bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution and insights into the structure and function of the DedA superfamily containing TMEM41B and VMP1
Authors: Okawa Fumiya , Hama Yutaro , Zhang Sidi , Morishita Hideaki , Yamamoto Hayashi , Levine Tim P. , Mizushima Noboru
Published: March 2021

TMEM41B and VMP1 are endoplasmic reticulum (ER)-localizing multi-spanning membrane proteins required for ER-related cellular processes such as autophagosome formation, lipid droplet homeostasis and lipoprotein secretion in eukaryotes. Both proteins have a VTT domain, which is similar to the DedA domain found in bacterial DedA family proteins. However, the molecular function and structure of the DedA and VTT domains (collectively referred to as DedA domains) and the evolutionary relationships among the DedA domain-containing proteins are largely unknown. Here, we conduct a remote homology search and identify a new clade consisting mainly of bacterial proteins of unknown function that are members of the Pfam family PF06695. Phylogenetic analysis reveals that the TMEM41, VMP1, DedA and PF06695 families form a superfamily with a common origin, which we term the DedA superfamily. Coevolution-based structural prediction suggests that the DedA domain contains two reentrant loops facing each other in the membrane. This topology is biochemically verified by the substituted cysteine accessibility method. The predicted structure is topologically similar to that of the substrate-binding region of Na+-coupled glutamate transporter solute carrier 1 (SLC1) proteins. A potential ion-coupled transport function of the DedA superfamily proteins is discussed.

This article has an associated First Person interview with the joint first authors of the paper.
Metal(II) Ion Dependence of the Structures and Properties of Square-Grid Coordination Polymers of Tetrabromobenzenedicarboxylate and Pyrazine as Bridging Ligands
Authors: Kumagai Hitoshi , Setoyama Norihiko , Kawata Satoshi , Sakamoto Yoshiyuki
Published: March 2021

In this study, we report the synthesis and crystal structures of coordination polymers employing tetrabromobenzenedicarboxylate (Br4bdc2−) and pyrazine (pyz). Uncoordinated pyz molecules are stabilized between the layers by both hydrogen H-bonding and π–π stacking interactions in [M(Br4bdc)(pyz)(H2O)2](pyz), where M = Co(II) and Zn(II). In addition, water molecules are incorporated between the layers in [Cu(Br4bdc)(pyz)(H2O)2](H2O) owing to Jahn–Teller distortion of the Cu(II) ions, which prevents π–π stacking interactions between the pyz and Br4bdc2−. Depending on the metal(II) centers, structural changes that occur during the heating and hydration processes exhibit different behavior. Co(II) compound slowly changes structure by heating and rapidly recovers the crystalline state in air. Conversely, Zn(II) compound assumes the amorphous phase by heating and slowly yields the crystalline phase in ambient conditions. Although the Cu(II) compound also shows structural changes by heating, the dehydrated phase exhibits hydrophobic characteristics. Ion conductivity measurements of the as-synthesized forms show conductivities of 1.9 × 10−6 Scm−1, 4.6 × 10−7 Scm−1, and 1.3 × 10−6 Scm−1, for the Co(II), Zn(II), and Cu(II) complexes at 90 °C and 95% relative humidity (RH), respectively. The relatively low values of the as-synthesized Co(II) and Zn(II) compounds are attributed to the H-bonding interaction and π–π stacking of pyz molecules, which prevent the dynamics of the pyz molecules needed for proton conduction.
Self-Assembly of Peptide-Containing Mesogens: Thermotropic Liquid-Crystalline Properties and Macroscopic Alignment of Amphiphilic Bioconjugates
Authors: Eimura Hiroki , Niwa Anna , Uchida Junya , Kato Takashi
Published: March 2021

Thermotropic liquid crystals having tripeptide moieties are reported. A series of peptide chains including arginine-glycine-aspartic acid (RGD), glycine-glycine-aspartic acid (GGD), and triglycine (GGG) moieties is connected to a rigid-rod core through a flexible tetraoxyethylene spacer. These bioconjugated mesogens form intermolecular hydrogen bonds through amide groups in the tripeptide moieties. It is found that side chains in the tripeptide-conjugated mesogens constrain intermolecular hydrogen bonding in the bulk states, which affects the formation of the liquid-crystalline phases. The rigid-rod mesogens bearing RGD and GGD peptide sequence exhibit smectic phases with high thermal stability of the mesophases. The liquid-crystalline assemblies of the mesogen-containing peptides are macroscopically oriented by mechanical shearing. The present design of bioconjugated liquid crystals could lead to the development of new self-assembled materials for biological applications.
Recognition of Target Site in Various Forms of DNA and RNA by Peptide Nucleic Acid (PNA): From Fundamentals to Practical Applications
Authors: Liang Xingguo , Liu Mengqin , Komiyama Makoto
Published: March 2021

Peptide nucleic acid (PNA) is a DNA analog, in which the sugar-phosphate backbone in DNA is replaced by poly[N-(2-aminoethyl)glycine]. Since its discovery in the early 1990s, PNA has been widely employed in chemistry, biochemistry, medicine, nanotechnology, and many other fields. This account surveys recent developments on the design of PNA derivatives and their applications. In the first part, PNAs for sequence-specific recognition of DNA and RNA (single-strands, double-strands, G-quadruplexes, i-motifs, and others) are comprehensively covered. Modifications of nucleobases and of the main chain effectively promote both the strength of binding and the selectivity of recognition. In the second half of this account, practical applications of PNA are presented. Structural restraints, induced by complex formation of PNA with DNA and RNA substrates, lead to selective transformation of target sites to desired structures. Applications to regulation of gene expression, gene editing, construction of sophisticated nanostructures, and others are also described. Advantages and disadvantages of PNAs, compared with other sequence-recognizing molecules hitherto reported, are discussed in terms of various physicochemical and biological features.
Συλλογική σύνθεση σεσκιτερπενοειδών
Authors: Δεμερτζίδου Βαρβάρα
Published: March 2021

