Histologically assessed hepatocyte ballooning is a key feature discriminating non-alcoholic steatohepatitis (NASH) from steatosis (NAFL). Reliable identification underpins patient inclusion in ...clinical trials and serves as a key regulatory-approved surrogate endpoint for drug efficacy. High inter/intra-observer variation in ballooning measured using the NASH CRN semi-quantitative score has been reported yet no actionable solutions have been proposed.
A focused evaluation of hepatocyte ballooning recognition was conducted. Digitized slides were evaluated by 9 internationally recognized expert liver pathologists on 2 separate occasions: each pathologist independently marked every ballooned hepatocyte and later provided an overall non-NASH NAFL/NASH assessment. Interobserver variation was assessed and a ‘concordance atlas’ of ballooned hepatocytes generated to train second harmonic generation/two-photon excitation fluorescence imaging-based artificial intelligence (AI).
The Fleiss kappa statistic for overall interobserver agreement for presence/absence of ballooning was 0.197 (95% CI 0.094–0.300), rising to 0.362 (0.258–0.465) with a ≥5-cell threshold. However, the intraclass correlation coefficient for consistency was higher (0.718 0.511–0.900), indicating ‘moderate’ agreement on ballooning burden. 133 ballooned cells were identified using a ≥5/9 majority to train AI ballooning detection (AI-pathologist pairwise concordance 19–42%, comparable to inter-pathologist pairwise concordance of between 8–75%). AI quantified change in ballooned cell burden in response to therapy in a separate slide set.
The substantial divergence in hepatocyte ballooning identified amongst expert hepatopathologists suggests that ballooning is a spectrum, too subjective for its presence or complete absence to be unequivocally determined as a trial endpoint. A concordance atlas may be used to train AI assistive technologies to reproducibly quantify ballooned hepatocytes that standardize assessment of therapeutic efficacy. This atlas serves as a reference standard for ongoing work to refine how ballooning is classified by both pathologists and AI.
For the first time, we show that, even amongst expert hepatopathologists, there is poor agreement regarding the number of ballooned hepatocytes seen on the same digitized histology images. This has important implications as the presence of ballooning is needed to establish the diagnosis of non-alcoholic steatohepatitis (NASH), and its unequivocal absence is one of the key requirements to show ‘NASH resolution’ to support drug efficacy in clinical trials. Artificial intelligence-based approaches may provide a more reliable way to assess the range of injury recorded as “hepatocyte ballooning”.
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•Hepatocyte ballooning identification underpins regulatory-approved drug efficacy endpoints in clinical trials.•We report substantial variation in ballooned cell identification by expert hepatopathologists.•Our data suggest that ballooning is too subjective for its presence or complete absence to be used as a trial endpoint.•A ‘concordance atlas’ of cells identified as ballooned by multiple pathologists can be used to train AI-based image analysis.•AI-based approaches may provide a more reliable way to assess the range of injury recorded as hepatocyte ballooning.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We use the 2004-2016 China prefecture-level city data to construct a STIRPAT-based spatial econometric model as an empirical test for the driving factors of city carbon emissions. Results show that ...China's city carbon emissions exert significant spatial spillover effects and high-emission club agglomeration characteristics. The relationship between city carbon emissions and the city's own economic development has an "inverted U" shape, whereas city carbon emissions and the economic development of neighboring cities exhibit a "J"-shaped relationship. The improvement of energy efficiency is not only conducive to controlling the carbon emissions of the city itself but also beneficial to regulating carbon emissions in neighboring cities. The coal-based energy structure will significantly increase the carbon emissions of the city itself and those of the neighboring cities. Population density will increase the city's own carbon emissions but reduce carbon emissions in neighboring cities due to the siphon effect. Traffic facilitation and industry structure in a city will lead to an increase in carbon emissions in neighboring cities. Foreign direct investment will benefit the city's own carbon emission control.
The global obesity rate has risen at an alarming rate in recent decades, and “fatness” has become an increasingly serious public health problem. At the same time, the loss of working hours and ...increased medical costs caused by air pollution have a wide range of direct and indirect effects on the health of the population and the macroeconomy. Against this background, using data from the China Family Panel Survey (CFPS) and thermal inversion as instrumental variables, this study analyzes the effect of air pollution on the risk of obesity among residents. We employ a two-stage least squares method to identify the effects of air pollution on the risk of obesity. The findings indicate that for a 1 μg/m³ increase in the annual average PM2.5 concentration at the county level, the obesity level increases significantly by 0.0286. This result is credible after a series of robustness checks; male groups, less-educated groups, and rural residents are more sensitive to the negative effects of air pollution. Finally, policy suggestions are provided.
