bluuebunny/crossref_metadata_2025 huggingface dataset:
APRENDIZAGEM SIGINIFICATIVA E A FORMAÇÃO DE PROFESSORES
Authors: Nunes Barato Mariana , da Silva Monalisa , Bitencourt Machado Lisandro
Published: June 2022

"O presente artigo apresenta uma análise de parte dos dados obtidos por meio de um questionário aplicado a professores de Matemática da rede pública de ensino de escolas do litoral norte do Rio Grande do Sul. Este instrumento de coleta de dados é oriundo de um projeto de pesquisa desenvolvido no Instituto Federal de Educação, Ciência e Tecnologia do Rio Grande do Sul, campus Osório, intitulado “Aprendizagem Significativa e Formação de Professores”, e tem por objetivos analisar as práticas docentes dos envolvidos, a partir da presença ou ausência de uma estruturação que desencadeie um máximo potencial de aprendizagem significativa e verificar se os seus diferentes níveis de formação acadêmica influenciam nessa estruturação em sala de aula. A estruturação das práticas docentes dos professores participantes foi avaliada a partir de questionamentos que envolviam a unidade temática Álgebra, mais especificamente o estudo de Funções para o ensino médio. A fim de atingir os objetivos propostos no presente trabalho, foi desenvolvida pesquisa bibliográfica sobre as temáticas de Ensino de Matemática, Álgebra, Aprendizagem Significativa e Metodologia e Análise de Dados. Os resultados apresentaram uma forte banalização do termo “Aprendizagem Significativa” nos discursos dos professores envolvidos que, em sua totalidade, não satisfizeram aos parâmetros mínimos indicados por essa teoria."
MAPEAMENTO SISTEMÁTICO DOS PRODUTOS EDUCACIONAIS DOS PROGRAMAS PROFISSIONAIS DE PÓS-GRADUAÇÃO DA UTFPR QUE TRATAM DE TECNOLOGIAS DIGITAIS NO ENSINO DE MATEMÁTICA
Authors: Loss Taniele , Ferreira Mocrosky Luciane , R. G. e Silva Hussein Fabiana , Souza Motta Marcelo
Published: June 2022

"Este artigo apresenta um panorama de produtos educacionais que utilizam as Tecnologias Digitais no ensino de Matemática, direcionados ao Ensino Fundamental II e ao Ensino Médio, produzidos nos Programas de Mestrado Profissional da Universidade Tecnológica Federal do Paraná (UTFPR) no período de 2017 a 2021. Nesta direção, realizamos uma pesquisa qualitativa utilizando como procedimento inventariante um mapeamento sistemático. A pesquisa ocorreu no mês de março de 2021 nos repositórios institucionais da UTFPR. Primeiramente, no site da instituição, identificamos os programas profissionais que tratavam do objeto em estudo. Na sequência, investigamos os endereços específicos das produções acadêmicas destes programas e após aplicação dos protocolos de pesquisa, obtivemos o retorno de 15 produtos educacionais. Após a leitura flutuante e fichamento das dissertações e dos produtos, os categorizamos em quatro focos temáticos, que são: sequências didáticas, objetos de aprendizagem, sites educacionais e oficinas. Os resultados apontam para a relevância dos produtos educacionais pois apresentam possibilidades de uso pedagógico das tecnologias digitais aliadas aos processos educacionais de Matemática, podendo o professor adequá- los conforme o seu contexto escolar. Por fim, frisamos que esta metodologia é flexível podendo ser readaptada por outros pesquisadores, acarretando dados diferentes dos apresentados neste trabalho."
ANÁLISE DE ERROS NO CONTEÚDO DE ÁLGEBRA NO 8° E 9° ANO DO ENSINO FUNDAMENTAL: ESTUDO DE CASO
Authors: Beatriz Moreski Artuzo Andreyna , Riva Fernando , Maria de Souza Albani Jaqueline
Published: June 2022

"Neste estudo, analisamos e categorizamos as possíveis dificuldades de estudantes do 8º e 9º ano do Ensino Fundamental na resolução de problemas de álgebra. A perspectiva adotada baseia-se na abordagem teórica da análise de erros, no ensino de matemática, e tem enquanto premissa a noção de que um erro pode revelar vários tipos de conhecimento implícito não necessariamente detectados em uma avaliação comum. Nesse sentido, propomos uma categorização de prováveis dificuldades vivenciadas por 17 alunos do 8º e 9º ano, em uma amostra de 48 discentes, a partir de “perguntasmodelo”. A amostra inclui duas escolas públicas diferentes do interior do Estado do Paraná, sendo uma delas localizada na periferia do Município de Pato Branco e a outra na sua região central. Depois de analisar os exercícios respondidos pelos discentes e aplicar categorias geradas para cada grupo, sem desconsiderar o eventual peso de barreiras individuais, realizamos duas atividades lúdicas específicas, atentando-se ao tipo de dificuldade de cada grupo. Os resultados sugerem que as atividades lúdicas, especialmente, aquelas pensadas a partir das dificuldades do discente, ideia de situação proposta pela Teoria dos Campos Conceituais de Gérard Vergnaud, podem auxiliar na compreensão e emergência de conhecimentos implícitos. Além disso, foram essenciais para despertar e elevar o interesse pela matemática, sobretudo, entre os estudantes cujo histórico de aprendizado havia sido de maior dificuldade em avaliações anteriores a esse estudo."
From a Hetero- to a Methylotrophic Lifestyle: Flash Back on the Engineering Strategies to Create Synthetic Methanol-User Strains
Authors: Peiro Camille , Vicente Cláudia M. , Jallet Denis , Heux Stephanie
Published: June 2022