Οι σεσκιτερπενοειδείς λακτόνες (SLs) αποτελούν μια πολυάριθμη οικογένεια φυσικών προϊόντων που χαρακτηρίζονται από δομική πολυμορφία και πολυπλοκότητα. Η ύπαρξη του α-μεθυλενο-γ-λακτονικού δακτυλίου στα μόρια των SLs αποτελεί χαρακτηριστικό δομικό τους στοιχείο και σε αυτήν οφείλεται κατά κύριο λόγο η εμφάνιση της κυτταροτοξικής τους δράσης, καθιστώντας τες πολλά υποσχόμενους αντικαρκινικούς παράγοντες. Παρά το συνεχές ενδιαφέρον από τους συνθετικούς χημικούς, η σύνθεση των SLs εξακολουθεί να αποτελεί πρόκληση, καθώς καθίσταται εξαιρετικά δύσκολος ο σχεδιασμός μιας συλλογικής συνθετικής πορείας που όχι μόνο να παρέχει ικανές ποσότητες για βιολογικές δοκιμές, αλλά και να οδηγεί σε επαρκώς διαφοροποιημένες δομές και των δύο ισομερών μορφών των λακτονών (6,12- και 8,12-). Σκοπός της παρούσας διατριβής, ήταν η ανάπτυξη μιας συνθετικής πορείας πρόσβασης σε δομές σεσκιτερπενοειδών α-μεθυλενο-γ-λακτονών μέσω ενός κατάλληλου κοινού ενδιαμέσου (common scaffold), το οποίο μέσω κατάλληλων μετασχηματισμών θα οδηγήσει σε δομές που πληρούν τα παραπάνω κριτήρια για μία κατά το δυνατόν πλήρη συλλογική σύνθεση σεσκιτερπενοειδών. Αρχικά, περιγράφεται η τυπική σύνθεση του φυσικού προϊόντος σαρκαντραλακτόνη A μέσω αντίδρασης κυκλοϊσομερείωσης, της οποίας και πραγματοποιείται σχολιασμός του προτεινόμενου μηχανισμού βάσει DFT υπολογισμών. Εν συνεχεία, πραγματοποιείται η ρετροσυνθετική ανάλυση και η σύνθεση του νέου α-μεθυλενο-γ-λακτονικού κοινού ενδιαμέσου, μέσα από την οποία παρουσιάζεται μια νέα μέθοδος αλλυλικής χλωρίωσης της R-καρβόνης, καθώς και μια νέα αντίδραση φωτοχημικής syn-8,12-λακτονοποίησης με χρήση ιωδίου και PIDA υπό συνθήκες ορατού φωτός. Μέσω της ίδιας πορείας πραγματοποιείται ο σχηματισμός και ενός 6,12-λακτονικού παραγώγου. Κατόπιν, το κοινό ενδιάμεσο μετασχηματίζεται μέσω κατάλληλων αλκυλιώσεων είτε σε trans-ενύνιο με σκοπό τη σύνδεση της νεοαναπτυχθείσας συνθετικής πορείας με αυτής των φουρανοσεσκιτερπενοειδών που αναπτύχθηκε προγενέστερα από την ερευνητική μας ομάδα, είτε σε cis-ελεμανολίδιο, το οποίο με τη σειρά του μέσω αντίδρασης επέκτασης δακτυλίου Cope οδηγεί σε δομές γερμακρανολιδίων και γουαϊανολιδίων. Παράλληλα, πραγματοποιείται διερεύνηση συνθηκών για την 6-υποκατάσταση του κοινού ενδιαμέσου μέσω αντιδράσεων στο αντίστοιχο θειο-υλίδιο, και τα συντιθέμενα παράγωγα υπόκεινται σε απόπειρες αλκυλίωσης.
Global equity in protection of pregnant frontline workers
Authors: Jaffe Elana F. , Karron Ruth A. , Krubiner Carleigh B. , Wonodi Chizoba B. , Beigi Richard H. , Sheffield Jeanne S. , Faden Ruth R.
Published: March 2021

Vaccination of frontline workers against COVID-19 is underway in some countries. With women comprising a majority of health, education, and other essential workforces, many on the front lines of the pandemic response will be pregnant at the time that they are offered COVID-19 vaccines. However, pregnant people were not included in any of the COVID-19 vaccine trials that regulatory agencies evaluated when considering authorization. Without pregnancy-specific data, pregnant frontline workers in some settings are being denied COVID-19 vaccines. In other settings, pregnant frontline workers are able to access these same vaccines, but are faced with the burden of decision-making in the absence of an explicit recommendation for use and without pregnancy-specific data. While permissive recommendations for use in pregnancy are ethically preferable to unjustly denying vaccine access, objectives to protect the frontline workforce will fall short until there is evidence to support explicit recommendations for COVID-19 vaccination in pregnancy. In this article, we provide three actionable recommendations to ensure equitable protection of pregnant frontline workers as vaccines against COVID-19 continue to be developed and rolled out globally. First, efforts must be taken now to leverage critical opportunities for narrowing the evidence gaps around currently authorized COVID-19 vaccines in pregnancy. Next, action in the near term is needed to preempt evidence gaps for COVID-19 vaccines still in development. Finally, in the absence of an explicit recommendation for use in pregnancy, and while pregnancy-specific data lags behind, pregnant people should be prioritized for alternate preventive and treatment measures. Achieving equitable protection for those who are pregnant and serving on the frontlines of the pandemic will require no less.
Traduzione e rispetto filologico: alcune osservazioni sulla traduzione di alcune poesie della scuola siciliana al Labestrad della UFF
Authors: Bonomini Guido Alberto
Published: March 2021

