The tigecycline resistance gene tetX has an expensive fitness cost based on increased outer membrane permeability and metabolic burden in Escherichia coli.

Livestock-derived tetX-positive Escherichia coli with tigecycline resistance poses a serious risk to public health. Fitness costs, antibiotic residues, and other tetracycline resistance genes (TRGs) are fundamental in determining the spread of tetX in the environment, but there is a lack of relevant studies. The results of this study showed that both tetO and tetX resulted in reduction in growth and an increased in the metabolic burden of E. coli, but the presence of doxycycline reversed this phenomenon. Moreover, the protection of E. coli growth and metabolism by tetO was superior to that of tetX in the presence of doxycycline, resulting in a much lower competitiveness of tetX-carrying E. coli than tetO-carrying E. coli. The results of RNA-seq showed that the increase in outer membrane proteins (ompC, ompF and ompT) of tetX-carrying E. coli resulted in increased membrane permeability and biofilm formation, which is an important reason for fitness costs. Overall, the increased membrane permeability and metabolic burden of E. coli is the mechanistic basis for the high fitness cost of tetX, and the spread of tetO may limit the spread of tetX. This study provides new insights into the rational use of tetracycline antibiotics to control the spread of tetX.

HAMIL: High-Resolution Activation Maps and Interleaved Learning for Weakly Supervised Segmentation of Histopathological Images.

Semantic segmentation of histopathological images is important for automatic cancer diagnosis, and it is challenged by time-consuming and labor-intensive annotation process that obtains pixel-level labels for training. To reduce annotation costs, Weakly Supervised Semantic Segmentation (WSSS) aims to segment objects by only using image or patch-level classification labels. Current WSSS methods are mostly based on Class Activation Map (CAM) that usually locates the most discriminative object part with limited segmentation accuracy. In this work, we propose a novel two-stage weakly supervised segmentation framework based on High-resolution Activation Maps and Interleaved Learning (HAMIL). First, we propose a simple yet effective Classification Network with High-resolution Activation Maps (HAM-Net) that exploits a lightweight classification head combined with Multiple Layer Fusion (MLF) of activation maps and Monte Carlo Augmentation (MCA) to obtain precise foreground regions. Second, we use dense pseudo labels generated by HAM-Net to train a better segmentation model, where three networks with the same structure are trained with interleaved learning: The agreement between two networks is used to highlight reliable pseudo labels for training the third network, and at the same time, the two networks serve as teachers for guiding the third network via knowledge distillation. Extensive experiments on two public histopathological image datasets of lung cancer demonstrated that our proposed HAMIL outperformed state-of-the-art weakly supervised and noisy label learning methods, respectively. The code is available at https://github.com/HiLab-git/HAMIL.

Mapping algorithms for predicting EuroQol-5D-3L utilities from the assessment test of chronic obstructive pulmonary disease.

To predict 3-Level version of European Quality of Life-5 Dimensions (EQ-5D-3L) questionnaire utility from the chronic obstructive pulmonary disease (COPD) assessment test (CAT), the study attempts to collect EQ-5D-3L and CAT data from COPD patients. Response mapping under a backward elimination procedure was used for EQ-5D score predictions from CAT. A multinomial logistic regression (MLR) model was used to identify the association between the score and the covariates. Afterwards, the predicted scores were transformed into the utility. The developed formula was compared with ordinary least squares (OLS) regression models and models using Mean Rank Method (MRM). The MLR models performed as well as other models according to mean absolute error (MAE) and root mean squared error (RMSE) evaluations. Besides, the overestimation for low utility patients (utility ≤ 0.6) and underestimation for near health (utility > 0.9) in the OLS method was improved through the means of the MLR model based on bubble chart analysis. In conclusion, response mapping with the MLR model led to performance comparable to the OLS and MRM models for predicting EQ-5D utility from CAT data. Additionally, the bubble charts analysis revealed that the model constructed in this study and MRM could be a better predictive model.

Mental health resources and its equity in Central South of China: A case study of Hunan Province.

