bluuebunny/crossref_metadata_2025 huggingface dataset:
Extensão Rural e cibercultura: o facebook como ferramenta de promoção da política nacional de assistência técnica e extensão rural
Authors: Andrade Bruno De Oliveira , Tauk Santos Maria Salett
Published: June 2020

A pesquisa analisa as ações de comunicação da Associação Brasileira das Entidades Estaduais de Assistência Técnica e Extensão Rural (Asbraer) nas redes sociais virtuais, especificamente o Facebook. A intenção é compreender até que ponto o trabalho da Asbraer no Facebook contribui na promoção dos princípios da Política Nacional de Assistência Técnica e Extensão Rural (Pnater). O estudo utiliza técnicas combinadas de coleta e análise de dados, com ênfase na Netnografia ou Etnografia Virtual, uma abordagem metodológica que busca se utilizar dos pressupostos da Etnografia para análise do ciberespaço. A pesquisa elencou as seguintes categorias, para análise: Ater e desenvolvimento sustentável; Ater e agricultura ecológica; Ater, construção da cidadania e democratização da gestão da política pública; Ater e relações de gênero, geração e etnia. Os resultados evidenciaram que, apesar de a Asbraer publicar conteúdos com regularidade em sua Linha do Tempo no Facebook, poucas vezes contempla as preocupações apresentadas nos princípios da Pnater. Identificamos igualmente que a rede virtual da Associação, e seus seguidores, é caracterizada por poucas interações entre os nós ali presentes.
Pesquisa-Ação agroflorestal: uma abordagem metodológica
Authors: Cardoso Joel Henrique , Santos Jaqueline Sgarbi , Medeiros Fabrício Sanches
Published: June 2020

O presente artigo sistematiza a trajetória de um projeto de pesquisa-ação agroflorestal, apresentando o método e sua aplicação para a construção de conhecimentos agroecológicos sobre sistemas agroflorestais (SAF’s) sucessionais. O trabalho foi desenvolvido no território da Serra dos Tapes, RS e contou com a participação de agricultores familiares, técnicos, estudantes e consumidores interessados em construir sistemas agroalimentares agroecológicos. Os conhecimentos sobre SAF’s e tecnologias agroflorestais são concretizados nas Unidades Experimentais Participativas (UEP’s), que além de ser um laboratório vivo para ação-reflexão-ação daqueles diretamente envolvidos com a atividade, também se mostra adequada para sensibilizar e instrumentalizar outros atores. Conclui-se que as sementes estão plantadas e o estudo dos SAF’s em processos de pesquisa-ação participativa responde de forma muito promissora a demanda de redesenho agroecológico dos sistemas agroalimentares do território da Serra dos Tapes, RS.
Usos da propriedade rural e a nova legislação ambiental no município de Pelotas, RS: uma conciliação viável?
Authors: Nino Letícia Bauer , Dos Anjos Flávio Sacco
Published: June 2020

O direito de propriedade rural sofreu transformações importantes ao longo do tempo no Brasil. A instituição do conceito de função social da terra e, mais recentemente, a função ambiental dos recursos naturais tem incidido fortemente ao questionar a concepção absoluta e individualista que se impôs, durante muito tempo, sobre a sociedade em geral. Este trabalho centrou-se em algumas indagações centrais, a saber: Como se apresentam as representações sociais dos atores sociais do município de Pelotas/RS sobre o uso dos recursos naturais, em que pese a emergência de um novo marco jurídico que regula as atividades agropecuárias, em meio aos objetivos conservacionistas ou da sustentabilidade ambiental? Por outro lado, cabe indagar: é possível conciliar os interesses dos produtores, suas práticas e representações sociais sobre a propriedade e uso racional dos recursos produtivos com o esforço da sociedade em preservar a integridade dos ecossistemas? Para responder o problema de pesquisa, desenvolveu-se uma pesquisa qualitativa, na qual foram realizadas onze entrevistas individuais semi-estruturadas. As percepções dos atores sociais ouvidos expressam a realidade do setor agropecuário e um ambiente real de incertezas. A análise do conteúdo das entrevistas revelou também que o conflito, ainda claramente perceptível entre as diferentes posições, está passando por um processo de ajustamento, seja através da adaptação à legislação ambiental e das exigências da sustentabilidade quanto às práticas sociais, seja no sentido da adoção de novas posturas e superação frente à concepção patrimonialista que marca a história brasileira.
O Direito Internacional entre a saúde e o comércio: estudo de caso do acesso ao medicamento Truvada como profilaxia anti-HIV/AIDS no Brasil
Authors: Pozzatti Junior Ademar , Trindade Igor Pascual
Published: June 2020

Este trabalho investiga em que medida o regime jurídico que tutela os direitos de propriedade intelectual conflita com o direito internacional dos direitos humanos no acesso à saúde, analisando como esse conflito tem efeitos sobre o acesso aos medicamentos antirretrovirais no Brasil, especificamente a Profilaxia Pré-Exposição feita com o medicamento Truvada. Os resultados da investigação sugerem que o direito de propriedade intelectual – que tem por objetivo a preservação dos segredos de produção, para o aprimoramento da pesquisa e desenvolvimento –, se sobrepõe a outros bens jurídicos igualmente tutelados pelo direito internacional, como o direito à saúde, obstaculizando, assim, o acesso a medicamentos e tratamentos médicos, que são pilares para a proteção e garantia do direito humano à saúde. Metodologicamente, o trabalho será estruturado em uma abordagem dialética, com vistas a traçar um comparativo entre os dois regimes jurídicos internacionais, para vislumbrar como as suas incoerências impactam na governança global. Como método de procedimento técnico, a pesquisa é apresentada por meio de análise bibliográfica e documental, utilizando-se dos textos dos tratados internacionais, assim como da revisão bibliográfica da área.
International legal protection of copyrights in the medical sphere of BRICS countries
Authors: Akhmadova Maryam Abdurakhmanovna
Published: June 2020

