bluuebunny/crossref_metadata_2025 huggingface dataset:
Features of high-filled composites based on various brands of polyvinyl alcohol
Authors: Studenikina L. N. , Domareva S. Y. , Golenskikh Y. E. , Matveeva A. V.
Published: September 2021

Composites based on polyvinyl alcohol (PVA) and polysaccharides (PS) have significant potential for use as compostable packaging materials, as well as in various fields of crop production. PVS are produced by the industry of various brands that differ in molecular weight (MM) and the residual content of vinyl acetate (BA) groups, and as a result - the degree of hydrolysis. Depending on the brand of PVA and the nature of the filler, such properties of composites based on them as water resistance, strength, degree of bioconversion, etc.will differ significantly. The purpose of the work: a comprehensive assessment of the properties of high-filled composites based on PVA of various brands, differing in the degree of hydrolysis, and polysaccharides. Objects of research: composites obtained by direct combination of a 5% solution of PVA (grades 1799, VS-05, BP-05, KurarayPoval 3-83) and PS powder (wood microcellulose - MCD, corn native starch - KK), with and without the addition of a plasticizer (P) - glycerin, followed by dehydration in air or in a vacuum drying cabinet. Based on the presence of external defects after dehydration and the strength characteristics of the material, it was found that for PVA-1799 it is possible to achieve a filling degree of 80 vol.%, for a PVA BP-05, VS-05 KurarayPoval and 3-83-no more than 50 vol.% without plasticizer and up to 70 vol.% in the presence of a plasticizer. It is noted that when filling PVA with starch up to 50 vol.% dehydrated composites are transparent or semi-transparent, which gives them additional advantages as packaging materials (including film). For composites based on PVA-1799, it was found that the maximum water absorption (250% by weight) has a PVA filled with MCD (20: 80 vol.%), and the introduction of a plasticizer (5 vol.% ) significantly reduces the degree of water absorption (up to 150% by weight), which is not typical for this brand of PVA filled with CC (water absorption was about 50% by weight with and without plasticizer). Composites based on PVA grades VS-05, BP-05, KurarayPoval 3-83 dissolve in water at room temperature for 5-10 minutes. During the preliminary assessment of the biodegradation of the studied PVA-1799 composites, it was found that micro-cracks and areas with immobilized microbiota were observed in the polymer matrix during microscopy after 6 months of composting and soil testing, however, no significant damage to the integrity of the polymer of this brand occurred during the specified composting period, which emphasizes the complex nature of the biodegradation of PVA with high MM and low content of VA groups.
Investigation of the elastic and hysteresis properties of tread rubber tires with silica
Authors: Krotova O. A. , Shashok Z. S. , Uss E. P. , Lyushtyk A. Y. , Karmanova O. V.
Published: September 2021

The influence of different types of silica, differing in quality characteristics, on the complex modulus of rubbers, their elastic modulus, loss modulus, and also on the tangent of angle of mechanical loss are investigated. Mineral fillers silica 1 and silica 2 are introduced at a dosage of 80.00 phr into filled elastomeric compositions based on combination of synthetic styrene-butadiene and polybutadiene rubbers, used for the manufacture of treads for passenger tires. The tests are carried out on a dynamic mechanical analyzer by cyclic compression of vulcanizates in the temperature range 20–70°С. It is established that vulcanizates with silica 2 are characterized by 8–56% lower value of the complex modulus. It is revealed that rubbers containing a silica 2, depending on temperature, have 13–36% lower values of the elastic modulus and 19–46% lower values of the loss modulus in comparison with samples filled with silica 2. It is determined that in the temperature range from 20 to 70°C vulcanizates with silica 2 are characterized by 7–12% lower values of the tangent of angle of mechanical loss. As a result of the study, it is established that it is the most expedient to introduce mineral filler silica 2 into the formulation of tread rubber compounds for passenger tires. This will make it possible to obtain vulcanizates with increased elasticity and adhesion to the road surface, as well as lower heat losses to the environment and fuel consumption.
The possibility of using innovative models to refine the most optimal approach to managing the behavior of a commercial organization
Authors: Lapshina M. L. , Lukina O. O.
Published: September 2021

Practical modeling uses not only theoretical approaches, but also management issues, therefore, it is not entirely correct to compare theoretical and mathematical models. The concept of demand exists as an independent unit, has an independent meaning, and the demand model is represented in the form of an increasing curve and, like any model, contains various explicit and implicit conditions. The paper provides an analysis of existing classification approaches on the adaptation of economic and mathematical models in the issue of finding the most appropriate criteria for optimality from the point of view of using the mathematical apparatus. A detailed representation of the top-level structure is given, reflecting the basic requirements for the information necessary for drawing up a model passport, and conditions are also given that limit the area of existence of an operator that determines the corresponding payment matrix of an arbitrary game. The possibility of establishing the number of restrictions on the used variants of the game, which does not change the content of the game, is analyzed, which will allow choosing the most optimal strategies for each case. The proposed and justified, from the point of view of mathematical formalization, approach to making the most optimal decision on managing the behavior of a commercial organization based on preliminary monitoring of economic functioning is of interest from the point of view of the following aspects: the possibility of identifying the key elements that determine the system in choosing a format that characterizes the state of the elements of interest; development of a virtual model that reproduces the behavioral features of the modeled system.
Research of the possibilities of the national innovative environment for the implementation of financial technologies
Authors: Serebryakova N. A. , Kolmykova T. S. , Grivachev E. A. , Klykova S. V.
Published: September 2021