The failure of the global food system to produce food in a sustainable way needs to change urgently, and a solid push to harmonize low-carbon food production with stable supply security is the right ...direction in which modern agriculture must evolve, but it is more difficult for large food-producing countries, and finding the right practices or systems to help policymakers or producers address this dilemma is critical. This requires political will, increased financing and top-level design. Digital inclusive finance (DIFI) embodies the financial concept of a community of human destiny, and it is worth examining whether this more inclusive and comprehensive financial service can shoulder the “responsibility” of “ensuring food security and reducing carbon emissions” in agriculture. This paper takes China's grain production system as an example, measures the coordinated development level of food production ensuring supply and reducing carbon emissions, and then analyzes the overall and regional characteristics of it. It is found that the coordinated development trend of China's food production ensuring supply and reducing carbon emissions is relatively stable during 2011–2020, fluctuating slightly above and below 0.9, and the central region has the highest level of coordinated development. The empirical results show that DIFI has led to a 4.3 percentage point increase in the level of coordinated development of food production ensuring supply and reducing carbon emissions during the decade, showing a stronger spatial spillover effect on neighboring regions than the local effect. At the same time, in the research of regional division in China, the impact of DIFI on the level of coordinated development of food production ensuring supply and reducing carbon emissions varies across regions, with typical uneven characteristics, and the promotion effect is more significant in the central and northern regions of China. Overall, this paper provides a simple tool for policy makers or producers to understand the balance between guaranteed output and low-carbon development of agricultural production activities. This paper will provide a methodological basis for assessing and standardizing low-carbon agricultural practices, innovating financial development models and systems, and promoting sustainable agriculture.
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•Measuring coordinated development level of ensuring food supply and low-carbon.•Digital inclusive finance had increased the coordinated development level by 4.3%.•Digital inclusive finance also had a significant spatial spillover effect.•The role of digital inclusive finance showed a typical non-equilibrium feature.•The study's results could help to sustainable agriculture in agricultural country.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Enhancing forestry carbon sequestration capacity is an important way for China to achieve carbon neutrality. As such, carbon sink insurance and financial subsidies are important exploration contents ...for China to build a policy support system for forestry carbon sink. Based on the theoretical framework of the dynamic stochastic general equilibrium model, this study constructs a theoretical model of a forestry economic system under risk shock. Moreover, it discusses the influence of carbon sink insurance and financial subsidies on the ability of forestry to sequester carbon and increase carbon sink. Then, it explores ways to optimize the allocation of carbon sink insurance and fiscal subsidies policy tools. The results show that the operators participating in forestry carbon sink projects not only improve the forestry carbon sink ability but also enhance their own welfare level. In the case of no premium subsidy, carbon sink insurance cannot directly improve the forestry carbon sink ability but can improve the economic benefits and welfare level of operators and stabilize forest carbon sink supply. Furthermore, when the premium subsidy ratio is high enough, the method of “carbon sink insurance + premium subsidy” will improve the forestry carbon sink effect. Both direct financial subsidy and premium subsidy can improve the ability of forestry to sequester carbon and increase carbon sink and improve operators’ welfare level. However, the environmental efficiency of premium subsidy is greater than that of direct financial subsidy. Therefore, under the constraints of fiscal budget, the direct fiscal subsidy and the method of “carbon sink insurance + premium subsidy” should be used in coordination, and the carbon sink insurance premium subsidy should be given priority.
•Construct the theoretical model of forestry economic system under the influence of risk.•Effects of carbon sink insurance and fiscal subsidies on forestry carbon sequestration capacity and individual welfare.•How to coordinate insurance policy with fiscal policy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Introduction:
The current ordinal fibrosis staging system for nonalcoholic steatohepatitis (NASH) has a limited dynamic range. The goal of this study was to determine if second-harmonic generated ...(SHG) quantifiable collagen fibrillar properties (qFP) and their derived qFibrosis score capture changes in disease progression and regression in a murine model of NASH, in which disease progression can be induced by a high fat sugar water (HFSW) diet and regression by reversal to chow diet (CD).
Methods:
DIAMOND mice were fed a CD or HFSW diet for 40 to 52 weeks. Regression related changes were studied in mice with diet reversal for 4 weeks after 48 to 60 weeks of a HFSW diet.
Results:
As expected, mice on HFSW developed steatohepatitis with stage 2 to 3 fibrosis between weeks 40 and 44. Both the collagen proportionate area and the qFibrosis score based on 15 SHG-quantified collagen fibrillar properties in humans were significantly higher in mice on HFSW for 40 to 44 weeks compared to CD fed mice. These changes were greatest in the sinusoids (Zone 2) with further increase in septal and portal fibrosis related scores between weeks 44 and 48. Diet reversal led to decrease in qFibrosis, septal thickness, and cellularity with greatest changes in Zone 2. Specific qFPs associated with progression only, regression only, or both processes were identified and categorized based on direction of fibrosis change.
