bluuebunny/crossref_metadata_2025 huggingface dataset:
A Case Report on Ischaemic Cardiomyopathy with
Severe Left Ventricular Dysfunction
Authors: Misbah Ul Haq Mohammed , Munaf Ur Razzak Mohammed , Ahmed Nazish
Published: December 2021

Ischaemic cardiomyopathy is a condition that arises when heart muscle is weakened because of coronary artery disease or a heart attack. Left ventricular (LV) dysfunction occurs when the left ventricle is either defective or damaged, thus disrupting healthy function. Normal LV function can be perturbed because of several causes. Some cardiac defects such as valvular malformations or conditions block the passage of blood into the body. Effective and cost-effective treatment is available for such patients that can reduce both morbidity and mortality. Herein, the authors present the case of a 69-year-old male who was brought to the emergency department with a history of hypertension on medication. Later, the patient was transferred to the cardiology department. The patient was brought to the hospital after midnight and had bleeding gums, and experienced bleeding from the site of needle puncture. Earlier reports showed that the international normalised ratio was >6.0, and the 2D echocardiogram showed large LV blood clots, mild LV dysfunction, mild mitral regurgitation, and aortic valve stenosis. Finally, the patient was diagnosed with ischaemic cardiomyopathy associated with LV dysfunction. During discharge, the patient and patient’s representative were counselled in layman’s language about the conditions and prognosis of the disease, the use and adherence to medications, lifestyle modifications, and were advised to review back to the cardiologist.
Molecular Identification and Antifungal
Susceptibility Profiles of Non-albicans Candida
Species Clinical Isolates
Authors: Diba Kambiz , Makhdoomi Khadijeh , Aboutalebian Shima
Published: December 2021

Background: There is an increasing incidence of life-threatening systemic mycoses, specifically fulminant infections by the Candida species in hospitalised patients and in those who are immunocompromised. Management of the limited number of antifungal drugs currently available requires the identification of infections containing drug-resistant isolates.

Objectives: The aim of this study was to identify the non-albicans Candida species as azole-resistant fungi, isolated from sputum and bronchoalveolar lavage specimens of hospitalised cases.

Methods: The subjects included hospital-acquired infection (HAI) cases, with a primary diagnosis using a direct microscopic examination, performed for the detection of probable fungi. The molecular tests of PCR-restriction fragment length polymorphism (RFLP) and real-time PCR were performed to confirm the identity and molecular typing of the Candida isolates. Antifungal susceptibility testing (AFST), by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution (BMD) minimum inhibitory concentration (MIC) (M27-A2) method, was performed on the hospital-isolated
Candida species.

Results: During 24 months, from August 2014 to September 2016, a total of 198 samples were obtained from cases with proven HAI. The results of experimental studies on the specimens showed 93 (47%) positive cases for a fungal or bacterial infection, of which 54 (58%) had a fungal infection. It was hypothesised that all of the isolated organisms were causative agents of the HAI.

Conclusions: The results showed that the medium CHROMagar™ Candida is an accessible and easy-to-use method for the identification of infection, but not as accurate and reliable as PCR-RFLP and real-time PCR methods. Results also showed decreasing susceptibility to azoles (itraconazole in this study) of the Candida species.
Diversity and nitrogen-fixing activity of cyanoprokaryotes in the sphagnum cover of swamps in northeast European Russia
Authors: Patova Elena N. , Sivkov Michail D.
Published: December 2021

New knowledge has been obtained about the diversity and functional characteristics of cyanoprokaryotes associated with sphagnum mosses in bog complexes of the boreal zone of the European North and the Subpolar Urals. 19 species of diazotrophic cyanoprokaryotes were identified. The quantitative characteristics of nitrogen-fixing cyanoprokaryotes in epiphytic groups of sphagnum mosses and their seasonal changes were studied. It was revealed that Nostoc paludosum, N. punctiforme, Microchaete tenera form the basis of the dominant complexes of cyanoprokaryotes, actively fixing nitrogen in the studied communities. It was shown that N2 fixation in communities of the same type in the studied geographic regions had similar values. For a floodplain bog in the taiga zone, seasonal measurements of N2 fixation and quantitative indicators of cyanoprokaryotes associated with the sphagnum mosses Sphagnum riparium and S. angustifolium were carried out. N2 fixation in the season was more dependent on temperature conditions. On average, from 1.2 to 12.3 thousand colonies of nitrogen-fixing cyanoprokaryotes were recorded per 1 cm2 of sphagnum moss sod. The maximum values of the rates of N2 fixation, measured by the method of acetylene reduction, were noted in the range of 0.55–3.59 mg C2H4 m–2h–1. The maximum values of seasonal N2 fixations were 3,5 g C2H4 m–2 for S. angustifolium and 4,6 g C2H4 m–2 for S. riparium.
John Maynard Keynes Between Old and New Institutionalism
Authors: Miranda Cavalcante Carolina , De Oliveira Boff Emmanoel
Published: December 2021