OBJECTIVES: Mental health resources are an important basis for coping with mental health services. The equity is an important index of a reasonable allocation of health resources. This study aims to evaluate the mental health resources and its equity allocation in Hunan Province, which is one of the typical central south areas of China, so as to provide reference for the development of mental health in China and other areas. METHODS: Data related to mental health resources was obtained from the Project of Mental Health Resources in Hunan Province, which was conducted by the Department of Hunan Mental Health Center in 2019. The Gini coefficient, the Theil index and other indicators were employed to quantitatively evaluate the equity of mental health resources' allocation. RESULTS: By the end of 2018, there were a total of 141 mental health institutions in Hunan Province of China, the bed density was 5.31 beds per 10,000 people, the ratio of doctors to nurses was 2.20, the number of outpatients of mental health institutions was 1288,047 per year. The mental health resources' allocation in terms of demographic dimension were in a preferred status with the Gini values all less than 0.3, and the Gini values for mental health resources`allocation in terms of geographical dimension ranged from 0.24 to 0.35. The Theil index for mental health allocation in terms of demographic dimension was lower than 0.05, and the Theil index for mental health allocation in terms of geographical dimension ranged from 0.04 to 0.11. CONCLUSIONS: The shortage of mental health resources is still the priority issue to be increased and optimized by policy-makers in Hunan in the future, especially the human resources. Moreover, the utilization of mental health resources was low though its equity was fair. Policy-makers need to consider the high utilization and geographical accessibility of health resources among different regions to ensure people in different regions could get access to available health services.

A sustainable and economic strategy to reduce risk antibiotic resistance genes during poultry manure bioconversion by black soldier fly Hermetia illucens larvae: Larval density adjustment.

Black soldier fly (Hermetia illucens) larvae (BSFL) are common insects that are known for bioconversion of organic waste into a sustainable utilization resource. However, a strategy to increase antibiotic resistance gene (ARG) elimination in sustainable and economic ways through BSFL is lacking. In the present study, different larval densities were employed to assess the mcr-1 and tetX elimination abilities, and potential mechanisms were investigated. The application and economic value of each larval density were also analyzed. The results showed that the 100 larvae cultured in 100 g of manure group had the best density because the comprehensive disadvantage evaluation ratio was the lowest (14.97%, good bioconversion manure quality, low ARG deposition risk and reasonable larvae input cost). Further investigation showed that mcr-1 could be significantly decreased by BSFL bioconversion (4.42 ×107 copies/g reduced to 4.79 ×106-2.14 ×105 copies/g)(P＜0.05); however, mcr-1 was increasingly deposited in the larval gut with increasing larval density. The tetX abundance was stabilized by BSFL bioconversion, except that the abundance at the lowest larval density increased (1.22 ×1010 copies/g increase, 34-fold). Escherichia was the host of mcr-1 and tetX in all samples, especially in fresh manure; Alcaligenes was the host of tetX in bioconversion manure; and the abundance of Alcaligenes was highly correlated with the pH of bioconversion manure. The pH of bioconversion manure was extremely correlated with the density of larvae. Klebsiella and Providencia were both hosts of tetX in the BSF larval gut, and Providencia was also the host of mcr-1 in the BSF larval gut. The density of larvae influenced the bioconversion manure quality and caused the ARG host abundance to change to control the abundance of ARGs, suggesting that larval density adjustment was a useful strategy to manage the ARG risk during BSFL manure bioconversion.

Foreign Direct Investment, Regional Innovation, and Green Economic Efficiency: An Empirical Test Based on the Investigation of Intermediary Effect and Threshold Effect.