The subject of this research is multilateral international acts in the area of copyright that were joined by the BRICS countries – Berne Convention, Universal Copyright Convention, TRIPS Agreement, etc., as well as bilateral agreements between the governments of Russia and Brazil in 2007, Russia and India in 1994, Russia and China in 1992, Russia and South Africa in 2014, which regulate different legal aspects of realization of joint scientific and technological activity, namely in the sphere of medicine. Attention is focused on the problematic moments associated with the spread of copyright regime upon certain objects of medical activity. The scientific novelty of this work consists in articulation of the problem and approaches to its research. The authors comes to the conclusion that the BRICS countries have formed a sufficient international legal system for the protection of copyrights with one, but serious flaw substantiated by the refusal of India and Brazil to join the Agreement of World Intellectual Property Organization. Proliferation of scientific information through the Internet requires more stringent regulation on the international level, since it inflicts substantial damage to the authors of scientific works.
From Neolithic towards space revolution: emergence of a new means of socio-natural interaction
Authors: Ursul Arkadii Dmitrievich
Published: June 2020

The subject of this research is the ongoing drastic transformations in interactions between nature and humankind at the stage of space exploration. Earth’s material production will continue being developed, but at the same time, a completely new process will emerge, brought about by human interaction with extraterrestrial natural environment. This means predictions of taking production into outer space, especially heavy industry, which was even conceptualized by Konstantin Tsiolkovsky. Special importance in its development will be played by extraterrestrial mining industry. The author demonstrates that sustainable mining will continue to on Earth even after development of space mining, and these processes will be closely connected. Without development of space mining, it would be practically impossible to continue exploring space or ensure space security. It will be space mining that will play the defining role in formation of a new, space means of socio-natural interaction, which will define further evolution of our civilization in broad exploration of the Universe.
SPANXN2 functions a cell migration inhibitor in testicular germ cell tumor cells
Authors: Zhu Fang , Bo Hao , Liu Guangmin , Li Ruixue , Liu Zhizhong , Fan Liqing
Published: June 2020

Background

SPANX family members are thought to play an important role in cancer progression. The SPANXN2 is a gene expressed mainly in normal testis, but its role in testicular germ cell tumors (TGCTs) has yet to be investigated. TGCT is one of the most common solid tumors in young men and is associated with poor prognosis; however, effective prognostic indicators remain elusive. Therefore, we investigated the role of SPANXN2 in TGCT development.

Methods

SPANXN2 expression levels were validated by quantitative real-time polymerase chain reaction (qRT-PCR) analyses of 14 TGCT samples and five adjacent normal tissue samples. SPANXN2 was transiently overexpressed in TGCT cells to study the consequences for cell function. The effects of SPANXN2 on cell migration were evaluated in transwell and wound healing assays. The effects on cloning ability were evaluated in colony formation assays. MTT assays and cell cycle analysis were used to detect the effects of SPANXN2 on cell proliferation. The expression levels of EMT- and AKT-related proteins in cells overexpressing SPANXN2 were analyzed by Western blotting.

Results

Compared with adjacent normal tissues, the Gene Expression Profiling Interactive Analysis database showed SPANXN2 expression was downregulated in TGCTs which was consistent with the qRT-PCR analysis. SPANXN2 overexpression reduced cell migration and colony formation capability and downregulated expression of EMT- and AKT-related proteins, Vimentin, Snail, AKT, and p-AKT.

Conclusion

Our results suggest that SPANXN2 regulates TGCT cell migration via EMT- and AKT-related proteins although its role in the occurrence and development of TGCT remains to be fully elucidated.
An indirect high iodine (131I) effective dose used for thyroid ablation in patients with thyroid cancer. Is the method of measurement important?
Authors: Al‐Shakhrah Issa A.
Published: June 2020

Background

Radiation effective dose to the red bone‐marrow, a critical organ in the therapy of differentiated thyroid carcinoma (DTC) with radioiodine‐131 (131I), cannot be measured directly. As radioiodine concentration is comparable in blood and most organs, and is believed to be similar in red marrow, the effective dose to the blood seems to be a good first‐order approximation of the radiation effective dose to the hematopoietic system and a better means to quantifying exposure from therapy compared to the total amount of activity administered.

Purpose

We applied four formulas (Lassmann et al (standard) [2008], Eur J Nucl Med Molecul Imaging, 35:1405–1412), (Thomas et al. [1993], Nucl Med Biol, 20:157–162), (Sisson et al. [2003], J Nucl Med, 44:898–903; Ha¨nscheid et al. [2009], Endocr Relat Cancer, 16:1283–1289) and (Ha¨nscheid et al. [2006], J Nucl Med, 47:648–654) and compared between the estimated values of the effective dose that were obtained by three formulas and those obtained by the standard one.

Materials and methods

Twenty‐seven patients, 22 women and 5 men, suffering from DTC were enrolled in this study. Whole‐body probe measurements and blood collections (2 mL whole‐blood samples) were conducted at 2, 6, 24, 48, 72–96 h after the administration of 131I to obtain time–activity curves. Whole‐body measurements were performed as conjugate view (anterior and posterior) counts by scintillation camera imaging.

Results

By comparing the values of blood effective dose that were obtained by applying Thomas et al. [1993], Nucl Med Biol, 20:157–162; Sisson et al. [2003], J Nucl Med, 44:898–903 and Ha¨nscheid et al. [2009], Endocr Relat Cancer, 16:1283–1289, and Ha¨nscheid et al. [2006], J Nucl Med, 47:648–654, techniques, with those obtained by (Lassmann et al (standard technique) [2008], Eur J Nucl Med Molecul Imaging, 35:1405–1412), we found that these values are, respectively, 15.0%, 40.0%, and 41.0% more than those obtained by using the standard method. To our knowledge no papers have been published previously that compare between these dosimetric approaches.