The article is devoted to the study of an important scientific and practical problem on the disclosure of factors and conditions that stimulate the introduction of innovations in the financial sector. It has been studied that the processes of introducing digital technologies are relevant in all spheres of the economy. The financial environment is highly receptive to digital adoption. The emphasis is made on the fact that the Bank of Russia as a mega-regulator is implementing a number of projects that stimulate the introduction of financial technologies in the country's banking sector. The main infrastructure projects of the Bank of Russia aimed at stimulating the development of fintech are considered. Among them: a unified biometric system, a system of fast payments, a marketplace of the Bank of Russia, a system for transmitting financial messages. The study revealed the weakness of the national regulatory system for the creation and implementation of digital technologies in the financial environment. The urgency of adapting the norms of financial law to the rapid spread of digital technologies has been substantiated. It has been proven that the acceleration of the pace of implementation of technological innovations not only opens up new opportunities for business improvement, but also carries obvious and hidden risks. Analysis of the research materials made it possible to structure the main potential threats that accompany the spread of digital technologies. It is concluded that it is necessary to develop systemic measures to create a favorable national innovation environment that stimulates financial innovation.
The arrowhead-Jacobsthal sequence
Authors: Akuzum Yesım , Deveci Omur
Published: September 2021

In the present investigation, we define the arrowhead-Jacobsthal sequence by the arrowhead matrix defined with the help of the characteristic polynomial of the generalized order-k Jacobsthal numbers. Next, we derive various properties of the arrowhead-Jacobsthal sequence by using its generating matrix. Also, we give connections between Fibonacci, Jacobsthal, Pell and arrowhead-Jacobsthal numbers.
Распространение вариантов вируса SARS-COV-2, вызывающих озабоченность (VOC) и интерес (VOI) на основе количества их геномов, депонированных в базу данных GISAID за неделю с 04.09. по 10.09.2021 г.
Authors: Дмитриева Людмила , Чумачкова Елена , Краснов Ярослав , Осина Наталья , Сафронов Валентин , Иванова Александра , Карнаухов Игорь , Караваева Татьяна , Щербакова Светлана , Кутырев Владимир
Published: September 2021

В обзоре представлен анализ геновариантов вируса SARS-CoV-2, вызывающих озабоченность (VOC) и интерес (VOI) на основе их геномов в базе GISAID за неделю с 04.09. по 10.09.2021 г.
Ursodeoxycholic acid breaks antitumor immunosuppression by inducing CHIP-mediated TGF-β degradation
Authors: Shen Ying , Lu Chao , Song Zheng , Qiao Chen , Ye Jian , Chen Jin , Zhang Cheng , Ma Ze , Chen Tao , Li Xu , Lin Aifu , Jufeng Guo , Wang Jianli , Cai Zhijian
Published: September 2021

Blocking TGF-β signaling is critical to enhance antitumor immunity. However, there is still no effective TGF-β signaling inhibitors in clinic. Here, we show that clinical medicine ursodeoxycholic acid (UDCA) phosphorylates TGF-β at T282 site via TGR5-cAMP-PKA axis, leading to the increased binding of TGF-β and CHIP. Then, CHIP ubiquitinates TGF-β at K315 site, initiating p62-dependent autophagy sorting and subsequent TGF-β degradation. By degrading TGF-β, UDCA greatly enhances antitumor immunity through restraining Treg differentiation and activation in tumor-bearing mice. In addition, UDCA synergizes with anti-PD-1 to induce stronger antitumor immunity and tumor-specific immune memory in tumor-bearing mice. Notably, UDCA also reduces TGF-β and Tregs in peripheral blood of healthy volunteers and tumor patients. Therapy combining anti-PD-1 or anti-PD-L1 with UDCA has much better efficacy in tumor patients. Thus, our results uncover a novel mechanism for TGF-β signaling regulation and reveal UDCA as a ready-made TGF-β signaling inhibitor in enhancing antitumor immunity.
Tumor Heterogeneity in VHL Drives Metastasis in Clear Cell Renal Cell Carcinoma
Authors: Hu Junhui , Tan Ping , Ishihara Moe , Bayley Nicholas , Schokrpur Shiruyeh , Reynoso Jeremy , Jat Parmjit , Snick Jacques Van , Knudsen Beatrice , Chin Arnold , Prins Robert , Graeber Thomas , Xu Hua , Wu Lily
Published: September 2021

To study the impact of intratumoral VHL heterogeneity observed in patient ccRCC primary tumors, we engineered VHL gene deletion in three RCC models, including a new primary tumor cell line derived from an aggressive metastatic ccRCC. The VHL gene-deleted (VHL-KO) cells underwent epithelial-to-mesenchymal transition (EMT) and showed diminished proliferation and tumorigenicity compared to the parental, VHL-expressing (VHL+) cells. Renal tumors with either VHL+ or VHL-KO cells alone exhibit minimal metastatic potential. Interestingly, tumors with both cells displayed rampant lung metastasis, highlighting a novel cooperative metastatic mechanism. The poorly proliferative VHL-KO cells stimulated the proliferation, EMT and motility of neighboring VHL+ cells. We found that periostin (POSTN), a protein product overexpressed and secreted by VHL- cells, promoted metastasis by enhancing the motility of VHL-WT cells and facilitating vascular escape of tumor cells. Genetic deletion or antibody blockade of POSTN dramatically suppressed lung metastases in our preclinical models. Our work suggests a new strategy to halt progression in ccRCC by disrupting the critical metastatic crosstalk between heterogeneous cell populations within a tumor.
Gradient Copolymerization towards High-performance Monocomponent Polymers for Energy and Charge Storages
Authors: Zhu Yuanwei , Lu Wanlong , Qiao Nan , Cui Huize , Hu Zhipeng , Shen Zichao , Yu Jinde , Liu Bo , Zhang Shuwen , Nie Yongjie , Li Guochang , Li Shengtao , Lu Guanghao
Published: September 2021

