bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on landscape design of rural linear space——Taking the design of Haiou Island Rural pedestrian street as an example
Authors: Wang ZhongWei , Du Zhaoming , Li Pengnan
Published: July 2021

Based on the rural regional characteristics, this paper analyzes the types and characteristics of linear space, and discusses the landscape design strategies of rural linear space in the context of territoriality. Specifically, it explores the landscape design path of rural linear space through spatial sequence fabric, detail context narrative, local materials and technology vocabulary application, and takes the landscape design of Haiou Island Rural pedestrian street as an example to do a further practical demonstration.
Experimental Study on Vegetation Restoration of Abandoned Land in Desert Steppe Nonferrous Metal Mine
Authors: Hao Rong , Dan Shan , Tiegang Zhang , Xiaoli Wang , Xunan Wu
Published: July 2021

Taking the mine dump in nonferrous metal mine as the research object in desert steppe Inner Mongolia, according to the artificial remodeling of the landforms and the characteristics of water and soil erosion, the vegetation restoration model tests on the dumping site were carried out. The ecological effects of four vegetation restoration measures on soil and water storage were analyzed which including shrubs, shrubgrass, grass and natural restoration of vegetation. The research results showed that compared with the natural restoration plant community, the soil surface water content of the three planting restoration measures increased obviously, the soil organic matter content increased but the change difference was not obvious. The vegetation coverage of shrub-grass was 67%, and the aboveground biomass was 132 g/m2. The vegetation restoration measure of shrub-grass had stronger wind-proof and soil-fixing ability than other measures, the vegetation coverage reaches 67% and the above-ground biomass is 132 g/m2. Efficacy evaluation was carried out by the grey correlation method, and Comprehensive benefit of shrubs, shrub-grass and grass all reached higher value. The most comprehensive benefit was the shrub-grass measure, which reached 0.68, and the smallest was shrubs measure also reached 0.60. Three measures cloud be applied to the vegetation restoration of desert steppe metal mining areas, and shrub-grass measure was the best.
A study on the Health Warning of Provincial Capital Cities in China based on the Normalized Model
Authors: Qian Guoquan , Wang Jinxiang , Nie Xiaoying , Li Mingtao , Gao Tianpeng
Published: July 2021

Along with the rapid advance of urbanization, urban disease appear. For detection city disease earlier, the ecological city is put in this article. The ecological city is regarded as the human body to plan, construct and manage city with the thought of “law in the human body”. The city’s population, land, water, air, transportation, culture, are considered as the body’s nerves, muscles, blood, breath, limbs and the vigor, respectively. And a quantitative standard is determined for each object of study. If the quantitative value is abnormally large or small, it indicates that the city is unhealthy, the early warning system for city will put forward, the causes will lookup and the treatment will give.
Study on the adsorption of heavy metals by biochar modified with different modifiers under room temperature
Authors: Ding Jiajia , Tian Yu , Lu Tao , Kang Jiang
Published: July 2021

In order to obtain an environment-friendly biochar adsorption material with excellent adsorption performance, the biochar made from corn straw was modified with FeCl3, Na2S and KMnO4as modifiers, and the adsorption effect of biochar on several heavy metal ions in water before and after modification was studied. The properties of biochar before and after modification were characterized by SEM, XRD, FTIR and BET, and the adsorption mechanism was discussed. The results showed that the three modified reagents could effectively improve the adsorption capacity of biochar for three heavy metal ions in water, and the adsorption effect was still good at room temperature. The adsorption difference is related to the specific surface area, pore structure, aromatic structure and SiO2content of biochar. The adsorption mechanism mainly includes the complexation reaction between physical adsorption and surface functional groups. This study is beneficial to promote the resource utilization of agricultural and forestry waste biomass, and provides a certain reference basis for related research.
Fe-doped carbon aerogels from sodium alginate for the removal of methylene blue
Authors: Zhai Zuozhao , Ren Bin , Zhang Lihui , Liu Zhenfa
Published: July 2021

In this article, Fe-doped carbon aerogels from sodium alginate were used for the removal of methylene blue (MB) in water. Under acidic condition, the sample carbonized at 700 °C (T700) undergoes Fe-C micro-electrolysis to produce highly chemically active Fe2+ and [H] to degrade MB. Under neutral or alkaline conditions, Fe2+ produced by Fe-C micro-electrolysis become Fe(OH)3, which can effectively adsorb MB. In addition, when T700 combines with H2O2 to form Fenton system, the MB removal efficiency was significantly improved. The Fe-doped carbon aerogels can be used in wastewater treatment and when combine the materials with H2O2 can greatly improve the MB removal efficiency.
Social network, environmental cognition and organic fertilizer application behavior of small farmers
Authors: Peng Li , Yang Qingxian
Published: July 2021

