Circular economy (CE) has attracted so much attention around the world as it can contribute to the balance between economic development and environmental sustainability, to address the increasing critical resources scarcity and environmental issues. Small and medium-sized enterprises (SMEs) in China are a major driving force in the economy with 43 million SMEs in 2020. Most of them maintain the traditional economic development method of “take–use”, without considering the environment. This has caused great harm to the environment and resource availability. Therefore, Chinese SMEs must adopt CE in their business to address this issue. The current study aims to explore the key barriers  and enablers  for Chinese SMEs CE adoption. The current study employs a systematic review approach with thematic analysis to identify the internal and external barriers and enablers of CE adoption among SMEs. Moreover, a CE ecosystem has been proposed for identifying the key actors in the CE system, which will be beneficial for policy-makers to take into account when drafting and adjusting CE laws and regulations.  In recent years, the circular economy (CE) has gained much attention globally since it has been regarded as a promising approach to tackle the problems between resource usage and environmental impacts . There hThe current study aims to systematically review the important enablers and barriers, using a proposed CE ecosystem concept as a framework for the review. The current study aims to answer the question, “What are the important enablers and barriers for Chinese SMEs to adopt CE principal in their business”? The current study seeks to make two theoretical contributions to the literature. First, this study views the CE practice of Chinese SMEs by adopting a systematic literature review method. Since most research focuses on CE promotion and implementation at a national level and large-scale enterprises’ involvement in China, little attention is paid to the role of Chinese SMEs in the CE, and factors that influence its development. Therefore, this research fills the academic gap in this field. Second, the proposed CE ecosystem framework is integrated by CE system and ecosystem, which will be beneficial for discovering different actors in the closed-loop ecological, economic system, to better cooperate with the completion of circular sustainable development.The current study also has a significant practical contribution. First, it allows policymakers to see the influencing factors for Chinese SMEs to adopt CE and design a comprehensive and effective CE development plan for its future implementation. Second, the CE ecosystem framework enables other key actors to find their own positions and understand their relationship with other actors to collaborate.This paper is structured as follows: China’s rapid economic development over the last thirty years has led to the rapid destruction of the environment, which is detrimental to people’s health and to social development ,10. Consconceptual introduction stage. Chinese scholars firstly introduced the concept named as recycling economy or circular economy (CE) in 1998. The State Environmental Protection Administration of China (SEPA) found the principles of recycling economy conducive to environmental protection, so it promoted this concept nationwide by supporting CE research, carrying out pilot projects of municipal and provincial cleaner production and proposing to the State Council to develop CE. In 2002, the importance of CE implementation in China was mentioned in the Second Global Environment Facility. The first period, from 1998 up to 2002, is generally regarded as the national government decision-making stage. Since 2003, the Central Government proposed the scientific development concepts where the CE was believed as critical to long-term economic strategies. In 2004, the National Development and Reform Commission (NDRC) was appointed to be fully in charge of CE implementation and promotion, which enabled CE to become China’s basic national policy. In 2005, the State Council made a plan for CE and proposed to integrate CE into the 11th Five-year Planning Outline for National Economic and Social Development. From 2003 to 2005 is the nationwide pilot demonstration and CE development stage. In October 2005, the first list of pilot entities was issued by the NDRC, which included 56 enterprises, 13 industrial parks, seven provinces, five cities, and one town. In December 2007, the second list was announced, and the total number of pilot entities increased to 178. Since 1 January 2009, the first CE law named as circular economy (CE) Promotion Law of the People’s Republic of China was enacted. It is indicated that the CE implementation was actively and comprehensively promoted top-down within China. In 2013, the Development Strategy and the Immediate Action Plan of circular economy (CE) was issued for making strategic planning and specific arrangements towards CE development, ultimately to comprehensively improve the level of ecological civilisation [Post 2005 can be seen as the lisation .China’s CE practices can be demonstrated from three levels, macro-level, meso-level, and micro-level . The macro-level mainly refers to city or regional scale, and focuses on the development of eco-cities, eco-municipalities, or eco-provinces via policies and regulations . applyinThe meso-level mainly centres on industrial clusters or eco-industrial parks where sustainable designs can improve resource efficiency and product up-gradation to achieve industrial symbiosis; meanwhile, the green supply chain inside ensures and improves the resource circulation within the region ,16. YongAt the micro-level, enterprises in production, such as factories, agricultural product producers and other manufactures, are stimulated to apply cleaner production and eco-design of manufacturing plants, waste management to their real-life work practices . Eco-desIn brief, at the micro-level, enterprises need to permeate environmental protection thinking into their products and management, such as environmental design, clean products and the like. At the meso-level, enterprises in the ecological park should exchange resources through cooperation and create environmental protection supply chains to achieve industrial symbiosis. At the macro-level, the formulation of national and regional policies and regulations can significantly promote the CE development at the meso and micro levels.According to the National Law of the People’s Republic of China on the Promotion of Small and Medium-sized Enterprises (2002), SMEs in China refers to enterprises under various ownerships established in China’s territory. Their scales in production and operation are small and medium-sized, which are in line with the industrial and the State requirements, and offer more job opportunities. The classification criteria of SMEs, formulated by the department under the State Council, are the number of employees, volume of sale, total assets, and business types. More specifically, these are enterprises with fewer than 2000 employees, an annual turnover less than 300 million RMB, or total assets equal or less than 400 million RMB .China’s SMEs play a vital role in contributing to the country’s social, economic, and industrial development. According to Zeng, et al. , more thIn order to improve and alleviate the heavy energy consumption and environmental pollution, the Chinese government has been taking action since 1996, and more than 150,000 polluting SMEs, were either closed, suspended, merged or transformed. However, these measures only work temporarily . AlthougCE proposes a closed-loop economy and aims to minimise waste and emissions, and maximise the usage of resources via its four different loops, such as product-life extension, redistribution/reuse, remanufacturing, and recycling ,23. To cThe CE Ecosystem can be regarded as the conceptual framework for exploring the influencing actors in the CE process. Unfortunately there is limited literature and research on CE Ecosystems. Mainly the actors in CE are identified as policy-makers, investors, academics and educators, designers, consumers and users, brands or companies, manufacturers, and material experts . The curAccording to Petticrew and Roberts , systemaAccording to Jones, Coviello and Tang , the plaThe in-depth literature search is conducted primarily in three databases: ScienceDirect, Business Source Complete, and ProQuest. For the sake of improving the searching efficiency and effectiveness, there are several exclusion standards to assess. For each database, the key phrases are applied within the title, abstract and keywords. The research publication time covers the last 10 years between 2010 and 2020, and the language is restricted to English only. The publication type is confined as peer-reviewed journal articles. As a result, 551 articles were at the time identified as potentially relevant to the topic. After applying all inclusion criteria above, the final review sample was reduced to 31 articles. These articles explicitly focus on the influencing factors for SMEs’ CE adaption, which enriches the actors of the CE ecosystem. As a result, the barriers and enablers for Chinese SMEs’ CE adoption will be identified for theoretical and practical usages. In order to illustrate the distinct features of current research on Chinese SMEs’ CE adoption circumstance, an inductive, interpretation-based approach of theme identification is conducted . The next stage is the thematic analysis of all the chosen articles. After re-reading all the selected articles, the initial codes for themes are targeted and concluded in Microsoft Excel which is a useful tool for theme identification. The initial codes for themes from each article are put together for comparison and further modifications. To sum up, the whole analysis process follows the rules of validating coding by returning to the full-text article and comparing it to other articles in the sample. After the first round coding, the first-order themes for each article which are related to the research questions are captured. Then, all the first-order themes are mapped, grouped and sorted. Based on it, the second-order themes are concluded for a higher-order level. The second-order themes are then grouped into thematic areas on an even higher level of abstraction in terms of meaning, purpose and coding of the articles. After it, the first-order and the second-order themes can be cross-checked. In the end, themes and associated articles are assigned to one of two main taxonomies focusing on the role of Chinese SMEs’ critical enablers and barriers in this process, respectively.n = 26) and (ii) Enablers for SMEs’ CE Adoption (n = 29). The selected articles comprise thematic areas that were developed from second-order themes and, as the smallest entity, first-order themes. The latter part demonstrates the key actors in the CE ecosystem. The thematic areas and themes are concluded in According to the results of the thematic analysis, the 31 reviewed articles can be classified into two main themes, (i) Barriers for SMEs’ CE Adoption  and capabilities . The next section discusses the emerging themes in details.The barriers for SMEs’ adoption of CE can be viewed as internal and external barriers . The intThe second-order themes, internal barriers, include two first-order themes: resources and capabilities, which deeply explores the internal influencing factors of SMEs. resources, most of SMEs lack capital and investment from investors, due to their small turnover, which leads SMEs to pay more attention to their own profitability and seek survival and future development [In terms of elopment ,33. Furtelopment ,34,35. Selopment . In addielopment . In termelopment ,38. capabilities, first, most SMEs lack knowledge and/or creativity in organisational culture due to China’s complex bureaucratic system. For this reason many business owners or managers have not realised the importance of, or comprehend the essence and vision of CE adoption [Regarding adoption . For exaadoption . Second,adoption , the lifPolitical Aspect, Economic Aspect, Social Aspect and Legal Aspect. This group primarily examines the external factors which constrain the SMEs’ CE adoption.The second-order theme external barriers emerged from the first-order themes are political aspect, lack of government support, exemplified by unclear and outdated guidelines on CE for SMEs, training courses for workers, less funding opportunities and effective taxation policies, has been noted as a large issue for SMEs’ CE adoption [First, from the adoption ,39. The adoption . In addiadoption . economic perspective, the operation of SMEs and their decisions to implement CE are associated with the national economic system and national funding mechanism [From the echanism . As the echanism . The curechanism . view of the society, the public or customer awareness in CE is not strong enough to stimulate SMEs to comply with public or market needs, which is the catalyst for conversion to the CE [legal perspective, as Garcés-Ayerbe, Rivera-Torres, Suárez-Perales and Leyva-de la Hiz [Thirdly, from the o the CE . Lastly,e la Hiz  state; Ce la Hiz . While these barriers have been identified, it is also recognized that these barriers can gradually be overcome given enough time. Essential to this process is the understanding of the key actors involved in the whole process of the CE ecosystem.The second group of papers are focussed on the Enablers for SMEs’ CE adoption. These enablers can be classified into Internal Enablers and External Enablers. As the barriers and enablers for SMEs’ CE adoption are interrelated factors, the chosen papers are mainly focused on these themes . Resources and Capabilities, and first-order themes; Network, Innovation, Reputation and Finance.The third-order Internal Enablers are composed of second-order themes; resource perspective, the network is considered as the facilitator for knowledge sharing and coordination with various stakeholders [Drawing from eholders ,43. Firseholders ,32,34. Weholders . Second,eholders ,34,45. Teholders . Specifieholders . Customeeholders . The netcapability aspect entails Innovation, Reputation and Finance. Firstly, innovation is the main driving force for SMEs to achieve organisational transformation and CE adoption. Innovation can be divided into three levels, business model innovation, organisational innovation and product innovation. Business model innovation is primarily supported by cooperation with large companies, which can compensate for each other’s deficiency to promote CE practices [Next, ractices . The orgractices . Regardiractices . innovation towards CE, the core is that SMEs should mainly focus on their upstream and downstream business to capture resources [In terms of esources . Meanwhiesources . Such opesources . It has esources ,36. Political Aspect, Social Aspect, Environmental Aspect, and Legal Aspect.The third-order theme External Enablers derived from the second-order themes political perspective, firstly, government incentive, including tax reduction, subsidies, compensation, venture capital, investment, other financial facilitation and chances to participate in government’s programmes, motivates SMEs to adopt and implement CE the most [In the the most ,48. It ethe most . social aspect, media exposure is the fastest and most efficient way for the public to acquire CE and push SMEs to conduct CE practices. By increasing media exposure, public awareness of CE and sustainable development can be quickly cultivated, which facilitates the development of CE practices at all levels of society. SMEs exposed for violating or failing CE laws and regulations by media will receive pressure from the public and even get a penalty from local government. Community and social requirements are the suggestions and complain to the SMEs, which may harm the neighbouring environment [From the ironment . environmental aspect, the CE adoption and practice can enable local environment recover bit by bit and benefit the community and society, which serves the driving force for enterprises to contribute themselves to the local community and improve their reputation [In terms of the putation . legal aspect, the enactment of CE laws and regulations strengthens the binding force to the SMEs, which drives them to make decisions and implement CE [Lastly, in the ement CE ,49. Compement CE . For exaement CE . China’sement CE .The current study is conducted via a systematic literature review to address the research questions, the key barriers and enablers of SMEs’ CE adoption in China. On the basis of the results, the key barriers and enablers for Chinese SMEs’ CE adoption are identified and concluded. Taking Chinese SMEs as individuals, its CE adoption practice can be explored into two sides, its internal and external influencing factors. The internal side of SMEs is focused on its resources and capabilities, while its external sides are on political, economic, social, environmental, and legal aspects.With respect to resources, the barriers for most SMEs to adopt CE are limited funds, lack of investment, inadequate time, lack of technology, technical resources, and technical specialists. Limited finance can only support SMEs’ daily business operation and may end up with a limited turnover, which leads to less attractive to investors. Moreover, the whole process of CE acquisition, adoption, and implementation need substantial time , which iIn order to solve these problems and get SMEs better involved in CE practices, the network is the critical facilitator. The network includes collaboration with large enterprises, industrial clusters, and stakeholder involvement. Strategic partnerships with large enterprises enable SMEs to use their own advantages to exchange resources with large companies or upstream and downstream companies, thereby making up for the lack of funds, technology, and resources. Industrial clusters can facilitate SMEs to grasp the latest trend in the industry, understand the policies, regulations, and technologies of CE, to optimise resources enjoy public facilities to reduce expenditures, and ultimately achieve industrial symbiosis. Stakeholder involvement can inspire each stakeholder, such as customer, supplier, manufacturer and the like, to understand CE and proactively participate in the CE practices, which is conducive to stimulating SMEs to conduct CE practices with initiatives. In terms of SMEs’ capabilities, lack of human creativity and short life expectancy is shown as the barriers. Lack of human creativity leads to organisational culture and leadership without considering the environment or CE as part of their strategy into their business. SMEs’ short survival time makes it harder to adopt and implement CE. Given the above, innovation, reputation, and finance are the major enabling factors to address them. First, innovation covers business model innovation, organisational innovation and product innovation. Business model innovation, such as cooperation with large companies, can enable SMEs to gain resource and technological advantages while improving their business chains and opening up new markets. Organisational innovation adjusts the organisational structure, such as adding CE specialist or department, changing the organisational operation mode to focus on stakeholders collaboration, and promoting CE culture. Product innovation is obtained by integrating eco-design into the existing products, which adds values for the products and shape the competitiveness of the company, to enhance the viability of SMEs. Second, adopting CE to their business can reflect the corporate social responsibility and set a good example of compliance with laws and regulations, contributing to keeping talents and improving prestige. Third, although the investment of CE adoption is vast at the beginning, from a long-term consideration, it can necessarily reduce costs and continuously achieve values.From the political perspective, lack of government support in clear guidance for SMEs, training, funding supports, and inefficient bureaucratic administration greatly affected the participation of SMEs . TherefoIn the view of the environment, the recovery of the local environment has been seen as the enabling factor for SMEs, which wants to build a positive social image and benefit its community. Lastly, from the legal side, the compulsion of CE laws and regulations is an essential stimulating factor for SMEs to introduce CE. However, in some regulations, the information is not clear, and the actual situation of SMEs is not considered, which also causes SMEs to avoid the implementation of CE to some extent.As described, after identifying the key barriers and enablers, the key actors in CE ecosystem can be enriched and concluded, namely, as business owners, managers, employees, technical specialist, media, regulator, institution agencies, and banks. These actors in the CE ecosystem framework will be conductive for probing the CE implementations.Although there are many pieces of research studying CE implementation and SMEs’ CE practices, most of them concentrate on the European countries’ SMEs, China’s national or industrial level CE practices. It is evident to find out from the current literature that there is a gap in exploring how SMEs introduce and implement CE in their business operation in China and what are the obstacles and driving forces for them. In order to handle these issues, the current study tries to set up a CE ecosystem framework where the key actors in CE system can be identified to promote the future CE adoption and implementation in China, which contributes to the literature in this field. There are several practical implications. From the government and policy maker’s view, the barriers and enablers identified and actors involved for SMEs can be considered when making and adjusting policies, as SMEs are the primary driving force of GDP. The regulations and laws should consider SMEs practical situations and their downsides compared with large enterprises. From the academic perspective, the CE ecosystem can not only be used in SMEs’ CE adoption but also can be the guidance for other directions in the CE system.Although this research has both theoretical and practical values, there are still several limitations that should be considered. First, this research is only based on peer-reviewed journal articles. Second, the research topic is focused on Chinese’ SMEs CE adoption, which is quite broad. Different industries, locations, firm sizes, and so forth, will have different barriers and enablers. Moreover, the level of CE adoption is not specified. Thirdly, there are only three searching engines  used in the research, which may exclude some other valuable journals from the other searching engine. Fourthly, this research is a systematic review based on other researchers’ views rather than the actual visits and interviews, which may have different understandings and interpretations.The future research in this topic can be further examined within specific industries within a country. Cross country comparison of SMEs can also advance our knowledge of CE ecosystem, which can be impacted by local regulation or global phenomena such as climate change. The research method will combine systematic review and interviews, which can be tested through a theoretical and practical scenario.