La traduzione che abbia uno scopo didattico deve sempre rispettare la voce dell’ autore, quindi non è possibile ricreare il testo conmere finalità artistiche. L’esperienza della traduzione di alcune poesie della scuola siciliana ci ha costretto ad avvicinarci al testo e aggiungere delle note per spiegare dei termini topici.
Perché io son nata poeta, non santa: a voz da mulher e a poesia de Gaspara Stampa
Authors: De Souza Beatriz Rodrigues
Published: March 2021

Ao longo dos anos, o amor foi representado de diferentes formas e em meios de comunicação diversos. O poeta italiano Petrarca, por exemplo, expressa seu sentimento por Laura usando a forma tida como perfeita: o soneto; além disso, seu amor é sempre puro e sua musa sempre calada. É assim, sem voz e apenas para admiração, que as mulheres aparecem na maioria das obras de arte, refletindo os ideais sociais do período em que estão. Porém, surgem autoras que subvertem essa ideia; é o caso, por exemplo, de Gaspara Stampa, poeta do Cinquecento italiano. Embora a autora siga a forma poética consagrada por Petrarca, usa sua poesia para manifestar seu sentimento e, assim, consegue ser uma voz feminina em um meio em que existem poucas oportunidades de expressão para as mulheres. Neste artigo, a figura da poeta é colocada em oposição ao modelo imposto a partir de uma citação de outra autora italiana, Sibilla Aleramo; embora as autoras sejam separadas por séculos, percebe-se que a visão de amor e do feminino que prevalece em ambos os períodos é aquela masculina. Faz-se, então, necessário o estudo dos escritos dessas e outras mulheres para que haja um espaço para suas (e nossas) vozes.
Barreiras no caminho do tradutor: como lidar com elas?
Authors: Santos Maria Aparecida Cardoso , Isse Renan
Published: March 2021

A tradução é um processo milenar. Desde a antiguidade, homens e mulheres traduzem textos, sejam eles orais ou escritos. A tradução, enquanto processo, consiste na transposição de um texto de uma dada língua de partida para uma determinada língua de chegada. Apesar de tantos anos de tradução, ainda há o que se falar sobre o texto traduzido e a tradução. A tradução precisou buscar seu lugar nos estudos acadêmicos para se desvencilhar de áreas afins que pudessem englobá-la, como a linguística. Dessa forma, criou-se a Teoria da tradução enquanto suporte teórico para analisar algumas situações e ajudar a atribuir à disciplina a devida autonomia que ela merece. Quando saímos do campo teórico e nos direcionamos à tradução enquanto prática, no entanto, a recepção é outra. Até que ponto o senso comum é capaz de interferir e pré-julgar a prática tradutória? O presente artigo busca discutir alguns tópicos importantes referentes ao processo de tradução, além de desenvolver uma reflexão sobre o nosso comportamento, enquanto (futuros) tradutores.
A Loba
Authors: Arêas Alcebíades , Belizário Edvaldo Sampaio
Published: March 2021

Tradução do conto La Lupa, de Giovanni Verga
O Código Florestal de 2012 sob a ótica do Supremo Tribunal Federal: a consolidação do retrocesso socioambiental
Authors: Moreira Danielle De Andrade , Marques de Carvalho de Oliveira Daniela , Rêgo Teixeira Lima Letícia Maria
Published: March 2021

Este artigo objetiva demonstrar que, além da dificuldade de implementação das normas ambientais já existentes, o Direito Ambiental enfrenta novo desafio: a edição de diplomas normativos tendentes a reduzir direitos socioambientais já positivados.  O Código Florestal de 2012 se insere neste contexto e é, até o momento, o principal exemplo concretizado de diminuição da proteção ao meio ambiente, em desrespeito ao princípio da vedação ao retrocesso socioambiental, cuja função é garantir que o nível de proteção alcançado pelos direitos socioambientais não seja reduzido, impedindo agressões ao núcleo essencial do direito fundamental ao meio ambiente ecologicamente equilibrado.  Para o estudo dos retrocessos promovidos pela nova legislação florestal, foi realizado levantamento bibliográfico e documental, acompanhado de catalogação e análise crítica do material selecionado.  A metodologia adotada incluiu levantamento, sistematização e análise qualitativa dos acórdãos do Supremo Tribunal Federal relativos às ações judiciais que questionavam a constitucionalidade de diversos dispositivos do novo Código Florestal.  Ao declarar a constitucionalidade da grande maioria das alterações da Lei 12.651/2012, o Supremo Tribunal Federal confirmou e consolidou um conjunto de retrocessos normativos em matéria de meio ambiente, esvaziando de modo substancial a orientação do princípio da vedação ao retrocesso socioambiental.
Como as cidades brasileiras estão lidando com o Airbnb? Colocando a regulação em perspectiva
Authors: Souza Rafael Braga de , Leonelli Gisela Cunha Viana
Published: March 2021

Nos últimos anos, empresas tem florescido no ambiente digital a partir de premissas do compartilhamento de produtos e serviços. O Airbnb é uma empresa que opera dentro dessa lógica conhecida como Economia do Compartilhamento e tem gerado impactos no ambiente urbano. Nesse sentido, cidades, principalmente na Europa e nos EUA, tem estabelecido marcos regulatórios com estratégias variadas visando ampliar os benefícios e mitigar os impactos negativos dessa plataforma. No entanto, é desconhecida a legislação voltada para o Airbnb no Brasil e sua abordagem. O objetivo desse trabalho é contrastar as legislações brasileiras concernentes ao Airbnb com os marcos regulatórios internacionais. A partir de revisão bibliográfica e da análise das legislações brasileiras, constatou-se que as estas tem abordagens que não exercem efetivo controle e monitoramento sobre o Airbnb. Além disso distanciam-se das legislações internacionais em termos de problemática enfrentada, estas buscam garantir habitação à preços acessíveis, enquanto as brasileiras privilegiam a concorrência mais equilibrada com o mercado de hospedagem. Palavras-chave: Airbnb; Regulação Urbana; Economia do Compartilhamento; dinâmica imobiliária; Mercado de hospedagem
Os bens comuns e o controle de desafetação de bens públicos
Authors: Tepedino Gustavo José Mendes , Peçanha Danielle Tavares , Dana Simone Cohn
Published: March 2021