Small farmers are the main organizational form of agricultural production and management in China, and it is very important to study their organic fertilizer application behavior to promote the development of green agriculture in China. Based on the survey data of 334 small farmers in Sichuan Province, this paper uses bivariate Probit model to analyze the influence of social network and environmental cognition on organic fertilizer application behavior. The research shows that:(1) The application of commercial organic fertilizer and farmyard manure by small farmers has a significant complementary effect.(2) Social network has a significant positive impact on organic fertilizer application behavior, and there are significant differences between kinship social network and friendship social network on organic fertilizer application behavior.(3) The level of environmental cognition has a significant positive effect on the application behavior of organic fertilizer. Therefore, it is necessary not only to make full use of and expand the social network of small farmers, but also to pay attention to improving their environmental awareness and promoting organic fertilizer application behavior.
Research on assessment technology method of high efficiency air cleaners
Authors: Jin Huang , Hao Shen , Xiaoxin Zhang , Ling Lin , Zhenhai Li , Jun Chen , Wei Wu , Baozhu Wang
Published: July 2021

In the face of the increasingly severe situation of air pollution, the research on evaluation technology and method of high-efficiency air pollution control equipment in China is being advanced. This paper discusses the background and significance of the research on high efficiency air cleaner evaluation techniques and methods, and introduces the General Ideas and principles of the research on high efficiency air cleaner evaluation techniques and methods, the technical methods of high efficiency air cleaner evaluation are established, including the evaluation object and scope of application, basic requirements of high efficiency air cleaner qualitative evaluation, quantitative evaluation requirements of key evaluation indicators, testing, calculation and evaluation methods, etc., the application of the research results of air cleaner will facilitate the production and consumption of air cleaner products.
Exogenous abscisic acid alleviates the toxicity of nickel in wheat seedlings
Authors: Li Xue , Zhang Ming , Gao Tian-peng
Published: July 2021

In order to evaluate the effects of exogenous abscisic acid (ABA) in alleviating nickel (Ni) stress in wheat plants. We studied the changes of biochemical and physiological in wheat seedlings exposed to 250 μM Ni with or without different treatments of ABA. Exposed to Ni (250 μM) caused adverse effect on growth of wheat seedlings, which was accompanied by increased the concentrations of superoxide anion（O2−） and malondialdehyde (MDA). However, exogenous application of ABA (2.5 and 5 μM) alleviated the Ni-induced inhibition of plant growth, decreased the concentrations of O2− and MDA in wheat shoots. Further, application of ABA significantly modulated the activities of antioxidant enzymes and enhanced content of proline and soluble sugar in Ni-stressed wheats, but the application of 20 μM of ABA had no different significantly response for these parameters. The results indicated that application of ABA enhanced the antioxidant defense activities in Ni-stressed wheats, thus alleviating Ni-induced oxidative injury and enhancing Ni tolerance.
Research on Safety Evaluation and Sustainable Conservation Strategy of Tunbao Buildings--An example of residential buildings in Benzhai, Anshun, Guizhou
Authors: Jiahao Gao , Luxi Lu , Tianke Zhang
Published: July 2021

Tunbao architecture is a combination of defensive and residential architecture of Ming Dynasty, and is an important material substrate of Tunbao culture. With the accelerated pace of urbanization, the population of Anshun Tumbao has moved out, aging has increased and natural catalysis has led to the dilapidation and decay of the dwelling architecture, which lacks certain conservation measures. This paper takes Anshun Tunbao residential buildings in Guizhou as an example, and summarizes the development of residential buildings in this village through literature and field research, and summarizes the current problems of preservation. The results of this study are presented in the form of a graded “point-to-point” conservation strategy, which is intended to provide a theoretical reference for the conservation and restoration of historical buildings in the Han ethnic area of Guizhou.
Study on the Sustainable Planning and High Efficiency Utilization of Rural Areas Based on Ecological-Production-Living Space – A Case Study of Shuihu Village, Hengdong County, China
Authors: Wang Zhiyuan , Zhang Kao , Yi Hanling , Lv Jingtong , Li Xin , Yuan Zeqi , Bedra Komi Bernard
Published: July 2021

Rural planning is an important part of territorial spatial planning. The study of rural “Ecological-production-living Space” is the key part in optimizing the land spatial development and improving the spatial planning system, which is significant for the sustainable planning and for high efficiency utilization of rural areas. In this study we take Shuihu village, Hengdong County, China, as a case study. (1) The paper applies the Analytic Hierarchy Process to construct a multi-factor evaluation system of villages “Ecological-production-living Space” for their development and construction, agricultural production conditions and ecological function suitability. Establishing the hierarchy model of rural “Ecological-production-living Space” and affecting weight values to each evaluation factor. (2) Using GIS multi-factor grid, we comprehensively evaluate the village space and identify as well as its dominant function. In the plan, the agricultural production as the leading function and as ecological and living space accounts for 36.25% of the area of the village field. The ecological production accounted for 51.71%, the development and construction accounts for 9.67%. (3) Apply rural complex concept to guide space usage separately from the production space (production and living space) , ecological space (ecological living and ecological production space), living space (living ecology and production space) ecological production and living space, to improve the ecological conservation and energy efficiency of agricultural production, to build ecological agriculture, modern agriculture and liveable idyllic community. Through these above parts, we hope to achieve the sustainable development model of rural area and high efficiency utilization of land resources.
Enhanced syntrophic propionate degradation and methane production by granular activated carbon in AnSBR
Authors: Fan Yiyang , Chen Qiyi , Yan Han , Li Jianzheng
Published: July 2021