The effects of chiral stationary phase, mobile phase component, mobile phase ratio, and temperature on etoxazole separation were also studied. Etoxazole enantiomers were baseline separated on Lux Cellulose-1, Chiralpak IC, and Chiralpak AD chiral columns, and partially separated on Lux Cellulose-3 chiral column under normal-phase HPLC. However, the complete separation on Lux Cellulose-1, Chiralpak IC, and partial separation on Chiralpak AD were obtained under reverse-phase HPLC. Normal-phase HPLC presented better resolution for etoxazole enantiomers than reverse-phase HPLC. Thermodynamic parameters, including ΔH and ΔS, were also calculated based on column temperature changes from 10 °C to 40 °C, and the maximum resolutions (Rs) were not always acquired at the lowest temperature. Furthermore, the optimized method was successfully applied to determine etoxazole enantiomers in cucumber, cabbage, tomato, and soil. The results of chiral separation efficiency of etoxazole enantiomers under normal-phase and reverse-phase HPLC were compared, and contribute to the comprehensive environmental risk assessment of etoxazole at the enantiomer level.The chiral separation of etoxazole enantiomers on Lux Cellulose-1, Lux Cellulose-3, Chiralpak IC, and Chiralpak AD chiral columns was carefully investigated by normal-phase high performance liquid chromatography and reverse-phase high performance liquid chromatography (HPLC). Hexane/isopropanol, hexane/ Chiral pesticides have become a hotspot in the field of pesticide research. About 30% of commercial pesticides are chiral ,2. HowevRS)-5-tert-butyl-2-phenetole, CAS 153233-91-1  [Etoxazole [(233-91-1 ] is a di of 1:1) ,14,15,16Enantiomer separation of chiral pesticides is the first step in enantiomer risk assessment. Many methods have been reported for chiral separation, including normal-phase high performance liquid chromatography (NP-HPLC) , reverseThe separation methods of etoxazole enantiomers include reverse-phase HPLC , normal-k1 and k2), selectivity factor (α), and resolution factor (Rs). Rs > 1.5 was considered as baseline separation. When hexane/isopropanol (HEX/IPA) was used as mobile phase under normal-phase HPLC, etoxazole enantiomers could be baseline separated on Lux Cellulose-1, Lux Cellulose-3, Chiralpak IC, and Chiralpak AD chiral columns. The maximum Rs on Lux Cellulose-1 (98/2), Lux Cellulose-3 (98/2), Chiralpak IC (90/10), and Chiralpak AD (90/10) were 4.50, 3.14, 13.21, and 15.45, respectively. Chiralpak AD had the best separation efficiency for etoxazole enantiomers under normal-phase HPLC with HEX/IPA as mobile phase. When hexane/n-butanol (HEX/BuOH) was used as mobile phase, etoxazole enantiomers got a baseline separation on Lux Cellulose-1, Chiralpak IC, and Chiralpak AD columns, and partial separation on the Lux Cellulose-3 column. The maximum Rs on Lux Cellulose-1 (98/2), Lux Cellulose-3 (98/2), Chiralpak IC (95/5), and Chiralpak AD (98/2) columns was 2.46, 1.18, 14.98, and 8.41, respectively. Moreover, the separation efficiency of Chiralpak IC and Chiralpak AD were much better than that of Lux Cellulose-1 and Lux Cellulose-3, which indicated the 3,5-dichlophenyl carbamate group in Chiralpak IC and Chiralpak AD chiral columns had better chiral recognition for etoxazole enantiomers under normal-phase HPLC conditions. In general, a lower proportion of alcohol led to a longer elution time and better resolution under normal-phase HPLC. In accordance with this phenomenon, the retention factor (k) and resolution factor (Rs) increased with decreasing ratio of alcohol in the mobile phase.The chiral separation of etoxazole enantiomers was performed on normal-phase HPLC and reverse-phase HPLC . Table 12O) was used as the mobile phase under reverse-phase conditions, etoxazole enantiomers could be baseline separated on Lux Cellulose-1, Chiralpak IC and partially separated on Chiralpak AD columns. Lux Cellulose-3 had no separation capability for etoxazole enantiomers. The maximum Rs on Lux Cellulose-1 (85/15), Chiralpak IC (80/20), and Chiralpak AD (85/15) were 2.68, 5.84, and 1.22, respectively. Chiralpak IC had the best separation efficiency for etoxazole enantiomers under reverse-phase conditions when using MEOH/H2O as the mobile phase. When acetonitrile/water (ACN/H2O) was used as the mobile phase, etoxazole enantiomers achieved baseline separation on Lux Cellulose-1, Lux Cellulose-3, Chiralpak IC, and partial separation on Chiralpak AD columns. The maximum Rs on Lux Cellulose-1 (90/10), Lux Cellulose-3 (60/40), Chiralpak IC (60/40), and Chiralpak AD (60/40) were 3.94, 6.30, 9.40, and 1.02, respectively. Different separation capabilities were observed even on the same chiral column, when MEOH/H2O and ACN/H2O were used as the mobile phase. Methanol is both a hydrogen bond donor and acceptor, whereas acetonitrile is only a weak hydrogen bond acceptor. Therefore, the different separation abilities of methanol and acetonitrile may be induced by different hydrogen bond interactions involved in the mobile phase, etoxazole enantiomers, and the chiral stationary phase. In general, a lower proportion of organic solvent led to a longer elution time and better resolution in reverse-phase HPLC. In accordance with this phenomenon, the retention factor (k) and resolution factor (Rs) of etoxazole enantiomers increased with decreasing ratio of methanol or acetonitrile in the mobile phase in most cases. However, the Rs on Lux Cellulose-1 increased with increasing content of acetonitrile in the mobile phase, and the maximum Rs was observed at an ACN/H2O ratio of 90/10. Comparing the chiral separation results obtained from normal-phase and reverse-phase HPLC, the normal-phase HPLC presented better separation efficiency for etoxazole enantiomers than reverse-phase HPLC.When methanol/water (MEOH/H2O = 95/5 and ACN/H2O =80/20), Lux Cellulose-3 (MEOH/H2O = 90/10 and ACN/H2O = 70/30), Chiralpak IC (MEOH/H2O = 90/10 and ACN/H2O = 80/20), and Chiralpak AD (MEOH/H2O = 90/10 and ACN/H2O = 60/40) columns, in terms of separation resolution and retention time. The results indicated that temperature had a significant effect on the interaction between etoxazole enantiomers and different chiral stationary phases under both reverse-phase and normal-phase HPLC. Generally, lower temperature often results in better resolution, longer retention time, and wider peaks. In accordance with this phenomenon, the k1, k2, and Rs of etoxazole enantiomers decreased with increasing temperature on four chiral columns regardless of whether reverse-phase or normal-phase HPLC was used for separation. For instance, the k1, k2, and Rs decreased from 0.53 to 0.41, 2.70 to 1.23, and 11.29 to 8.15 on Chiralpak IC with HEX/IPA ratio of 70/30 under normal-phase conditions. Likewise, the k1, k2, and Rs decreased from 0.59 to 0.42, 1.22 to 0.79, and 4.91 to 3.91 on Chiralpak IC with MEOH/H2O ratio of 90/10 in reverse-phase HPLC. However, temperature sometimes has little effect on chiral separation. For instance, the chiral separation of etoxazole enantiomers on Chiralpak AD with MEOH/H2O ratio of 90/10 showed that the maximum Rs = 1.14 was obtained at 40 °C.Column temperature is an important parameter for chiral separation and contributes to revealing the chiral recognition mechanism. In this study, the effects of temperature on etoxazole enantiomeric separation were carefully studied from 10 °C to 40 °C on Lux Cellulose-1, Lux Cellulose-3, Chiralpak IC, and Chiralpak AD columns under normal-phase and reverse-phase conditions, respectively . Table SH) and entropy (ΔS) based on the retention factor  and selectivity(α) obtained from Lux Cellulose-1, Lux Cellulose-3, Chiralpak IC, and Chiralpak AD columns under different temperatures  over 0.896. The ΔH values of etoxazole enantiomers on four chiral columns under normal-phase HPLC ranged from −1.91 KJ/mol to −24.53 KJ/mol when HEX/IPA and HEX/BuOH were used as the mobile phase. Likewise, the ΔH values of etoxazole enantiomers on the four chiral columns under reverse-phase HPLC ranged from −6.24 KJ/mol to −15.02 KJ/mol when MEOH/H2O and ACN/H2O were used as the mobile phase. The negative value of ΔH indicated the process of etoxazole enantiomer transfer from the mobile phase to different CSPs was mainly driven by enthalpy under normal-phase and reverse-phase HPLC. ΔΔH and ΔΔS values were ranged from −1.82 KJ/mol to −12.70 KJ/mol and from−1.15 J/mol to −31.25 J/mol on the four chiral columns under normal-phase and reverse-phase HPLC, respectively. The negative ΔΔH implied the lower temperature could lead to better resolution, which was clarified in temperature study. Moreover, the negative values of ΔΔH also implied that the ΔH of the second enantiomer was more negative than the first eluted enantiomer, which indicated the CSPs have stronger interaction with the second eluted enantiomer than the first one. Hydrogen bonding, π–π interaction, and dipole–dipole interaction were the main forces in chiral separation according to previous study , Lux Cellulose-3 , Chiralpak IC , and Chiralpak AD  columns, individually. Separations were conducted using an isocratic elution with solvent A , limit of quantitation (LOQ) and stability were used to assess the performance of the analytical method. The linearity of the method was studied by analyzing the blank standard and the matrix-matched standard at six  concentrations. Matrix effects were evaluated through comparing the slopes of the calibration curves obtained in matrix and in solvent. The linearity was the linear regression of etoxazole enantiomer area versus the injected concentration. The LOD was defined as the etoxazole enantiomer concentration that produced a signal-to-noise (S/N) ratio of 3, while the LOQ was the concentration that produced an S/N ratio of 10. The recoveries and relative standard deviation (RSD) were adopted to assess the accuracy and precision of the developed analytical method, respectively. The stability of etoxazole stock solution was checked monthly and it was found that etoxazole was stable for at least three months at −20 °C.Homogenized samples (5 g) of cucumber, cabbage, tomato, and soil were thawed in 50 mL polypropylene centrifuge tubes at room temperature. In total, 25 mL of ethyl acetate, 1 g of sodium chloride, and 3 g of anhydrous sodium sulfate were added to the tube. The mixture was shaken for 20 min at 25 °C with 280 rpm rotational speed in a constant temperature oscillator, exposed to ultrasonic vibration for 10 min, and then centrifuged at 3500 rpm for 5 min. The extract was filtered through 5 g of anhydrous sodium sulfate for dehydration. All the extraction steps were repeated with another 25 mL of ethyl acetate. The combined extracts were evaporated to near dryness using a rotary vacuum evaporator at 40 °C and reconstituted in 1.0 mL of acetonitrile. The resulting residue was filtered through a 0.22 µm filter and transferred into a 2 mL sample vial for reverse-phase chiral HPLC analysis. Five replicates were performed for each fortification level.k = (t − t0)/t0), separation factor (α = k2/k1), and resolution factor (Rs = (2(t2 − t1)/(w1 + w2))), where t0 is the void time, t is the retention time, k is the retention factor, and w is the peak width of etoxazole enantiomers.Separation parameters were calculated using the