The article considers the possible compatibility (in epistemological and ontological terms) of the conceptions of convention and institutions in the thought of John Maynard Keynes, Thorstein Veblen and Douglass North. We argue, first, that while Veblen suggests an approach to institutions based on instincts, North sustains an approach to institutions based on rational choice, which implies distinct conceptions about institutions and the social world. We then present Keynes's ontological commitments and the epistemological implications of his ontology. We conclude that there is a background ontological compatibility between Keynes and the late North in that both accept that the socioeconomic world is fundamentally uncertain and non-ergodic; also that Keynes is epistemologically closer to North than Veblen in studying the economy as a market system embedded in social institutions; and finally that Keynes's treatment of individual action is closer to Veblen’s than North’s, in that both Keynes and Veblen see human action as based on instincts and not only on rationality.
PROBLEMS OF TERMINOLOGY WITHIN THE CONCEPT OF «UKRAINIAN LAND ART»
Authors: Gamaliia Kateryna , Lisova Nataliia
Published: December 2021

Abstract. Fundamental art studies in the field of land art are not yet available in Ukraine, and individual articles in periodicals do not reveal the principles of the formation of the actual Ukrainian art of the environment, its features and differences from abroad land art. To date, the phenomenon of Ukrainian land art has not received its own term and for thirty years in a row uses the borrowed foreign name «land art», while the uniqueness of domestic environmental art is an indisputable fact. The article considers the peculiarities of the formation of land art abroad and in the system of Ukrainian contemporary art. The analysis and clarification of terminology related to land art in Ukraine has been carried out. The author's term for the phenomenon of the Ukrainian land art is offered. The study found that the application of the foreign term «land art» to the domestic art of interaction with the environment is not exhaustive, because it does not reveal the full range of creative communication of artists with the environment and is too narrow in relation to it. At that time, the term «mystectvo dovkillja» («art of the environment»), introduced by P. Bevza, is too wide a range of artistic creativity, where «environment» is used in the sense of «environment» as one that contains the entire surrounding space. Therefore, it isn't inexpedient to apply the foreign term «land art» to the creative practices of Ukrainian artists. At the same time, «art of the environment» is too abstract a concept for the term «land art», which aims at a specific creative interaction with the earth. Environmental art aims to decorate and equip a person's place of residence, which expresses his utilitarianism and may include: both landscape art and landscape design and monumental art, site-specific art, ecological art, as preservation and repair of the Earth's resources, etc. Domestic artists work with natural materials in the natural environment in order to create a new art product. Accordingly, instead of the term «Ukrainian land art» it is appropriate to use the term «pryrodotvorche mystectvo» («natural creative art»), because the context of the Ukrainian art form is characterized by creative interaction with the natural environment and materials as a way to create a new art product. Theoretical research of the work is the basis for further in-depth scientific development of the problem, namely, the phenomenon of land art in the system of contemporary art of Ukraine.
Invitro mycoparasitism activity of Trichoderma spp against Fusarium solani inciting root rot of chickpea ( Cicer arietinum L.)
Authors: Andoji Yogesh Suresh , S Sutar Aruna
Published: December 2021

Root rot of chickpea (Cicer arietinum L.) is caused by Fusarium solani. This paper describes the efficacy of Trichoderma spp. against sensitive and resistant isolates of F, solani by dual culture method under invitro conditions. Trichoderma virens, T. atroviride, T. viride, T. harzianum, T. koningiopsis, T. stilbohypoxyli,and T. pseudokoningii species were used for the antagonistic study. Results indicate that all Trichoderma species showed great antagonistic activity. But among them, T. virens, T. atroviride, T. viride showed 90% and 80 % antagonistic activity than others in case of a sensitive isolate of test fungus. The resistant isolate of the pathogen was restricting the antagonism to some extent.
Callus induction and chemical characterization of cell suspension cultures of jojoba (Simmondsia chinensis L.)
Authors: Akram Muhammad , Aftab Faheem
Published: December 2021

Jojoba (Simmondsia chinensis L.) oil is also known as liquid wax or fixed oil. It is an important metabolite of jojoba having commercial importance in cosmetics as well as a potential biofuel source. We presented an efficient system for in vitro establishment of cell suspension cultures (CSC) from proliferating friable calluses. For this purpose, cotyledon, internode, and leaf explants were cultured on MS medium + 1, 2, 4, 6, 8 or 10 µM 2, 4-Dichlorophenoxyacetic acid (2, 4-D), α-Naphthalene acetic acid (NAA) alone or in combination with 1 or 2 µM N6-benzylaminopurine (BAP) or Kinetin. Results demonstrated that 100% healthy, friable and variegated calluses were obtained on 8 µM, 10 µM 2, 4-D or 2, 4-D 10 µM + 2 µM BAP and represented as callus lines (CL) CL-1, CL-2 or CL-3, respectively, after 38 days. One-gram callus tissue per CL was then immersed in the respective liquid medium and agitated on an orbital shaker at 60-70 rpm under the growth room conditions (25 ± 2 °C, 16 h light period) for the preparation of CSC. After 15 days, CSC was sieved and large clumps were removed. Growth measurement of CSC was determined by cell counting, packed cell volume (PCV) and cell viability. The highest number of viable cells was obtained at 2.57 OD with CL-3, where PCV was highest (0.35 ml) on CL-1 of 38 days old calluses. 2,3,5-Triphenyltetrazolium chloride was a reliable approach for the determination of cell viability of CSC.
The Regulators Associated With N6-Methyladenosine in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma Reveal New Clinical and Prognostic Markers
Authors: Tan Shuzhen , Li Zesong , Li Kai , Li Yingqi , Liang Guosheng , Tang Zhenye , Kang Jianhao , Chen Wenqing , Li Minhua , Zou Zhilin , Pi Guoliang , Zhu Xiao
Published: December 2021