Conclusion

Highly overestimated or highly underestimated results obtained by a certain method or technique, compared with those obtained by the standard method, are not desirable, they tend to exaggerate in applying radiation protection procedures, by increasing or decreasing, which, in both cases, become far from the realistic or recommended procedures. As an operating philosophy, the objective of radiation safety practices simply should not be to keep radiation doses within legal limits or maximum permissible doses (MPDs), but to keep them “as low as reasonably achievable” (ALARA concept). MPDs should not be considered as thresholds below which exposure to radiation is of no concern, they are not assumed to be totally risk free, and any reasonable technique for reducing radiation dose may have potential benefits in the long run.
A Critical Review on Synthesis of Aluminum Metallic Composites through Stir Casting: Challenges and Opportunities
Authors: Singh Ashish Kumar , Soni Sanjay , Rana Ravindra Singh
Published: June 2020

Aluminum metallic composites (AMCs) have been recognized as promising material exhibiting excellent functional and structural properties that can be significantly tailored to meet the industrial demands as well as to meet the design criteria for many applications such as aerospace, automobiles, marine, defense, and so on. Herein, an effort is made to provide an extensive overview of the various processing techniques adopted for the development of AMCs. Various processing kinetics of stir casting technique are elaborated comprehensively in terms of existing challenges, conceivable modifications incorporated in it. Considering the critical assessment on mechanical properties made through various kinds of literature, an electromagnetic stir‐squeeze casting synergically equipped with ultrasonic transducing probe and bottom pouring attachments is recommended as the most appropriate processing technique for the development of AMCs. Moreover, appropriate recommendations regarding process variables and additives/modifiers, and potential future research opportunities are also addressed significantly to encourage the ongoing and upcoming researchers, which lead this critical Review toward novelty and uniqueness.
Imidazodipyridines via DMAP Catalyzed Domino N−H Carbonylation and 6π‐Electrocyclization: Synthetic Scope and Application
Authors: Zhang Kena , El Bouakher Abderrahman , Lévaique Hélène , Bignon Jérome , Retailleau Pascal , Alami Mouad , Hamze Abdallah
Published: June 2020

In this work, we report a domino reaction for access to highly functionalized imidazo[1,2‐a:5,4‐b′]dipyridines simply by stirring Boc2O in the presence of DMAP as a catalyst with readily prepared 3‐amino‐2‐(vinyl)imidazo[1,2‐a]pyridine. This methodology enables the synthesis of highly functionalized imidazodipyridines. The process proved to be compatible with a wide variety of substrates. The synthetic potential of this method was illustrated by performing a Suzuki‐Miyaura coupling on 4‐phenylimidazo‐dipyridin‐2‐ol derivatives. Screening of the biological activity of the newly generated compounds led to the identification of a new hit. Compound 7 l exhibits good antiproliferative activity in the submicromolar range against the human colon cancer cell line.

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Diffuse infantile hepatic hemangiomas in a patient with Beckwith–Wiedemann syndrome: A new association?
Authors: Macchiaiolo Marina , Markowich Anna H. , Diociaiuti Andrea , Gonfiantini Michaela V. , Buonuomo Paola S. , Rana Ippolita , Monti Lidia , El Hachem May , Bartuli Andrea
Published: June 2020

Beckwith–Wiedemann syndrome (BWS) is an overgrowth syndrome, caused by alterations in a cluster of imprinted genes located within the chromosome region 11p15.5. Common clinical features are overgrowth, macroglossia, lateralized overgrowth, abdominal wall defects, neonatal hypoglycemia and an increased risk of embryonal tumors, such as hepatoblastomas. Periodic screening for abdominal tumors is recommended. Vascular tumors are uncommon in BWS. Diffuse infantile hepatic hemangiomas (DIHHs) are rare vascular tumors with potentially lethal complications, in particular acquired consumptive hypothyroidism, high‐output cardiac failure, liver failure and abdominal compartment syndrome. We describe a 2‐month‐old patient with hallmark clinical features of BWS and confirmed a genetic diagnosis with mosaic paternal uniparental disomy of chromosome 11p15.5 (UPD[11]pat). The patient developed hepatomegaly and elevated alpha‐fetoprotein (AFP) and was therefore suspected of having a hepatoblastoma. Abdominal echo‐color Doppler and a CT‐scan allowed diagnosis of DIHHs. She was closely monitored and underwent treatment with propranolol. Oral propranolol was effective in reducing hepatic lesions without side effects. This report may suggest that vascular tumors can also be associated with BWS.
Genome‐wide association study of rate of cognitive decline in Alzheimer's disease patients identifies novel genes and pathways
Authors: Sherva Richard , Gross Alden , Mukherjee Shubhabrata , Koesterer Ryan , Amouyel Philippe , Bellenguez Celine , Dufouil Carole , Bennett David A. , Chibnik Lori , Cruchaga Carlos , del‐Aguila Jorge , Farrer Lindsay A. , Mayeux Richard , Munsie Leanne , Winslow Ashley , Newhouse Stephen , Saykin Andrew J. , Kauwe John S.K. ,   the Alzheimer's Disease Genetics Consortium, Crane Paul K. , Green Robert C.
Published: June 2020

Introduction

Variability exists in the disease trajectories of Alzheimer's disease (AD) patients. We performed a genome‐wide association study to examine rate of cognitive decline (ROD) in patients with AD.

Methods

We tested for interactions between genetic variants and time since diagnosis to predict the ROD of a composite cognitive score in 3946 AD cases and performed pathway analysis on the top genes.