Engineering microorganisms to grow on alternative feedstocks is crucial not just because of the indisputable biotechnological applications but also to deepen our understanding of microbial metabolism. One-carbon (C1) substrate metabolism has been the focus of extensive research for the prominent role of C1 compounds in establishing a circular bioeconomy. Methanol in particular holds great promise as it can be produced directly from greenhouse gases methane and carbon dioxide using renewable resources. Synthetic methylotrophy, i.e. introducing a non-native methanol utilization pathway into a model host, has therefore been the focus of long-time efforts and is perhaps the pinnacle of metabolic engineering. It entails completely changing a microorganism’s lifestyle, from breaking up multi-carbon nutrients for growth to building C-C bonds from a single-carbon molecule to obtain all metabolites necessary to biomass formation as well as energy. The frontiers of synthetic methylotrophy have been pushed further than ever before and in this review, we outline the advances that paved the way for the more recent accomplishments. These include optimizing the host’s metabolism, “copy and pasting” naturally existing methylotrophic pathways, “mixing and matching” enzymes to build new pathways, and even creating novel enzymatic functions to obtain strains that are able to grow solely on methanol. Finally, new approaches are contemplated to further advance the field and succeed in obtaining a strain that efficiently grows on methanol and allows C1-based production of added-value compounds.
Multifunctional Smart Bone Implants: Fiction or Future?—A New Perspective
Authors: Peres Inês , Rolo Pedro , Soares dos Santos Marco P.
Published: June 2022

Implantable medical devices have been developed to provide multifunctional ability to numerous bioapplications. In the scope of orthopaedics, four methodologies were already proposed to design implant technologies: non-instrumented passive implants, non-instrumented active implants, instrumented passive implants and instrumented active implants. Even though bone replacements are among the most performed surgeries worldwide, implant failure rates can still exceed 10%. Controversial positions multiply in the scientific community about the potential of each methodology to minimize the burden related to implant failures. In this perspective paper, we argue that the next technological revolution in the field of implantable bone devices will most likely emerge with instrumented active implants as multifunctional smart devices extracorporeally controlled by clinicians/surgeons. Moreover, we provide a new perspective about implant technology: the essence of instrumented implants is to enclose a hybrid architecture in which optimal implant performances require both smart instrumentation and smart coatings, although the implant controllability must be ensured by extracorporeal systems.
Vimentin Tail Segments Are Differentially Exposed at Distinct Cellular Locations and in Response to Stress
Authors: Lois-Bermejo Irene , González-Jiménez Patricia , Duarte Sofia , Pajares María A. , Pérez-Sala Dolores
Published: June 2022

The intermediate filament protein vimentin plays a key role in cell signaling and stress sensing, as well as an integrator of cytoskeletal dynamics. The vimentin monomer consists of a central rod-like domain and intrinsically disordered head and tail domains. Although the organization of vimentin oligomers in filaments is beginning to be understood, the precise disposition of the tail region remains to be elucidated. Here we observed that electrophilic stress-induced condensation shielded vimentin from recognition by antibodies against specific segments of the tail domain. A detailed characterization revealed that vimentin tail segments are differentially exposed at distinct subcellular locations, both in basal and stress conditions. The 411–423 segment appeared accessible in all cell areas, correlating with vimentin abundance. In contrast, the 419–438 segment was more scantily recognized in perinuclear vimentin and lipoxidative stress-induced bundles, and better detected in peripheral filaments, where it appeared to protrude further from the filament core. These differences persisted in mitotic cells. Interestingly, both tail segments showed closer accessibility in calyculin A-treated cells and phosphomimetic mutants of the C-terminal region. Our results lead us to hypothesize the presence of at least two distinct arrangements of vimentin tail in cells: an “extended” conformation (accessible 419–438 segment), preferentially detected in peripheral areas with looser filaments, and a “packed” conformation (shielded 419–438 segment), preferentially detected at the cell center in robust filaments and lipoxidative stress-induced bundles. These different arrangements could be putatively interconverted by posttranslational modifications, contributing to the versatility of vimentin functions and/or interactions.
Acheulean Diversity in Britain (MIS 15-MIS11): From the Standardization to the Regionalization of Technology
Authors: García-Medrano Paula , Shipton Ceri , White Mark , Ashton Nick
Published: June 2022

The appearance of the Acheulean and the production of new bifacial tools marked a revolution in human behavior. The use of longer and complex operative chains, with centripetal and recurrent knapping, adapted to different raw materials, created long useful edges, converging in a functional distal end. How and why these handaxes vary has been the subject of intense debates. Britain provides a clearly defined region at the edge of the hominin occupied world for discussing variation in Acheulean assemblages. The environmental changes from MIS 15 to MIS 11 are significant in understanding population change, with probable breaks in evidence during MIS 14 and MIS 12, followed by several sites during the long stable climate of MIS11c. In this latter period, different Acheulean technological expressions appear to coexist in Britain. This paper draws together different studies, combining technology and geometric morphometrics to analyze handaxes from six British sites: Brandon Fields, Boxgrove (Q1B), High Lodge, Hitchin, Swanscombe (UMG), and Elveden. Compared to the earlier Acheulean of MIS 15, the assemblages of MIS 13 show increased standardization and the use of soft hammer percussion for thinning mid-sections and butts of tools, or sharpening tips through tranchet removals. Although there is regional population discontinuity through MIS12 there is no evidence of a marked change in technology after this glacial period. Rather, there is a development towards more intense shaping with the same underlying techniques, but with flexibility in imposed handaxe form. From MIS11 there appear to be distinctive localized traditions of manufacture, which suggest that a recognition of place and territories had developed by this time. These are expressed over medium time-scales of several thousand years and have significance for how we view cultural expression and transmission.
High Wind Speed Prevents the Establishment of the Disease Vector Mosquito Aedes albopictus in Its Climatic Niche in Europe
Authors: Adeleke Emmanuel Damilare , Shittu Ridwan Adeyemi , Beierkuhnlein Carl , Thomas Stephanie Margarete
Published: June 2022

