bluuebunny/crossref_metadata_2025 huggingface dataset:
Conhecimento técnico dos profissionais de saúde quanto ao manejo da sífilis e a sua relação com a Educação Permanente em Saúde
Authors: Câmara Lívia de Souza , Silva Leila Rangel da , Guerra Beatriz Cristina de Oliveira , Monnerat Isabela da Costa , Martins Carlos José , Veras Regina Claudia , Moraes Larissa Araújo de Lima , Pinheiro Izabela da Silva , Teixeira Selma Villas Boas , Ribeiro Marcelle Sampaio de Freitas Guimarães
Published: February 2021

Objetivo: Mapear o conhecimento técnico dos profissionais de saúde quanto ao manejo da sífilis e a sua relação com a Educação Permanente em Saúde. Metodologia: Estudo de revisão integrativa, realizado no período de novembro de 2020. Foram encontradas 793 publicações, sendo 459 no Portal BVS e 334 no Portal de Periódicos CAPES. A amostra final foi constituída por 10 artigos sendo 08 artigos do Portal BVS e 02 artigos do Portal Periódicos CAPES. Resultados: A abordagem metodológica foi na totalidade quantitativa nas temáticas sífilis congênita e sífilis na gestação, sendo 3 estudos internacionais e 7 nacionais. Lacunas de conhecimento foram encontradas como definição de casos de sífilis congênita, uso de testes sorológicos e escolha alternativas de antibióticos para tratamento de gestantes alérgicas à penicilina. Apenas dois estudos utilizaram ferramentas tecnológicas para educação permanente e demonstraram efeito positivo no incremento do conhecimento dos profissionais de saúde. Conclusão: Faz-se necessária publicação de mais estudos que avaliem conhecimento e a produção de ferramentas de Educação Permanente em Saúde para a melhoria da qualidade no manejo da sífilis.
Quality of olive oils and olive bagasse oil and their use in thermal processes
Authors: Cestario Andresa Caroline de Oliveira , Meira Kamilla Ulchak , Contiero Robinson Luiz , Rosa Cassia Inês Lourenzi Franco
Published: February 2021

Olive oil is recognized due to its different properties, however, its most used form is in cold preparation, as there is still the belief that, once heated, olive oil would lose its beneficial properties to health and even form toxic substances. Thus, in order to assess the quality of olive oils and olive bagasse oil subjected to different temperatures and their use in thermal processes, the present study was developed at the Laboratory of Medicinal Plants, belonging to the State University's Department of Agronomy of Maringá. The following analyzes were performed when the oils reached temperatures of 10, 25 (room temperature), 140, 180, 220 and 260°C: acidity, peroxide index, iodine index and measurement of absorbance at 232 and 270 nm (ultraviolet). After the results obtained are compared with the standards of Codex Alimentarius, the Agência Nacional de Vigilância Sanitária, the Ministério da Agricultura, Pecuária e Abastecimento and the International Olive Council, it is concluded that even after heating, in most of the evaluated parameters, the oils remained in compliance with legislation, which can then be used in thermal processes.
Interpersonal human relations: a profile of the literature on social skills
Authors: Francica Jefferson Oliveira , Siqueira Marcio , Souza Anselmo Cordeiro de , Biazzi Sideli , Zukowsky-Tavares Cristina
Published: February 2021

This study aimed to investigate the trends of available national contributions on social skills in scientific journals indexed in the area of psychology. This is a narrative review of the scientific literature on the field of social skills in Brazil carried out in the Index Psi database. We have observed 36 articles that met the selection criteria established. Among the main results, we highlight that a prevalent publications profile was presented with children and adolescents as the main target audience, and the Del Prette Social Skills Inventory as an instrument for data collection. We highlight interventions to appropriate the repertoire of social skills in all stages of human development since childhood, with special care for the male sex. It is concluded that the reasonable amount of articles on social skills, are directed to approaches already traditional in the literature with strong influence in the field of psychological and educational studies in general. The panorama evidenced in the present study suggests opening up on the horizon an extensive and important agenda for a better understanding of social skills in the Brazilian scenario, in relation to its association with topics still little investigated, namely, health promotion in the territory, professional categories, lifestyle and quality of life related to health, and the still emerging themes of spirituality and religiosity.
Tempo de coleta para determinação dos coeficientes de digestibilidade de nutrientes em equinos
Authors: Oliveira Clistenes Gomes de , Oliveira Júnior Gregório Murilo de , Silva Raquel Moura , Rodrigues Paula Gomes , Brito Claudson Oliveira , Santos Thailine Santana , Souza Douglas Melo de , Silva Camilla Mendonça
Published: February 2021

Objetivou-se avaliar três métodos de coleta de fezes utilizados para estimar os coeficientes de digestibilidade de nutrientes para equinos. Os tratamentos consistiram em três métodos de coleta de fezes, sendo eles: método de coleta total (controle); método da Liginina purificada LIPE® com cinco dias de coleta de fezes (LIPE3) e o método da LIPE® com três dias de coleta de fezes (LIPE5). Para isto, foram utilizados seis equinos machos castrados, sem raça definida, com peso médio 442,3±33,3kg. Considerou-se três métodos de coleta e seis repetições. Foram calculados os coeficientes de digestibilidade da matéria seca, matéria orgânica, proteína bruta, extrato etéreo, hemicelulose, fibra em detergente neutro (CDFDN) e ácido (CDFDA) e carboidratos não estruturais (CDCNE). O CDFDN e CDFDA foram maiores (P<0,01) nos métodos LIPE® (três e cinco dias de coleta). O CDCNE foi maior no método LIPE® com cinco dias de coleta. Além disso, a taxa de recuperação fecal do indicador LIPE® foram elevadas, independente do período de coleta. O método de coleta total de fezes e os métodos com coleta parcial de fezes durante três ou cinco dias com utilização de LIPE® podem ser utilizados para se determinar os coeficientes de digestibilidade da matéria seca, matéria orgânica, extrato etéreo, proteína bruta e hemicelulose em equinos de forma confiável.
Tenda do abraço: Uma metodologia de cuidado guiada pelo afeto
Authors: Costa Jackeline de Freitas , Nelson Isabel Cristina Amaral de Sousa Rosso , Couto Gleiber , França Raiane Caroline da Silva
Published: February 2021