Results

Suggestive associations (P < 1.0 × 10−6) were observed on chromosome 15 in DNA polymerase‐γ (rs3176205, P = 1.11 × 10−7), chromosome 7 (rs60465337,P = 4.06 × 10−7) in contactin‐associated protein‐2, in RP11‐384F7.1 on chromosome 3 (rs28853947, P = 5.93 × 10−7), family with sequence similarity 214 member‐A on chromosome 15 (rs2899492, P = 5.94 × 10−7), and intergenic regions on chromosomes 16 (rs4949142, P = 4.02 × 10−7) and 4 (rs1304013, P = 7.73 × 10−7). Significant pathways involving neuronal development and function, apoptosis, memory, and inflammation were identified.

Discussion

Pathways related to AD, intelligence, and neurological function determine AD progression, while previously identified AD risk variants, including the apolipoprotein (APOE) ε4 and ε2 variants, do not have a major impact.
A Multi‐responsive Fluorescent Probe Reveals Mitochondrial Nucleoprotein Dynamics with Reactive Oxygen Species Regulation through Super‐resolution Imaging
Authors: Yang Guanqing , Liu Zhengjie , Zhang Ruilong , Tian Xiaohe , Chen Juan , Han Guangmei , Liu Bianhua , Han Xinya , Fu Yao , Hu Zhangjun , Zhang Zhongping
Published: June 2020

Understanding the biomolecular interactions in a specific organelle has been a long‐standing challenge because it requires super‐resolution imaging to resolve the spatial locations and dynamic interactions of multiple biomacromolecules. Two key difficulties are the scarcity of suitable probes for super‐resolution nanoscopy and the complications that arise from the use of multiple probes. Herein, we report a quinolinium derivative probe that is selectively enriched in mitochondria and switches on in three different fluorescence modes in response to hydrogen peroxide (H2O2), proteins, and nucleic acids, enabling the visualization of mitochondrial nucleoprotein dynamics. STED nanoscopy reveals that the proteins localize at mitochondrial cristae and largely fuse with nucleic acids to form nucleoproteins, whereas increasing H2O2 level leads to disassociation of nucleic acid–protein complexes.
Persistent Room Temperature Phosphorescence from Triarylboranes: A Combined Experimental and Theoretical Study
Authors: Wu Zhu , Nitsch Jörn , Schuster Julia , Friedrich Alexandra , Edkins Katharina , Loebnitz Marcel , Dinkelbach Fabian , Stepanenko Vladimir , Würthner Frank , Marian Christel M. , Ji Lei , Marder Todd B.
Published: June 2020

Achieving highly efficient phosphorescence in purely organic luminophors at room temperature remains a major challenge due to slow intersystem crossing (ISC) rates in combination with effective non‐radiative processes in those systems. Most room temperature phosphorescent (RTP) organic materials have O‐ or N‐lone pairs leading to low lying (n, π*) and (π, π*) excited states which accelerate kisc through El‐Sayed's rule. Herein, we report the first persistent RTP with lifetimes up to 0.5 s from simple triarylboranes which have no lone pairs. RTP is only observed in the crystalline state and in highly doped PMMA films which are indicative of aggregation induced emission (AIE). Detailed crystal structure analysis suggested that intermolecular interactions are important for efficient RTP. Furthermore, photophysical studies of the isolated molecules in a frozen glass, in combination with DFT/MRCI calculations, show that (σ, B p)→(π, B p) transitions accelerate the ISC process. This work provides a new approach for the design of RTP materials without (n, π*) transitions.
Metal–Ligand Cooperativity of the Calix[4]pyrrolato Aluminate: Triggerable C−C Bond Formation and Rate Control in Catalysis
Authors: Ebner Fabian , Sigmund Lukas Maximilian , Greb Lutz
Published: June 2020

Metal‐ligand cooperativity (MLC) had a remarkable impact on transition metal chemistry and catalysis. By use of the calix[4]pyrrolato aluminate, [1]−, which features a square‐planar AlIII, we transfer this concept into the p‐block and fully elucidate its mechanisms by experiment and theory. Complementary to transition metal‐based MLC (aromatization upon substrate binding), substrate binding in [1]− occurs by dearomatization of the ligand. The aluminate trapps carbonyls by the formation of C−C and Al−O bonds, but the products maintain full reversibility and outstanding dynamic exchange rates. Remarkably, the C−C bonds can be formed or cleaved by the addition or removal of lithium cations, permitting unprecedented control over the system's constitutional state. Moreover, the metal‐ligand cooperative substrate interaction allows to twist the kinetics of catalytic hydroboration reactions in a unique sense. Ultimately, this work describes the evolution of an anti‐van't Hoff/Le Bel species from their being as a structural curiosity to their application as a reagent and catalyst.
Magnetically Induced CO2Methanation Using Exchange‐Coupled Spinel Ferrites in Cuboctahedron‐Shaped Nanocrystals
Authors: Rivas‐Murias Beatriz , Asensio Juan M. , Mille Nicolas , Rodríguez‐González Benito , Fazzini Pier‐Francesco , Carrey Julian , Chaudret Bruno , Salgueiriño Verónica
Published: June 2020

Magnetically induced catalysis can be promoted taking advantage of optimal heating properties from the magnetic nanoparticles to be employed. However, when unprotected, these heating agents that are usually air‐sensitive, get sintered under the harsh catalytic conditions. In this context, we present, to the best of our knowledge, the first example of air‐stable magnetic nanoparticles that: 1) show excellent performance as heating agents in the CO2methanation catalyzed by Ni/SiRAlOx, with CH4yields above 95 %, and 2) do not sinter under reaction conditions. To attain both characteristics we demonstrate, first the exchange‐coupled magnetic approach as an alternative and effective way to tune the magnetic response and heating efficiency, and second, the chemical stability of cuboctahedron‐shaped core–shell hard CoFe2O4–soft Fe3O4nanoparticles.
Encapsulation and delivery of protein from within poly(sulfobetaine) hydrogel beads
Authors: Erfani Amir , Flynn Nicholas H. , Aichele Clint P. , Ramsey Joshua D.
Published: June 2020