Polymers with excellent dielectric and electret capabilities are crucial for energy storage films, organic electronics and environmental filtrations. Nanocomposites is an emerging effective method, but the characteristics of complicated preparation, poor uniformity and high cost restrict its massive and practical applications. Here, we propose a gradient copolymerization strategy with controllable micro-phase interfaces for dielectric capability modulation, and gradient ethylene-styrene copolymer (PESt) exhibits extraordinarily enhanced dielectric, electrical insulating and electret properties against polyethylene and polystyrene. PESt exhibits a dielectric energy density towards 23 J·cm− 3, far exceeding commercially applied polymers and is comparable to nano-composites. By applying PESt as electret layer in organic field-effect transistors, largely enhanced memory window, optimized stability and field-effect mobility over 27 cm2·V− 1·s− 1 are achieved. Finally, PESt electret is employed in environmental filtrations with 20% enhancement in filtration efficiency. The simplicity and processability of gradient copolymerization against nano-composite, further suggest its potential in designing high-performance dielectric/electret polymers.
Comparison of Exercise and Physical activity routine and Health Status among Apparently Healthy Nigerian Adults Before and During COVID-19 Lockdown
Authors: Ewah Patrick Ayi , Oyeyemi Adetoyeje Y , Oyeyemi Adewale L , Oghumu Saturday N , Awhen Peter Agba , Ogaga Mary , Edet Lucy Inyang
Published: September 2021

Background: COVID-19 is a pandemic that ravaged the world in manners that were never seen in the recent past and one of the measures to stem the tide-off this ravaging pandemic is a stay-at-home order referred to as lockdown. This study compares the physical activity status and perceived health of Nigerians before and during the lockdown. ResultsSocial media platform users (n = 205) were surveyed using a two-part questionnaire. The 1st part elicited the socio-demographic characteristics of the subject. In the 2nd part, information about their exercise and physical activity, general health, and economic palliatives as offered by the government, non-governmental organizations, and philanthropists were elicited. The frequency of exercise was significantly more (p < 0.05) during the lockdown than before the lockdown. The duration and intensity of the exercise per week were comparable. There was also a negative relationship between the Body Mass Index, frequency, and duration of exercise before and during the lockdown. The subjects also perceived their health as worse during (3.70 ± 1.05) the lockdown than before (3.95 ± 0.97) lockdown (Z = -3.69, p = 0.00). Conclusion: Overall, for these cohorts of social media platform users, lockdown did not adversely affect their exercise routine. It is recommended that there should be specific admonition on exercise as an important Instrumental Activity of Daily Living (IADL). Therefore, while this pandemic lockdown lasts and beyond, the safety measures to follow while partaking in this IADL, should be included in the public health recommendation.
Chemical and Sensory discrimination of coffee: Impacts of the planting altitude and fermentation
Authors: Oliveira Emanuele Catarina da Silva , Luz José Maria Rodrigues da , Castro Marina Gomes , Filgueiras Paulo Roberto , Guarçoni Rogério Carvalho , Castro Eustáquio Vinicius Ribeiro , Silva Marliane de Cássia Soares da , Pereira Lucas Louzada
Published: September 2021

Edaphoclimatic conditions, planting altitudes, soil, the microbiome of plants and fruits, genotypes, and postharvest processing are variables that contribute to the chemical and sensory quality of the coffee. Thus, the objective of this study was to evaluate the impacts of planting altitude and fermentation of fruits on the chemical and sensory quality of the coffee using nuclear magnetic resonance (NMR) and linear discriminant analysis (LDA). Cherry coffees were harvested in 8 points of altitudes between 826 and 1078.08 meters. A completely randomized design with 8 planting altitudes, 5 fermentation processes, and 5 repetitions was performed. Lipids, trigonelline, citrate, and malate were the compounds that most contribute to the chemical discrimination of coffee in the altitudes below 969 m. While, in the high altitudes (> 1000 m), this discrimination was due to the HMF, quinic acid, caffeine, and formic acid and the global notes of coffee drink were higher than 80 points. In fermented coffee, the LDA of the chemical data indicates the formation of five clusters, showing how the compounds can suffer changes depending on the form of processing used in coffee. The best score was observed in samples of 1078.08 m and dry fermentation and only in 969 m was observed significant difference between spontaneous fermentation and induced fermentation. Thus, coffee sensory scores were dependent on planting and fermentation methods and NMR and LDA techniques proved to be important in chemical and sensory discrimination of coffees.
Assessment of Morphological Mutations and Genetic Components in MMS and EMS Induced Chilli Cultivars, NS 1101 and NS 1701DG
Authors: HASAN NAZARUL , Choudhary Sana , Jahan Mehjabeen , Sharma Nidhi , Naaz Neha
Published: September 2021