Syntrophic degradation of propionate has been regarded as a limiting factor for methane formation in anaerobic digestion (AD) processes, due to its easier production but harder degradation than other volatile fatty acids. In the present study, 20 g/L granular activated carbon (GAC) was introduced into an anaerobic sequence batch reactor (AnSBR) and the enhancement of propionate degradation and methane production was evaluated with another AnSBR without GAC as a control. Inoculated with the same excess activated sludge, both AnSBRs were synchronously started up at 35 °C with the fed propionate increased gradually from the initial 340 mg/L to the final 1700 mg/L. The results showed that the introduction of GAC made the AnSBR get steady state 6 days earlier. With the fed propionate of about 1700 mg/L in the steady state, the average specific methane production and biomass was enhanced from 0.20 to 0.25 L/L·d, and 7.72 to7.96 g/L, respectively, by the introduced GAC. The results suggested that the GAC had functioned in stimulating microbial growth and enhancing direct interspecies electron transfer between hydrogen-producing acetogens and methanogens, which had resulted in the enhanced propionate degradation and methane production.
Research on the Spatio-temporal Differences in the Living Standards of the Counties under the Shandong Province
Authors: Cui Hongwu , Yang Qian
Published: July 2021

Using the method of district statistics to verify the correlation of NPP-VIIRS night light data and GDP, the difference between counties in Shandong from 2012 to 2019 can be analysed and the changes of living standards can be quantified. After obtaining the total value of night light brightness in each county, the coefficient of variation is used to calculate the degree of dispersion of each county, and then the regional differences of each city in 2019 and the inter-annual changes from 2012 to 2019 are analyzed and displayed. In conclusion, living standards of different countries in Shandong are different, and the difference becomes obvious with the growth of GDP. However,the difference of living standards of most countries becomes smaller in recent years.
Research on the policy of renewable energy development in China
Authors: Xi Chen , Ting Guo , Zhi’an Feng , Wei Qian
Published: July 2021

On the 19th National Congress of the Communist Party of China, It is stressed that that China will establish and improve the economic system of green and low-carbon circular development and promote the reform of energy system and develop the renewable energy, and then it is urgent for China to not only master the basic laws of the world’s renewable energy development, comply with the trend and trend of energy reform, but also promote the development of renewable energy based on national conditions and regional conditions, so as to achieve higher quality development of economy and society.
Designing a supply chain network under a dynamic discounting-based credit payment program
Authors: Tsao Yu-Chung , Setiawati Mutia , Linh Vu Thuy , Sudiarso Andi
Published: July 2021

This study examines the effects of dynamic discounting based credit payment on a supply chain network design problem. Dynamic discounting based credit payment is a supply chain finance policy wherein the supplier provides a credit period to a distribution center (DC) with a discount applied if the DC pays the supplier before the end of the credit period. This study also considers the time value of money and applies discounted cash flows to formulate a model that determines the DC’s optimal replenishment cycle, selling price, and influence area while maximizing the present value of the total profit. The continuous approximation approach is applied to formulate a mathematical model of the problems, and an algorithm based on non-linear optimization is established to solve the problem. A numerical example and a sensitivity analysis are provided to present the proposed model and solution approach and to illustrate the effect of each cost on the decisions and profit.
Smile Attractiveness Evaluation of Patients Selected for a U.S.-Based Board Certification Examination
Authors: Soh Jen , Wang Zheng Dong , Zhang Wei Bing , Kau Chung How
Published: July 2021

Objectives The aims of this study were to assess smile attractiveness of a collection of 68 smiling photographs of successfully treated cases submitted to the American Board of Orthodontics (ABO) clinical examination and identify variables that influence the assessment.

Materials and Methods A panel of 81 non-Caucasian assessors from various clinical disciplines were instructed to score the smile attractiveness on a visual analog scale from 1 (least attractive) to 10 (most attractive) and to select which components contributed to a lesser attractive smile. The mean, standard deviations (SDs), and quartiles of the smile attractiveness were obtained with descriptive statistics. Multilinear regression analysis was performed to investigate the scores of the perceived quality of smile attractiveness when the clinical disciplines and gender of the assessors were the factors taken into consideration. Receiver operating characteristic (ROC) curve was generated to establish the relationship between smile attractiveness and the achievement of a perfect smile.

Results The mean (SD) rating of each clinical photograph of the anterior occlusion on smiling ranged from 3.11 (1.47) as the least attractive smile to 7.59 (1.45) as the most attractive smile. The overall mean (SD) score for smile attractiveness was 5.30 (1.10). Problems associated with teeth, gingiva, and lips corresponded with a reduction of the smile attractiveness score by 1.56, 1.82, and 1.47, respectively. Gender was not associated with smile attractiveness ratings. Orthodontists, periodontists, and prosthodontists demonstrated no difference in the ratings, while plastic surgeons were more critical than orthodontists regarding smile attractiveness.

Conclusions This study suggested that only 2 out of 68 AOB validated treatment finishes had a perfect and attractive smile.
Novel Indigenous Probiotic Lactobacillus reuteri Strain Produces Anti-biofilm Reuterin against Pathogenic Periodontal Bacteria
Authors: Widyarman Armelia Sari , Theodorea Citra Fragrantia
Published: July 2021

Objective The aim of this study was to evaluate the effect of reuterin produced by a novel probiotic strain of Lactobacillus reuteri against periodontal biofilms.