O presente trabalho tem como objeto de estudo a teoria dos bens comuns, cujo acesso ganha destaque quando associado à efetividade dos direitos fundamentais. Nessa direção, correlata se faz a análise dos bens públicos e de sua afetação (ou não) a interesse coletivo, com enfoque nas funções por eles exercidas. Das três categorias de bens apresentadas pelo Código Civil, os bens de uso comum do povo são os que mais se aproximam dos bens comuns, embora não haja identidade, já que os primeiros se fundam na tradicional racionalidade proprietária expressa pela dicotomia "propriedade pública” e “propriedade privada". Ainda assim, existem zonas de convergências entre as matérias, que suscitam discussões e incremento do repertório jurisprudencial. Além de a incorporação ao patrimônio público não representar, por si só, garantia de afetação dos bens ao interesse coletivo, existe intenso debate acerca do controle de desafetações de bens públicos de uso comum, diante da possível conversão em dominicais e posterior alienação, muitas vezes, contrária à lógica dos Commons. Daí a necessidade de critérios objetivos e sólidos que promovam tratamento e gestão adequada destes bens, de modo que o regime da propriedade se encontre vinculado ao cumprimento da função social, visando promover os direitos fundamentais.
Editorial
Authors: Camello Thereza Cristina Ferreira
Published: March 2021

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The management of urinary tract infections in older patients within an urgent care out-of-hours setting
Authors: Dexter Justine , Mortimore Gerri
Published: March 2021

This article critically analyses the prevalence, assessment and management of urinary tract infections (UTIs) in patients over the age of 65, in an urgent care out-of-hours service in order to enhance care. It is undertaken from the perspective of working as an Advanced Nurse Practitioner (ANP). A synopsis of UTI is presented, examining the epidemiology and aetiology. The process of assessment, diagnosis and management of UTI in older people is appraised based on current evidence. Difficulties associated with the recognition of UTI in elderly are evaluated. Finally, recommendations are made for the improvement of future practice as an ANP.
COVID-19 vaccines and vaccine administration
Authors: Gordon Charlotte , Porteous Debbie , Unsworth John
Published: March 2021

This article provides an overview of current COVID-19 vaccines available within the UK, including their mode of action, storage and handling. It outlines the recommendations on priority groups for vaccination and provides insight into the training recommendations for vaccinators.
Idiopathic pulmonary fibrosis: a more common condition than you may think
Authors: Tremayne Penny , John Clark Samuel
Published: March 2021

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive incurable lung disease that affects a significant amount of people in the UK. Many health professionals have a limited understanding of IPF, which can result in a delayed diagnosis and inadequate care for individuals and their families. This article aims to provide an overview of IPF and help to enhance health professionals' understanding of the disease, thus contributing towards improving the care that IPF sufferers receive. This article provides a definition of IPF and explores its pathophysiology. It discusses the causes and risk factors for developing the condition, examines how IPF is diagnosed and details the treatment options available for IPF patients.
Is Peer Instruction in Primary School Feasible? : The Case Study in Slovenia
Authors: Pavlin Jerneja , Čampa Tina
Published: March 2021

An evidence-based, interactive teaching method peer instruction (PI) is promoted to support effectiveness over more commonly used teaching methods. Usually it is proposed for the university and upper secondary school. The research reports on the implementation of the PI approach in teaching subject Science and Technology (S&T) in the 4th grade of primary school. The aim of this research was to verify the feasibility of this approach for much younger students in primary school by evaluating the students’ progress in the subject S&T, identifying the differences in individual progress in relation to students’ general learning success, and determining students’ opinions about the approach and where no desired progress has been made. In a selected Slovenian primary school, a classroom with 26 students (age 9 – 10) was included in the study and 5 different content areas (Earth’s motion, Matter, Magnetism, Forces and motion, and Electricity) were taught using this PI approach. Results show that students made progress in all content areas and no differences were identified in the progress of individual students in terms of general learning success. Students were satisfied with the approach, although more than half of them found the multiple-choice questions as too difficult. Although the PI approach is successful, teachers must be aware that some persistent and widespread misunderstandings may still remain and require additional intervention.
When Prospective Biology Teachers Visualize their Beliefs about Teaching and Learning by Drawing it, is it more than a Reproduction of their Experienced School Lessons?
Authors: Schumacher Fabian , Wilde Matthias
Published: March 2021

Professional teaching competence is significantly influenced by beliefs about teaching and learning. Prospective teachers start their teacher training with quite persistent beliefs about learning processes. These beliefs are mainly influenced by the way they experienced their own lessons as a student at school. Previous biology lessons at school might be linked to the imagined biology lessons of prospective teachers. We interpret these future lessons as a representation of their beliefs about teaching and learning. The present study investigated how prospective teachers remembered their previous biology lessons as well as how they imagine the lessons they will conduct in the future. The drawings of 181 prospective biology teachers in Germany (Mage = 22.1; SD = 3.6; 64.1 % female) were analyzed using the Draw-a-Science-Teacher-Test Checklist (DASTT-C). Results of the study indicate that the lessons they experienced were mainly teacher-centered, whereas the lessons they imagined were mainly student-centered. Results of a chi-square-test indicate that there is no connection between these two drawings of biology lessons. This suggests that experiences from one’s own schooling may have no connection with the way prospective teachers would like to teach in the future. The results of this study might be used as a basis for further studies examining the development of prospective biology teachers’ beliefs about teaching and learning.
Influence of calcination temperature on the fluorescence and magnetic properties of Gd2O3:Tb3+, K+ nanoparticles
Authors: Zhou Hao , Fu Rong , Yang Chunlin , Ou Meigui , Xue Chengjie
Published: March 2021

G
d

2

O

3

:

T
b

3
+

nanoparticles were synthesized by using diethylene glycol as a solvent and doped with 3 mol%

K

+

ions.