A change in the genetic makeup of a plant is an essential prerequisite for the breeding programs and induce mutagenesis is an important approach to create the variations within crop germplasm. The main objective of this study is to find the mutants in chemically treated M2 chilli plant populations. Since, mutagenesis in chilli plants was induced through EMS and Cd to increase the genetic variability that results in thirteen mutant plants at M2 generation from the genetic background of chilli varieties NS 1101 and NS 1701 DG, respectively. Most of the mutant phenotypes observed felled within qualitative and quantitative characteristics the seven major categories including plant height, leaf shape, leaf color, branch, and flower color, fruits, 1000 seed weight, yield, and root length. The inter-population differences were carried out through analysis of variance of quantitative traits of chemically treated chilli populations. Results reflect increased mean value in quantitative traits that could validate the improvement over the parental lines. Fruit number and seed weight were the main priority traits in the selection of high yield plants and these quantitative traits have a strong association with the yield of the plant. Genetic variability induced by chemical mutagens in chilli can integrate into further chilli breeding programs as new crop germplasm with improved agronomic traits. Mutants selected from 0.2% treated chilli populations can be used to develop an efficient and fast crop variety of chilli with desirable traits. The present study about the genetic variability induced by chemical mutagenesis provides more opportunities to bring diversity in the genetic makeup of chilli plant for improvement of the desirable traits.
Magnitude of self-medication practice and the associated factors among adult household members living in western region, Tanzania
Authors: Manhyabili Mussa S. , Bwire George M. , Maziku Lubinza , Matee Mecky .I. N.
Published: September 2021

Background: Self-medication practice (SMP) is the use of medication without the prescription of health care professionals. The major problems associated with self-medication practice have been drug resistance, drug side effects, wastage of resources, and serious health hazards including death. This study was conducted to assess the magnitude and factors associated with self-medication practice among adult household members in Shinyanga Municipal Council (SMC).Methods: A community based cross-sectional study was conducted in SMC, in September and October 2020. A multistage cluster random sampling was used to select study participants. Variables such as socio-demographic factors and reasons for SMP were summarized using frequencies and percentages. Chi square and logistic regression test were used to identify factors associated with SMP. All statistics were done using SPSS version 25.Results: In total 422 adult household members were studied, the magnitude of SMP among adult household members in SMC was 86%. The major symptom of illness that lead to SMP were headache 75(38.9%), fever 71 (37%) and cough 52 (27.1%) while paracetamol 84(43.8%), Ampiclox 30 (15.5%) and artemether lumefantrine 25 (13%) were the commonly used drugs. Perceptions of illness as mild 141(38.8%)and previous experience of self-medication138(38%) were the reasons for SMP. Participants who did not complete secondary education were seven times more likely to practice SMP as compared to those who had university education (adjusted odds ratio [aOR] =7.136, 95%CI=1.447-35.180, P=0.016). Participants with average household income (AHI) (<180,000 TSH=<78USD) were less likely to practice SMP compared to those with AHI (B 180,000Tsh) (aOR = 0.424, 95%CI = 0.214 – 0.840, P = 0.014).Conclusion: The magnitude of SMP in Shinyanga Municipal was found to be high.SMP was significantly associated with level of education and average monthly household income. Strengthening of the community’s awareness on the side effects of SMP including antimicrobial resistance in the study area is recommended.
Illness trajectory of metastatic breast cancer: A qualitative narrative study
Authors: Sajadian Akram
Published: September 2021

Purpose: Breast cancer is accompanied with different psychological consequences. This study investigate to describe the physical, emotional, social, and spiritual characteristics of illness trajectory of metastatic breast cancer (MBC).Method: This is a qualitative study, in which repeated in-depth interviews with 15 MBC patients were conducted. The interview data were transcribed verbatim and analysed as a text, using a qualitative biographic narrative approach.Results: Patient’s narratives about the illness trajectories revealed various physical, cognitive, emotional, social, and spiritual needs at the time of breast cancer diagnosis, and the incidence of metastasis. Positive experiences including personal growth, and negative feelings such as rejection and isolation were reported as patient’s narratives about living with MBC. At the anticipatory phase, the Patient’s narratives were classified into pessimistic and optimistic predictions which were affected by spiritual attitude. Similarly, spiritual as well as religious beliefs were highlighted in psychological reactions and patient’s point of view about death.Conclusions: The MBC trajectory is complicated and each phase of the MBC trajectory includes characteristic tasks and focal points. To move away from the predominant traditional approach towards a more comprehensive and better-targeted service, an increased understanding of the complexities of the MBC trajectory is necessary.
Anticonvulsant Activity, Molecular Modeling and Synthesis of Spirooxindole-4H-Pyran Derivatives using a Novel Reusable Organocatalyst
Authors: Emami Leila , Moezi Leila , Amiri-Zirtol Leila , Pirsalami Fatemeh , Divar Masoumeh , Solhjoo Aida , Khabnadideh Soghra
Published: September 2021