N6-methyladenosine (m6A) methylation is of significant importance in the initiation and progression of tumors, but how specific genes take effect in different lung cancers still needs to be explored. The aim of this study is to analyze the correlation between the m6A RNA methylation regulators and the occurrence and development of lung cancer. The data of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were obtained through the TCGA database. We systematically analyzed the related pathological characteristics and prognostic factors by applying univariate and multivariate Cox regression, as well as LASSO Cox regression. Some of 23 m6A regulators are identified as having high expression in lung cancer. In addition, risk score has been shown to be an independent prognostic factor in lung cancer. Our research not only fully reveals that m6A regulators and clinical pathological characteristics are potentially useful with respect to survival and prognosis in different lung tumors but also can lay a theoretical root for the treatment for lung cancer—notably, to point out a new direction for the development of treatment.
m6A Modification-Mediated DUXAP8 Regulation of Malignant Phenotype and Chemotherapy Resistance of Hepatocellular Carcinoma Through miR-584-5p/MAPK1/ERK Pathway Axis
Authors: Liu Zefeng , Lu Jin , Fang He , Sheng Jiyao , Cui Mengying , Yang Yongsheng , Tang Bo , Zhang Xuewen
Published: December 2021

Hepatocellular carcinoma (HCC) has a poor prognosis due to its high malignancy, rapid disease progression, and the presence of chemotherapy resistance. Long-stranded non-coding RNAs (lncRNAs) affect many malignant tumors, including HCC. However, their mechanism of action in HCC remains unclear. This study aimed to clarify the role of DUXAP8 in regulating the malignant phenotype and chemotherapy resistance in HCC. Using an in vivo xenograft tumor model, the regulatory functions and mechanisms of lncRNA DUXAP8 in the progression and response of HCC to chemotherapy were explored. It was found that DUXAP8 was significantly upregulated in a patient-derived xenograft tumor model based on sorafenib treatment, which is usually associated with a relatively poor prognosis in patients. In HCC, DUXAP8 maintained its upregulation in the expression by increasing the stability of m6A methylation-mediated RNA. DUXAP8 levels were positively correlated with the proliferation, migration, invasion, and chemotherapy resistance of HCC in vivo and in vitro. In the mechanistic study, it was found that DUXAP8 competitively binds to miR-584-5p through a competing endogenous RNA (ceRNA) mechanism, thus acting as a molecular sponge for miR-584-5p to regulate MAPK1 expression, which in turn activates the MAPK/ERK pathway. These findings can provide ideas for finding new prognostic indicators and therapeutic targets for patients with HCC.
Septins in Stem Cells
Authors: Schuster Tanja , Geiger Hartmut
Published: December 2021

Septins were first described in yeast. Due to extensive research in non-yeast cells, Septins are now recognized across all species as important players in the regulation of the cytoskeleton, in the establishment of polarity, for migration, vesicular trafficking and scaffolding. Stem cells are primarily quiescent cells, and this actively maintained quiescent state is critical for proper stem cell function. Equally important though, stem cells undergo symmetric or asymmetric division, which is likely linked to the level of symmetry found in the mother stem cell. Due to the ability to organize barriers and be able to break symmetry in cells, Septins are thought to have a significant impact on organizing quiescence as well as the mode (symmetric vs asymmetric) of stem cell division to affect self-renewal versus differentiation. Mechanisms of regulating mammalian quiescence and symmetry breaking by Septins are though still somewhat elusive. Within this overview article, we summarize current knowledge on the role of Septins in stem cells ranging from yeast to mice especially with respect to quiescence and asymmetric division, with a special focus on hematopoietic stem cells.
Multifunctional Chiral Three-Dimensional Phosphite Frameworks Showing Dielectric Anomaly and High Proton Conductivity
Authors: Yu S. S. , Xu C. Y. , Pan X. , Pan X. Q. , Duan H. B. , Zhang H.
Published: December 2021

Chair 3D Co(II) phosphite frameworks have been prepared by the ionothermal method. It belongs to chiral space group P3221, and the whole framework can be topologically represented as a chiral 4-connected qtz net. It shows a multistep dielectric response arising from the reorientation of Me2-DABCO in the chiral cavities. It can also serve as a pron conductor with high conductivity, 1.71 × 10−3 S cm−1, at room temperature, which is attributed to the formation of denser hydrogen-bonding networks providing efficient proton-transfer pathways.
Synergistic Combination of Facile Thiol-Maleimide Derivatization and Supramolecular Solvent-Based Microextraction for UHPLC–HRMS Analysis of Glutathione in Biofluids
Authors: Yan Mengmeng , Gao Feng , Chen Meng , Hu Qi , Yang Yuqin , Chen Kedian , Wang Penglong , Lei Haimin , Ma Qiang
Published: December 2021