Environmentally suitable habitats ofAedes albopictus(Ae. albopictus) in Europe are identified by several modeling studies. However, it is noticeable that even after decades of invasion process in Europe, the vector mosquito has not yet been established in all its environmentally suitable areas. Natural barriers and human-mediated transport play a role, but the potential of wind speed to explainAe. albopictus’absences and its inability to establish in its suitable areas are largely unknown. This study therefore evaluates the potential of wind speed as an explanatory parameter of the non-occurrence ofAe. albopictus. We developed a global ecological niche model with relevant environmental parameters including wind speed and projected it to current climatic conditions in Europe.Differences in average wind speed between areas of occurrence and non-occurrence ofAe. albopictuswithin its modeled suitable areas were tested for significance. A second global ecological niche model was trained with the same species records and environmental parameters, excluding windspeed parameters. Using multiple linear regression analyses and a test of average marginal effect, the effect of increasing wind speed on the average marginal effect of temperature and precipitation on the projected habitat suitability was estimated. We found that climatically suitable and monitored areas whereAe. albopictusis not established (3.12 ms-1 ± 0.04 SD) have significantly higher wind speed than areas where the species is already established (2.54 ms-1 ± 0.04 SD). Among temperature-related bioclimatic variables, the annual mean temperature was the most important variable contributing to the performance of both global models. Wind speed has a negative effect on the predicted habitat suitability ofAe. albopictusand reduces false-positive rates in model predictions. With increasing wind speed, the average marginal effect of annual mean temperatures decreases but that of the annual precipitation increases. Wind speed should be considered in future modeling efforts aimed at limiting the spread and dispersal ofAe. albopictusand in the implementation of surveillance and early warning systems. Local-scale data collected from fieldwork or laboratory experiments will help improve the state of the art on how wind speed influences the distribution, flight, and dispersal activity of the mosquito.
Quantifying the Spatial–Temporal Patterns and Influencing Factors of Agricultural Carbon Emissions Based on the Coupling Effect of Water–Land Resources in Arid Inland Regions
Authors: Wang Lingge , Zhu Rui , Yin Zhenliang , Chen Zexia , Lu Rui , Fang Chunshuang
Published: June 2022

Agricultural carbon emissions are supposed to be a fundamental component of the regional carbon cycle in regions with intense agricultural activities. However, the patterns and controls of agricultural carbon emissions based on the water–land resource coupling effect remain poorly understood in arid inland regions. Thus, we constructed a research framework combining water and land resources with agricultural carbon emissions to assess the linkage of water–land–agricultural carbon emissions in arid inland regions. The agricultural carbon emission measurement model and water–land resource coupling coordination degree model (WLCD) were used for exploring the spatial and temporal patterns of agricultural carbon emissions and water–land elements. The interaction between societal , economic , and ecological factors on agricultural carbon emissions was clarified using the logarithmic mean Divisia index (LMDI). The applicability of the method was verified in the Zhangye oasis in northwest China. The results are as follows: 1) from 2012 to 2019, the agricultural carbon emissions in Zhangye increased first and then declined, with 96% of which mainly coming from chemical fertilizers and plowing; 2) the coupling coordination index of water–land resources in Zhangye increased from 0.3715 in 2012 to 0.5399 in 2019, an increase of 45.33%, indicating a conversion from mild disordered to basic coordination; 3) regarding the effects among the factors, the economic output of agricultural water resource, cropland area per capita, and population (the water and land resource ratio and agricultural carbon emission intensity) exerted positive (negative) impacts on agricultural carbon emissions. Accordingly, it is suggested that the green and low-carbon development strategies for oasis agriculture require a high level of integrated planning and management of water and land resources, as well as comprehensive consideration of low-carbon agriculture and elements related to water and land.
A Cluster-Based Technique for Identifying and Grouping Oily Waste Types Generated From Marine Oil Spill Response Operations
Authors: Hafezi Mohammad Hesam , Daisy Naznin Sultana , Liu Lei
Published: June 2022