G
d

2

O

3

:

T
b

3
+

,

K

+

nanoparticles were calcinated at 600°C, 700°C, 800°C, and 900°C and subjected to the analysis of x-ray diffractometer, transmission electron microscope, Fourier transform infrared spectrometer, fluorescence spectroscopy, and magnetization. The experimental results showed that as the calcination temperature increased from 600°C to 800°C, the morphology and particle size of the

G
d

2

O

3

:

T
b

3
+

,

K

+

nanoparticles did not change significantly; whereas when the calcination temperature rose from 800°C to 900°C, the structure of

G
d

2

O

3

particles changed from cubic to monoclinic. As the temperature increased (below 800°C), the crystallinity of the cubic particles increased and the surface defects of the particles decreased, resulting in an increase in fluorescence intensity. For the monoclinic particles, the fluorescence intensity was significantly decreased and the magnetization was increased. The measured magnetic results confirmed the good paramagnetism of the synthesized nanoparticles.
Optical and electrical programmable computing energy use comparison
Authors: Cole Chris
Published: March 2021

Optical computing has been proposed as a replacement for electrical computing to reduce energy use of math intensive programmable applications like machine learning. Objective energy use comparison requires that data transfer is separated from computing and made constant, with only computing variable. Three operations compared in this manner are multiplication, addition and inner product. For each, it is found that energy use is dominated by data transfer, and that computing energy use is a small fraction of the total. Switching to optical from electrical programmable computing does not reduce energy use.
Comparative proteomics reveals mechanisms that underlie insecticide resistance in Culex pipiens pallens Coquillett
Authors: Zhang Chongxing , Shi Qiqi , Li Tao , Cheng Peng , Guo Xiuxia , Song Xiao , Gong Maoqing
Published: March 2021

Mosquito control based on chemical insecticides is considered as an important element of the current global strategies for the control of mosquito-borne diseases. Unfortunately, the development of insecticide resistance of important vector mosquito species jeopardizes the effectiveness of insecticide-based mosquito control. In contrast to target site resistance, other mechanisms are far from being fully understood. Global protein profiles among cypermethrin-resistant, propoxur-resistant, dimethyl-dichloro-vinyl-phosphate-resistant and susceptible strain ofCulex pipiens pallenswere obtained and proteomic differences were evaluated by using isobaric tags for relative and absolute quantification labeling coupled with liquid chromatography/tandem mass spectrometric analysis. A susceptible strain ofCulex pipiens pallensshowed elevated resistance levels after 25 generations of insecticide selection, through iTRAQ data analysis detected 2,502 proteins, of which 1,513 were differentially expressed in insecticide-selected strains compared to the susceptible strain. Finally, midgut differential protein expression profiles were analyzed, and 62 proteins were selected for verification of differential expression using iTRAQ and parallel reaction monitoring strategy, respectively. iTRAQ profiles of adaptation selection to three insecticide strains combined with midgut profiles revealed that multiple insecticide resistance mechanisms operate simultaneously in resistant insects ofCulex pipiens pallens. Significant molecular resources were developed forCulex pipiens pallens, potential candidates were involved in metabolic resistance and reducing penetration or sequestering insecticide. Future research that is targeted towards RNA interference of the identified metabolic targets, such as cuticular proteins, cytochrome P450s, glutathione S-transferases and ribosomal proteins proteins and biological pathways (drug metabolism—cytochrome P450, metabolism of xenobiotics by cytochrome P450, oxidative phosphorylation, ribosome) could lay the foundation for a better understanding of the genetic basis of insecticide resistance inCulex pipiens pallens.
Improved diagnostic prediction of the pathogenicity of bloodstream isolates of Staphylococcus epidermidis
Authors: VanAken Shannon M. , Newton Duane , VanEpps J. Scott
Published: March 2021

With an estimated 440,000 active cases occurring each year, medical device associated infections pose a significant burden on the US healthcare system, costing about $9.8 billion in 2013. Staphylococcus epidermidis is the most common cause of these device-associated infections, which typically involve isolates that are multi-drug resistant and possess multiple virulence factors. S. epidermidis is also frequently a benign contaminant of otherwise sterile blood cultures. Therefore, tests that distinguish pathogenic from non-pathogenic isolates would improve the accuracy of diagnosis and prevent overuse/misuse of antibiotics. Attempts to use multi-locus sequence typing (MLST) with machine learning for this purpose had poor accuracy (~73%). In this study we sought to improve the diagnostic accuracy of predicting pathogenicity by focusing on phenotypic markers (i.e., antibiotic resistance, growth fitness in human plasma, and biofilm forming capacity) and the presence of specific virulence genes (i.e., mecA, ses1, and sdrF). Commensal isolates from healthy individuals (n = 23), blood culture contaminants (n = 21), and pathogenic isolates considered true bacteremia (n = 54) were used. Multiple machine learning approaches were applied to characterize strains as pathogenic vs non-pathogenic. The combination of phenotypic markers and virulence genes improved the diagnostic accuracy to 82.4% (sensitivity: 84.9% and specificity: 80.9%). Oxacillin resistance was the most important variable followed by growth rate in plasma. This work shows promise for the addition of phenotypic testing in clinical diagnostic applications.
Knowledge, perceptions and attitude of Egyptian physicians towards biobanking issues
Authors: Abdelhafiz Ahmed Samir , Sultan Eman A. , Ziady Hany H. , Sayed Douaa M. , Khairy Walaa A.
Published: March 2021

Objectives

Collection and storage of biospecimens and data for biobanking raise many ethical concerns. Stakeholders’ opinions about these ethical issues are important since they can help in the development of ethical guidelines to govern biobanking activities. Physicians are among the important stakeholders since they contact potential participants and could be biobank users. The goal of this study is to evaluate the perceptions and attitude of Egyptian physicians towards ethical issues in biobanking.