Glutathione (GSH) is the most abundant non-protein thiol in biofluids, enabling diverse physiological functions. Among the proposed methods for GSH detection, ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry (HRMS) has the advantages of high sensitivity and efficiency. In this study, a novel analytical method was developed for the determination of GSH using supramolecular solvent (SUPRAS)-based dispersive liquid–liquid microextraction (DLLME) and UHPLC–HRMS. N-Laurylmaleimide was dissolved in tetrahydrofuran, which served three functions: 1) precipitate the proteins present in the biofluid sample, 2) provide a reaction environment for derivatization, and 3) enable the use of SUPRAS as the dispersing agent. Critical parameters were optimized based on single factor testing and response surface methodology. The established method was validated in terms of linearity, accuracy, precision, and successful quantitative analysis of GSH in saliva, urine, and plasma samples. Experimental results showed that SUPRAS as an extraction solvent was particularly suitable for the extraction of GSH from complex matrices. The current study provides a useful tool for accurate measurements of GSH concentrations, which could potentially be used for clinical diagnostics.
Brain-Computer Interfaces and Creative Expression: Interface Considerations for Rehabilitative and Therapeutic Interactions
Authors: Scott Stephanie M. , Raftery Chris
Published: December 2021

By translating brain signals into new kinds of outputs, Brain-Computer Interface (BCI) systems hold tremendous potential as both transformative rehabilitation and communication tools. BCIs can be considered a unique technology, in that they are able to provide a direct link between the brain and the external environment. By affording users with opportunities for communication and self-expression, BCI systems serve as a bridge between abled-bodied and disabled users, in turn reducing existing barriers between these groups. This perspective piece explores the complex shifting relationship between neuroadaptive systems and humans by foregrounding personal experience and embodied interaction as concepts through which to evaluate digital environments cultivated through the design of BCI interfaces. To underscore the importance of fostering human-centered experiences through technologically mediated interactions, this work offers a conceptual framework through which the rehabilitative and therapeutic possibilities of BCI user-system engagement could be furthered. By inviting somatic analysis towards the design of BCI interfaces and incorporating tenets of creative arts therapies practices into hybrid navigation paradigms for self-expressive applications, this work highlights the need for examining individual technological interactions as sites with meaning-making potentiality, as well as those conceived through unique exchanges based on user-specific needs for communication. Designing BCI interfaces in ways that afford users with increased options for navigation, as well as with the ability to share subjective and collective experiences, helps to redefine existing boundaries of digital and physical user-system interactions and encourages the reimagining of these systems as novel digital health tools for recovery.
Landslide Susceptibility Zoning Using C5.0 Decision Tree, Random Forest, Support Vector Machine and Comparison of Their Performance in a Coal Mine Area
Authors: Su Qiaomei , Tao Weiheng , Mei Shiguang , Zhang Xiaoyuan , Li Kaixin , Su Xiaoye , Guo Jianli , Yang Yonggang
Published: December 2021

The main purpose of this study is to establish an effective landslide susceptibility zoning model and test whether underground mined areas and ground collapse in coal mine areas seriously affect the occurrence of landslides. Taking the Fenxi Coal Mine Area of Shanxi Province in China as the research area, landslide data has been investigated by the Shanxi Geological Environment Monitoring Center; adopting the 5-fold cross-validation method, and through Geostatistics analysis means the datasets of all non-landslides and landslides were divided into 80:20 proportions randomly for training and validating models. A set of 15 condition factors including terrain, geological, hydrological, land cover, and human engineering activity factors (distance to road, distance to mined area, ground collapse density) were selected as the evaluation indices to construct the susceptibility assessment model. Three machine learning algorithms for landslide susceptibility prediction (LSP) including C5.0 Decision Tree (C5.0), Random Forest (RF), and Support Vector Machine (SVM) have been selected and compared through the Areas under the Receiver Operating Characteristics (ROC) Curves (AUC), and several statistical estimates. The study revealed that for these three models the value range of prediction accuracies vary from 83.49 to 99.29% (in the training stage), and 62.26–73.58% (in the validation stage). In the two stages, AUCs are between 0.92 to 0.99 and 0.71 to 0.80 respectively. Using Jenks Natural Breaks algorithm, three LSPs levels are established as very low, low, medium, high, and very high probability of landslide by dividing the indices of the LSP. Compared with RF and SVM, C5.0 is considered better in five categories according to quantities and distribution of the landslides and their area percentage for different LSP zones. Four factors such as distance to road, lithology, profile curvature, and ground collapse density are the most suitable condition factors for LSP. The distance to mine area factor has a medium contribution and plays an obvious role in the occurrence of landslides in all the models. The result reveals that C5.0 possesses better prediction efficiency than RF and SVM, and underground mined area and ground collapse sifnigicantly affect significantly the occurrence of landslides in the Fenxi Coal Mine Area.
A Granular Thermodynamic Model to Describe the Temperature/Mechanical Characteristics of Sandy Soil
Authors: Zhou Rui , Gao Siyuan , Wang Wei
Published: December 2021