In the event of a marine oil spill and its subsequent response operations, different types of oily wastes are generated in large quantities, and their management is a significant challenge that oil spill responders face. The goal of this study is to develop a comprehensive pattern recognition modeling framework for deriving and grouping a set of unique clusters that separate different types of oily wastes from each other. The main idea is to group oily wastes based on their unique characteristics, such as the percentage of oil, percentage of water, percentage of mineral matter, and percentage of organic matter. Each cluster has a relatively homogeneous pattern of pollution characteristics. Prior to implementing the cluster analysis technique, it is important to evaluate and transform the raw oily waste data using well-defined criteria. An advanced machine learning technique, fuzzy C-means clustering algorithm, is employed to classify the oily wastes. The Kolmogorov–Smirnov tests are employed to examine the statistical significance of clustered data. Results show a heterogeneous diversity in seven identified clusters in relation to different types of oily wastes. The cluster-based analysis method presented in this article is an integral part of an integrated optimization-based model which will provide valuable inputs for adjustment of the existing management practices, enhancement of short-term pollution control strategies, and development of long-term oily waste management policies. The output of this study would provide a better tool to waste characterization and sorting steps that are required to immediately separate recovered waste to support downstream response efforts. This result of this study also supports the overall goal of minimizing impact on the environment by ensuring the maximum amount of recovered waste can be recycled or disposed in an environmentally friendly fashion. Moreover, properly classified, sorted, and labeled waste will greatly help with downstream steps of packaging, transportation, and tracking of waste, and as a result, it will minimize total waste management time and costs, under the constraints involving waste storage and transport capacities, waste pre-treatment and treatment facility capacities, and environmental regulatory compliance, as well as other operational and logistic constraints.
Identification of a Recurrence Gene Signature for Ovarian Cancer Prognosis by Integrating Single-Cell RNA Sequencing and Bulk Expression Datasets
Authors: Zhang Yongjian , Huang Wei , Chen Dejia , Zhao Yue , Sun Fusheng , Wang Zhiqiang , Lou Ge
Published: June 2022

Ovarian cancer is one of the most common gynecological malignancies in women, with a poor prognosis and high mortality. With the expansion of single-cell RNA sequencing technologies, the inner biological mechanism involved in tumor recurrence should be explored at the single-cell level, and novel prognostic signatures derived from recurrence events were urgently identified. In this study, we identified recurrence-related genes for ovarian cancer by integrating two Gene Expression Omnibus datasets, including an ovarian cancer single-cell RNA sequencing dataset (GSE146026) and a bulk expression dataset (GSE44104). Based on these recurrence genes, we further utilized the merged expression dataset containing a total of 524 ovarian cancer samples to identify prognostic signatures and constructed a 13-gene risk model, named RMGS (recurrence marker gene signature). Based on the RMGS score, the samples were stratified into high-risk and low-risk groups, and these two groups displayed significant survival difference in two independent validation cohorts including The Cancer Genome Atlas (TCGA). Also, the RMGS score remained significantly independent in multivariate analysis after adjusting for clinical factors, including the tumor grade and stage. Furthermore, there existed close associations between the RMGS score and immune characterizations, including checkpoint inhibition, EMT signature, and T-cell infiltration. Finally, the associations between RMGS scores and molecular subtypes revealed that samples with mesenchymal subtypes displayed higher RMGS scores. In the meanwhile, the genomics characterization from these two risk groups was also identified. In conclusion, the recurrence-related RMGS model we identified could provide a new understanding of ovarian cancer prognosis at the single-cell level and offer a reference for therapy decisions for patient treatment.
Effectiveness of Ultrasound Imaging in Assessing the Palpation Skills of Rotating Physicians
Authors: Huang Peizhen , Zheng Bin , Liu Shan , Xu Lin , Chen Chengchun , Zhan Shubei
Published: June 2022

As an important means of physical examination, palpation is usually limited to the physical examination before surgery and used as an auxiliary method for disease diagnosis in the field of surgery. In practice, palpation is also used in every aspect of the surgical procedure, and its application is of great significance to surgery. The purpose of this study was to investigate the ability of ultrasound imaging to assess the ability of rotating physicians to locate musculoskeletal structures by palpation. Rotating physicians were asked to palpate and locate the long head tendon of the biceps (LHB), posterior tibialis (TPT), acromioclavicular joint (ACJ), and medial tibiofemoral joint (TFJ) spaces on two volunteer models. After positioning, a truncated steel needle was attached to the skin and parallel to the palpable structure, and the position of the steel needle relative to the designated structure was assessed by ultrasound imaging, using the Cohen kappa test to study the inter-rater agreement. The results showed that the assessor’s Kappa coefficient for judging the location of all structures was 0.816, LHB was 1.00, TPT was 0.912, ACJ gap was 0.796, and TFJ medial space was 0.844, and the success rate of palpation for TPT was 62.2%, TFJ medial space was 37.8%, ACJ clearance was 24.3%, and LHB was 8.1%. In conclusion, the teaching methods of anatomy and palpation skills need further improvement, and ultrasound imaging is an effective tool for assessing palpation skills.
Missing Data in Sea Turtle Population Monitoring: A Bayesian Statistical Framework Accounting for Incomplete Sampling
Authors: Omeyer Lucy C. M. , McKinley Trevelyan J. , Bréheret Nathalie , Bal Gaëlle , Petchell Balchin George , Bitsindou Abdon , Chauvet Eva , Collins Tim , Curran Bryan K. , Formia Angela , Girard Alexandre , Girondot Marc , Godley Brendan J. , Mavoungou Jean-Gabriel , Poli Laurène , Tilley Dominic , VanLeeuwe Hilde , Metcalfe Kristian
Published: June 2022