Fifteen derivatives of spirooxindole-4H-pyran (A1-A15) were subjected to evaluate through intravenous infusion of pentylenetetrazole (PTZ) induced epilepsy mouse models. Four doses of the compounds (20, 40, 60, 80 mg/kg) were tested in comparison to diazepam as positive control. The resulted revealed that compounds A3 and A12 were the most active compounds and indicated significant anticonvulsant activity in the PTZ test. The tested compounds were prepared via a multicomponent reaction using graphene oxide (GO) based on the 1-(2-aminoethyl) piperazine as a novel heterogeneous organocatalyst. The prepared catalyst (GO-A.P.) was characterized using some diverse microscopic and spectroscopic procedures as well. The results showed high catalytic activity of the catalyst in the synthesis of spirooxindole-4H-pyran derivatives. The GO-A.P. catalyst was reusable at least for 5 times with no significant decrease in its catalytic action. In silico assessment of physico chemical activity of all compounds also were done which represented appropriate properties. Finally, molecular docking study was performed to achieve their binding affinities as γ-aminobutyric acid-A (GABA‐A) receptor agonists as a plausible mechanism of their anticonvulsant action. Binding free energy values of the compounds represented strongly matched with biological activity.
The Impact of Health Status of Academic Staff on Attitudes towards COVID-19 Vaccination
Authors: Safi Mohammed , Hemdan Ahmad M. , Opoku Maxwell , Mustafa Ashraf
Published: September 2021

Background
The outbreak of COVID-19 has had overwhelming effects on human lives, properties, and access to essential services in the society. Consequently, the manufacturing of vaccine was envisaged a milestone in effort towards ‘normalizing’ the world. With discourses around the efficacy of the vaccines, it is unclear whether having a health condition could influence once decision to accept the vaccine or encourage others to receive the vaccine. This study attempted to contribute towards this debate by assessing the impact of health status on attitude towards the COVID-19 vaccine.
Methods
A questionnaire, known as, the Attitude towards COVID-19 Vaccination Scale was developed to collect data from participants at school contexts. A total of 1047 participants completed questionnaire from 22 countries. The data was subjected to a two-way factorial analysis of variances.
Results
The result showed a direct effect of health status of individuals on attitude towards COVID-19 vaccination. It appears that healthier individuals are more willing to accept the vaccine than those who indicated they had minor or chronic health conditions. Also, individuals who were vaccinated appears to be more receptive towards the vaccine than those who were yet to receive the vaccine. Moreover, it emerged that the more the educated individuals have, the more likely they would hold favourable disposition, less hesitant and open to vaccination than those with little or no education.
Conclusions
The results call for more deliberate approach by countries to promote the use of the vaccines especially among those underlying health condition. Other implications of the study are discussed in more detail.
The book herbaria of Jacob Breyne (1637-1697) in the collection of Naturalis Biodiversity Center (Leiden, the Netherlands).
Authors: de Jong Marco , Duistermaat Leni , Stefanaki Anastasia , Andel Tinde van
Published: September 2021

Historic herbaria can provide a wealth of information on a diversity of topics, including the past occurrence of plants, their abundance, names and uses. The collection of Naturalis Biodiversity Center in Leiden, the Netherlands, contains two book herbaria by Jacob Breyne (1637–1697) of Danzig. These herbaria, dated 1659 and 1673, contain a total of 105 specimens in various states of intactness, and with or without original labels. The identity of the specimens in the Leiden Breyne herbaria had not been completely assessed. Here we discuss the taxa represented within these two historic herbaria as well as the information contained in the handwritten texts within them. The two Breyne herbaria combined were found to contain 62 species, representing 24 plant families. Both herbaria contain several species now rare around Gdańsk, including two species currently considered regionally extinct (Swertia perennis L. and Dactylorhiza viridis (L.) R.M. Bateman, Pridgeon & M.W. Chase). Labels with the specimens give a range of information on the collecting locations, ecology, abundance and/or use of the species. The Leiden Breyne herbaria reveal changes in the flora of northern Poland over the course of three centuries, as well as pre-Linnaean nomenclature, historic uses of plants and (international) correspondence between scientists.
EGFR inhibition reverses resistance to lenvatinib in hepatocellular carcinoma cells
Authors: He Xiaoping , Hikiba Yohko , Suzuki Yoshimasa , Nakamori Yoshinori , Kanemaru Yushi , Sugimori Makoto , Sato Takeshi , Nozaki Akito , Chuma Makoto , Maeda Shin
Published: September 2021

Background
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Lenvatinib is approved as a first-line treatment for unresectable HCC. The therapeutic duration of lenvatinib is limited by resistance, but the underlying mechanism is unclear.
Methods
To establish lenvatinib-resistant cells, Hep3B cells were initially treated with 3 µM lenvatinib. The concentration was gradually increased by 1µM or 0.5µM per week and it reached to 7.5µM 2 months after the initial exposure to lenvatinib. The biological characteristics of these cells were analyzed by ERK activation in the MAPK signaling pathway and a human phospho‐receptor tyrosine kinase (RTK) antibody array. Factors possibly related to lenvatinib resistance were analyzed using inhibitors, and cell proliferation was analyzed.
Results
We established lenvatinib-resistant HCC cells (LR cells) by long-term exposure to lenvatinib. Lenvatinib reduced ERK activation in the parent cells, but not in the LR cells. RTK array analysis showed that the activities of EGFR and insulin-like growth factor 1 receptor (IGF1R)/insulin receptor (INSR) were significantly increased in LR cells, whereas the activities of other RTKs were unchanged. Erlotinib, a widely used EGFR inhibitor, downregulated ERK activation in LR cells. The proliferation of LR cells will also be affected when lenvatinib is combined with erlotinib to treat LR cells. In contrast, inhibition of IGFR/INSR did not affect ERK activation or cell proliferation. Scavenging of reactive oxygen species (ROS) ameliorated the enhanced EGFR activation in LR cells.
Conclusions
Lenvatinib resistance was induced by enhanced EGFR activation, possibly via ROS accumulation, in lenvatinib-resistant cells.These findings may enable the development of lenvatinib combination therapies for HCC.
WITHDRAWN: Transcriptional signatures associate with the clinical outcomes of immune checkpoint inhibitor treatment in advanced bladder cancer
Authors: Cheng Wen
Published: September 2021