Materials and Methods L. reuteri LC382415 (an indigenous Indonesian strain) was cultured in Man, Rogosa, and Sharpe (MRS) agar in anaerobic conditions for 24 hours. To isolate reuterin, L. reuteri was suspended in 300-mM glycerol in MRS broth and incubated under anaerobic conditions for 3 hours, and the supernatant fraction was filtered. The presence of reuterin was confirmed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE), and its concentration was determined. The effect of reuterin on Porphyromonas gingivalis ATCC 33277 and T. denticola ATCC 35405 biofilms was evaluated using biofilm assays. Biofilms were formed by incubating bacteria in 96-well microplates for 48 hours. A dose-dependent experiment was performed with reuterin concentrations of 12.5, 25, 50, and 100 μg/mL on biofilms. The inhibitory effect was measured at 1, 3, 6, and 24 hours. The biofilm masses were measured at 490 nm. Statistical analysis was using one-way ANOVA.

Results The SDS-PAGE assay confirmed the presence of reuterin (52 kDa) in the culture supernatant of the L. reuteri strain. Reuterin in a concentration as low as 12.5 μg/mL significantly inhibited single- and mixed-species biofilms (p < 0.05).

Conclusions This is the first study to demonstrate the promising effect of reuterin isolated from L. reuteri LC382415 against periodontal bacteria. Further studies are warranted to explore the mechanism of this active component.
Mechanism of the formation of proton transfer pathways in photosynthetic reaction centers
Authors: Sugo Yu , Saito Keisuke , Ishikita Hiroshi
Published: July 2021

Significance

The crystal structures of photosynthetic reaction centers from purple bacteria (PbRCs) and photosystem II show large structural similarity. However, the proposed mechanisms of proton transfer toward the terminal electron acceptor quinone (Q
B
) are not consistent. In particular, not His-L190, which is an H-bond partner of Q
B
, but rather Glu-L212, which is ∼6 Å away from Q
B
, was assumed to be the direct proton donor for Q
B
. We demonstrate that the H-bond between His-L190 and Q
B
is a low-barrier H-bond, which facilitates proton transfer from singly protonated His-L190 to Q
B
. Furthermore, Glu-L212 is not a direct H-bond donor for Q
B
. However, it facilitates proton transfer toward deprotonated His-L190 via water molecules after Q
B
H
2
forms and leaves the PbRC.
Fairness, technology and the ethics of Paralympic sport classification
Authors: McNamee Mike , Parnell Richard , Vanlandewijck Yves
Published: July 2021

Fairness in sport is a widely shared meritocratic norm. Its application is usually restricted to equality of opportunity to compete for victory. Paralympic sports lay down a further challenge in that equality of opportunity must be shaped by considerations of fairness, evidenced by the development of discrete competition categories to construct fair and meaningful contests. In this article, we extend these philosophical ideas to consider how Fair Equality of Opportunity might operate in the context of Paralympic sports classification. We articulate three conceptions of fairness relevant to these sports: (i) background fairness; (ii) procedural fairness; and (iii) stakes fairness. We critically review the International Paralympic Committee's Policy on Sport Equipment in relation to the first two conceptions and argue that greater clarification, theorization and rule modification is required if physical prowess, as opposed to equipment technology, is to be assured as the dominant determinant of Paralympic athletic success.
Mimicry: just wing it. Wing shape comparison between a mimicking swallowtail and its toxic model
Authors: Nixon Kyra J A , Parzer Harald F
Published: July 2021

Female eastern tiger swallowtails (Papilio glaucus) are well-known wing coloration mimics of the toxic pipevine swallowtail (Battus philenor). Given that forewing shape is an important component of butterfly flight behaviour found in unpalatable species, we hypothesized that the mimicking females also mimic the forewing shape of their poisonous model. Thus, we predicted that mimicking eastern tiger swallowtails have a more similar wing shape to their model compared with their non-mimicking conspecific morphs. In order to test this, we compared the forewing of the model with mimicking and non-mimicking eastern tiger swallowtail morphs using a standard geometric morphometrics approach. Contrary to our hypothesis, we found significant differences of forewing shape between the two species, with no overlap, regardless of the morph. However, mimicking and non-mimicking female eastern tiger swallowtails were significantly different from each other in wing shape. This indicates that either pleiotropic effects, possibly owing to wing coloration mimicry, or selection for different flight patterns in mimics informed the evolution of forewings in this species. Additionally, we found sexual dimorphism in forewing shape within each species, which supports research indicating that both sexual selection and sex-specific natural selection are important drivers in wing shape evolution.
Responding to Ecological Transformation: Mental Models, External Constraints, and Manager Decision-Making
Authors: Clifford Katherine R , Cravens Amanda E , Knapp Corrine N
Published: July 2021

Ecological transformation creates many challenges for public natural resource management and requires managers to grapple with new relationships to change and new ways to manage it. In the context of unfamiliar trajectories of ecological change, a manager can resist, accept, or direct change, choices that make up the resist-accept-direct (RAD) framework. In this article, we provide a conceptual framework for how to think about this new decision space that managers must navigate. We identify internal factors (mental models) and external factors (social feasibility, institutional context, and scientific uncertainty) that shape management decisions. We then apply this conceptual framework to the RAD strategies (resist, accept, direct) to illuminate how internal and external factors shape those decisions. Finally, we conclude with a discussion of how this conceptual framework shapes our understanding of management decisions, especially how these decisions are not just ecological but also social, and the implications for research and management.
Distinct Causal Influences of Dorsolateral Prefrontal Cortex and Posterior Parietal Cortex in Multiple-Option Decision Making
Authors: Woo Tsz-Fung , Law Chun-Kit , Ting Kin-Hung , Chan Chetwyn C H , Kolling Nils , Watanabe Kei , Chau Bolton K H
Published: July 2021