Monitoring how populations respond to sustained conservation measures is essential to detect changes in their population status and determine the effectiveness of any interventions. In the case of sea turtles, their populations are difficult to assess because of their complicated life histories. Ground-derived clutch counts are most often used as an index of population size for sea turtles; however, data are often incomplete with varying sampling intensity within and among sites and seasons. To address these issues, we: (1) develop a Bayesian statistical modelling framework that can be used to account for sampling uncertainties in a robust probabilistic manner within a given site and season; and (2) apply this to a previously unpublished long-term sea turtle dataset (n = 17 years) collated for the Republic of the Congo, which hosts two sympatrically nesting species of sea turtle (leatherback turtle [Dermochelys coriacea] and olive ridley turtle [Lepidochelys olivacea]). The results of this analysis suggest that leatherback turtle nesting levels dropped initially and then settled into quasi-cyclical levels of interannual variability, with an average of 573 (mean, 95% prediction interval: 554–626) clutches laid annually between 2012 and 2017. In contrast, nesting abundance for olive ridley turtles has increased more recently, with an average of 1,087 (mean, 95% prediction interval: 1,057–1,153) clutches laid annually between 2012 and 2017. These findings highlight the regional and global importance of this rookery with the Republic of the Congo, hosting the second largest documented populations of olive ridley and the third largest for leatherback turtles in Central Africa; and the fourth largest non-arribada olive ridley rookery globally. Furthermore, whilst the results show that Congo’s single marine and coastal national park provides protection for over half of sea turtle clutches laid in the country, there is scope for further protection along the coast. Although large parts of the African coastline remain to be adequately monitored, the modelling approach used here will be invaluable to inform future status assessments for sea turtles given that most datasets are temporally and spatially fragmented.
Historic Wooden Shipwrecks Influence Dispersal of Deep-Sea Biofilms
Authors: Moseley Rachel D. , Hampel Justyna J. , Mugge Rachel L. , Hamdan Leila J.
Published: June 2022

Wood arrives on the seabed from natural and anthropogenic sources (e.g., wood falls and wooden shipwrecks, respectively) and creates seafloor habitats for macro-, meio- and microbiota. The way these habitats shape microbial communities and their biogeographic patterns in the deep sea requires study. The objective of this work was to investigate how historic wooden-hulled shipwrecks impact the dispersal of wood-colonizing microbial biofilms. The study addressed how proximity to wooden shipwrecks shapes diversity, richness, and community composition in the surrounding environment. Study sites included two historic shipwrecks in the northern Gulf of Mexico identified as wooden-hulled sailing vessels dating to the late 19th century. Two experimental microbial recruitment arrays containing pine and oak samples were deployed by remotely operated vehicle proximate (0–200 m) to each shipwreck and used to establish new wooden habitat features to be colonized by biofilms. The experiments remained in place for approximately 4 months, were subsequently recovered, and biofilms were analyzed using 16S rRNA gene amplification and sequencing for bacteria and archaea and ITS2 region amplification and sequencing for fungi to determine alpha diversity metrics and community composition. The work examined the influence of wood type, proximity to shipwrecks, and environmental context on the biofilms formed on the surfaces. Wood type was the most significant feature shaping bacterial composition, but not archaeal or fungal composition. Proximity to shipwrecks was also a significant influence on bacterial and archaeal composition and alpha diversity, but not on fungal communities. In all 3 domains, a peak in alpha diversity and richness was observed on pine and oak samples placed ~125 m from the shipwrecks. This peak may be evidence of an ecotone, or convergence zone, between the shipwreck influenced seabed and the surrounding seafloor. This study provides evidence that historic wooden shipwrecks influence microbial biofilm dispersal in the deep sea.
Lipoprotein(a) Modulates Carotid Atherosclerosis in Metabolic Syndrome
Authors: Cremonini Anna Laura , Pasta Andrea , Carbone Federico , Visconti Luca , Casula Matteo , Elia Edoardo , Bonaventura Aldo , Liberale Luca , Bertolotto Maria , Artom Nathan , Minetti Silvia , Contini Paola , Verzola Daniela , Pontremoli Roberto , Viazzi Francesca , Viviani Giorgio Luciano , Bertolini Stefano , Pende Aldo , Montecucco Fabrizio , Pisciotta Livia
Published: June 2022

Background and Aim: High lipoprotein(a) [Lp(a)] is a well-established cardiovascular (CV) risk factor, but the effect of mildly elevated Lp(a) on CV health is largely unknown. Our aim was to evaluate if Lp(a) is associated with the severity of carotid atherosclerosis (CA) in the specific subset of metabolic syndrome (MetS).

Patients and Methods: Subjects with diagnosed MetS and ultrasound-assessed CA were enrolled. Those patients were categorized according to the severity of CA (moderate vs. severe), and the circulating levels of Lp(a) alongside with clinical, anthropometric, and biochemical data were collected.

Results: Sixty-five patients were finally included: twenty-five with moderate and forty with severe CA (all with asymptomatic disease). Intergroup comparison showed Lp(a) as the only significantly different variable [6 (2–12) mg/dl vs. 11.5 (6–29.5) mg/dl; p = 0.018]. Circulating levels of Lp(a) were also confirmed as the only variable independently associated with severity of CA at logistic regression analysis [OR 2.9 (95% CI 1.1–7.8); p = 0.040]. ROC curve analysis for Lp(a) confirmed a serum level of 10 mg/dl as the best cut-off value [AUC 0.675 (95% CI 0.548–0.786)]. Although sensitivity and specificity were suboptimal (69.0 and 70.4%, respectively)—likely due to the small sample size—this result is in line with those previously reported in the literature.

