dependence may potentially serve as a biomarker for demyelination processes (e.g., in multiple sclerosis and Alzheimer's disease). Magn Reson Med 79:1650-1660, 2018. © 2017 International Society for Magnetic Resonance in Medicine.