following equations: retention factor (k) and separation factor (α) obtained at different temperatures were used to calculate the standard enthalpy (ΔH) and entropy (ΔS) based on van’t Hoff equation.R is the universal gas constant (8.314 J/mol K), T is the absolute temperature, φ is the phase ratio, ΔH represents the molecular enthalpy, and ΔS is the molecular entropy of enantiomers between the mobile phase and the chiral stationary phase. ΔΔH represents the value of ΔH2 − ΔH1 and ΔΔS represents the value of ΔS2 − ΔS1. The values of −ΔH/R and (ΔS/R + lnφ) could be calculated from the slope and intercept based on Equation (1). Likewise, the values of −ΔΔH/R and ΔΔS/R could also be obtained from the slope and intercept according to Equation (2).In order to study the thermodynamic effects on etoxazole enantiomers separation, the retention factor (H and ΔS, were calculated based on temperature change from 10 °C to 40 °C. Moreover, the optimized method was successfully applied to determination of etoxazole enantiomers in cucumber, cabbage, tomato, and soil. Such results systematically compared the separation efficiency of etoxazole enantiomers under normal-phase and reverse-phase conditions, and contribute to the comprehensive environmental risk assessment of etoxazole at the enantiomer level.In the context of this study, the chiral separation of etoxazole enantiomers on Lux Cellulose-1, Lux Cellulose-3, Chiralpak IC, and Chiralpak AD chiral columns was fully investigated by normal-phase and reverse-phase HPLC. The effects of the chiral stationary phase, mobile phase component, mobile phase ratio, and temperature on separation resolution were carefully investigated. Etoxazole enantiomers were baseline separated on Lux Cellulose-1, Chiralpak IC, Chiralpak AD chiral columns, and partially separated on the Lux Cellulose-3 chiral column under normal-phase HPLC. Furthermore, complete separation on Lux Cellulose-1, Chiralpak IC columns, and partial separation on Chiralpak AD were obtained under reverse-phase HPLC. Normal-phase HPLC presented better separation resolution for etoxazole enantiomers than reverse-phase HPLC. Thermodynamic parameters, including Δ


The graft hepatic artery orifice is tiny in living donor liver transplantation, and therefore, it is more difficult to reconstruct the hepatic artery than in deceased donor liver transplantation. In situ, multi‐vessel hepatic artery reconstruction in living donor liver transplantation is time‐consuming, and reconstructions are often complicated if the hepatic graft has several stumps. We describe two living donor liver transplants using back‐table microsurgical angioplasty to combine two hepatic artery stumps to create a single orifice, and sequential single‐vessel hepatic artery reconstruction in the recipient. Briefly, we used double‐needle interrupted sutures for the two hepatic artery stumps with a biangular stay‐suture method in back‐table microsurgical angioplasty. Each suture was placed from the inner side of the arterial wall to the outer side, which allowed for safe and reliable suturing. After placing the interrupted sutures in the anterior wall, we turned over the vessels in the cold storage on the back table and placed interrupted sutures in the posterior wall. In the recipient, the single stump of the graft was anastomosed to the recipient's hepatic artery using an interrupted pattern and a surgical microscope. The postoperative courses of the donors and recipients were uneventful. Back‐table hepatic artery angioplasty is a feasible option to overcome the complexities of multi‐vessel arterial reconstruction in living donor liver transplantation. We recommend performing secure multi‐vessel hepatic arterial reconstruction adapted to the clinical scenario. Using simple appropriate anastomosis, back‐table microsurgical angiography may provide good results in living donor liver transplantation. Back‐table hepatic artery angioplasty is a feasible option to overcome the complexities of multi‐vessel arterial reconstruction in living donor liver transplantation. Although most left‐lobe grafts have a single artery, such as the left hepatic artery or replaced left hepatic artery, there are sometimes two or three arteries such as A2, A3, or A4. According to the Hiatt classification, in 1000 grafts,22.1A 1‐year‐old boy with end‐stage Alagille syndrome was admitted to our hospital for evaluation as a candidate for LDLT. On admission, the patient's pediatric end‐stage liver disease score was 18, and his mother, aged 43 years, was the only living donor candidate. The mother's height and body weight were 156 cm and 51 kg, respectively. Multidetector row computed tomography (CT)  was used for preoperative dynamic CT evaluation. We performed a simulation of the donor hepatectomy, which was performed using SYNAPSE VINCENT three‐dimensional CT software (Fujifilm). The predicted left lateral segment graft volume was 196 mL, which was sufficiently large for the pediatric recipient because the graft–recipient weight ratio was 2.37%. Three‐dimensional CT angiography revealed that A2 originated separately from the left gastric artery, A3 + A4 originated from the left hepatic artery, and the cystic artery originated from A4 Figure . In the We sacrificed A4 by dissecting the proximal conduit to the bifurcation of the cystic artery, and we ligated the distal stump of A4 because of the left lateral graft and the original artery of A3, A4, cystic artery stump was anastomosed with the A2 stump in an interrupted pattern under the surgical microscope during back‐table angioplasty, to avoid redundancy in the shape of A2 and A3 after angioplasty. We anastomosed the A3 + A4 conduit  to A2 to replace the hepatic artery because the caliber of the left gastric artery was not a size match to the A3 + A4 conduit, and the length of A2 was sufficient to anastomose to the A3 + A4. In the recipient, the single stump of the graft was anastomosed to the recipient's right hepatic artery, which was approximately 1 mm in diameter, using an interrupted pattern under the surgical microscope Figure . It took2.2A 31‐year‐old man with acute on chronic liver failure secondary to alcohol was emergently admitted to our hospital for evaluation as a candidate for LDLT. On admission, his model for end‐stage liver disease score was 22, and his mother, aged 52 years, was the living donor candidate. Her height and body weight were 156 cm and 51 kg, respectively, and the recipient's height and body weight were 157 cm and 52 kg, respectively. Multidetector row CT was used for preoperative dynamic CT. Figure 3This angioplasty procedure of the multiple graft hepatic arteries is performed under microsurgical scope. After the procurement of living donor graft, typically, donor organs are kept at a static temperature of 4°C in preservation solution. After portal vein perfusion, the microsurgeon reconstructed the hepatic artery with continuous zoom magnification of approximately × 10 using a surgical microscope (Carl Zeiss) in cold storage. The arterial anastomoses were performed using 9‐0 monofilament suture . We used a double‐needle suture and an interrupted pattern for the two hepatic artery stumps, with a biangular stay‐suture method. Each suture was placed from the inner side of the arterial wall to the outer side, which was safe and reliable. After placing the interrupted sutures in the anterior wall, we turned over the vessel in the cold storage on the back table, and placed interrupted sutures in the posterior wall. We placed a sprint tube  into the reconstructed hepatic artery from the stump to prevent back wall suturing in ex vivo angioplasty. The most important points in hepatic arterial reconstruction in LDLT using this angioplasty are correct anatomical reconstruction of all hepatic arteries in the partial graft and anastomosing the hepatic arteries between the donor and recipient, while taking care of size mismatch, kinking, and redundant anastomosis of the reconstructed artery.4In case 1, the patency of A2 and A3 was confirmed by CT on postoperative day 7 Figure , B. The In case 2, the patency in the anterior and posterior hepatic artery was confirmed using CT on postoperative day 7 Figure . The pos5Hepatic artery reconstruction is one of the most complex procedures in LDLT because of the smaller arterial diameter, shorter stump, and increased risk of hepatic artery‐related complications, which lead to pivotal complications.We currently perform hepatic artery reconstruction with interrupted sutures using a surgical microscope. Tanaka et al,Although the microsurgical approach appears time‐consuming and complicated, it is the best approach in pediatric patients and patients with a small‐caliber hepatic artery of <2 mm.Regarding left‐lobe grafts, we also recommend both middle and left hepatic arterial reconstruction to prevent biliary stricture. However, multi‐vessel hepatic arterial reconstruction requires more time to reconstruct multiple arteries and is often complicated because there is not always an adequately sized matching inflow artery in the recipient for multi‐vessel arterial grafting. For these reasons, we recommend back‐table microsurgical angioplasty to combine the two hepatic artery stumps into one orifice followed by sequential single hepatic artery reconstruction in the recipient. Lee et al also reported that back‐table angioplasty to combine the two hepatic artery stumps into one orifice was easy and safe in the right‐lobe graft during LDLT.In our institute, sequential hepatic artery reconstruction after hepatic vein and portal vein reconstruction or donor graft harvest is performed by the same surgeon performing the angioplasty of the hepatic artery of the graft, while carefully considering size mismatch, kinking, and redundant anastomosis. The authors of a previous study found that the ideal hepatic arterial reconstruction was a short and non‐redundant anastomosis fashioned between the recipient and donor hepatic arteries. The authors demonstrated that using a long graft artery was an independent risk factor for early hepatic artery thrombosis.We use an interrupted anastomosis pattern. As a consideration, multi‐vessel hepatic arterial reconstruction may rescue graft arterial flow when one artery becomes thrombosed. However, we have no experience with rescue cases with multi‐vessel hepatic arterial reconstruction, judging the patency of the reconstructed hepatic artery according to the postoperative CT imaging.The most important points in hepatic arterial reconstruction in LDLT are non‐redundant and non‐kinking anatomical reconstruction of all hepatic arteries in the partial graft, and anastomosing the hepatic arteries between the donor and recipient to prevent hepatic artery thrombosis.In conclusion, back‐table microsurgical angioplasty is feasible for complex multi‐vessel arterial reconstruction in LDLT. We recommend performing secure multi‐vessel hepatic arterial reconstruction by adapting to the clinical scenario. By selecting a simple appropriate anastomosis, back‐table microsurgical angiography may provide good results in LDLT.6www.edanzediting.com/ac) for editing a draft of this manuscript.We thank Jane Charbonneau, DVM, from Edanz Group (Conflict of Interest: Authors declare no conflict of interests for this article.