Methods

A cross-sectional online survey was designed and distributed with the target group between November 2019 and January 2020.

Results

The questionnaire was completed by 223 physicians. While 65.5% reported hearing the term "Biobanking" before, 45.7% knew that there are biobanks in Egypt. Participants had a general positive attitude towards the value of biobanks in research. About 73% agreed that biobanks can share biospecimens with international research organizations, but only 42.6% supported collaboration with pharmaceutical companies, and 44% agreed to the use of user fees by biobanks. About 48% supported the use of broad consent in biobanks, and 73.1% believed that donors of biospecimens should be informed about results of research performed on their biospecimens.

Conclusion

Although many Egyptian physicians heard about biobanking, they had limited knowledge about the existence of biobanks in Egypt. They had concerns about commercialization, use of broad consent and user fees. A knowledge gap exists among these stakeholders, which should be covered by different educational activities. Community discussions should start to reach consensus about the issues of commercialization and return of research results.
Analysis of treatment cost and persistence among migraineurs: A two-year retrospective cohort study in Pakistan
Authors: Khan Kamran , Arain Mudassar Iqbal , Asghar Muhammad Arif , Rehman Ahad Abdul , Ghoto Muhammad Ali , Dayo Abdullah , Imtiaz Muhammad Suleman , Rana Mohsin Hamied , Asghar Muhammad Asif
Published: March 2021

Objectives

The persistence pattern of anti-migraine drugs’ use among migraineurs is very low in the United States and different European countries. However, the cost and persistence of antimigraine drugs in Asian countries have not been well-studied. Hence, the present study aimed to evaluate the treatment cost and persistence among migraineurs in Pakistan.

Methods

Data from prescriptions collected from migraineurs who visited the Outpatient Department (OPD) of different public and private sector tertiary-care hospitals of Karachi, Pakistan were used to conduct this retrospective cohort study from 2017 to 2019. The minimum follow up period for each migraineur was about 12 months for persistence analysis while dropped-out patients data were also included in survival analysis as right censored data. Pairwise comparisons from Cox regression/hazards ratio were used to assess the predictors of persistence with the reference category of non-binary variables i.e. hazard ratio = 1 for low frequency migraineurs and NSAIDs users. Persistence with anti-migraine drugs was estimated using the Kaplan-Meier curve along with the Log Rank test.

Results

A total of 1597 patients were included in this study, 729 (45.6%) were male and 868 (54.3%) were female. Non-steroidal anti-inflammatory drugs (NSAIDs) were the most prescribed class of drug initially for all classes of migraineurs (26.1%). Of them, 57.3% of migraineurs discontinued their treatment, 28.5% continued while 14.8% were switched to other treatment approaches. Persistence with initial treatment was more profound in female (58.8%) patients compared to males while the median age of continuers was 31 years. The total cost of migraine treatment in the entire study cohort was 297532.5 Pakistani Rupees ($1901.1). By estimating the hazard ratios (HR) using the Cox regression analysis, it can be observed that patients with high frequency (HR, 1.628; 95%CI, 1.221–2.179; p<0.0001) migraine, depression (HR, 1.268; 95%CI, 1.084–1.458; p<0.0001), increasing age (HR, 1.293; 95%CI, 1.092–1.458; p<0.0001), combination analgesics (HR, 1.817; 95%CI, 0.841–2.725; p = 0.0004) and prophylaxis drugs (HR, 1.314; 95%CI, 0.958–1.424; p<0.0001) users were at a higher risk of treatment discontinuation. However, patients with chronic migraine (HR, 0.881; 95%CI, 0.762–0.912; p = 0.0002), epileptic seizure (HR, 0.922; 95%CI, 0.654–1.206; p = 0.0002), other comorbidities (HR, 0.671; 95%CI, 0.352–1.011; p = 0.0003) and users of triptan(s) (HR, 0.701; 95%CI, 0.182–1.414; p = 0.0005) and triptan(s) with NSAIDs (HR, 0.758; 95%CI, 0.501–1.289; p<0.0001) had more chances to continue their initial therapy.

Conclusion

Similar to western countries, the majority of migraineurs exhibited poor persistence to migraine treatments. Various factors of improved persistence were identified in this study.
The diagnostic accuracy of digital PCR, ARMS and NGS for detecting KRAS mutation in cell-free DNA of patients with colorectal cancer: A systematic review and meta-analysis
Authors: Ye Peng , Cai Peiling , Xie Jing , Wei Yuanyuan
Published: March 2021

Introduction

Before anti-EGFR therapy is given to patients with colorectal cancer, it is required to determineKRASmutation status in tumor. When tumor tissue is not available, cell-free DNA (liquid biopsy) is commonly used as an alternative. Due to the low abundance of tumor-derived DNA in cell-free DNA samples, methods with high sensitivity were preferred, including digital polymerase chain reaction, amplification refractory mutation system and next-generation sequencing. The aim of this systemic review and meta-analysis was to investigate the accuracy of those methods in detectingKRASmutation in cell-free DNA sample from patients with colorectal cancer.

Methods

Literature search was performed in Pubmed, Embase, and Cochrane Library. After removing duplicates from the 170 publications found by literature search, eligible studies were identified using pre-defined criteria. Quality of the publications and relevant data were assessed and extracted thereafter. Meta-DiSc and STATA softwares were used to pool the accuracy parameters from the extracted data.