Urothelial bladder cancer (UBC) is one of the most lethal cancers worldwide, the 5-year survival rate remain poor with platinum-based chemotherapy regimens as the standard of cancer treatment protocol. Recent FDA approval of a programmed death ligand-1 (PD-L1) inhibitor, atezolizumab, in advanced UBC patients is changing the therapeutic landscape. Although the response to anti-PD-L1 is correlated to PD-L1 expression and tumor mutation burden, the molecule determinants of responsiveness or non-responsiveness to immune checkpoint inhibitor (ICI) is largely unknown. A published immunotherapy cohort with whole exome sequencing, RNAseq and clinic outcome data for 29 metastatic urothelial cancer patients was used, paralleled with The Cancer Genome Altas Bladder Cancer cohort for validation. Genomic mutational profiling, mutational signature, a panel genes in antigen presentation and interferon signaling in bladder cancer were delineated with little correlation with durable clinic benefit (DCB) or non-DCB of PD-L1 inhibitor treatment. Whereas, characterized immune-responsive or resistant associated genes showed differentially expressed between DCB group and non-DCB group. Further more, transcriptional signature and transcriptional regulators between DCB and non-DCB were identified from transcripome data. Our exploratory analyses provided multidimension view of complexity of determinants of immune-responsiveness and suggest the influences of transcriptional reprogram in immune checkpoint blockage therapy.
Management of Phlegmasia Cerulea Dolens Caused by a Giant Leiomyoma
Authors: Ekkel Elisabeth , Chandran Tara , Qasawa Ryan , Trpkovski Michael , Hans Sachinder
Published: September 2021

This case is of a young female with a large uterine leiomyoma causing phlegmasia cerulea dolens with thrombosis of the left common and left external iliac veins. She underwent mechanical thrombectomy to temporize the condition until she could be evaluated by gynecology-oncologist to remove the cause of venous obstruction. Prior to hysterectomy, suprarenal inferior vena cava filter was placed. Less than 12 hours post hysterectomy she developed recurrent thrombosis involving the left common and external iliac veins. She underwent repeat mechanical thrombectomy with wall stent placement in the left common iliac vein with resolution of her symptoms.
Selected ‘Starter Kit’ energy system modelling data for Chile (#CCG)
Authors: Cannone Carla , Allington Lucy , Pappis Ioannis , Barron Karla Cervantes , Usher Will , Pye Steve , Howells Mark , Walker Miriam Zachau , Ahsan Aniq , Charbonnier Flora , Halloran Claire , Hirmer Stephanie , Taliotis Constantinos , Sundin Caroline , Sridha Vignesh , Ramos Eunice , Brinkerink Maarten , Deane Paul , Gritsevskyi Andrii , Moura Gustavo , Rouget Arnaud , Rogner Holger , Quirós-Tortós Jairo , Angulo-Paniagua Jam
Published: September 2021

Energy system modelling can be used to assess the implications of different scenarios and support improved policymaking. However, access to data is often a barrier to energy system modelling, causing delays. Therefore, this article provides data that can be used to create a simple zero order energy system model for Chile, which can act as a starting point for further model development and scenario analysis. The data are collected entirely from publicly available and accessible sources, including the websites and databases of international organizations, journal articles, and existing modelling studies. This means that the dataset can be easily updated based on the latest available information or more detailed and accurate local data. These data were also used to calibrate a simple energy system model using the Open Source Energy Modelling System (OSeMOSYS) and three stylized scenarios (Fossil Future, Least Cost and Net Zero by 2050) for 2020–2050. The assumptions used and results of these scenarios are presented in the appendix as an illustrative example of what can be done with these data. This simple model can be adapted and further developed by in-country analysts and academics, providing a platform for future work.
Selected ‘Starter Kit’ energy system modelling data for Ecuador (#CCG)
Authors: Cannone Carla , Allington Lucy , Pappis Ioannis , Barron Karla Cervantes , Usher Will , Pye Steve , Howells Mark , Walker Miriam Zachau , Ahsan Aniq , Charbonnier Flora , Halloran Claire , Hirmer Stephanie , Taliotis Constantinos , Sundin Caroline , Sridha Vignesh , Ramos Eunice , Brinkerink Maarten , Deane Paul , Gritsevskyi Andrii , Moura Gustavo , Rouget Arnaud , Rogner Holger , Quirós-Tortós Jairo , Angulo-Paniagua Jam
Published: September 2021

Energy system modelling can be used to assess the implications of different scenarios and support improved policymaking. However, access to data is often a barrier to energy system modelling, causing delays. Therefore, this article provides data that can be used to create a simple zero order energy system model for Ecuador, which can act as a starting point for further model development and scenario analysis. The data are collected entirely from publicly available and accessible sources, including the websites and databases of international organizations, journal articles, and existing modelling studies. This means that the dataset can be easily updated based on the latest available information or more detailed and accurate local data. These data were also used to calibrate a simple energy system model using the Open Source Energy Modelling System (OSeMOSYS) and three stylized scenarios (Fossil Future, Least Cost and Net Zero by 2050) for 2020–2050. The assumptions used and results of these scenarios are presented in the appendix as an illustrative example of what can be done with these data. This simple model can be adapted and further developed by in-country analysts and academics, providing a platform for future work.
Nexus between financial innovations, remittances and credit performance: Evidence from augmented ARDL and nonlinear ARDL
Authors: Qamruzzaman Md.
Published: September 2021