Our knowledge about neural mechanisms underlying decision making is largely based on experiments that involved few options. However, it is more common in daily life to choose between many options, in which processing choice information selectively is particularly important. The current study examined whether the dorsolateral prefrontal cortex (dlPFC) and posterior parietal cortex (PPC) are of particular importance to multiple-option decision making. Sixty-eight participants received anodal high definition-transcranial direct current stimulation (HD-tDCS) to focally enhance dlPFC or PPC in a double-blind sham-controlled design. Participants then performed a multiple-option decision making task. We found longer fixations on poorer options were related to less optimal decisions. Interestingly, this negative impact was attenuated after applying anodal HD-tDCS over dlPFC, especially in choices with many options. This suggests that dlPFC has a causal role in filtering choice-irrelevant information. In contrast, these effects were absent after participants received anodal HD-tDCS over PPC. Instead, the choices made by these participants were more biased towards the best options presented on the side contralateral to the stimulation. This suggests PPC has a causal role in value-based spatial selection. To conclude, the dlPFC has a role in filtering undesirable options, whereas the PPC emphasizes the desirable contralateral options.
Small Nucleus Accumbens and Large Cerebral Ventricles in Infants and Toddlers Prior to Receiving Diagnoses of Autism Spectrum Disorder
Authors: Shiohama Tadashi , Ortug Alpen , Warren Jose Luis Alatorre , Valli Briana , Levman Jacob , Faja Susan K , Tsujimura Keita , Maunakea Alika K , Takahashi Emi
Published: July 2021

Early interventions for autism spectrum disorder (ASD) are increasingly available, while only 42–50% of ASD children are diagnosed before 3 years old (YO). To identify neuroimaging biomarkers for early ASD diagnosis, we evaluated surface- and voxel-based brain morphometry in participants under 3YO who were later diagnosed with ASD. Magnetic resonance imaging data were retrospectively obtained from patients later diagnosed with ASD at Boston Children’s Hospital. The ASD participants with comorbidities such as congenital disorder, epilepsy, and global developmental delay/intellectual disability were excluded from statistical analyses. Eighty-five structural brain magnetic resonance imaging images were collected from 81 participants under 3YO and compared with 45 images from 45 gender- and age-matched nonautistic controls (non-ASD). Using an Infant FreeSurfer pipeline, 236 regionally distributed measurements were extracted from each scan. By t-tests and linear mixed models, the smaller nucleus accumbens and larger bilateral lateral, third, and fourth ventricles were identified in the ASD group. Vertex-wise t-statistical maps showed decreased thickness in the caudal anterior cingulate cortex and increased thickness in the right medial orbitofrontal cortex in ASD. The smaller bilateral accumbens nuclei and larger cerebral ventricles were independent of age, gender, or gestational age at birth, suggesting that there are MRI-based biomarkers in prospective ASD patients before they receive the diagnosis and that the volume of the nucleus accumbens and cerebral ventricles can be key MRI-based early biomarkers to predict the emergence of ASD.
The size of apolipoprotein (a) is an independent determinant of the reduction in lipoprotein (a) induced by PCSK9 inhibitors
Authors: Blanchard Valentin , Chemello Kévin , Hollstein Tim , Hong-Fong Clément Chong , Schumann Friederike , Grenkowitz Thomas , Nativel Brice , Coassin Stefan , Croyal Mikaël , Kassner Ursula , Lamina Claudia , Steinhagen-Thiessen Elisabeth , Lambert Gilles
Published: July 2021

Aims

Lipoprotein (a) [Lp(a)] is a lipoprotein species causatively associated with atherosclerosis. Unlike statins, PCSK9 inhibitors (PCSK9i) reduce Lp(a), but this reduction is highly variable. Levels of Lp(a) are chiefly governed by the size of its signature protein, apolipoprotein (a) [apo(a)]. Whether this parameter determines some of the reduction in Lp(a) induced by PCSK9i remains unknown. We aimed to investigate if the Lp(a) lowering efficacy of PCSK9i is modulated by the size of apo(a), which is genetically determined by the variable number of KIV domains present on that protein.

Methods and results

The levels of Lp(a) and the size of apo(a) were assessed in plasma samples from 268 patients before and after treatment with PCSK9i. Patients were recruited at the Outpatient Lipid Clinic of the Charité Hospital (Berlin) between 2015 and 2020. They were hypercholesterolaemic at very high cardiovascular disease risk with low-density lipoprotein (LDL)-cholesterol levels above therapeutic targets despite maximally tolerated lipid-lowering therapy. Patients received either Alirocumab (75 or 150 mg) or Evolocumab (140 mg) every 2 weeks. Apo(a), apoB100, and apoE concentrations as well as apoE major isoforms were determined by liquid chromatography high-resolution mass spectrometry. Apo(a) isoforms sizes were determined by western blot. PCSK9i sharply reduced LDL-cholesterol (−57%), apoB100 (−47%), and Lp(a) (−36%). There was a positive correlation between the size of apo(a) and the relative reduction in Lp(a) induced by PCSK9i (r = 0.363, P = 0.0001). The strength of this association remained unaltered after adjustment for baseline Lp(a) levels and all other potential confounding factors. In patients with two detectable apo(a) isoforms, there was also a positive correlation between the size of apo(a) and the reduction in Lp(a), separately for the smaller (r = 0.350, P = 0.0001) and larger (r = 0.324, P = 0.0003) isoforms. The relative contribution of the larger isoform to the total concentration of apo(a) was reduced from 29% to 15% (P < 0.0001).