Objectives: This study aimed to evaluate early- and long-term outcomes in patients who undergo muscle flap coverage (MFC) for prosthetic graft infections (PGIs) at the groin or thigh.Materials and Methods: We retrospectively retrieved and analyzed data on infected wound cures, recurrence, graft and limb salvage, and survival of patients who underwent MFC for PGI at the groin or thigh between 2000 and 2018.Results: There were eight patients in our cohort: six had groin PGIs and two had thigh PGIs. Moreover, of these patients, seven were treated from sartorius muscles and one from a gracilis muscle. The indicated wounds healed in all eight patients, but two patients died during hospitalization. Three patients suffered recurrence within 8 months, one of which overcame the infection and achieved wound cure without graft removal, with negative pressure wound therapy. No patients lost their limbs during the follow-up term . Finally, four patients (50%) survived without removal of the infected graft for longer than 2 years.Conclusion: MFC can be a curative treatment for PGI, but there remains a possibility of a recurring infection thereafter. We have performed MFC for prosthetic graft infections (PGIs) at the groin or thigh in eight patients. The clinical features of these patients are summarized in this study, and their early- and long-term outcomes are discussed with respect to PGI treatment issues.Infection is one of the most serious complications of prosthetic grafts. It can have catastrophic results without adequate treatment. The groin is the most common site for postoperative graft infection in vascular surgery. Usually, optimal treatment involves removing the infected graft and extra-anatomical bypass to detour the infected region, with the use of appropriate antibiotics. Muscle flap coverage (MFC) is an alternative procedure to maintain blood flow without graft removal; its effectiveness has been demonstrated in some reviews.The Institutional Review Board of Kokura Memorial Hospital, Kitakyushu City, Japan, approved the study design .Between April 2000 and June 2018, eight patients (seven men and one woman) underwent MFC for PGI (six at the groin and two at the thigh) at Steel Memorial Yawata Hospital, Kokura Memorial Hospital, and Saiseikai Yahata General Hospital. We retrospectively reviewed their data, such as preoperative characteristics, surgical information, and outcomes.We obtained approval documents for this paper from the two living patients. Since the other six patients are known to have died, or have been missing for more than 5 years, their written approval was judged to be unnecessary by the Institutional Review Board of Saiseikai Yahata General Hospital, Kitakyushu City, Japan.Graft sites that produced purulent discharges were irrigated twice a day with warmed saline containing 4% povidone-iodine and were treated with appropriate intravenous antibiotics. These procedures were continued, together with debridement of any necrotic tissue, until the infection localized, as determined by clinical findings and CT scan. When the purulent discharge from the skin fistula continued for more than 1 week, FC could then be planned. However, graft salvage was not considered suitable for patients who suffered graft occlusion, infection spreading throughout the length of the graft, bleeding (which implies anastomotic line infection), or systemic sepsis.For the sartorius muscle flap  were intravenously administered for at least 1 week and, when necessary, continued until the laboratory data and physical findings indicated that the infection had resolved. Subsequently, oral antibiotics were prescribed for as long as the attending doctor considered necessary. The closed suction drain was removed when the discharge volume decreased to 30 mL per day.Patients were followed-up for 1–3 months to check their surgical wounds, including graft patency, using physical examinations, duplex ultrasound, and laboratory data. If infection recurred, the healthcare provider recommended that the patient be hospitalized.Graft salvage and death were set as primary endpoints, while cure of the indicated wound, infection recurrence, and additional treatment after infection recurrence were set as secondary ones. A final review was conducted in June 2020, and outcomes were evaluated up to 2 years following MFC.The eight patients’ clinicopathological details and re-, intra-, and postsurgical information are summarized in The group of patients with the better prognosis, who were alive with graft salvage at 2 years after MFC , and those with the worse prognosis, who died within 1 year , showed no marked differences in clinicopathological characteristics, surgical findings, or duration of antibiotic use. However, three of four patients in the worse prognosis group had serum albumin concentrations <3.0 g/dL, had chronic kidney disease (CKD) requiring hemodialysis, and were non-ambulatory, whereas all patients in the better prognosis group had albumin concentrations ≥3.0 g/dL, had no CKD, and were ambulatory. Several muscles can be used to reach these goals, with the sartorius muscle flap most frequently reported, with satisfactory outcomes. A theoretical advantage of using this muscle is that no second soft tissue defect is required to harvest the donor flap. Although Ali et al. found that this muscle was often ischemic or inflamed from invasive infection with an occluded superficial femoral artery (SFA), Töpel et al. found no significant difference in muscle viability, infection recurrence, loss of vascular reconstruction, or limb salvage between patent and occluded SFAs. In addition to the sartorius muscle, use of the rectus femoris muscle and the gracilis muscle has been widely reported. These muscles are located away from the active infection at the infected graft. In addition, ischemia is not a concern if the SFA is occluded because the vessel is nourished via a branch from the deep femoral artery. The rectus femoris muscle is bulky and long and has a wide arc of rotation; it is a very mobile flap for use as a graft overlap. Wübbeke et al. described in a systemic review that the superiority of sartorius and rectus femoris muscles with respect to amputation or mortality was not demonstrated; however, the vascular graft loss rate was lower after rectus femoris muscle flap reconstruction. Mirzabeigi et al. found no significant difference in rates for complications or graft salvage and concluded that the sartorius muscle was an effective first-line approach, as rectus femoris muscle flaps might increase functional morbidity and necessitate second donor sites. Morasch et al. also found that using the rectus femoris muscle caused more morbidity and functional deficits than using the gracilis muscle.The goals of MFC for PGI in the groin are adequate coverage of the underlying prosthetic graft material and elimination or control of infection in a single procedure without discontinuing blood flow to the lower extremity. However, early mortality rates ranged from 0% to 24%, which suggests that these procedures are too invasive for fragile patients with graft infections; the indications should be carefully determined. Since patients who suffer from graft infection are often nutritionally depleted, with significant comorbidities, graft infection is not their only issue, and the indications for this invasive treatment for graft infection should be determined carefully.MFCs from these muscles initially had a high success rate in the indicated wound healing and high limb salvage rates. Conversely, May et al. reported that six of seven patients with graft losses underwent NPWT before MFC and concluded that MFC performed soon after initial wound complication presentation improved vascular graft salvage. Svensson et al. reported 2 early bleeding and 3 late pseudoaneurysms in 33 patients with vascular groin infections who were treated by NPWT and concluded that vascular graft infections of the groin treated with NPWT were at greater risk of developing infection-related complications, which were associated with higher rates of amputation and death.NPWT is another method for graft salvage. Berger et al. and Dosluoglu et al., respectively, showed that among patients with Szilagyi III wounds, 14 of 17 patients (82%) and 10 of 12 patients (83%) achieved wound healing. was added whenever possible. This most desirable treatment was also performed if graft salvage by MFC or NPWT failed or if graft infection recurred.We did not always attempt graft salvage by MFC in patients with PGIs. If a patient was able to tolerate the invasive surgery, the infected graft was excised, and subsequent revascularization Therefore, these factors might be helpful in deciding on MFC.In this series, four patients were alive with graft salvage 2 years after MFC, and the other four died within 1 year. Obvious differences between the better and the worse prognosis group were serum albumin concentrations on the day before surgery, CKD, and the ability to walk unaided. These variables are reportedly independent predictors for ischemic wound healing or life-threatening outcomes in patients who undergo open bypass for critical limb ischemia.As observed in this series, recurrence of graft infection or graft occlusion will occur even if the MFC operative wound appears to achieve healing with a patent graft. Accordingly, we strongly emphasize the importance of lifelong surveillance.MFC is a useful procedure for PGI at the groin or thigh. However, recurrence might occur at any time, even when the indicated wound has healed.