Results

A total of 33 eligible studies were identified for this systemic review and meta-analysis. After pooling, the overall sensitivity, specificity, and diagnostic odds ratio were 0.77 (95%CI: 0.74–0.79), 0.87 (95%CI: 0.85–0.89), and 23.96 (95%CI: 13.72–41.84), respectively. The overall positive and negative likelihood ratios were 5.55 (95%CI: 3.76–8.19) and 0.29 (95%CI: 0.21–0.38), respectively. Area under curve of the summarized ROC curve was 0.8992.

Conclusion

Digital polymerase chain reaction, amplification refractory mutation system, and next-generation sequencing had overall high accuracy in detectingKRASmutation in cell-free DNA sample. Large prospective randomized clinical trials are needed to further convince the accuracy and usefulness ofKRASmutation detection using cfDNA/liquid biopsy samples in clinical practice.

Trial registration

PROSPERO CRD42020176682;https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176682.
Assessing the impacts of short-course multidrug-resistant tuberculosis treatment in the Southeast Asia Region using a mathematical modeling approach
Authors: Han Win Min , Mahikul Wiriya , Pouplin Thomas , Lawpoolsri Saranath , White Lisa J. , Pan-Ngum Wirichada
Published: March 2021

This study aimed to predict the impacts of shorter duration treatment regimens for multidrug-resistant tuberculosis (MDR-TB) on both MDR-TB percentage among new cases and overall MDR-TB cases in the WHO Southeast Asia Region. A deterministic compartmental model was constructed to describe both the transmission of TB and the MDR-TB situation in the Southeast Asia region. The population-level impacts of short-course treatment regimens were compared with the impacts of conventional regimens. Multi-way analysis was used to evaluate the impact by varying programmatic factors (eligibility for short-course MDR-TB treatment, treatment initiation, and drug susceptibility test (DST) coverage). The model predicted that overall TB incidence will be reduced from 246 (95% credible intervals (CrI), 221–275) per 100,000 population in 2020 to 239 (95% CrI, 215–267) per 100,000 population in 2035, with a modest reduction of 2.8% (95% CrI, 2.7%–2.9%). Despite the slight reduction in overall TB infections, the model predicted that the MDR-TB percentage among newly notified TB infections will remain steady, with 2.4% (95% CrI, 2.1–2.9) in 2020 and 2.5% (95% CrI, 2.3–3.1) in 2035, using conventional MDR-TB treatment. With the introduction of short-course regimens to treat MDR-TB, the development of resistance can be slowed by 38.6% (95% confidence intervals (CI), 35.9–41.3) reduction in MDR-TB case number, and 37.6% (95% CI, 34.9–40.3) reduction in MDR-TB percentage among new TB infections over the 30-year period compared with the baseline using the standard treatment regimen. The multi-way analysis showed eligibility for short-course treatment and treatment initiation greatly influenced the impacts of short-course treatment regimens on reductions in MDR-TB cases and percentage resistance among new infections. Policies which promote the expansion of short-course regimens and early MDR-TB treatment initiation should be considered along with other interventions to tackle antimicrobial resistance in the region.
Mycobacterium leprae promotes triacylglycerol de novo synthesis through induction of GPAT3 expression in human premonocytic THP-1 cells
Authors: Tanigawa Kazunari , Hayashi Yasuhiro , Hama Kotaro , Yamashita Atsushi , Yokoyama Kazuaki , Luo Yuqian , Kawashima Akira , Maeda Yumi , Nakamura Yasuhiro , Harada Ayako , Kiriya Mitsuo , Karasawa Ken , Suzuki Koichi
Published: March 2021

Mycobacterium leprae (M. leprae) is the etiological agent of leprosy, and the skin lesions of lepromatous leprosy are filled with numerous foamy or xanthomatous histiocytes that are parasitized by M. leprae. Lipids are an important nutrient for the intracellular survival of M. leprae. In this study, we attempted to determine the intracellular lipid composition and underlying mechanisms for changes in host cell lipid metabolism induced by M. leprae infection. Using high-performance thin-layer chromatography (HPTLC), we demonstrated specific induction of triacylglycerol (TAG) production in human macrophage THP-1 cells following M. leprae infection. We then used [14C] stearic acid tracing to show incorporation of this newly synthesized host cell TAG into M. leprae. In parallel with TAG accumulation, expression of host glycerol-3-phosphate acyltransferase 3 (GPAT3), a key enzyme in de novo TAG synthesis, was significantly increased in M. leprae-infected cells. CRISPR/Cas9 genome editing of GPAT3 in THP-1 cells (GPAT3 KO) dramatically reduced accumulation of TAG following M. leprae infection, intracellular mycobacterial load, and bacteria viability. These results together suggest that M. leprae induces host GPAT3 expression to facilitate TAG accumulation within macrophages to maintain a suitable environment that is crucial for intracellular survival of these bacilli.
Risk factors of precancerous cervical lesions: The role of women’s socio-demographic, sexual behavior and body mass index in Amhara region referral hospitals; case-control study
Authors: Taye Birhan Tsegaw , Mihret Muhabaw Shumye , Muche Haymanot Alem
Published: March 2021

Background

Cervical cancer remains one of the major public health challenges in low and middle-income countries including Ethiopia. There was a scarce of evidence regarding the effect of woman’s socio-demographic characteristics and body mass index on the development of precancerous cervical lesions in Ethiopia. Therefore, the current study aimed at identifying the risk factors of precancerous cervical lesions among women visiting referral hospitals for cervical cancer screening in Amhara national regional state.

Methods

A hospital-based case-control study was conducted from 22 December 2019 to 8 April 2020 among 200 women including 67 visual inspections with acetic acid (VIA) positive women (i.e., cases) and 133 visual inspections with acetic acid (VIA) negative women (i.e., controls). The study was conducted at randomly selected referral hospitals in Amhara national regional state. Data were collected mainly through face to face interview and chart review using structured questionnaire and checklist respectively. Data were then entered to EpiData version 4.6 and exported to SPSS version 25 for analysis. Binary logistic regression model was fitted and variables with p-value of < 0.2 at bivariable logistic regression analysis were candidates for the multivariable analysis. Level of significance was claimed based on adjusted odds ratio (AOR) with 95% confidence interval (CI) at p-value of ≤ 0.05.