The motivation for this study is to assess the impact of financial innovation and remittances on bank-based financial institutions’ credit performance in Bangladesh for the period 1981–2019. The study applies augmented ARDL (AARDL) and nonlinear ARDL (NARDL) to identify both long-run and short-run effects and directional causality by performing non-granger casualty tests. AARDL confirms the presence of a long-run association between financial innovation, remittance, trade openness, FDI, and credit performance, which is measured by non-performing loans. In the long run, financial innovation and FDI volatility expose a positive link with NPLs, but remittance inflows and trade openness establish a negative association. Asymmetry shocks in financial innovation reveal a positive relationship with credit performance. In contrast, the asymmetric shock of remittance and trade openness unveil a negative tie to credit performance, especially in the long run. Furthermore, directional causality provides evidence to support a feedback hypothesis explaining causality between financial innovation and credit performance, as well as remittance inflows and credit performance. These findings suggest that credit performance is guided by future development in remittances and financial innovation; thus, closer attention from policymakers and financial experts is persistent to capitalize or mitigate the impact of the financial system.
A Farmer's Fear: Ehrlichiosis, a Tick-borne Disease
Authors: Gopalan Chaya , Nguyen Nhan , Kist William
Published: September 2021

Ehrlichiosis (Ehrlichia chaffeensis), a bacterial infection transmitted by ticks, and its complications are examined here in a case-based learning approach. This case scenario describes a person who was bitten by a tick while farming and the complications they experienced. Students are presented with a patient case scenario that entails a detailed assessment of the patient’s physical status, medical history, vital signs, laboratory values, and treatment methods so as to provide a complete picture of the pathophysiology of ehrlichiosis. This case scenario can be used to teach physiology or pathophysiology of infection and inflammation topics in clinical courses such as nursing, physician assistant, pharmacy, and other allied health programs.
Metabolism and Nutrition: Integration of Concepts in a Holistic Approach to Teaching Metabolism
Authors: Clark James
Published: September 2021

Metabolism and nutrition are interrelated factors of human physiology, so much so that they cannot be thought about independently of each other. Yet, the way that either nutrition or metabolism is often discussed leads to questions about how well this interrelationship is understood. This paper will discuss how clarifying terminology and incorporating the interrelationship between metabolism and nutrition in instruction can combat many of the biases and misconceptions that get perpetuated to students. This should allow students to be better prepared for their future roles in healthcare.
Effect of Fractions from Lycopus lucidus Turcz. Leaves on Genomic DNA
Oxidation and Matrix Metalloproteinase Activity
Authors: Lim Sun Young , Chen Jingwen , Na Eun
Published: September 2021

Aim and Objective:

We investigated the inhibitory effects of fractions from Lycopus
lucidus Turcz. leaves on genomic DNA oxidation, Nitric Oxide (NO) production, and Matrix
Metalloproteinase (MMP) activity.

Material and Methods:

Oxidative damage of genomic DNA was detected after Fenton reaction with
H2O2 using DNA electrophoresis. Western blotting was performed to compare the expression levels
of MMP-2 in phorbol 12-myristate 13-acetate (PMA)-induced HT-1080 cells. Lipopolysacchride
(LPS)-induced NO production in RAW 264.7 cells was measured using Griess reagent.

Results:

All fractions (n-Hexane, 85% aq. MeOH, n-BuOH, and water fractions) from the leaves of
L. lucidus Turcz. significantly inhibited intracellular production of reactive oxygen species (ROS)
(p<0.05). Particularly, 85% aq. MeOH and n-BuOH fractions showed higher ROS inhibitory
activity than the other fractions. n-Hexane, 85% aq. MeOH, n-BuOH and water (0.05 mg/mL)
fractions significantly inhibited oxidative DNA damage by 57.97%, 68.48%, 58.97%, and 68.39%,
respectively (p <0.05). Treatment of RAW 264.7 cells with each fraction reduced LPS-induced NO
production in a dose-dependent manner (p<0.05). n-Hexane and 85% aq. MeOH fractions notably
reduced MMP-2 secretion levels in the culture supernatants from HT-1080 cells.

Conclusion:

Overall, these results indicated that L. lucidus Turcz. leaves can be exploited as plant
based sources of antioxidants in the pharmaceutical, cosmetic, nutraceutical, and food industries.
Factors Promoting Alkene Migratory Insertion into Metal-nitrogen Bond
During Hydroamination in Recent Studies
Authors: Han Wenlai
Published: September 2021

:

Migratory insertion is a fundamental organometallic transformation that enables the functionalization
of an unsaturated bond. Recent reports on catalytic hydroamination provide evidence
that supports an intermolecular migratory insertion pathway featuring alkene insertion into metalnitrogen
(M-N) bonds. This article presents factors influencing the rate of migratory insertion in latetransition
metal-catalyzed hydroamination, including steric and electronic effects from ligands, alkenes,
and metal centers, along with stabilization from coordinated amine intermediates and ordered
transition states.
Adverse Drug Reactions of Acetaminophen and Ibuprofen in the Paediatric Population: Analysis of the Italian Spontaneous Reporting Database
Authors: Pelliccia Valentina , Rossi Serena , Zollino Ilaria , Quagliarella Francesco , Buonocore Giuseppe
Published: September 2021

Background:

Acetaminophen and ibuprofen are the only antipyretics drugs approved in
children, and are considered safe and well tolerated. However, data regarding the adverse drug reaction
(ADR) profile of these drugs in children are scattered.