Based on the granular-solid-hydrodynamic theory, the constitutive model considering the thermo-hydro-mechanical (THM) coupled action is established, and the dilatancy property of sandy soil under coupled high mechanical pressure and temperature is simulated. The relationship between the energy dissipation and the macroscopic stress-strain changes at the grain level of saturated sandy soil is connected by defining the transfer coefficient and the energy function, without considering the concepts of yield surface and hardening parameters in classical plastic mechanics. Additionally, the changes in temperature, relative density and confining pressure during the shearing process cause particle rolling, slipping and friction. The energy dissipation in this process is described by defining the concept of particle entropy and particle temperature. In the calculation, the isotropic compression test, drained and undrained shear test of sandy soil under high stress are simulated respectively. The validity of the model is proved by comparing with the test results. Meanwhile, the stress-strain relationship and pore pressure variation law of sandy soil under different temperatures are predicted. The results show that the effect of temperature on shear strength is limited, and the pore pressure will gradually increase and become stable with the increase of temperature. Thus, this work establishes the soil THM coupled model from the perspective of micro energy dissipation, which can provide new theoretical support for the prediction of natural disasters such as landslides and debris flow.
Element Distribution and Migration Behavior in the Copper Slag Reduction and Separation Process
Authors: Zuo Zongliang , Feng Yan , Luo Siyi , Dong Xinjiang , Li Xiaoteng , Ren Dongdong , Yu Qingbo , Guo Jianxiang
Published: December 2021

Copper slag is a solid pollutant with high recyclability. Reduction and separation are regarded as effective disposal methods. However, during the melting process, the separation and migration behavior of elements in the copper slag is complicated. Thus, the formation of pollutants cannot be controlled merely by optimizing the operation parameters. The elemental distribution and migration behavior are discussed in this work. In reduction experiments, the copper slag smelting liquid was divided into three layers: a reduction slag layer, a reactive boundary layer, and an iron ingot layer. Reduction slag and ingot iron were on the top and bottom of the liquid, respectively. Residual carbon oozed at the interface. C can react with reducible “O” atoms, which exist in 2FeO·SiO2, Fe3O4, and CuO. Meanwhile, CO was generated and overflowed from the liquid layer. After reduction by C or CO, metallic iron and copper were produced and migrated to the iron ingot layer. In the liquid, S gradually diffused into the upper layer. Some of the ZnO and CuS spilled from the liquid into the flume. After reduction, CaO·SiO2 was generated and moved to the upper layer.
Economic Analysis of Developing a Sustainable Aviation Fuel Supply Chain Incorporating With Carbon Credits: A Case Study of the Memphis International Airport
Authors: Sharma Bijay P , Yu T. Edward , English Burton C. , Boyer Christopher N.
Published: December 2021

Sustainable aviation fuel (SAF) has been considered as a potential means to mitigate greenhouse gas (GHG) emissions from the aviation sector, which is projected to continuously expand. This study examines the impact of developing a SAF sector along with carbon credits on carbon equivalent emissions from aviation using a Stackelberg leader-follower model that accounts for economic interaction between SAF processor and feedstock producers. The modeling framework is applied to an ex-ante optimization of commercial scale SAF production for the Memphis International Airport from the switchgrass-based alcohol-to-jet pathway. Results suggest that supplying 136 million gallons of SAF to the Memphis International Airport annually could reduce 62.5% of GHG emissions compared to conventional jet fuel (CJF). Incorporating with carbon credits, SAF could lower GHG emissions by about 65% in total from displacing CJF and generate additional welfare gains ranging between $12 and $51 million annually compared to the case without carbon credits. In addition, sensitivity analysis suggests advancing SAF conversion rate from biomass could lower the SAF break-even considerably and enhance the competitiveness of SAF over CJF.
The Influence of Host Country’s Environmental Regulation on Enterprises’ Risk Preference of Multinational Investment
Authors: Peng Cheng , Jiang Hui
Published: December 2021

At present, China is in an important period of promoting high-quality economic development. In order to promote enterprises to “go global” and realize high-quality foreign investment, China advocates enterprises to abide by the environmental protection laws and regulations of the host country and standardize their environmental protection behaviors in foreign investment cooperation. However, the impact of the host country’s environmental regulation on Chinese enterprise’s multinational investment risk preference has not been paid enough attention. This paper makes an empirical analysis on how the host country’s environmental regulation affects the enterprises’ risk preference of multinational investment (MIRP) by using the samples of A-share listed companies in China from 2010 to 2018 and emphatically examines the moderating effects of enterprise’s green technology innovation and social responsibility on the relationship between host country’s environmental regulation and enterprises’ MIRP. It is found that, on the whole, the environmental regulation of the host country will significantly promote the enterprises’ MIRP. The green technology innovation will positively moderate the impact of the environmental regulation of host country on enterprises’ MIRP, while the engagement of corporate social responsibility will inhibit this positive impact.
A Novel, Benchmark-Centered, Eco-Impact Rating System for Sunscreens and Sunscreen Formulation Design
Authors: Kunze Gernot , Schlifke Alexander , Jackson Eileen , Hefner Nicola , Berg Katja , Vollhardt Jürgen
Published: December 2021