Conclusions

The size of apo(a) is an independent determinant of the response to PCSK9i. Each additional kringle domain is associated with a 3% additional reduction in Lp(a). This explains in part the variable efficacy of PCSK9i and allows to identify patients who will benefit most from these therapies in terms of Lp(a) lowering.
The curious case of a massive right heart thrombosis: a case report
Authors: Artico Jessica , Belgrano Manuel , Bussani Rossana , Sinagra Gianfranco
Published: July 2021

Background

Intraventricular masses are a relatively rare condition ranging from asymptomatic to potentially life-threatening situations.

Case summary

Herein, we report a case of a 49-year-old woman under investigation for a massive right ventricular (RV) mass who underwent complete investigation for possible differential diagnosis, in the suspect of RV tumour. Multimodality imaging with cardiac computed tomography and magnetic resonance imaging showed the presence of a massive thrombus partially obliterating the right ventricle. Surgical removal of the mass showed a large area of stratified thrombosis with an underlying area of endocardial fibrosis. The patient has been then discharged in good clinical condition and with lifetime oral anticoagulation.

Discussion 

Massive RV thrombosis is a rare yet potentially fatal condition. Invasive management is preferable and lifetime anticoagulation is required to reduce possible downstream thrombotic complications.
Recurrent embolisms despite adequate anticoagulant therapy in a patient with prosthetic heart valves and atrial fibrillation: a case report
Authors: Marschall Alexander , Rodriguez Torres Diego , Rueda Liñares Andrea , Martí Sánchez David
Published: July 2021

Background

Antithrombotic management in patients with atrial fibrillation (AF) that have undergone heart valve surgery may be challenging, especially in the context of thromboembolic events during follow-up. The combination of pharmacological therapies with modern transcatheter interventions allows these more complex cases to be overcome.

Case summary

We present the case of a 66-year-old female with a history of AF and mechanical aortic and mitral valve replacement, which was admitted to the hospital complaining of dizziness and unsteady gait. A computerized tomography scan of the brain confirmed the diagnosis of embolic stroke. Two years later, the patient complained of sudden onset of chest pain, accompanied by electrocardiographic abnormalities and elevated high-sensitivity troponin T. Emergency cardiac catheterization revealed embolic myocardial infarction with distal occlusion of the obtuse marginal artery. Again, 2 years later, the patient suffered a new cerebral embolic event. Given the adequate anticoagulation therapy throughout almost the entire clinical course, percutaneous left atrial appendage closure was proposed as an adjunct to vitamin K antagonist treatment. Notably, intraprocedural transoesophageal echocardiography revealed the presence of a previously undetected left atrial appendage thrombus, thus an embolic protection device was used during the procedure, which was successfully carried out without complications.

Discussion

This case report demonstrates the complexity of the antithrombotic management in patients with AF and prosthetic heart valves, and highlights the importance of an individualized approach, integrating new therapeutic strategies to achieve success, in patients that present thromboembolic events despite adequate anticoagulation therapy.
Regulation of fractone heparan sulfate composition in young and aged subventricular zone neurogenic niches
Authors: Kerever Aurelien , Nagahara Fumina , Keino-Masu Kazuko , Masu Masayuki , van Kuppevelt Toin H , Vivès Romain R , Arikawa-Hirasawa Eri
Published: July 2021

Fractones, specialized extracellular matrix structures found in the subventricular zone (SVZ) neurogenic niche, can capture growth factors, such as basic fibroblast growth factor, from the extracellular milieu through a heparin-binding mechanism for neural stem cell (NSC) presentation, which promotes neurogenesis. During aging, a decline in neurogenesis correlates with a change in the composition of heparan sulfate (HS) within fractones. In this study, we used antibodies that recognize specific short oligosaccharides with varying sulfation to evaluate the HS composition in fractones in young and aged brains. To further understand the conditions that regulate 6-O sulfation levels and its impact on neurogenesis, we used endosulfatase Sulf1 and Sulf2 double knockout (DKO) mice. Fractones in the SVZ of Sulf1/2 DKO mice showed immunoreactivity for the HS epitope, suggesting higher 6-O sulfation. While neurogenesis declined in the aged SVZ of both wild-type and Sulf1/2 DKO mice, we observed a larger number of neuroblasts in the young and aged SVZ of Sulf1/2 DKO mice. Together, these results show that the removal of 6-O-sulfation in fractones HS by endosulfatases inhibits neurogenesis in the SVZ. Our findings advance the current understanding regarding the extracellular environment that is best suited for NSCs to thrive, which is critical for the design of future stem cell therapies.
Effect of ABT-263 on Intestinal Fibrosis in Human Myofibroblasts, Human Intestinal Organoids, and the Mouse Salmonella typhimurium Model
Authors: Johnson Laura A , Rodansky Eva S , Tran Anhdao , Collins Stephen G , Eaton Kathryn A , Malamet Benjamin , Steiner Calen A , Huang Sha , Spence Jason R , Higgins Peter D R
Published: July 2021