Aim:

The aim of our study is to evaluate the ADRs of acetaminophen and ibuprofen through an observational
study over a period of 15 years (January 2005-April 2020). Reports of suspected ADRs
to the active substances ‘acetaminophen’ and ‘ibuprofen’ are listed and accessible through the
Italian spontaneous reporting database (RAM system) by AIFA (Pharmacovigilance of the Italian
Drug Agency).

Methods:

Acetaminophen ADRs in paediatric populations were 15% of cases, with more frequent
involvement of skin and soft tissue (54.36%) and gastrointestinal apparatus (44.09%); liver dysfunction
accounts for 5.67%.

Results:

Ibuprofen paediatric ADRs were 26%: skin and soft tissues in 63.16% of cases, gastrointestinal
tract in 47.75%, hematemesis and melena in 6.38%; kidney injury in 2.25% of cases.

Conclusion:

Children aged 2 to 11 are more frequently affected by ADRs than infants and adolescents.
The risk of gastrointestinal and renal side effects is significantly higher with ibuprofen. Hepatobiliary
side effects are more frequently linked to acetaminophen. Potentially fatal ADRs have
been reported sporadically for both drugs.
Protective Effects of Omega-3 Fatty Acids Supplementation Against Renal Parenchymal Scarring in Children with Acute Pyelonephritis: Results of a Pilot Clinical Trial
Authors: Sedighi Iraj , Taheri-Moghadam Ghazal , Emad-Momtaz Hossein , Vaseghi Golnaz , Eshraghi Azadeh , Asnaashari Farzaneh , Mehrpooya Maryam
Published: September 2021

Aim::

This trial aimed to determine if supplementation with omega-3 fatty acids as an adjunct
therapy to antibiotic treatment can have protective effects against renal scar formation after
acute pyelonephritis (APN) in pediatric patients.

Background:

Current evidence points out that besides antibiotic treatment, early administration of
antioxidant and anti-inflammatory compounds may be effective in reducing the occurrence of renal
damage following APN in children.

Objective:

The main endpoint of the trial was the comparison of the development of renal scarring
formation after APN in an omega-3 fatty acids-treated group and in a control-treated group.

Methods:

This prospective randomized, controlled trial study was conducted from March 2016 to
May 2018 on 60 children with a diagnosis APN in a tertiary hospital in Iran. After the diagnosis of
APN based on the clinical signs and symptoms, urine analysis, urine culture, and dimercaptosuccinic
acid renal scan (DMSA scan), the patients were randomly allocated into either the control
group (n=30 patients: received standard antibiotic treatment only) or the intervention group (n=30
patients: received standard antibiotic-treatment in combination with oral omega-3 fatty acids based
on the children’s weight for three consecutive days). A second DMSA scan was performed for the
patients at a minimum of six months after treatment. The development of renal scars was evaluated
by comparing the baseline DMSA scan lesions with the follow-up DMSA scan lesions.

Results:

Fifty patients, including 26 and 24 individuals in the control and intervention groups, respectively,
completed the entire course of the study. Renal parenchymal involvement based on the
baseline DMSA scan was similar in the two groups (p-value =0.85, 0.90, and 0.53 regarding the
right, left, and both kidney units together, respectively). Although comparison of the follow-up
DMSA scan lesions to the baseline DMSA scan lesions considering the right and left kidneys as separate
units between two groups did not reach the significant level, when considering both left and
right kidney units together, results showed a statistically significant difference between groups in
favor of the intervention group (p-value =0.04).

Conclusions:

Although preliminary, the results of this study showed that administration of omega-3
fatty acids, a natural supplement with well-known anti-inflammatory and antioxidant properties, as
an adjunct therapy to standard antibiotic treatment might significantly reduce the incidence of the
occurrence renal scarring following APN in children. Confirmation of these results requires further
studies.

Clinical Trial Registeration:

This trial was registered to Iranian Clinical Trials Registry with the
trial number IRCT2015062922965N1.
Recent Advances in Nanomaterial-based Luminescent ATP Sensors
Authors: Zhou Xiaomeng , Shang Li
Published: September 2021

:

Adenosine 5'-triphosphate (ATP) plays a significant role in biological processes and the
ATP level is closely associated with many diseases. In order to detect ATP in live cells, tissues, and
body fluids with high sensitivity and selectivity, researchers have developed various sensing strategies.
Particularly, owing to the distinct physicochemical properties of nanomaterials and the high
sensitivity of fluorescence, a lot of efforts have been devoted to developing nanomaterials-based
approaches for fluorescent ATP sensing in recent years. In this review, we focus on the current
development of nanomaterial-based fluorescent ATP sensors and discuss the sensing mechanisms
in detail. The advantages and disadvantages of ATP sensing using different kinds of nanomaterials,
including carbon nanomaterials, metal nanoparticles, semiconductor quantum dots, metal-organic
frameworks, and up-conversion nanoparticles have been thoroughly compared and discussed. Finally,
current challenges and future prospects in this field are examined.