Conclusion:
Complementing recent human studies, these findings support the concept that changes of disease progression and regression can be assessed using SHG-based image quantification of fibrosis related parameters.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK, VSZLJ
Government-led national comprehensive demonstration cities for Energy Conservation and Emission Reduction Fiscal Policy (ECERFP) are pivotal for China in addressing environmental governance. Using a ...panel dataset covering 278 Chinese cities from 2003 to 2019, this study adopts the staggered difference-in-differences (DID) approach to investigate the synergistic impacts of ECERFP on pollution and carbon reduction. The findings indicate that ECERFP contributes to a 3% improvement in pollution reduction performance, a 1.5% enhancement in carbon reduction performance, and a 4% overall increase in combined pollution and carbon reduction efforts. Furthermore, the study examines the heterogeneous effects of ECERFP on environmental performance. ECERFP significantly influences the synergistic efforts in pollution and carbon reduction by fostering green innovation, enhancing energy allocation, and optimizing industrial structures. This study both theoretically and empirically outlines the specific pathways and mechanisms through which “incentive-based” green fiscal policy promotes synergistic pollution and carbon reduction, thus providing a pragmatic foundation for enhancing the role of fiscal policy in environmental governance.
•The collaborative effect of the energy conservation and emission reduction fiscal policy (ECERFP) in China is investigated.•The ECERFP is conducive to improving environmental efficiency.•The mechanism through which ECERFP affects synergy in mitigating pollution and carbon emissions.•The heterogeneous effects of ECERFP on synergy in mitigating pollution and carbon emissions are also investigated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Linkages between air pollution and individual subjective well-being (SWB) are theorized as a key component of the United Nations Sustainable Development Goals. Using the China Family Panel Studies ...(CFPS) covering 12,668 residents who were interviewed for five consecutive times during 2010–2018, we find significant negative effects of air pollution on individual SWB via the change of the respondent's physical health level, physical exercise behavior and obesity risk. Specifically, a one standard deviation increase in county's annual average PM2.5 concentrations, instrumented by thermal inversion, is associated with a 2.45 standard deviations decrease in individual SWB level. In particular, people who are male, young people, less educated group, urban resident and live in eastern or western China are more sensitive to air pollution. This paper provides new insights into the health costs of air pollution.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: Many clinical trials with potential drug treatment options for non-alcoholic fatty liver disease (NAFLD) are focused on patients with non-alcoholic steatohepatitis (NASH) stages 2 and 3 ...fibrosis. As the histological features differentiating stage 1 (F1) from stage 2 (F2) NASH fibrosis are subtle, some patients may be wrongly staged by the in-house pathologist and miss the opportunity for enrollment into clinical trials. We hypothesized that our refined artificial intelligence (AI)-based algorithm (qFibrosis) can identify these subtle differences and serve as an assistive tool for in-house pathologists. Methods: Liver tissue from 160 adult patients with biopsy-proven NASH from Singapore General Hospital (SGH) and Peking University People’s Hospital (PKUH) were used. A consensus read by two expert hepatopathologists was organized. The refined qFibrosis algorithm incorporated the creation of a periportal region that allowed for the increased detection of periportal fibrosis. Consequently, an additional 28 periportal parameters were added, and 28 pre-existing perisinusoidal parameters had altered definitions. Results: Twenty-eight parameters (20 periportal and 8 perisinusoidal) were significantly different between the F1 and F2 cases that prompted a change of stage after a careful consensus read. The discriminatory ability of these parameters was further demonstrated in a comparison between the true F1 and true F2 cases as 26 out of the 28 parameters showed significant differences. These 26 parameters constitute a novel sub-algorithm that could accurately stratify F1 and F2 cases. Conclusion: The refined qFibrosis algorithm incorporated 26 novel parameters that showed a good discriminatory ability for NASH fibrosis stage 1 and 2 cases, representing an invaluable assistive tool for in-house pathologists when screening patients for NASH clinical trials.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In this study, we match the weather data at the prefecture-level city level in China with the data of listed firms in China, and examine the impact of high-temperature weather on the labour ...productivity and firm response strategies. We find that high-temperature weather is negatively correlated with labour productivity. The impact is more pronounced in Non-SOEs, heat-sensitive industries, and in the southern region. The additional analysis showed that firms can alleviate the negative impact of high-temperature weather by increasing employee compensation, and carrying out digital transformation. High-temperature weather prompts firms to reduce the number of blue-collar occupations and increase the number of white-collar occupations. This study highlights the urgency of the impact of current climate warming on emerging economies from the perspective of employees, enriches the cross-study of labour and climate economics, and provides suggestions for firms to alleviate the negative impact of high-temperature weather and improve production efficiency.
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
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