Conclusion: Lp(a) is independently associated with severity of CA in the subgroup of MetS patients.
Contribution of Tocopherols in Commonly Consumed Foods to Estimated Tocopherol Intake in the Chinese Diet
Authors: Zhang Yu , Qi Xin , Wang Xueyan , Wang Xuefang , Ma Fei , Yu Li , Mao Jin , Jiang Jun , Zhang Liangxiao , Li Peiwu
Published: June 2022

Vitamin E is an essential fat-soluble nutrient mainly found in vegetable oils, nuts, and other foods. In this study, we evaluated the contribution of commonly consumed foods to the vitamin E dietary intake of the population in relation to their consumption practices. In addition, the vitamin E intakes of Chinese residents were compared in different regions of China and in different years. The results showed that vegetable oil was the main source of vitamin E dietary intake for Chinese residents, accounting for 46.76% of total dietary intake of vitamin E, followed by cereals, vegetables, meat, aquatic products, eggs, legumes, nuts, fruits and dairy products. Among all vegetable oils, rapeseed oil was the highest contributor of vitamin E, accounting for 10.73% of all foods. Due to dietary habits and regional differences, vitamin E intake also varies greatly among residents in different regions of China and has increased yearly from 1982 to 2020. This study provides with scientific evidence for reasonable VE supplementation.
Reaching the “Hard-to-Reach” Sexual and Gender Diverse Communities for Population-Based Research in Cancer Prevention and Control: Methods for Online Survey Data Collection and Management
Authors: Myers Katie J. , Jaffe Talya , Kanda Deborah A. , Pankratz V. Shane , Tawfik Bernard , Wu Emily , McClain Molly E. , Mishra Shiraz I. , Kano Miria , Madhivanan Purnima , Adsul Prajakta
Published: June 2022

Purpose

Around 5% of United States (U.S.) population identifies as Sexual and Gender Diverse (SGD), yet there is limited research around cancer prevention among these populations. We present multi-pronged, low-cost, and systematic recruitment strategies used to reach SGD communities in New Mexico (NM), a state that is both largely rural and racially/ethnically classified as a “majority-minority” state.

Methods

Our recruitment focused on using: (1) Every Door Direct Mail (EDDM) program, by the United States Postal Services (USPS); (2) Google and Facebook advertisements; (3) Organizational outreach via emails to publicly available SGD-friendly business contacts; (4) Personal outreach via flyers at clinical and community settings across NM. Guided by previous research, we provide detailed descriptions on using strategies to check for fraudulent and suspicious online responses, that ensure data integrity.

Results

A total of 27,369 flyers were distributed through the EDDM program and 436,177 impressions were made through the Google and Facebook ads. We received a total of 6,920 responses on the eligibility survey. For the 5,037 eligible respondents, we received 3,120 (61.9%) complete responses. Of these, 13% (406/3120) were fraudulent/suspicious based on research-informed criteria and were removed. Final analysis included 2,534 respondents, of which the majority (59.9%) reported hearing about the study from social media. Of the respondents, 49.5% were between 31-40 years, 39.5% were Black, Hispanic, or American Indian/Alaskan Native, and 45.9% had an annual household income below $50,000. Over half (55.3%) were assigned male, 40.4% were assigned female, and 4.3% were assigned intersex at birth. Transgender respondents made up 10.6% (n=267) of the respondents. In terms of sexual orientation, 54.1% (n=1371) reported being gay or lesbian, 30% (n=749) bisexual, and 15.8% (n=401) queer. A total of 756 (29.8%) respondents reported receiving a cancer diagnosis and among screen-eligible respondents, 66.2% reported ever having a Pap, 78.6% reported ever having a mammogram, and 84.1% reported ever having a colonoscopy. Over half of eligible respondents (58.7%) reported receiving Human Papillomavirus vaccinations.

Conclusion

Study findings showcase effective strategies to reach communities, maximize data quality, and prevent the misrepresentation of data critical to improve health in SGD communities.
Quinolones as a Potential Drug in Genitourinary Cancer Treatment—A Literature Review
Authors: Kloskowski Tomasz , Frąckowiak Sylwia , Adamowicz Jan , Szeliski Kamil , Rasmus Marta , Drewa Tomasz , Pokrywczyńska Marta
Published: June 2022

Quinolones, broad-spectrum antibiotics, are frequently prescribed by urologists for many urological disorders. The mechanism of their bactericidal activity is based on the inhibition of topoisomerase II or IV complex with DNA, which consequently leads to cell death. It has been observed that these antibiotics also act against the analogous enzymes present in eukaryotic cells. Due to their higher accumulation in urine and prostate tissue than in serum, these drugs seem to be ideal candidates for application in genitourinary cancer treatment. In this study, an extensive literature review has been performed to collect information about concentrations achievable in urine and prostate tissue together with information about anticancer properties of 15 quinolones. Special attention was paid to the application of cytotoxic properties of quinolones for bladder and prostate cancer cell lines. Data available in the literature showed promising properties of quinolones, especially in the case of urinary bladder cancer treatment. In the case of prostate cancer, due to low concentrations of quinolones achievable in prostate tissue, combination therapy with other chemotherapeutics or another method of drug administration is necessary.
The Application of Biopsy Density in Transperineal Templated-Guided Biopsy Patients With PI-RADS<3
Authors: Zhu Hai , Ding Xue-fei , Lu Sheng-ming , Ding Ning , Pi Shi-yi , Liu Zhen , Xiao Qin , Zhu Liang-yong , Luan Yang , Han Yue-xing , Chen Hao-peng , Liu Zhong
Published: June 2022

Background

In patients with multiparameter magnetic resonance imaging (mpMRI) low-possibility but highly clinical suspicion of prostate cancer, the biopsy core is unclear. Our study aims to introduce the biopsy density (BD; the ratio of biopsy cores to prostate volume) and investigates the BD-predictive value of prostate cancer and clinically significant prostate cancer (csPCa) in PI-RADS<3 patients.