Background

Intestinal fibrosis and subsequent intestinal obstruction are common complications of Crohn’s disease (CD). Current therapeutics combat inflammation, but no pharmacological therapy exists for fibrostenotic disease. Pathological persistence of activated intestinal myofibroblasts is a key driver of fibrosis in CD. In other organ systems, BH-3 mimetic drugs that affect Bcl-2 apoptotic pathways induce apoptosis in activated myofibroblasts and reduce fibrogenic gene expression, thereby reducing fibrosis.

Methods

We evaluated the proapoptotic and antifibrotic efficacy of several classes of BH-3 mimetics in 2 in vitro fibrogenesis models. The candidate molecule, ABT-263, was advanced to a 3-dimensional human intestinal organoid (HIO) model. Finally, the therapeutic efficacy of ABT-263 was evaluated in the mouse Salmonella typhimurium intestinal fibrosis model.

Results

The BH-3 mimetics induced apoptosis, repressed fibrotic protein expression, and reduced fibrogenic gene expression in normal human intestinal myofibroblasts. The BH-3 mimetics that target Bcl-2 and Bcl-xl demonstrated the greatest efficacy in vitro. The ABT-199 and ABT-263 induced apoptosis and ameliorated fibrogenesis in the in vitro myofibroblast models. In the HIO model, ABT-263 inhibited fibrogenesis and induced apoptosis. In the mouse S. typhimurium model, dose-dependent reduction in macroscopic pathology, histological inflammation, inflammatory and fibrotic gene expression, and extracellular matrix protein expression indicated ABT-263 may reduce intestinal fibrosis.

Conclusions

In vitro, the antifibrotic efficacy of BH-3 mimetics identifies the Bcl-2 pathway as a druggable target and BH-3 mimetics as putative therapeutics. Reduction of inflammation and fibrosis in the mouse intestinal fibrosis model by ABT-263 indicates BH-3 mimetics as potential, novel antifibrotic therapeutics for Crohn’s disease.
Temporal Issues Relating to BIT Dispute Resolution
Authors: Murphy Sean D
Published: July 2021

An investor–State tribunal formed under a bilateral investment treaty (BIT) may be called upon to determine its jurisdiction ratione temporis based on various ‘critical dates’ such as: the date of entry into force of the BIT; the date when the investment was made; the date when the investor acquired the requisite nationality; the date of the alleged breach; the date when the investor first acquired knowledge of the alleged breach and of its loss; and/or the date when the dispute arose. When confronted with such temporal issues, tribunals over the past two decades have often reverted to the ‘secondary’ rules found in the International Law Commission’s 2001 Articles on the Responsibility of States for Internationally Wrongful Acts, and found in the law of treaties. This article identifies a series of propositions that may be extracted from recent investor–State jurisprudence concerning those secondary rules, with particular attention to application of the rule on non-retroactivity. Except in relatively limited situations, tribunals appear disinclined to find temporal jurisdiction over breaches or disputes that are based on pre-BIT acts. Consequently, this article considers as well recent jurisprudence on whether the host State’s alleged breach has a continuing or composite character, thus overcoming any temporal bar. While it would be excessive to say that the secondary rules in this area have provided the perfect means for addressing temporal issues, they appear to have generated a comprehensible framework within which investor–State tribunals are successfully operating.
Does preoperative dual antiplatelet therapy affect bleeding and mortality after total arch repair for acute type A dissection?
Authors: Xiao Fu-Cheng , Ma Wei-Guo , Ge Yi-Pen , Zhu Jun-Ming , Sun Li-Zhong
Published: July 2021

OBJECTIVES

Data are scarce and mixed regarding the impact of preoperative dual antiplatelet therapy (DAPT) on the surgical outcomes of acute type A aortic dissection (ATAAD). We seek to evaluate the impact of DAPT on bleeding-related events and early- and mid-term mortality after total arch replacement and frozen elephant trunk in such patients.

METHODS

This study comprised 48 ATAAD patients on preoperative DAPT and 418 without DAPT (the whole series, i.e. unmatched cohort), from which 45 matched pairs were selected by propensity score (matched cohort). Bleeding-related events (reoperation for bleeding, bleeding of ≥1500 ml within the first 12 h postoperatively or transfusion of ≥10 units of red blood cell or use of recombinant activated factor VII), operative mortality and mid-term survival were compared in the unmatched and matched cohorts. The impact of preoperative DAPT was evaluated with multivariable analysis.