Ultraviolet (UV) filter compounds are the key constituents in sunscreens that protect human skin from detrimental solar radiation. Some of these products have attracted public attention due to claims of their potential negative impact on the environment, in particular marine fauna and flora. At present, consumers who want to make an eco-conscious decision cannot find suitable product details and need to rely on fragmented information or complex scientific literature. The same is true for sunscreen developers, typically formulation chemists, who at present can only work with black- and whitelists which recommend or omit compounds. The ecological impact evaluation system proposed in this publication makes it easier to choose UV filters. Selection is based intrinsically on specialized knowledge which is built on environmental safety data. By embedding this in an existing in-silico sunscreen design system, new products can be created during the project’s design phase without time and cost intensive investigations. In contrast to currently available methods, the proposed tool includes comparison with a virtual market benchmark so users can determine whether a newly developed product will be an improvement on the state of the art in terms of environmental compatibility. The level of improvement can be displayed as a logo which has been designed to be immediately understandable to consumers. The system can be re-adjusted in regular time frames, depending on market development, to motivate and drive the sunscreen industry towards more eco-compatible products.
Major Evolutionary Transitions and the Roles of Facilitation and Information in Ecosystem Transformations
Authors: Robin Amanda N. , Denton Kaleda K. , Horna Lowell Eva S. , Dulay Tanner , Ebrahimi Saba , Johnson Gina C. , Mai Davis , O’Fallon Sean , Philson Conner S. , Speck Hayden P. , Zhang Xinhui Paige , Nonacs Peter
Published: December 2021

A small number of extraordinary “Major Evolutionary Transitions” (METs) have attracted attention among biologists. They comprise novel forms of individuality and information, and are defined in relation to organismal complexity, irrespective of broader ecosystem-level effects. This divorce between evolutionary and ecological consequences qualifies unicellular eukaryotes, for example, as a MET although they alone failed to significantly alter ecosystems. Additionally, this definition excludes revolutionary innovations not fitting into either MET type (e.g., photosynthesis). We recombine evolution with ecology to explore how and why entire ecosystems were newly created or radically altered – as Major System Transitions (MSTs). In doing so, we highlight important morphological adaptations that spread through populations because of their immediate, direct-fitness advantages for individuals. These are Major Competitive Transitions, or MCTs. We argue that often multiple METs and MCTs must be present to produce MSTs. For example, sexually-reproducing, multicellular eukaryotes (METs) with anisogamy and exoskeletons (MCTs) significantly altered ecosystems during the Cambrian. Therefore, we introduce the concepts of Facilitating Evolutionary Transitions (FETs) and Catalysts as key events or agents that are insufficient themselves to set a MST into motion, but are essential parts of synergies that do. We further elucidate the role of information in MSTs as transitions across five levels: (I) Encoded; (II) Epigenomic; (III) Learned; (IV) Inscribed; and (V) Dark Information. The latter is ‘authored’ by abiotic entities rather than biological organisms. Level IV has arguably allowed humans to produce a MST, and V perhaps makes us a FET for a future transition that melds biotic and abiotic life into one entity. Understanding the interactive processes involved in past major transitions will illuminate both current events and the surprising possibilities that abiotically-created information may produce.
Impact of NK Cell Activating Receptor Gene Variants on Receptor Expression and Outcome of Immunotherapy in Acute Myeloid Leukemia
Authors: Hussein Brwa Ali , Hallner Alexander , Wennström Lovisa , Brune Mats , Martner Anna , Hellstrand Kristoffer , Bernson Elin , Thorén Fredrik B.
Published: December 2021

Natural killer cells are important effector cells in the immune response against myeloid malignancies. Previous studies show that the expression of activating NK cell receptors is pivotal for efficient recognition of blasts from patients with acute myeloid leukemia (AML) and that high expression levels impact favorably on patient survival. This study investigated the potential impact of activating receptor gene variants on NK cell receptor expression and survival in a cohort of AML patients receiving relapse-preventive immunotherapy with histamine dihydrochloride and low-dose IL-2 (HDC/IL-2). Patients harboring the G allele of rs1049174 in the KLRK1 gene encoding NKG2D showed high expression of NKG2D by CD56bright NK cells and a favorable clinical outcome in terms of overall survival. For DNAM-1, high therapy-induced receptor expression entailed improved survival, while patients with high DNAM-1 expression before immunotherapy associated with unfavorable clinical outcome. The previously reported SNPs in NCR3 encoding NKp30, which purportedly influence mRNA splicing into isoforms with discrete functions, did not affect outcome in this study. Our results imply that variations in genes encoding activating NK cell receptors determine receptor expression and clinical outcome in AML immunotherapy.
Trajectory and Correlation of Intrinsic Capacity and Frailty in a Beijing Elderly Community
Authors: Liu Shuo , Kang Lin , Liu XiaoHong , Zhao SongQi , Wang XuePing , Li JiaoJiao , Jiang Shan
Published: December 2021

Objectives: The World Health Organization proposed intrinsic capacity (IC) model to guide the implementation of person-centered care plan aimed at preserving or reserving functional ability, especially in frail older adults. We aimed to show the trajectory of IC and the overlap between IC impairment and frailty and investigate the correlation between IC domains and frailty status transitions.

Method: Longitudinal observational study covering 230 community-dwelling older adults (mean age 84.0 ± 4.5 years) at baseline, and transition information at 2-year follow-up (n = 196). IC was measured by five domains: locomotion, cognition, vitality, psychological, and sensory. Frailty was defined by FRAIL Scale. IC and frailty status transitions were assessed. Logistic regression, odds ratios (OR) and 95% confidence interval (CI) were used for the analysis.