Methods

Patients underwent transperineal template–guided prostate biopsy from 2012 to 2022. The inclusion criteria were PI-RADS<3 with a positive digital rectal examination or persistent PSA abnormalities. BD was defined as the ratio of the biopsy core to the prostate volume. Clinical data were collected, and we grouped the patients according to pathology results. Kruskal–Wallis test and chi-square test were used in measurement and enumeration data, respectively. Logistics regression was used to choose the factor associated with positive biospy and csPCa. The receiver operating characteristic (ROC) curve was used to evaluate the ability to predict csPCa.

Results

A total of 115 patients were included in our study. Biopsy was positive in 14 of 115 and the International Society of Urological Pathology grade groups 2–5 were in 7 of all the PCa patients. The BD was 0.38 (0.24-0.63) needles per milliliter. Binary logistics analysis suggested that PSAD and BD were correlated with positive biopsy. Meanwhile, BD and PSAD were associated with csPCa. The ROC curve illustrated that BD was a good parameter to predict csPCa (AUC=0.80, 95% CI: 0.69-0.91, p<0.05). The biopsy density combined with PSAD increased the prediction of csPCa (AUC=0.90, 95% CI: 0.85-0.97, p<0.05). The cut-off value of the BD was 0.42 according to the Youden index.

Conclusion

In PI-RADS<3 patients, BD and PSAD are related to csPCa. A biopsy density of more than 0.42 needles per millimeter can increase the csPCa detection rate, which should be considered as an alternative biopsy method when we perform prostate biopsy in patients with PI-RADS<3.
Role of Sphingolipids in Multiple Myeloma Progression, Drug Resistance, and Their Potential as Therapeutic Targets
Authors: Petrusca Daniela N. , Lee Kelvin P. , Galson Deborah L.
Published: June 2022

Multiple myeloma (MM) is an incapacitating hematological malignancy characterized by accumulation of cancerous plasma cells in the bone marrow (BM) and production of an abnormal monoclonal protein (M-protein). The BM microenvironment has a key role in myeloma development by facilitating the growth of the aberrant plasma cells, which eventually interfere with the homeostasis of the bone cells, exacerbating osteolysis and inhibiting osteoblast differentiation. Recent recognition that metabolic reprograming has a major role in tumor growth and adaptation to specific changes in the microenvironmental niche have led to consideration of the role of sphingolipids and the enzymes that control their biosynthesis and degradation as critical mediators of cancer since these bioactive lipids have been directly linked to the control of cell growth, proliferation, and apoptosis, among other cellular functions. In this review, we present the recent progress of the research investigating the biological implications of sphingolipid metabolism alterations in the regulation of myeloma development and its progression from the pre-malignant stage and discuss the roles of sphingolipids in in MM migration and adhesion, survival and proliferation, as well as angiogenesis and invasion. We introduce the current knowledge regarding the role of sphingolipids as mediators of the immune response and drug-resistance in MM and tackle the new developments suggesting the manipulation of the sphingolipid network as a novel therapeutic direction for MM.
Modeling Kaempferol as a Potential Pharmacological Agent for COVID-19/PF Co-Occurrence Based on Bioinformatics and System Pharmacological Tools
Authors: Jiang Yong , Xie Yi-Zi , Peng Chen-Wen , Yao Kai-Nan , Lin Xue-Ying , Zhan Shao-Feng , Zhuang Hong-Fa , Huang Hui-Ting , Liu Xiao-Hong , Huang Xiu-Fang , Li Hang
Published: June 2022

Objective: People suffering from coronavirus disease 2019 (COVID-19) are prone to develop pulmonary fibrosis (PF), but there is currently no definitive treatment for COVID-19/PF co-occurrence. Kaempferol with promising antiviral and anti-fibrotic effects is expected to become a potential treatment for COVID-19 and PF comorbidities. Therefore, this study explored the targets and molecular mechanisms of kaempferol against COVID-19/PF co-occurrence by bioinformatics and network pharmacology.

Methods: Various open-source databases and Venn Diagram tool were applied to confirm the targets of kaempferol against COVID-19/PF co-occurrence. Protein-protein interaction (PPI), MCODE, key transcription factors, tissue-specific enrichment, molecular docking, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to clarify the influential molecular mechanisms of kaempferol against COVID-19 and PF comorbidities.

Results: 290 targets and 203 transcription factors of kaempferol against COVID-19/PF co-occurrence were captured. Epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase SRC (SRC), mitogen-activated protein kinase 3 (MAPK3), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 8 (MAPK8), RAC-alpha serine/threonine-protein kinase (AKT1), transcription factor p65 (RELA) and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) were identified as the most critical targets, and kaempferol showed effective binding activities with the above critical eight targets. Further, anti-COVID-19/PF co-occurrence effects of kaempferol were associated with the regulation of inflammation, oxidative stress, immunity, virus infection, cell growth process and metabolism. EGFR, interleukin 17 (IL-17), tumor necrosis factor (TNF), hypoxia inducible factor 1 (HIF-1), phosphoinositide 3-kinase/AKT serine/threonine kinase (PI3K/AKT) and Toll-like receptor signaling pathways were identified as the key anti-COVID-19/PF co-occurrence pathways.