Based on the theoretical mechanism analysis of FDI, regional innovation, and green economic efficiency, this article uses China's provincial panel data to calculate the provincial green economic efficiency level based on the three-stage DEA method and uses the system GMM model, intermediary effect model, and threshold model to empirically test the specific effects and transmission paths of FDI on the efficiency of the green economy. Research shows that FDI is one of the important factors that promote the improvement of green economic efficiency. Subregional tests have found that FDI has a significant regional heterogeneity in promoting the efficiency of the green economy. The mediation effect test found that the mediation effect of regional innovation is significant, and FDI can significantly promote the growth of green economic efficiency through regional innovation. The threshold effect analysis found that there are significant and effective double thresholds for regional economic levels, and the impact of FDI on green economic efficiency is heterogeneous within different threshold intervals. The research conclusions provide new inspiration for China to allocate FDI more rationally and efficiently under the new development pattern.

Heavy metal(loid) and Pb isotope compositions of black shale weathering profiles on the northern Yangtze Platform: insights into geochemical behavior, contamination assessment, and source apportionment.

Heavy metal(loid) (Cd, Co, Cr, Ni, Cu, Zn, Pb, V, Tl, and As) and Pb isotope compositions of two black shale weathering profiles were determined to investigate the geochemical behaviors of these toxic elements during black shale weathering and the heavy metal(loid) contamination and source apportionment of Pb in black shale-associated soils. Black shale has higher heavy metal(loid) concentrations than the upper continental crust and the worldwide average shale. In contrast, the surface soils have much higher heavy metal(loid) concentrations than the profile soils. The heavy metal(loid) concentrations in black shale-associated soils are higher than the Chinese and worldwide soil background values, except for Co and Pb. Black shale-associated soils, especially the surface soils, have higher average concentrations of As, Cd, Cr, Ni, Cu, and Zn than Chinese, Dutch, and Canadian soil guidelines. The enrichment factor (EF) and geoaccumulation index (Igeo) values indicate various degrees of heavy metal(loid) contamination in these soils, particularly for the heavy metals Cd, Tl, and V and metalloid As. Co and Pb contamination in these soils is not a current concern. According to the mass transfer coefficient (τTa,j) values, Cd, Co, Ni, and Zn show overall losses, and other metals (Cr, Cu, Pb, and V) exhibit different behavior in the studied black shale weathering profiles. Based on a simple binary Pb isotopic mixing model, black shale is the dominant contributor to the Pb in black shale-associated soils (70.5-91.1% to profile soils and 81.2-88.8% to surface soils), and vehicle exhaust contributes less (8.9-29.5%) to the Pb in profile soils. Vehicle exhaust can exert an impact on the Pb isotopic evolution at depth intervals of 60-80 cm below the soil surface.

Prejudice, Does It Exist or Not? Consumer Price Discrimination in Minority Entrepreneurship.

Many prior studies on minority entrepreneurship have found that some consumers display a strong bias against products from minority ventures. Not surprisingly, discrimination against products sold by minority-owned businesses increases the failure rate for such ventures. This paper seeks to verify the extent of consumer discrimination for minority products, and investigates whether it varies among different products. Building on insights from the theory of consumer discrimination, we conducted a comparative behavior experiment on 155 subjects for the expected pricing of two new products (common products and products with ethnic characteristics). Consistent with prior literature, we found that potential consumers held a bias against common products from minority ventures and offered a lower price. However, the theory of consumer discrimination could not be applied to the products with ethnic characteristics. Instead, potential consumers viewed ethnic characteristics products from minority ventures as being high quality and offered higher prices. This finding complements the theory of consumer discrimination and provides useful knowledge for minority entrepreneurs: minority entrepreneurs can employ price discrimination to strengthen the ethnic brand's impression by integrating ethnic cultural features into new products.

Causal assessment of sleep on coronary heart disease.