Results: The prevalence of frailty was 23.0% and increased up to 41.8% over two years. Regarding frailty transitions, 38.3% of older adults progressed to more frailty status, and 8.6% regressed to lesser frailty status. The prevalence of IC impairment was 67.9% and increased to 81.6% over two years. Regarding IC transitions, 49.2% of adults with no IC impairment at baseline kept stable, and 50.8% developed new IC impairment. Among individuals with IC impairment at baseline, 57.9% worsened, and 13.5% improved. Importantly, IC impairment at baseline existed in 42.4% robust adults, 83.3% pre-frail adults, and 93.3% frail adults. 47.1% individuals who kept non-frail status within two years experienced IC worsened transition. Univariable analysis illustrated that new impaired locomotion, vitality, cognition, and sensory domains increased the risk of non-frail progressed to frail status. After adjusting for covariables, new impaired locomotion (OR = 3.625, 95% CI: 1.348–9.747) and vitality domains (OR = 3.034, 95% CI: 1.229–7.487) were associated with a higher possibility of non-frail progressed to frail status.

Conclusion: IC impairment and frailty overlap and co-exist in older adults. IC impairment, especially new impairment in locomotion and vitality are associated with the transitions from non-frail to frail status. It is important that geriatricians tightly monitor IC trajectory and find the new impaired domains to take early action to minimize the public health burden of frailty.
Usefulness of Machine Learning for Identification of Referable Diabetic Retinopathy in a Large-Scale Population-Based Study
Authors: Yang Cheng , Liu Qingyang , Guo Haike , Zhang Min , Zhang Lixin , Zhang Guanrong , Zeng Jin , Huang Zhongning , Meng Qianli , Cui Ying
Published: December 2021

Purpose: To development and validation of machine learning-based classifiers based on simple non-ocular metrics for detecting referable diabetic retinopathy (RDR) in a large-scale Chinese population–based survey.

Methods: The 1,418 patients with diabetes mellitus from 8,952 rural residents screened in the population-based Dongguan Eye Study were used for model development and validation. Eight algorithms [extreme gradient boosting (XGBoost), random forest, naïve Bayes, k-nearest neighbor (KNN), AdaBoost, Light GBM, artificial neural network (ANN), and logistic regression] were used for modeling to detect RDR in individuals with diabetes. The area under the receiver operating characteristic curve (AUC) and their 95% confidential interval (95% CI) were estimated using five-fold cross-validation as well as an 80:20 ratio of training and validation.

Results: The 10 most important features in machine learning models were duration of diabetes, HbA1c, systolic blood pressure, triglyceride, body mass index, serum creatine, age, educational level, duration of hypertension, and income level. Based on these top 10 variables, the XGBoost model achieved the best discriminative performance, with an AUC of 0.816 (95%CI: 0.812, 0.820). The AUCs for logistic regression, AdaBoost, naïve Bayes, and Random forest were 0.766 (95%CI: 0.756, 0.776), 0.754 (95%CI: 0.744, 0.764), 0.753 (95%CI: 0.743, 0.763), and 0.705 (95%CI: 0.697, 0.713), respectively.

Conclusions: A machine learning–based classifier that used 10 easily obtained non-ocular variables was able to effectively detect RDR patients. The importance scores of the variables provide insight to prevent the occurrence of RDR. Screening RDR with machine learning provides a useful complementary tool for clinical practice in resource-poor areas with limited ophthalmic infrastructure.
Dipolar Order Parameters in Large Systems With Fast Spinning
Authors: Franks W. Trent , Tatman Ben P. , Trenouth Jonah , Lewandowski Józef R.
Published: December 2021

Order parameters are a useful tool for quantifying amplitudes of molecular motions. Here we measure dipolar order parameters by recoupling heteronuclear dipole-dipole couplings under fast spinning. We apply symmetry based recoupling methods to samples spinning under magic angle at 60 kHz by employing a variable flip angle compound inversion pulse. We validate the methods by measuring site-specific 15N-1H order parameters of a microcrystalline protein over a small temperature range and the same protein in a large, precipitated complex with antibody. The measurements of the order parameters in the complex are consistent with the observed protein undergoing overall motion within the assembly.
Friedreich's Ataxia Frequency in a Large Cohort of Genetically Undetermined Ataxia Patients
Authors: Brown Alexander F. , Parkinson Michael H. , Garcia-Moreno Hector , Mudanohwo Ese , Labrum Robyn , Sweeney Mary , Giunti Paola
Published: December 2021

Background: Patients with suspected genetic ataxia are often tested for Friedreich's ataxia (FRDA) and/or a variety of spinocerebellar ataxias (SCAs). FRDA can present with atypical, late-onset forms and so may be missed in the diagnostic process. We aimed to determine FRDA-positive subjects among two cohorts of patients referred to a specialist ataxia centre either for FRDA or SCA testing to determine the proportion of FRDA cases missed in the diagnostic screening process.

Methods: 2000 SCA-negative ataxia patients, not previously referred for FRDA testing (group A), were tested for FRDA expansions and mutations. This group was compared with 1768 ataxia patients who had been previously referred for FRDA testing (group B) and were therefore more likely to have a typical presentation. The phenotypes of positive cases were assessed through review of the clinical case notes.

Results: Three patients (0.2%) in group A had the FRDA expansion on both alleles, compared with 207 patients (11.7%) in group B. The heterozygous carrier rate across both cohorts was of 41 out of 3,768 cases (1.1%). The size of the expansions in the three FRDA-positive cases in group A was small, and their presentation atypical with late-onset.