RESULTS

In the unmatched cohort, bleeding of ≥1500 ml/12 h postoperatively was more common in the DAPT group (18.8% vs 8.4%, P = 0.020); operative mortality was 9.7%, which did not differ with DAPT (12.5% vs 9.3%, P = 0.48). Nor did bleeding-related events (54.2% vs 43.5%, P = 0.16) differ significantly between 2 groups. In the matched cohort, neither were drainage of ≥1500 ml/12 h (20% vs 6.7%, P = 0.063) and bleeding-related events (53.3% vs 42.2%, P = 0.30), nor operative mortality (13.8 vs 8.9%, P = 0.50) and mid-term survival (79.3% vs 76.4%, P = 0.93) significantly different between 2 groups. DAPT was not identified as a predictor for operative mortality [odd ratio (OR) 0.97, 95% confidence interval (CI) 0.31–3.08; P = 0.96; adjusted OR 1.28, 95% CI 0.22–7.20; P = 0.78] and bleeding-related events (OR 1.50, 95% CI 0.76–2.95; P = 0.24; adjusted OR 2.03, 95% CI 0.80–3.66; P = 0.14).

CONCLUSIONS

In patients with ATAAD undergoing total arch replacement and frozen elephant trunk, although preoperative DAPT led to more postoperative bleeding, it did not increase bleeding-related events nor operative mortality nor mid-term death. The results of this study imply that for patients with ATAAD, emergency surgical repair, even if as extensive as total arch repair, should not be contraindicated or delayed simply because of ongoing DAPT.
Bilinear Forms With Modular Square Roots and Twisted Second Moments of Half Integral Weight Dirichlet Series
Authors: Shkredov Ilya D , Shparlinski Igor E , Zaharescu Alexandru
Published: July 2021

We establish new results on equations and bilinear forms with modular square roots. The main motivation and application of these results is our new bound on the fourth moment of the error term in the asymptotic formula for the twisted second moment of half integral weight Dirichlet series on average over moduli.
Exploring “Return to Productivity” Among People Living With Burn Injury: A Burn Model System National Database Report
Authors: Sheckter Clifford C , Brych Sabina , Carrougher Gretchen J , Wolf Steven E , Schneider Jeffrey C , Gibran Nicole , Stewart Barclay T
Published: July 2021

Burn survivors experience barriers to returning to work. For those who do return to work, little is known regarding whether they achieve preinjury productivity (i.e., equivalent or gain in income compared to preinjury income). Identifying patients at risk of not achieving preinjury productivity is important for targeting services that support this population. They extracted occupational and income data through 24 months postinjury from the multicenter, longitudinal Burn Model System National Database. Annual income was reported in six groups: <$25k, $25k–50k, $50k–99k, $100k–149k, $150k–199k, and $>199k. Participants were classified by change in income at each follow-up (i.e., gain, loss, and equivalent). Explanatory variables included demographics, injury characteristics, insurance payer, employment status, and job type. Multilevel, multivariable logistic regression was used to model return to productivity. Four hundred fifty-three participants provided complete income data at discharge and follow-up. Of the 302 participants employed preinjury, 180 (60%) returned to work within 24 months postinjury. Less than half (138) returned to productivity (46% of participants employed preinjury; 77% of those who returned to work). Characteristics associated with return to productivity included older age (median 46.9 vs 45.9 years, OR 1.03, P = .006), Hispanic ethnicity (24% vs 11%, OR 1.80, P = 0.041), burn size >20% TBSA (33.7% vs 33.0%, OR 2.09, P = 0.045), and postinjury employment (54% vs 26%, OR 3.41, P < 0.001). More than half of employed people living with burn injury experienced loss in productivity within 24 months postinjury. Even if they return to work, people living with burn injuries face challenges returning to productivity and may benefit from vocational rehabilitation and/or financial assistance.
Early Palliative Care Consultation in the Burn Unit: A Quality Improvement Initiative to Increase Utilization
Authors: Carmichael Heather , Brackett Hareklia , Scott Maurice C , Dines Margaret M , Mather Sarah E , Smith Tyler M , Duffy Patrick S , Wiktor Arek J , Lambert Wagner Anne
Published: July 2021

Despite significant morbidity and mortality for major burns, palliative care consultation (PCC) is underutilized in this population. The purpose of this study is to examine the impact of a protocol using recommended “triggers” for PCC at a single academic burn center. This is a retrospective review of patient deaths over a 4-year period. The use of life-sustaining treatments, comfort care (de-escalation of one or more life-sustaining treatments), and do not attempt resuscitation (DNAR) orders were determined. The use of PCC was compared during periods before and after a protocol establishing recommended triggers for early (<72 hours of admission) PCC was instituted in 2019. A total of 33 patient deaths were reviewed. Most patients were male (n = 28, 85%) and median age was 62 years [IQR: 42–72]. Median-revised Baux score was 112 [IQR: 81–133]. Many patients had life-sustaining interventions such as intubation, dialysis, or cardiopulmonary resuscitation, often prior to admission. Amongst patients who survived >24 hours, 67% (n = 14/21) had PCC. Frequency of PCC increased after protocol development, with 100% vs 36% of these patients having PCC before death (P = .004). However, even during the later period, less than half of patients had early PCC despite meeting criteria at admission. In conclusion, initiation of life-sustaining measures in severely injured burn patients occurs prior to or early during hospitalization. Thus, value-based early goals of care discussions are valuable to prevent interventions that do not align with patient values and assist with de-escalation of life-sustaining treatment. In this small sample, we found that while there was increasing use of PCC overall after developing a protocol of recommended triggers for consultation, many patients who met criteria at admission did not receive early PCC. Further research is needed to elucidate reasons why providers may be resistant to PCC.