Conclusion: Kaempferol is a candidate treatment for COVID-19/PF co-occurrence. The underlying mechanisms may be related to the regulation of critical targets (EGFR, SRC, MAPK3, MAPK1, MAPK8, AKT1, RELA, PIK3CA and so on) and EGFR, IL-17, TNF, HIF-1, PI3K/AKT and Toll-like receptor signaling pathways. This study contributes to guiding development of new drugs for COVID-19 and PF comorbidities.
The Rapid and Long-Lasting Antidepressant Effects of Iridoid Fraction in Gardenia Jasminoides J.Ellis Are Dependent on Activating PKA-CREB Signaling Pathway
Authors: Ren Li , Zhang Hailou , Tao Weiwei , Chen Yin , Zou Zhilu , Guo XiaoYan , Shen Qinqin , Feng Quansheng , Hu Jingqing
Published: June 2022

Lag periods of therapeutic efficacy cause poor compliance of patients, which has made solutions for rapid antidepressants the most urgent need in the depression study field at present. We have identified through our previous studies the rapid antidepressant effects of the traditional herb Gardenia jasminoides J.Ellis [Rubiaceae] (GJ) and its standardized fractions. Through screening different fractions of GJ, we decided to place our focus on the iridoid fraction of GJ (GJ-IF).

Methods: 1. Tail suspension test (TST), forced swimming test (FST), and novelty suppressed-feeding test (NSFT) were performed in sequence on mice after GJ-IF administration. 2. Mice in the model group were under chronic unpredictable mild stress (CUMS) for 3 w. After GJ-IF treatment, mice were placed in an open field test (OFT), Sucrose preference test (SPT), NSFT, TST, and FST. 3. Western Blot was performed to examine the expression of brain-derived neurotrophic factor (BDNF), Synapsin 1, cyclic-AMP dependent protein kinase A (PKA), phosphorylated cyclic-AMP responsive element-binding protein (p-CREB), and cAMP response element-binding protein (CREB). 4. Mice in the test group were administrated with GJ-IF after intraperitoneal injection of PKA blocker H89.

Results: 1. GJ-IF treatment significantly reduced the immobility time of TST at 1 d and FST at 26 h. 2. GJ-IF reversed the deficits induced by 3 w CUMS in SPT, TST, FST, and NSFT at 1 d and 26 h. The antidepressant effects of a single dose of iridoid fraction could also last for at least 14 d. 3. The results of molecule studies suggested that a single dose of GJ-IF activated p-CREB at 2 h and the PKA-CREB pathway at 1 d. The expression of BDNF did not significantly change from 30 min to 1 d after GJ-IF administration. 4. Blockade of PKA-CREB signaling pathway reversed the antidepressant effects of GJ-IF at 1 d, but not 30 min and 2 h.

Conclusion: GJ-IF is the crucial component in the rapid antidepressant of GJ. Rapid and sustained antidepressant effects of GJ-IF were dependent on activating the PKA-CREB signaling pathway.
An Updated Meta-Analysis Based on the Preclinical Evidence of Mechanism of Aconitine-Induced Cardiotoxicity
Authors: Jiang Hong , Zhang Yating , Zhang Yi , Wang Xiaobo , Meng Xianli
Published: June 2022

Background: Most Aconitum species in traditional Chinese medicine have the effect of dispelling wind, dehumidifying, warming the meridian, and relieving pain. Aconitine is the characteristic chemical component with the function of anti-inflammation, analgesic, and heart-strengthening effects. However, improper use will produce cardiotoxicity and neurotoxicity. Currently, the mechanisms of cardiotoxicity caused by aconitine are wheels within wheels without being fully disclosed. The systematic review and meta-analysis were therefore conducted to summarize the available evidence of myocardial toxicity caused by aconitine.

Methods: We searched PubMed, Embase, Web of Science, National Knowledge Infrastructure, WANFANG, and VIP information database for relevant preclinical studies. All the data were analyzed by RevMan version 5.3.

Results: Thirty-two studies met the final inclusion criteria, including both in vivo and in vitro study types. After aconitine treatment, the heart rate of animals was obviously abnormal, and the morphology and function of myocardial cells were significantly changed. Aconitine can induce changes in the electrophysiological activity of cardiac myocytes by regulating Na+, Ca2+, and K+ currents. Meanwhile, the mechanisms of cardiotoxicity of aconitine may be related to triggering mitochondrial dysfunction by inducing mitochondrial apoptosis and autophagy. It should not be ignored that the overactivation of NLRP3 inflammasome also exacerbates aconitine’s cardiotoxicity.

Conclusion: The altered ion channels and mitochondrial function, as well as the signaling pathways interacting with NLRP3, may deserve further study for aconitine-induced cardiotoxicity.
What We Have Learned so far From Single Cell Sequencing in Acute Kidney Injury
Authors: Buse Marc , Moeller Marcus J. , Stamellou Eleni
Published: June 2022

Acute Kidney injury is a major clinical problem associated with increased morbidity and mortality. Despite, intensive research the clinical outcome remains poor and apart from supportive therapy no other specific therapy exists. Single cell technologies have enabled us to get deeper insights into the transcriptome of individual cells in complex tissues like the kidney. With respect to kidney injury, this would allow us to better define the unique role of individual cell populations in the pathophysiology of acute kidney injury and progression to chronic kidney disease. In this mini review, we would like to give an overview and discuss the current major findings in the field of acute kidney injury through Single-Cell technologies.