Advancement of therapeutic protein therapies can be hindered by their poor stability and short in vivo half‐life. There is emerging evidence that biocompatible zwitterionic materials can prevent nonspecific interactions within proteins systems that contribute to protein instability. Here, zwitterionic hydrogel beads are synthesized from poly(sulfobetaine methyl methacrylate), pSB, using an inverse emulsion, free radical polymerization reaction technique. The transport properties within the zwitterionic hydrogels were characterized using 1H NMR diffusometry. Equilibrium water content as high as 0.90 was measured for the synthesized hydrogels. Our study revealed that the pSB hydrogels are nontoxic, ion responsive, and their swelling is temperature dependent. The zwitterionic hydrogel beads were capable of undergoing lyophilization without aggregation. Hydrogel beads were loaded with a model protein, bovine serum albumin (BSA), using a postfabrication loading technique. The protein loading was studied using confocal laser microscopy, indicating homogenous protein dispersion of up to 40 μg BSA/mg hydrogel within the beads. Furthermore, the release rate of the protein from the synthesized hydrogel was studied at different crosslinker to monomer ratios. The protein encapsulated within the zwitterionic hydrogel had slower rates of thermal aggregation compared to nonencapsulated protein in solution. Furthermore, the protein‐loaded inside the zwitterionic hydrogel better maintained its bioactivity.
Exploration of dual fatty acid amide hydrolase and cholinesterase inhibitory potential of some 3‐hydroxy‐3‐phenacyloxindole analogs
Authors: Tripathi Rati K. P. , Ayyannan Senthil R.
Published: June 2020

The dual inhibition of fatty acid amide hydrolase (FAAH) and cholinesterases (ChEs) has recently egressed as a novel strategy for the management of neurodegeneration. In the present work, a library of 3‐hydroxy‐3‐phenacyloxindole analogs was screened for FAAH and ChEs (acetylcholinesterase [AChE]/butyrylcholinesterase [BuChE]) inhibition. 1‐Benzyl‐3‐hydroxy‐3‐(2′,4′‐dibromophenacyl)oxindole (16), the most promising compound, showed a balanced multifunctional profile with FAAH (IC50 = 8.7 ± 0.3 nM, competitive and reversible), AChE (IC50 = 28 ± 3 nM, mixed and reversible), and BuChE (IC50 = 65 ± 8 nM, mixed and reversible) inhibition. The structure–activity relationship study predicted multifarious fundamental aspects crucial for the potency of these analogs. Furthermore, the structural geometry and rigidness bestowed by the oxindole moiety resulted in improved adherence of the compounds within the binding pockets of the target enzymes. Molecular docking studies of the docked conformations acknowledged numerous interactions for trenchant stabilization of inhibitor–enzyme complexes. Binding interaction and conformational alignment studies of stereoisomers of the lead inhibitors highlighted the importance of the (S)‐stereochemistry at C‐3 of the oxindole scaffold for potency and selectivity. Compound 16 also displayed an antioxidant potential surpassing that of ascorbic acid, and it was non‐neurotoxic. In silico molecular and ADMET properties anticipated druglikeness of the test compounds for oral use. Thus, compound 16 emerged as a new and interesting multifaceted candidate that could further be explored for its potential multitargeted role in the discovery of drugs for the treatment of Alzheimer's disease.
An insight on the restricted problem of 2 + 2 bodies with straight segment
Authors: Kumar Dinesh , Aggarwal Rajiv , Kaur Bhavneet
Published: June 2020

In the present paper, an effort to generalize the restricted problem of 2 + 2 bodies has been made by considering the primary bodies m1 and m2 to be a point mass and straight segment of length 2l, respectively. The motion of the two infinitesimal bodies mi, i = 3, 4 has been investigated, in which each mi, i = 3, 4 is moving in the gravitational field of mj, j = 1, 2, 3, 4 with i ≠ j. For the present problem, 14 equilibrium points are obtained, of which 6 are collinear and the rest are noncollinear. The length parameter l has a subsequent effect on the location of all the equilibrium points. Systematic stability analysis has been carried out by using the theory of perturbation. All the equilibrium points are found to be unstable.
On the donor substrate dependence of group‐transfer reactions by hydrolytic enzymes: Insight from kinetic analysis of sucrose phosphorylase‐catalyzed transglycosylation
Authors: Klimacek Mario , Sigg Alexander , Nidetzky Bernd
Published: June 2020

Chemical group‐transfer reactions by hydrolytic enzymes have considerable importance in biocatalytic synthesis and are exploited broadly in commercial‐scale chemical production. Mechanistically, these reactions have in common the involvement of a covalent enzyme intermediate which is formed upon enzyme reaction with the donor substrate and is subsequently intercepted by a suitable acceptor. Here, we studied the glycosylation of glycerol from sucrose by sucrose phosphorylase (SucP) to clarify a peculiar, yet generally important characteristic of this reaction: partitioning between glycosylation of glycerol and hydrolysis depends on the type and the concentration of the donor substrate used (here: sucrose, α‐d‐glucose 1‐phosphate (G1P)). We develop a kinetic framework to analyze the effect and provide evidence that, when G1P is used as donor substrate, hydrolysis occurs not only from the β‐glucosyl‐enzyme intermediate (E‐Glc), but additionally from a noncovalent complex of E‐Glc and substrate which unlike E‐Glc is unreactive to glycerol. Depending on the relative rates of hydrolysis of free and substrate‐bound E‐Glc, inhibition (Leuconostoc mesenteroides SucP) or apparent activation (Bifidobacterium adolescentis SucP) is observed at high donor substrate concentration. At a G1P concentration that excludes the substrate‐bound E‐Glc, the transfer/hydrolysis ratio changes to a value consistent with reaction exclusively through E‐Glc, independent of the donor substrate used. Collectively, these results give explanation for a kinetic behavior of SucP not previously accounted for, provide essential basis for design and optimization of the synthetic reaction, and establish a theoretical framework for the analysis of kinetically analogous group‐transfer reactions by hydrolytic enzymes.
Moving from the bench towards a large scale, industrial platform process for adeno‐associated viral vector purification
Authors: Adams Benjamin , Bak Hanne , Tustian Andrew D.
Published: June 2020