Conclusions: This study demonstrates that FRDA is very rare among patients who were referred purely for SCA testing without the clinical suspicion of FRDA. Such cases should be referred to specialist ataxia centres for more extensive testing to improve patient management and outcomes.
Immune Modulation as a Key Mechanism for the Protective Effects of Remote Ischemic Conditioning After Stroke
Authors: Abbasi-Habashi Sima , Jickling Glen C. , Winship Ian R.
Published: December 2021

Remote ischemic conditioning (RIC), which involves a series of short cycles of ischemia in an organ remote to the brain (typically the limbs), has been shown to protect the ischemic penumbra after stroke and reduce ischemia/reperfusion (IR) injury. Although the exact mechanism by which this protective signal is transferred from the remote site to the brain remains unclear, preclinical studies suggest that the mechanisms of RIC involve a combination of circulating humoral factors and neuronal signals. An improved understanding of these mechanisms will facilitate translation to more effective treatment strategies in clinical settings. In this review, we will discuss potential protective mechanisms in the brain and cerebral vasculature associated with RIC. We will discuss a putative role of the immune system and circulating mediators of inflammation in these protective processes, including the expression of pro-and anti-inflammatory genes in peripheral immune cells that may influence the outcome. We will also review the potential role of extracellular vesicles (EVs), biological vectors capable of delivering cell-specific cargo such as proteins and miRNAs to cells, in modulating the protective effects of RIC in the brain and vasculature.
LeGUI: A Fast and Accurate Graphical User Interface for Automated Detection and Anatomical Localization of Intracranial Electrodes
Authors: Davis Tyler S. , Caston Rose M. , Philip Brian , Charlebois Chantel M. , Anderson Daria Nesterovich , Weaver Kurt E. , Smith Elliot H. , Rolston John D.
Published: December 2021

Accurate anatomical localization of intracranial electrodes is important for identifying the seizure foci in patients with epilepsy and for interpreting effects from cognitive studies employing intracranial electroencephalography. Localization is typically performed by coregistering postimplant computed tomography (CT) with preoperative magnetic resonance imaging (MRI). Electrodes are then detected in the CT, and the corresponding brain region is identified using the MRI. Many existing software packages for electrode localization chain together separate preexisting programs or rely on command line instructions to perform the various localization steps, making them difficult to install and operate for a typical user. Further, many packages provide solutions for some, but not all, of the steps needed for confident localization. We have developed software, Locate electrodes Graphical User Interface (LeGUI), that consists of a single interface to perform all steps needed to localize both surface and depth/penetrating intracranial electrodes, including coregistration of the CT to MRI, normalization of the MRI to the Montreal Neurological Institute template, automated electrode detection for multiple types of electrodes, electrode spacing correction and projection to the brain surface, electrode labeling, and anatomical targeting. The software is written in MATLAB, core image processing is performed using the Statistical Parametric Mapping toolbox, and standalone executable binaries are available for Windows, Mac, and Linux platforms. LeGUI was tested and validated on 51 datasets from two universities. The total user and computational time required to process a single dataset was approximately 1 h. Automatic electrode detection correctly identified 4362 of 4695 surface and depth electrodes with only 71 false positives. Anatomical targeting was verified by comparing electrode locations from LeGUI to locations that were assigned by an experienced neuroanatomist. LeGUI showed a 94% match with the 482 neuroanatomist-assigned locations. LeGUI combines all the features needed for fast and accurate anatomical localization of intracranial electrodes into a single interface, making it a valuable tool for intracranial electrophysiology research.
An Overview of Appetite-Regulatory Peptides in Addiction Processes; From Bench to Bed Side
Authors: Shevchouk Olesya T. , Tufvesson-Alm Maximilian , Jerlhag Elisabet
Published: December 2021

There is a substantial need for new pharmacological treatments of addiction, and appetite-regulatory peptides are implied as possible candidates. Appetite regulation is complex and involves anorexigenic hormones such as glucagon-like peptide-1 (GLP-1) and amylin, and orexigenic peptides like ghrelin and all are well-known for their effects on feeding behaviors. This overview will summarize more recent physiological aspects of these peptides, demonstrating that they modulate various aspects of addiction processes. Findings from preclinical, genetic, and experimental clinical studies exploring the association between appetite-regulatory peptides and the acute or chronic effects of addictive drugs will be introduced. Short or long-acting GLP-1 receptor agonists independently attenuate the acute rewarding properties of addictive drugs or reduce the chronic aspects of drugs. Genetic variation of the GLP-1 system is associated with alcohol use disorder. Also, the amylin pathway modulates the acute and chronic behavioral responses to addictive drugs. Ghrelin has been shown to activate reward-related behaviors. Moreover, ghrelin enhances, whereas pharmacological or genetic suppression of the ghrelin receptor attenuates the responses to various addictive drugs. Genetic studies and experimental clinical studies further support the associations between ghrelin and addiction processes. Further studies should explore the mechanisms modulating the ability of appetite-regulatory peptides to reduce addiction, and the effects of combination therapies or different diets on substance use are warranted. In summary, these studies provide evidence that appetite-regulatory peptides modulate reward and addiction processes, and deserve to be investigated as potential treatment target for addiction.