Recently, intraoperative optical coherence tomography (iOCT) has evolved in the field of ophthalmic surgery. So far, the use of iOCT was mainly focused to lamellar keratoplasty, especially deep anterior lamellar keratoplasty (DALK) and Descemet membrane endothelial keratoplasty (DMEK). The aim of this study was to report our experiences with iOCT to introduce new possibilities of this application.We used iOCT in 18 patients who underwent the following surgeries: DALK, DMEK, penetrating keratoplasty, autologous limbal transplantation, transscleral suture fixation of a posterior chamber lens, pannus removal on corneal surface and newborn investigation in Peters’ anomaly. We obtained qualitative video data for all procedures.With the iOCT, the cannula placement during DALK preparation of the recipient cornea and bubble formation could be visualized to improve the success rate of the big bubble injection. In DMEK, the iOCT enables the visualization of Descemet’s membrane removal in the recipient and graft orientation as well as better control of graft attachment. The iOCT enables intraoperative visualization of the graft–host interface during penetrating keratoplasty. During autologous limbal transplantation, transscleral suture fixation of a posterior chamber lens and removal of corneal surface pannus the iOCT is capable of showing the thickness of lamellar preparations to avoid penetrations and to save healthy recipient’s tissue.The iOCT is a helpful device for intraoperative anterior segment imaging not only for DALK and DMEK. It is also beneficial in penetrating keratoplasty and every other form of lamellar preparation during corneoscleral surgery.The online version of this article (10.1007/s10792-020-01442-0) contains supplementary material, which is available to authorized users. Recently, intraoperative optical coherence tomography (iOCT) was established in the field of ophthalmic surgery. The first studies reported on the use of handheld iOCT devices , 2. HoweIn posterior lamellar keratoplasty, the Prospective Intraoperative and Perioperative Ophthalmic ImagiNg with Optical CoherEncE TomogRaphy (PIONEER) study  examinedIn Descemet membrane endothelial keratoplasty (DMEK), the iOCT can be used to enhance the visibility of the graft and can therefore support graft orientation and unfolding . Lately, the iOCT also was introduced to the field of glaucoma surgery by enabling visualization of trabecular aspiration or ab interno trabeculotomy; however, adjustments of wavelengths and oblique scanning are necessary for intraoperative use .The aim of this study is to report our experiences with the new iOCT Rescan® technique in anterior segment surgery, including DALK and DMEK and to evaluate new possibilities of this application.We used the iOCT  in 18 patients. The respective surgeries include two DALK, 8 DMEK, two penetrating keratoplasties, one autologous limbal transplantation, one transscleral suture fixation of a posterior chamber lens, two removals of corneal surface pannus, one examination of Peters’ anomaly in a newborn child and pterygium surgery. The iOCT scans can be directly viewed through the eyepiece of the microscope as well as on the observation monitor, simultaneously to the live surgery images. The scan location marker can be positioned with the foot control panel. The A-scan depth is 2.0 mm, and the axial resolution is 5.5 µm. Scan length can be adjusted between 3 and 16 mm. The scan can be rotated 360°. There are different scan modes available, including 1-line, 5-lines and a cross hair. We obtained the anonymized video data for all procedures. Intra- and postoperative video analysis was performed concerning the importance of the visualization during crucial surgical steps during different surgical procedures. Ethics committee statement for the analysis of anonymized was obtained by the ethics committee of the Albert-Ludwigs-University of Freiburg (10015/19).With the iOCT, the cannula placement during preparation of the recipient cornea could be visualized although the reflexes of the surgical instruments and the cannula did not always allow for a precise visualization of the cannula’s position in the deep corneal stroma Fig. a. FurtheThe iOCT enabled the visualization of the Descemet’s membrane removal in the recipient Fig. a, so thaDuring penetrating keratoplasty, the iOCT enabled intraoperative visualization of the anterior chamber Fig. a in caseDuring graft preparation on the healthy eye of a patient with complete unilateral limbal stem cell deficiency, the depth of the lamellar preparation could be assessed with the iOCT Fig.  to assurWith the iOCT, the flap preparation of the sclera, for the transscleral sutures underneath, could be visualized, enabling evaluation of the preparation depth Fig.  to allowIntraoperative scanning of the pannus and the remaining stroma was possible with the iOCT Fig.  which heThe iOCT enabled the surgeon to evaluate the anterior chamber with possible anterior synechia and attachment between lens and cornea in a newborn even though the cornea was completely opaque Fig. , Video 5During surgery, the iOCT could visualize the pterygium with the depth of its attachment to the cornea Fig. a. This cThe iOCT used in this case series enabled visualization of the complete anterior segment assisting far more surgical procedures than the previous reported DALK, DMEK and DSAEK including sclera for example. The visualization of the cannula and the bubble formation during DALK preparation can indeed be helpful for the surgeon, especially since the cornea may become opaque during the air injection. This is concordant to the findings of previous studies , 13. TheThe share of posterior lamellar keratoplasty is growing in the recent years , and regAlso, conventional penetrating keratoplasty may benefit from the use of iOCT. The evaluation of the corneal stroma and the anterior chamber can be helpful in cases of scarred and therefore opaque corneas to find the best trephination diameter and position in order to allow for safe suturing of the graft by avoiding trephination in thin areas of the recipient’s cornea. Also, the visualization of the interface during and after suturing may be helpful in special cases.Furthermore, the iOCT provides the opportunity of live assessment of the preparation depth in all cases of lamellar preparation in the anterior segment. This includes scleral flap preparation that is done for transscleral suture fixation of a posterior chamber lens or the lamellar graft preparation for an autologous limbal tissue graft. Corneal pannus or pterygium can be visualized during preparation to allow for an exact preparation depth to remove the diseased tissue completely and to avoid penetration of the globe. This may be especially helpful in cases of severe recurrent pterygium with deep infiltration of the cornea and the sclera and even in performing corneal biopsies . The iOCDisadvantages of the iOCT tested in this case series are the need for an additional person in the operating room, handling the iOCT. This might improve as all surgeons were at the beginning of their personal learning curve using iOCT. Furthermore, the iOCT-operator had to describe the OCT pictures to the surgeon in certain complicated surgical situations. Finally, the additional costs of the system have to be taken into account. In conclusion, the iOCT is a helpful device, not only for vitreoretinal surgery , 4, but Video 1. DALK: 0:00–0:26: Cannula placement and big bubble formation. 0:26–1:14: Visualization of Descemet’s membrane during excision of the anterior corneal stroma. (MP4 45484 kb)Video 2.DMEK: 0:00–0:25: Visualization of the graft orientation inside the anterior chamber. 0:25–0:51: Visualization of the graft–host interface during air injection to attach the graft. (MP4 44039 kb)Video 3.PKP: 0:00–0:30: Evaluation of the graft thickness and anterior chamber to find the best trephination diameter and the best place for trephining the recipient’s cornea. 0:30–0:33: Visualization of the wound area after suturing of the graft. (MP4 24752 kb)Video 4.Removal of corneal surface pannus: 0:00–0:07: Evaluation of the pannus and the thickness of the residual corneal stroma underneath. 0:07–0:21: Corneal stroma evaluation during pannus removal. 0:21–0:39: Corneal stroma and sclera thickness after pannus removal. (MP4 26980 kb)Video 5.Visualization of anterior synechiae in the anterior chamber in a patient with Peters’ anomaly through an opaque cornea. (MP4 17030 kb)Below is the link to the electronic supplementary material.


Neurology International was launched in 2009 and it has been published over the past eleven years by PAGEPress Publications [ications . Dr. MicNeurology International from PAGEPress and continue the legacy of this journal, and ensure that we serve well the neurosciences communities. Neurology International complements very well the MDPI portfolio of neurosciences journals, especially Neuroglia [NeuroSci [Brain Sciences [We are delighted to take over the publication of euroglia , NeuroScNeuroSci  and BraiSciences .MDPI will publish the fourth quarterly issue of 2020, and thereafter publish four quarterly issues as of 2021.Neurology International [Looking forward to publishing your research work in national !