In recent years, there has been a strong interest in the development and production of gene therapy products, especially those utilizing adeno‐associated virus (AAV) particles. This is evident with the growing number of clinical successes and agency approvals for AAV therapeutics. Due to this increased investment in this technology, a need exists for scalable commercial production methods to ensure adequate product supply as research in AAV shifts from bench‐scale development to clinical production. The purpose of this review is to summarize current scalable purification techniques that can be employed during the commercial manufacturing of AAV as well as highlight certain development considerations, such as adventitious agent removal and process development using the principals of quality by design.
Comparison of the Peritoneal Cancer Index and Dutch region count as tools to stage patients with peritoneal metastases of colorectal cancer
Authors: Verheij F S , Bakkers C , Eden W J , Aalbers A G J , Nienhuijs S W , Jóźwiak K , Hingh I H J T , Kok N F M
Published: June 2020

Background

Extent of peritoneal metastases (PM) is among the most powerful prognostic factors for survival after cytoreductive surgery (CRS). This study aimed to compare the Peritoneal Cancer Index (PCI) and the Dutch region count as tools for staging PM of colorectal cancer. The Dutch region count is a simpler classification that distinguishes seven rather than 13 abdominal regions. Presence or absence of PM is recorded.

Methods

This was a retrospective cohort study in two tertiary referral centres in the Netherlands. Consecutive patients with colorectal PM who were intentionally treated with CRS and subsequent hyperthermic intraperitoneal chemotherapy in 2016 and 2017 were included. The PCI and Dutch region count were both recorded during laparotomy. Correlation between scoring tools was calculated using Spearman's rank correlation coefficient. Diagnostic values were calculated for different cut-off values of the PCI, alongside the Dutch region count. The correlation of both scores was determined for the exploration and validation cohorts separately.

Results

In the exploration and validation cohorts, 73 and 85 patients respectively were included. Spearman's correlation coefficients of 0·897 and 0·961 were observed for continuous scores of the Dutch region count and PCI in the exploration and validation group respectively. A cut-off value of 20 for the PCI score and 5 for the Dutch region count showed 91·9 and 94·5 per cent sensitivity, and 81·8 and 91·7 per cent specificity, respectively.

Conclusion

The Dutch region count correlated well with the PCI score, and may help to simplify reporting of the extent of peritoneal disease.
Impact of oral preoperative and perioperative immunonutrition on postoperative infection and mortality in patients undergoing cancer surgery: systematic review and meta-analysis with trial sequential analysis
Authors: Buzquurz F , Bojesen R D , Grube C , Madsen M T , Gögenur I
Published: June 2020

Background

Infectious complications occur in 4–22 per cent of patients undergoing surgical resection of malignant solid tumours. Improving the patient's immune system in relation to oncological surgery with immunonutrition may play an important role in reducing postoperative infections. A meta-analysis was undertaken to evaluate the potential clinical benefits of immunonutrition on postoperative infections and 30-day mortality in patients undergoing oncological surgery.

Methods

PubMed, Embase and Cochrane Library databases were searched to identify eligible studies.

Eligible studies had to include patients undergoing elective curative surgery for a solid malignant tumour and receiving immunonutrition orally before surgery, including patients who continued immunonutrition into the postoperative period. The main outcome was overall infectious complications; secondary outcomes were surgical-site infection (SSI) and 30-day mortality, described by relative risk (RR) with trial sequential analysis (TSA). Risk of bias was assessed according to Cochrane methodology.

Results

Some 22 RCTs with 2159 participants were eligible for meta-analysis. Compared with the control group, immunonutrition reduced overall infectious complications (RR 0·58, 95 per cent c.i. 0·48 to 0·70; I2 = 7 per cent; TSA-adjusted 95 per cent c.i. 0·28 to 1·21) and SSI (RR 0·65, 95 per cent c.i. 0·50 to 0·85; I2 = 0 per cent; TSA-adjusted 95 per cent c.i. 0·21 to 2·04). Thirty-day mortality was not altered by immunonutrition (RR 0·69, 0·33 to 1·40; I2 = 0 per cent).

Conclusion

Immunonutrition reduced overall infectious complications, even after controlling for random error, and also reduced SSI. The quality of evidence was moderate, and mortality was not affected by immunonutrition (low quality). Oral immunonutrition merits consideration as a means of reducing overall infectious complications after cancer surgery.
Racial and ethnic disparities in mortality from gastric and esophageal adenocarcinoma
Authors: Laszkowska Monika , Tramontano Angela C. , Kim Judith , Camargo M. Constanza , Neugut Alfred I. , Abrams Julian A. , Hur Chin
Published: June 2020

Background

Racial/ethnic differences in mortality have not been well studied for either non‐cardia gastric cancer (NCGC) or cardia gastric cancer (CGC). The aim of this study was to examine the US mortality rates for these cancer subtypes, as well as esophageal adenocarcinoma (EAC) as a comparator.