Results

This study illustrates that the odds of being positive for precancerous cervical lesion (PCL) were higher among women who had body mass index (BMI) of <18.5 kg/m2 (AOR = 3.83; 95% CI: 1.26, 8.76), early coitarche (AOR = 3.15; 95% CI: 1.50, 11.49, history of using oral contraceptive pills (AOR = 2.74; 95% CI: 1.6, 7.4), lifetime sexual transmitted infections (AOR = 3.73; 95% CI: 2.5, 12.28) and multiple sexual partners (AOR = 3.23; 95% CI: 1.82, 9.29). On the other hand, participants’ BMI of ≥25 kg/m2 (AOR = 0.46; 95% CI: 0.36, 0.75) and level of education of college and above (AOR = 0.29; 95% CI: 0.23, 0.77) were identified to be protective factors of PCL.

Conclusion

Most of the determinants of precancerous cervical lesions were modifiable and mainly related to women’s socio-demographic characteristics, sexual behaviors and body mass index. Therefore, strengthening awareness on safe sexual practices and healthy life styles through information, education and communication (IEC), and behavioral change communication (BCC) would decrease the incidence of precancerous cervical lesions.
Risk factors for in-hospital mortality in laboratory-confirmed COVID-19 patients in the Netherlands: A competing risk survival analysis
Authors: Nijman Gerine , Wientjes Maike , Ramjith Jordache , Janssen Nico , Hoogerwerf Jacobien , Abbink Evertine , Blaauw Marc , Dofferhoff Ton , van Apeldoorn Marjan , Veerman Karin , de Mast Quirijn , ten Oever Jaap , Hoefsloot Wouter , Reijers Monique H. , van Crevel Reinout , van de Maat Josephine S.
Published: March 2021

Background

To date, survival data on risk factors for COVID-19 mortality in western Europe is limited, and none of the published survival studies have used a competing risk approach. This study aims to identify risk factors for in-hospital mortality in COVID-19 patients in the Netherlands, considering recovery as a competing risk.

Methods

In this observational multicenter cohort study we included adults with PCR-confirmed SARS-CoV-2 infection that were admitted to one of five hospitals in the Netherlands (March to May 2020). We performed a competing risk survival analysis, presenting cause-specific hazard ratios (HRCS) for the effect of preselected factors on the absolute risk of death and recovery.

Results

1,006 patients were included (63.9% male; median age 69 years, IQR: 58–77). Patients were hospitalized for a median duration of 6 days (IQR: 3–13); 243 (24.6%) of them died, 689 (69.9%) recovered, and 74 (7.4%) were censored. Patients with higher age (HRCS 1.10, 95% CI 1.08–1.12), immunocompromised state (HRCS 1.46, 95% CI 1.08–1.98), who used anticoagulants or antiplatelet medication (HRCS 1.38, 95% CI 1.01–1.88), with higher modified early warning score (MEWS) (HRCS 1.09, 95% CI 1.01–1.18), and higher blood LDH at time of admission (HRCS 6.68, 95% CI 1.95–22.8) had increased risk of death, whereas fever (HRCS 0.70, 95% CI 0.52–0.95) decreased risk of death. We found no increased mortality risk in male patients, high BMI or diabetes.

Conclusion

Our competing risk survival analysis confirms specific risk factors for COVID-19 mortality in a the Netherlands, which can be used for prediction research, more intense in-hospital monitoring or prioritizing particular patients for new treatments or vaccination.
Physiological skin FDG uptake: A quantitative and regional distribution assessment using PET/MRI
Authors: Nogami Munenobu , Zeng Feibi , Inukai Junko , Watanabe Yoshiaki , Nishio Mizuho , Kanda Tomonori , Ueno Yoshiko R. , Sofue Keitaro , Kono Atsushi K. , Hori Masatoshi , Ohnishi Akihito , Kubo Kazuhiro , Kurimoto Takako , Murakami Takamichi
Published: March 2021

Purpose

To retrospectively assess the repeatability of physiological F-18 labeled fluorodeoxyglucose (FDG) uptake in the skin on positron emission tomography/magnetic resonance imaging (PET/MRI) and explore its regional distribution and relationship with sex and age.

Methods

Out of 562 examinations with normal FDG distribution on whole-body PET/MRI, 74 repeated examinations were evaluated to assess the repeatability and regional distribution of physiological skin uptake. Furthermore, 224 examinations were evaluated to compare differences in the uptake due to sex and age. Skin segmentation on PET was performed as body-surface contouring on an MR-based attenuation correction map using an off-line reconstruction software. Bland–Altman plots were created for the repeatability assessment. Kruskal–Wallis test was performed to compare the maximum standardized uptake value (SUVmax) with regional distribution, age, and sex.

Results

The limits of agreement for the difference in SUVmean and SUVmax of the skin were less than 30%. The highest SUVmax was observed in the face (3.09±1.04), followed by the scalp (2.07±0.53). The SUVmax in the face of boys aged 0–9 years and 10–20 years (1.33±0.64 and 2.05±1.00, respectively) and girls aged 0–9 years (0.98±0.38) was significantly lower than that of men aged ≥20 years and girls aged ≥10 years (p<0.001). In women, the SUVmax of the face (2.31±0.71) of ≥70-year-olds was significantly lower than that of 30–39-year-olds (3.83±0.82) (p<0.05).

Conclusion

PET/MRI enabled the quantitative analysis of skin FDG uptake with repeatability. The degree of physiological FDG uptake in the skin was the highest in the face and varied between sexes. Although attention to differences in body habitus between age groups is needed, skin FDG uptake also depended on age.