Web of Science Core Collection. The searches demonstrate that chemoinformatics is by now a well-defined sub-discipline of chemistry, and one that forms an essential part of the chemical educational curriculum. There are three core journals for the subject: The Journal of Chemical Information and Modeling, the Journal of Cheminformatics, and Molecular Informatics, and, having established itself, chemoinformatics is now starting to export knowledge to disciplines outside of chemistry.This article presents a study of the literature of chemoinformatics, updating and building upon an analogous bibliometric investigation that was published in 2008. Data on outputs in the field, and citations to those outputs, were obtained by means of topic searches of the  Chemical Abstracts . Li et al. [Journal of Chemical Information and Modeling was again the largest source of articles from amongst the journals that were analyzed in their study. This short communication provides a bibliometric overview of the chemoinformatics literature up to the end of 2018 as represented in the Web of Science Core Collection (hereafter WoS) database from Clarivariate Analytics, and hence represents an update to, and an extension of, that presented in [In the first of these, Willett  found thi et al.  studied ented in . An appeThe WoS Topic search see  identifiJournal of Chemical Information and Modeling and for Molecular Informatics include those published in the previous incarnations of the journals  and where the IF column contains the 2018 impact factors for the eight sources where these are available . The most productive source is the published abstracts of the twice-yearly national meetings of the American Chemical Society (ACS). There were 220 of these, i.e., 10% of all of the items considered here; however, such conference presentations are very infrequently cited, contributing just 9 from the total of 25,188 citations discussed in Methods in Molecular Biology (which is a monograph series), all of the other sources in the table are academic journals; this is also the case for all but one of the next 25 sources when they are ranked in order of decreasing productivity, the sole exception being the 11th-ranked Lecture Notes in Computer Science, which is a monograph series that contains conference proceedings. The ACS abstracts and then Journal of Chemical Information and Modeling were also the two most productive sources in [Journal of Cheminformatics, which started publication in 2009, and Molecular Informatics, which started publication in 2010 as a successor to QSAR and Combinatorial Science. The latter journal has changed not only its name but also its subject focus since 100 of the 109 articles listed in Molecular Informatics, against just 9 from its two previous QSAR-focused incarnations.The 2195 outputs came from a total of 740 different sources, though no less than 513 of these provided only a single contribution. The 10 most productive sources are listed in ChemMedChem, Expert Opinion on Drug Discovery, Journal of Medicinal Chemistry, Journal of Molecular Graphics and Modelling, and Molecular Diversity). The exception in Journal of Chemical Education, and its presence here demonstrates that chemoinformatics has now become an accepted part of the chemical curriculum, with an entire issue of the journal devoted to the subject in 2016 [All but one of the sources in The outputs’ authors come from a total of 80 different countries, but the great majority of the outputs (93% of them) involve just the 10 countries listed in The 10 most productive organizations are listed in The 2195 chemoinformatics outputs had been cited by 25,188 outputs published in 5004 different sources up to the end of 2018, as shown in Scientific Reports that introduced a website for ADME  prediction had already attracted 538 citations by May 2020, despite only being published in March 2017 , further emphasizing the broadening recognition of the importance of chemoinformatics.PLoS ONE  included in the set of the 10 most productive sources shown in journals ,29) is oCanadian Journal of Fisheries and Aquatic Sciences and Journal of New Music Research are amongst the many on applications of machine learning that cite the article by Svetnik et al. in Each journal  in the WoS database is assigned to one or more of 255 subject categories, and it is hence possible to explore the extent of knowledge exports from the chemoinformatics cohort by considering the subject categories of the citing articles. One would expect the most frequent categories to come from the chemical, biological, and computer science categories and this is indeed the case, e.g., 4836 of the citing outputs were assigned the chemistry medicinal category, and 3911 and 3469 to the biochemistry molecular biology and computer science interdisciplinary applications categories, respectively. What is perhaps surprising is that at least one citation has come from no less than 216 of the 255 categories, many of which would seem on first glance to have little or no obvious relationship to chemoinformatics, but which do indeed have a relationship when examined more closely. For example, articles from the categories fisheries  and musiPediatric Surgery International on medical education in Africa [Fungal Genetics and Biology on building a database of fungal natural products [European Archives of Oto-Rhino-Laryngology on the evaluation of a software planning tool for cochlear implant surgery [There are many other non-obvious examples of knowledge export, such as an article from the surgery category in n Africa  that citn Africa , an artiproducts  that citproducts , and an  surgery  that cit surgery .Web of Science Core Collection up to and including 2018. While some of the findings reported here are analogous to those in a previous bibliometric study that was published in 2008 [Journal of Chemical Information and Modeling is still the most productive journal, the Journal of Cheminformatics and Molecular Informatics have clearly established themselves and can now be spoken of in the same breath when considering the core journals for the field. Next, chemoinformatics has become recognized as a well-defined sub-discipline that forms an essential part of the chemical educational curriculum, and one that is increasingly covered in the monograph literature. Finally, having established itself within the discipline of chemistry, it is now starting to export knowledge to a wide range of other disciplines.In conclusion, this paper reviewed the literature of chemoinformatics as delineated in the  in 2008 , at leasArticles on chemoinformatics may not, of course, contain that particular word; but those that do contain it may be assumed (with a fair degree of probability) to contain material about that subject. Publications for analysis were hence identified in May 2020 in exactly the same way as in  with a tIt will be clear from the above that there is now an extensive chemoinformatics literature. For those new to the field, the best single introduction to the subject is probably the book by Leach and Gillet , with a


In this work, we propose an intuitive and real-time model of the human arm active endpoint stiffness. In our model, the symmetric and positive-definite stiffness matrix is constructed through the eigendecomposition  The current generation of robotic manipulators has triggered new application scenarios in which robots can enter into direct interactions with unknown environments or humans to perform complex tasks . The the2) algorithm was proposed to accomplish variable impedance control for a given task. In [To address the impedance planning problem from a machine learning point of view, previous works proposed the use of model-free reinforcement learning (RL) algorithms. In , a polictask. In , the auttask. In  and eventask. In ) to traiAn alternative approach to the impedance learning through RL is learning from demonstration (LfD). In , a LfD-bIt is well known that human arm endpoint stiffness can be adapted to different task requirements and instabilities through changing posture  and muscInspired by the stiffness regulation capability of the human arm, some studies have made an attempt to transfer such an ability to robotic manipulators. In that direction, the first problem to address was the estimation of the human arm endpoint stiffness or joint stiffness, so that either the real-time stiffness profiles or the underlying impedance-regulation principles can be transferred to robotic manipulators. In , a practThe online human impedance estimation techniques were first proposed under the concept of teleimpedance control , for reaAs a continuation of our developments in this direction, in this work, we proposed a new, principally simplified, and intuitive online model of the human arm endpoint stiffness which significantly reduces the total unknown parameters to 4 and without computation of above Jacobians. The new model is based on the large dependency of the shape and orientation of the stiffness ellipsoid on the arm configuration. In fact, previous studies ,25 indicThe remainder of this paper is structured as follows: As shown in The remaining principal axis of the stiffness ellipsoid  and seven muscle co-contraction levels were estimated through perturbation experiments . ), participated in the model validation experiments.The experimental setup is illustrated in Six electromyography (EMG) sensors whose sampling rate was up to 1 kHz  were attached to the right arm’s selected muscles to record their activities. They were divided into three groups, i.e., the shoulder muscle group (with the anterior and posterior portions of the deltoid), the upper arm muscle group (with the biceps brachii and the triceps brachii) and the forearm muscle group . The EMG and IMU sensor setup is displayed in x, y, z, The KUKA robot was controlled in the position mode by an external PC through the fast research interface (FRI), in which a set of perturbation trajectories . The end effector position of the KUKA LWR was also stored in the external PC, where all the data were synchronized and saved.After wearing MVN Biomech suit and the EMG sensors, the subjects were required to contract each muscle separately to retrieve the MVC values. In the experiments, the processed (fully rectified and filtered) EMG signals were divided by the corresponding MVC values and the resulting percentages were shown visually to the subjects. Before starting the experiment for each trial, the MVN Biomech suit was calibrated with N-pose  to initialize the skeleton mode.To take into account the effect of muscular co-contractions on the arm endpoint stiffness, as noted before, three muscle groups were selected. In each arm configuration, for the first trial, the subjects were asked to keep the muscles as relaxed as possible. Instead, from the second to the seventh trial, they were asked to co-contract one muscle group at a time, and keep it at a specific level  by following the real-time feedback guidance, while relaxing the other two groups as much as possible.To make the experiment friendly to the subjects and guarantee that the samples covered most workspace of the human arm, we made a compromise for the number of positions. Here six equilibrium positions (subjects were asked to keep the same arm posture among different muscle activation states when at one position.) were predefined in the common workspace of the robot and the subject’s right arm, as shown in Each trial was repeated at least two times—the first one for the model training and the other one for the evaluation. For each subject, at least 84 (Raw data collection of IMU and EMG sensors was through wireless network and it was filtered online by a (finite impulse response) FIR filter and an internal filter respectively. The filtered data was used as the input of the proposed model in the following.The estimation of the human arm endpoint stiffness, which was used for model calibration and evaluation, was achieved by applying a displacement profile and the measurement of the restoring forces. x, y and z perturbation profiles. Next, the off-diagonal elements were calculated by using the data from The three diagonal terms of the translational Cartesian stiffness matrix were calculated by the The human arm endpoint stiffness matrices estimated from the displacements and forces are represented in As already mentioned in The identification of these parameters was achieved by minimizing the objective function with the training data set   KSH was The input of the active component The identified model parameters for the four subjects are listed in To evaluate the accuracy of the proposed model, the following function , where ITo provide a quantified comparison, the angle between the major principal axes of the measured and the predicted endpoint stiffness ellipsoids is used to evaluate the directional mismatch between the two. In addition, the relative error of the volume of the measured and the predicted endpoint stiffness ellipsoids is used to evaluate the size difference. To keep in line with the data depicted in x direction. One potential limitation is that the shape/volume mismatch may cause the reducing of modeling accuracy because of the movement of subject’s trunk was rigidly constrained only in x direction, where is in the experimental setup. In fact, in [y and z directions should be larger than the measured ones. It means that the true stiffness ellipses could be more circular and the shape/volume mismatch problem could be relieved.i-th predicted and measured ellipses area on X–Y or X–Z plane.On the other hand, for the size difference, the average relative error of ellipses area fined by  for eachIn this paper, we proposed a new human arm endpoint stiffness model, in which the stiffness matrix The proposed model offers several advantages. Firstly, the calibration and personalization of the model to an individual can be achieved through the identification of only four parameters. This implies that a small-scale experiment’s data would be sufficient to calibrate this model to match an individual’s physical characteristics. As it was shown in the last column of part. In ,24, the part. In  and besiThe price paid for the above substantial advantages is the average model error of around 20% evaluated by  which maThe model error is still acceptable for most applications mentioned before. In particular, for what concerns the stiffness ellipsoid’s geometry, according to the quantitative comparison in principal axes difference between the measured and predicted stiffness in last section, the constructed principal axes coincide with the experimentally measured ones with a limited error. In most applications, the stiffness geometry plays a dominant role compared to its volume. In fact, some tasks do not require specific stiffness values to be executed, but stiffness ranges along principal axes. An example is the assembly tasks , where the stiffness profile along the insertion must be higher than the others to comply with the environmental constraints. For this kind of application, the measurement error in the proposed model may not result in task failure. However, there are other applications that are more sensitive to the variation of stiffness values, which means that the task may fail because of the existence of a similar error. In this case, only relying on the task-related stiffness information recorded from human arm may be not sufficient. Nonetheless, by combining adaptive control approaches or reinforcement learning algorithms, a fine modulation of the modeled stiffness profile is expected to compensate for such an error.