Methods

We identified 14 164 individuals who died from NCGC, 5235 from CGC, and 13 982 from EAC in the Surveillance, Epidemiology, and End Results database between 2004 and 2016. Age‐adjusted incidence‐based mortality rates and corresponding annual percent changes (APCs) were calculated. Analyses were stratified by race/ethnicity, age, and stage of disease at diagnosis.

Results

The mortality rate in NCGC was two‐ to threefold higher in blacks, Hispanics, and Asians/Pacific Islanders (PI) than non‐Hispanic whites, and was significant across all age groups and stages of disease (P < .01). Mortality in CGC was higher in non‐Hispanic whites than blacks and Asians/PI, particularly in individuals in the 50‐64 year age group and those with stage IV disease. Mortality in EAC was two‐ to sixfold higher in non‐Hispanic whites than all other groups across all age groups and stages of disease. From 2004 to 2016, mortality rates were stable across all racial/ethnic groups in NCGC and CGC, and in minority groups with EAC, but have been rising in non‐Hispanic whites with EAC (APC 3.03, 95% CI 0.17‐5.96).

Conclusions

This is the largest study of incidence‐based mortality in CGC and NCGC and demonstrates racial/ethnic differences in mortality between these subtypes. Mortality rates for NCGC are highest in minority groups, and have been stable in recent years despite declining incidence. Mortality rates for CGC are marginally higher in middle‐aged non‐Hispanic whites with advanced disease, though have remained stable. In contrast, mortality in EAC has been rising for non‐Hispanic whites, in parallel to incidence. Further studies are needed to refine prevention strategies for high‐risk individuals dying from these specific cancer subtypes.
Electrochemically Assisted Growth of CsPbBr3‐Based Solar Cells Without Selective Contacts
Authors: Ramírez Daniel , Riveros Gonzalo , Díaz Patricia , Verdugo Javier , Núñez Gerard , Lizama Susy , Lazo Pamela , Dalchiele Enrique A. , Gau Daniel L. , Marotti Ricardo E. , Anta Juan A. , Contreras‐Bernal Lidia , Riquelme Antonio , Idigoras Jesús
Published: June 2020

In this work we report a simple and cost‐effective CsPbBr3‐based solar cell without ordinary selective contacts. To do so we follow an electrochemical approach consisting of three successive steps: (1) electrodeposition of PbO2 directly on top of FTO substrates, (2) heterogeneous phase reaction with gaseous HBr and (3) spin‐coating of methanolic CsBr solutions followed by annealing. This method is more adequate for large‐scale environmentally friendly production as it reduces chemical waste, particularly toxic lead. The resulting films were structurally and optically characterized showing good coverage of the FTO substrates, absence of defects such as pinholes and orthorhombic structure. Photovoltaic and impedance characterization was carried out by pressing a carbon coated metal spring onto the CsPbBr3 film until obtaining maximized open‐circuit potential (Voc) and short‐circuit photocurrent density (jsc) under simulated sunlight. The stabilized current at fixed voltage (SCFV) technique gave a maximum PCE value of 2.70 % close to devices with similar configuration. Impedance measurements demonstrated analogous behavior to that of state‐of‐art CsPbBr3 based solar cells, comprising a recombination arc at mid‐high frequencies, geometrical capacitance and ideality factors closed to 2, typical of SRH recombination in the perovskite bulk.
Biuret—A Crucial Reaction Intermediate for Understanding Urea Pyrolysis To Form Carbon Nitrides: Crystal‐Structure Elucidation and In Situ Diffractometric, Vibrational and Thermal Characterisation
Authors: Gross Peter , Höppe Henning A.
Published: June 2020

The crystal structure of biuret was elucidated by means of XRD analysis of single crystals grown through slow evaporation from a solution in ethanol. It crystallises in its own structure type in space group C2/c (a=15.4135(8) Å, b=6.6042(3) Å, c=9.3055(4) Å, Z=8). Biuret decomposition was studied in situ by means of temperature‐programmed powder XRD and FTIR spectroscopy, to identify a co‐crystalline biuret–cyanuric acid phase as a previously unrecognised reaction intermediate. Extensive thermogravimetric studies of varying crucible geometry, heating rate and initial sample mass reveal that the concentration of reactive gases at the interface to the condensed sample residues is a crucial parameter for the prevailing decomposition pathway. Taking these findings into consideration, a study on the optimisation of carbon nitride synthesis from urea on the gram scale, with standard solid‐state laboratory techniques, is presented. Finally, a serendipitously encountered self‐coating of the crucible inner walls by graphite during repeated synthetic cycles, which prove to be highly beneficial for the obtained yields, is reported.
Formation of Highly Ordered Molecular Porous 2D Networks from Cyano‐Functionalized Porphyrins on Cu(111)
Authors: Adhikari Rajan , Siglreithmaier Gretel , Gurrath Martin , Meusel Manuel , Kuliga Jan , Lepper Michael , Hölzel Helen , Jux Norbert , Meyer Bernd , Steinrück Hans‐Peter , Marbach Hubertus
Published: June 2020