OBJECTIVE: Sleep is an essential physiological process that protects our physical and mental health. However, the causality of the association between sleep and coronary heart disease (CHD) is unknown. Mendelian randomization (MR), using genetic variants as instrumental variables to test for causality, can infer credible causal associations. We applied a two-sample MR framework to determine the causal association between sleep (sleeplessness, sleep duration, and daytime dozing) and CHD by integrating summary-level genome-wide association study (GWAS) data. METHODS: Data included in this study were the GWAS summary statistics datasets from the C4D Consortium for CHD; Neale Lab UKB-a:13 Consortium for sleeplessness; Neale Lab UKB-a:9 Consortium for sleep duration and Neale Lab UKB-a:15 Consortium for daytime dozing. The conventional MR approach (inverse variance weighted, IVW) method and Egger method were used. Heterogeneity was calculated using each of the different MR methods where possible. Horizontal pleiotropy was evaluated by p-value of the MR-Egger intercept. RESULTS: The IVW method estimate indicated that the odds ratio (OR) (95% confidence interval, CI) for CHD was 3.924 (1.345-11.447) per standard deviation increase in sleeplessness (p = 0.012). Results were consistent in MR-Egger method (OR, 4.654; 95% CI, 1.191-18.186; p = 0.009). The genetically predicted sleeplessness was positively casually associated with CHD. The causal association between sleep duration (or daytime dozing) and CHD was not established. CONCLUSION: Our analysis provided evidence supporting a causal relationship between sleeplessness (not sleep duration or daytime dozing) and CHD.

The PROFILE of assessment program for internal medicine internship of Sun Yat-Sen University.

Objective: To reflectively look at the present methods by which the clinical competence of 5th-year medical students (i.e. interns) in Sun Yat-Sen University (SYSU) are assessed upon finishing internship rotation in internal medicine (IM). Methods: Current procedures for the competence assessment of end-of-rotation IM interns in the First Affiliated Hospital of SYSU were reviewed, along with a point-by-point appraisal based on the PROFILE approach to structured assessment, and, whenever possible, suggestions for future improvement. Results and discussions: On a scale of 1-10, with 10 being the best or the most ideal, our marks for current methods to assess end-of-rotation IM interns in terms of being Programmatic, Real-World, Outcome-based, Formative, Impactful, Learner-engaged, and Evaluation-guaranteed were 7, 9, 3, 4, 6, 8, and 1, respectively. The strengths, weaknesses as well as potential solutions in each of the seven aspects are also discussed separately. Conclusions: Current assessment program for IM internship is strong in being programmatic, real-world, educationally impactful and learner engaged, and has room for further improvement in its time-based arrangements, relative shortage of feedback provision, as well as a systematic lack of quality control measures.

Digital surgical templates for managing high-energy zygomaticomaxillary complex injuries associated with orbital volume change: a quantitative assessment.

PURPOSE: This study sought to introduce 3-dimensional (3D) virtual surgical planning and digital rapid-prototyping templates for zygomaticomaxillary complex (ZMC) injuries associated with orbital volume change and to evaluate the surgical outcomes quantitatively. PATIENTS AND METHODS: Eight patients who underwent open reduction and fixation for a ZMC injury with orbital volume change were studied. Computed tomographic (CT) scan of the zygomaticomaxillary area was performed before the operation in each case. Scanned data were converted into 3D models using Mimics software (Materialise, Brussels, Belgium) for surgical designs. Virtual surgical reductions and correlated guiding templates were designed using Mimics and Magics software (Materialise). The operations were performed with the help of prefabricated templates to reduce the fractures. A postoperative CT scan of each patient was obtained within 2 weeks after surgery, and quantitative measurements were made to assess the surgical outcomes. Preoperative volumes of the bilateral orbits were compared, and concordance with postoperative volumes of the bilateral orbits was assessed. Twenty-one pairs of distances from 7 marker points to 3 reference planes were measured to assess postoperative facial symmetry. RESULTS: Volumes of the injured orbits were significantly different from volumes of the uninjured orbits preoperatively (P < .05), whereas bilateral orbital volumes showed no statistically significant difference postoperatively (P > .05). In addition, 19 of the 21 pairs of bilateral distances showed no significant difference postoperatively (P > .05). CONCLUSIONS: Quantitative assessment showed that digitally designed, rapid-prototyping templates for ZMC fractures have a positive impact on restoring facial symmetry and concordance of bilateral orbital volumes.