Idiopathic portal hypertension (IPH) generally has a good prognosis and rarely results in liver transplantation. Furthermore, there are few reports of living donor liver transplantation (LDLT) for IPH with extrahepatic portal vein stenosis.We report the case of a 51-year-old female patient diagnosed with IPH more than 20 years ago. She suffered severe jaundice, massive ascites, and encephalopathy at the time of her visit to our hospital. The patient’s extrahepatic portal vein showed a scar-like stenosis, and the portal flow was completely hepatofugal. Collateral circulation such as the splenorenal shunt was well developed, and multiple splenic artery aneurysms up to 2 cm were observed in the splenic hilum. Her Model for End-Stage Liver Disease score increased to over 40 because of renal dysfunction, requiring temporary dialysis. We performed LDLT using her husband’s right lobe graft and splenectomy. The extrahepatic stenotic portal vein was completely resected, and the superficial femoral vein (SFV) graft collected from the recipient’s right leg was used for portal reconstruction as an interposition graft. Although the clinical course after LDLT had many complications, the patient was discharged on postoperative day 113 and has been fine for 2 years after LDLT. Histopathologically, the explanted liver had obliterative portal venopathy, nodular regenerative hyperplasia, and incomplete septal cirrhosis.This case showed that severe IPH is occasionally associated with extrahepatic portal vein stenosis and can be treated with LDLT with portal vein reconstruction using an interposition graft. It was also suggested that the SFV is a useful choice for the interposition graft. Idiopathic portal hypertension (IPH) comprises disorders that develop increased portal pressure in the absence of cirrhosis . The etiAlthough most IPH patients have a good prognosis with the treatment for esophageal varices and/or other complications due to portal hypertension, some develop end-stage liver failure and need for liver transplantation –5. It haSince IPH is considered to have portal hypertension at the presinusoidal level, there are few reports of LDLT for IPH with extrahepatic portal vein stenosis. Although it is unclear when and how the extrahepatic portal vein stenosis was completed in IPH, this situation required complicated portal vein reconstruction with interposition vein graft, jumping vein graft , or renoThe superficial femoral vein (SFV) seems to be the preferred option for vein grafts because of its caliber, wall thickness, and length obtained. An approximately 15–20 cm segment of the right-side SFV could be usually obtained from the recipient. The collection procedure is technically simple, and postoperative complications such as lower extremity temporary edema are usually not severe, with no permanent complications .Splenic artery aneurysms (SAAs), occurring in 7% to 17% of patients with cirrhosis, often result in catastrophic rupture after liver transplantation . SAAs arWe report a very rare case of end-stage IPH with extrahepatic portal vein stenosis and SAAs close to the hilum of the spleen. As the patient was so sick that she had to temporarily undergo dialysis, she could not get any preventive treatment against the SAAs before liver transplantation. We decided to perform LDLT and splenectomy with a complicated portal vein reconstruction using the SFV graft.A 51-year-old female patient was admitted to explore the possibility of liver transplantation for liver failure due to IPH. She had NRH on liver biopsy 20 years ago and was diagnosed with IPH. The patient’s extrahepatic portal vein showed a scar-like stenosis, and the portal flow was completely hepatofugal. Collateral circulation such as the splenorenal shunt was well developed, and dense calcification was observed at the site of splenomesenteric junction  of the graft was 1.26, which was rated as a sufficient large for the recipient. After total hepatectomy, the recipient’s right side SFV graft was harvested. The portal vein was dissected to the side of the pancreas, and the dorsal side of the pancreas was tunneled to confirm the splenic vein (SPV) and superior mesenteric vein (SMV). After clamping the SMV and SPV, the stenotic portal vein was completely resected, and the dense calcification of vascular endothelium was removed at the splenomesenteric junction. The SFV graft was anastomosed to the splenomesenteric junction in an end-to-side fashion. After right hepatic vein reconstruction and confirming the sufficient front flow of the portal vein, an end-to-end anastomosis was performed on the portal vein of the graft liver and the SFV graft Fig. .Fig. 3InThe clinical course after transplantation had many complications. An intraabdominal abscess due to grade B pancreatic fistula classified by international study group of pancreatic fistula (ISGPF)  after spThe clinical course after discharge was uneventful and the SFV graft patency was excellent at 2 years after LDLT Fig. .Fig. 5PoIPH is a rare disease characterized by portal hypertension without cirrhosis. The prognosis of IPH is considered as feasible with management for esophageal varices and/or splenomegaly by supportive treatments such as endoscopic, radiological, and surgical approach. The definite etiology of IPH is still uncertain, however, there are several theories that have been attributed to the potential pathogenesis of IPH. The contributing factors include immunological disorders, infections, and genetic variations .IPH rarely results in neither end-stage liver failure nor requiring liver transplantation. Past case reports for severe IPH requiring liver transplantation were summarized in Table When the disease duration of IPH had been long, the extrahepatic portal vein itself may occasionally become atrophic and scar-like because of the hepatofugal portal flow and/or unknown reasons. These situations may result in stenosis of the extrahepatic portal vein. To date, there is only one case report of liver transplantation for IPH with extrahepatic portal vein stenosis. In that case, a right lobe LDLT with renoportal anastomosis was performed using the recipient’s internal jugular vein graft for portal reconstruction . HoweverThe SFV graft obtained from the recipient is not only an autologous vein graft with no immune reaction, but also a very long vein graft with a sufficient diameter. A 15–20 cm length graft can be usually obtained, so the SFV graft alone can cover all the vein graft reconstruction in LDLT , 21. TheIn our case, anastomotic stenosis between the splenomesenteric junction and SFV graft occurred on POD 52, resulting in increasing ascites. Conservative treatments such as the use of diuretics did not succeed; the re-operation and balloon dilatation of the anastomotic stenosis were performed using the interventional radiology technique via the ileocolic vein. Possible reasons of anastomotic stenosis might include technical errors, and/or a twisting associated with the graft regeneration, but it is not clear. Despite the reason being unclear, a single attempt of balloon dilatation had completely solved the problem, therefore, we determined that this complication should not raise doubts about the usefulness of the SFV graft in portal reconstruction.The diagnosis of IPH is extremely difficult because the liver is usually atrophic and closely resembles cirrhosis in both clinical symptoms and diagnositic imaging in the late stage of IPH. Therefore, only histological findings obtained by liver biopsy will lead to the precise diagnosis of IPH preoperatively. Histopathologically, almost all patients with IPH have some degree of obliterative portal venopaty, furthermore, NRH and incomplete septal cirrhosis are also characteristic findings of IPH. Our patient had an NRH on liver biopsy and was diagnosed with IPH 20 years before the first visit to our hospital. The patient’s explanted liver showed evidence of obliterative portal venopathy, NRH, and incomplete septal cirrhosis, which were compatible with IPH, but not with end-stage cirrhosis.In conclusion, we reported a very rare case of end-stage IPH with extrahepatic portal vein stenosis and the SAAs close to the hilum of the spleen. This case showed that severe IPH is occasionally associated with extrahepatic portal vein stenosis and can be treated with LDLT with portal vein reconstruction using an interposition graft. It was also suggested that the SFV is a useful choice for the interposition graft.