We investigated the adsorption of three related cyano‐functionalized tetraphenyl porphyrin derivatives on Cu(111) by scanning tunneling microscopy (STM) in ultra‐high vacuum (UHV) with the goal to identify the role of the cyano group and the central Cu atom for the intermolecular and supramolecular arrangement. The porphyrin derivatives studied were Cu‐TCNPP, Cu‐cisDCNPP, and 2H‐cisDCNPP, that is, Cu‐5,10,15,20‐tetrakis‐(p‐cyano)‐phenylporphyrin, Cu‐meso‐cis‐di(p‐cyano)‐phenylporphyrin and 2H‐meso‐cis‐di(p‐cyano)‐phenylporphyrin, respectively. Starting from different structures obtained after deposition at room temperature, all three molecules form the same long‐range ordered hexagonal honeycomb‐type structure with triangular pores and three molecules per unit cell. For the metal‐free 2H‐cisDCNPP, this occurs only after self‐metalation upon heating. The structure‐forming elements are pores with a distance of 3.1 nm, formed by triangles of porphyrins fused together by cyano‐Cu‐cyano interactions with Cu adatoms. This finding leads us to suggest that two cyano‐phenyl groups in the “cis” position is the minimum prerequisite to form a highly ordered 2D porous molecular pattern. The experimental findings are supported by detailed density functional theory calculations to analyze the driving forces that lead to the formation of the porous hexagonal honeycomb‐type structure.
Highly Tough, Stretchable, Self‐Adhesive and Strain‐Sensitive DNA‐Inspired Hydrogels for Monitoring Human Motion
Authors: Chen Binggang , Wang Wenliang , Yan Xinxin , Li Shengran , Jiang Sangni , Liu Sanrong , Ma Xiaojing , Yu Xifei
Published: June 2020

Hydrogels used as strain sensors often rely on splicing tapes to attach them to surfaces, which causes much inconvenience. Therefore, to develop strain sensor hydrogels that possess both good mechanical properties and self‐adhesion is still a great challenge. Inspired by the multiple hydrogen bonding interactions of nucleobases in DNA, we designed and synthesized a series of hydrogels PAAm‐GO‐Aba/Tba/Aba+Tba comprising polyacrylamide (PAAm), graphene oxide (GO), acrylated adenine and thymine (Aba and Tba). The introduction of nucleobases helps hydrogels to adhere to various substrates through multiple hydrogen‐bonding interactions. It has also been found that the adhesive strength of hydrogels with nucleobases for hogskin increased to 2.5 times that of those without nucleobases. Meanwhile, these hydrogels exhibited good dynamic mechanical and self‐recovery properties. They can be directly attached to human skin as strain sensors to monitor the motions of finger, wrist, and elbow. Electrical tests indicate that they give precise real‐time monitoring data and exhibit good strain sensitivity and electrical stability. This work provides a promising basis from which to explore the fabrication of tough, self‐adhesive, and strain‐sensitive hydrogels as strain sensors for applications in wearable devices and healthcare monitoring.
Synthesis of Oligonucleotides containing the cis‐Interstrand Crosslink Produced by Mitomycins in their Reaction with DNA
Authors: Aguilar William , Zacarias Owen , Romaine Marian , Proni Gloria , Petrovic Ana G. , Abzalimov Rinat , Paz Manuel M. , Champeil Elise
Published: June 2020

Mitomycin C (MC) an antitumor drug and decarbamoylmitomycin C (DMC), a derivative of MC lacking the carbamoyl moiety, are DNA alkylating agents which can form DNA interstrand crosslinks (ICLs) between deoxyguanosine residues located on opposing DNA strands. MC forms primarily deoxyguanosine adducts with a 1“‐R stereochemistry at the guanine‐mitosene bond (1”‐α, trans) whereas DMC forms mainly adducts with a 1“‐S stereochemistry (1”‐β, cis). The crosslinking reaction is diastereospecific: trans‐crosslinks are formed exclusively at CpG sequences, while cis‐crosslinks are formed only at GpC sequences. Until now, oligonucleotides containing 1“‐β‐deoxyguanosine adducts or ICL at a specific site could not be synthesized, thus limiting the investigation of the role played by the stereochemical configuration at C1′′ in the toxicity of these compounds. Here, a novel biomimetic synthesis to access these substrates is presented. Structural proof of the adducted oligonucleotides and ICL were provided by enzymatic digestion to nucleosides, high resolution mass spectral analysis, CD spectroscopy and UV melting temperature studies. Finally, a virtual model of the 25‐mer 1”‐β ICL synthesized was created to explore the conformational space and structural features of the crosslinked duplex.
Development a clinical prediction model of the neurological outcome for patients with coma and survived 24 hours after cardiopulmonary resuscitation
Authors: Wang Hai , Tang Long , Zhang Li , Zhang Zheng‐Liang , Pei Hong‐Hong
Published: June 2020

Background

Cardiac arrest is still a global public health problem at present. The neurological outcome is the core indicator of the prognosis of cardiac arrest. However, there is no effective means or tools to predict the neurological outcome of patients with coma and survived 24 hours after successful cardiopulmonary resuscitation (CPR).

Hypothesis

Therefore, we expect to construct a prediction model to predict the neurological outcome for patients with coma and survived 24 hours after successful CPR.

Methods

A retrospective cohort study was used to construct a prediction model of the neurological function for patients with coma and survived 24 hours after successful CPR. From January 2007 to December 2015, a total of 262 patients met the inclusion and exclusion criteria.

Results

The predictive model was developed using preselected variables by a systematic review of the literature. Finally, we get five sets of models (three sets of construction models and two sets of internal verification models) which with similar predictive value. The stepwise model, which including seven variables (age, noncardiac etiology, nonshockable rhythm, bystander CPR, total epinephrine dose, APTT, and SOFA score), was the simplest model, so we choose it as our final predictive model. The area under the ROC curve (AUC), specificity, and sensitivity of the stepwise model were respectively 0.82 (0.77, 0.87), 0.72and 0.82. The AUC, specificity, and sensitivity of the bootstrap stepwise (BS stepwise) model were respectively 0.82 (0.77, 0.87), 0.71, and 0.82.

Conclusion

This new and validated predictive model may provide individualized estimates of neurological function for patients with coma and survived 24 hours after successful CPR using readily obtained clinical risk factors. External validation studies are required further to demonstrate the model's accuracy in diverse patient populations.