O presente trabalho tem como principal objetivo apresentar a Tenda do Abraço como uma metodologia de cuidado sistematizada no âmbito das Práticas Integrativas e Complementares em Saúde, dentro uma abordagem das Vivências Lúdicas Integrativas. É uma pesquisa de método qualitativo, foi realizada uma pesquisa-ação existencial. O público-alvo foram 48 estudantes da Faculdade de Enfermagem – FAEN da Universidade Estadual do Rio Grande do Norte - UERN. A tenda do abraço é uma metodologia itinerante de cuidado que evidencia a necessidade de cultivar novos olhares para si e para o outro, oportunizando momentos de cuidado, escuta, fala e toques. Por meio de um roteiro não engessado em que os sujeitos têm a possibilidade de cuidar de si e perceber a necessidade do cuidado com o outro, com o aparato das PICS. A Tenda do Abraço perpassa quatro etapas principais: acolhimento afetivo; tecendo saberes; conexões e reflexões; cooperação e autocuidado.  A Tenda do Abraço apresentou-se como uma metodologia de cuidado humanescente, sistematizada e potente para conexão consigo e com o outro, melhorando a qualidade das interações interpessoais dos universitários.
Preditores de recorrência de lesões autoprovocadas e de óbitos por suicídio em um estado brasileiro
Authors: Sousa Nágella Thaysa Bier de , Teixeira Letícia Oliveira Othon , Vedana Kelly Graziani Giacchero , Miasso Adriana Inocenti
Published: February 2021

Objetivos: caracterizar as lesões autoprovocadas e investigar preditores sociodemográficos e clínicos para recorrência de lesões autoprovocadas e para óbitos por suicídio no Estado do Mato Grosso Métodos: Trata-se de estudo transversal, analítico, de abordagem quantitativa, que incluiu todos os casos de lesões autoprovocadas e óbitos por suicídio registrados em sistemas de informação em saúde. Foram desenvolvidos modelos de regressão logística para analisar os preditores dos desfechos de interesse. Resultados: Os resultados revelaram 1507 notificações de lesões autoprovocadas, sendo que 1443 pessoas tiveram apenas uma lesão autoprovocada e 29 pessoas com recorrência de tais lesões. Das 1472 pessoas com lesão autoprovocada na primeira notificação, 424 foram a óbito. Houve maior chance de recorrência de lesão autoprovocada em pessoas com idade de 10 a 19 anos (OR 2,28, IC 95% 1,09 - 4,79), com algum tipo de deficiência ou transtorno (OR 1,85, IC 95% 1,13 - 3,03). Identificou-se menor chance de óbito por suicídio em pessoas com idade de 10 a 19 anos (OR 0,06, IC 95% 0,02 - 0,17), e de 20 a 59 anos (OR 0,23, IC 95% 0,10 - 0,54), com até oito anos de escolaridade (OR 0,23, IC 95% 0,15 - 0,36), mulheres (OR 0,21, IC 95% 0,13 - 0,32) e por autointoxicação intencional por medicamento (OR 0,17, IC 95% 0,08 - 0,38). Conclusão: Este estudo fornece subsídios para estratégias de vigilância à saúde da população para prevenção de suicídio, além de indicar a necessidade de ações que promovam notificação adequada pelos instrumentos disponibilizados nos serviços de saúde.
Importância do tecido ceratinizado para o sucesso na implantodontia
Authors: Nagai Thais Kazue , Santos Anderson Maikon de Souza , Machado Nathália Evelyn da Silva , Mendes Bruno Coelho , Lima Neto Tiburtino José de , Vasques Ana Maria Veiga , Dezan Junior Eloi , Faverani Leonardo Perez
Published: February 2021

Fundamento: uma boa condição dos tecidos moles é necessária para a longevidade de tratamentos com implantes dentários. Os tecidos moles periimplantares são semelhantes ao periodonto de proteção, sendo importante para oferecer uma barreira contra a agressão bacteriana ao tecido ósseo. Objetivo: o objetivo foi realizar uma revisão de literatura sobre a importância da mucosa queratinizada na implantodontia; analisando a relação entre a manutenção gengival e saúde periimplantar. Metodologia: bases de dados foram acessadas para realização da pesquisa de artigos publicados na literatura Odontológica, na língua portuguesa e inglesa, principalmente entre os anos de 2010 a 2019. As bases de dados acessadas foram: LILACS, PUBMED, Scielo e a Biblioteca Digital Brasileira de Teses e Dissertações (BDTD). As palavras chaves usadas foram: osseointegration AND periodontics AND mouth mucosa AND gingiva. Discussão: vários estudos, desde estudos animais à revisões sistemáticas de literatura foram realizadas para avaliar o papel do tecido ceratinizado na implantodotia, e observaram que este tecido atua positivamente, com melhora do selamento periimplantar, redução de inflamação local, melhora na realização da higiene local e menos casos de recessão tecidual. Conclusão: conclui-se que o tecido ceratinizado é fundamental para a saúde periimplantar, atuando tanto na saúde oral do paciente reabilitado, quanto na sua estética e funcionalidade.
Prokaryotic community composition and structure during Phaeocystis globosa blooms in the Beibu Gulf, China
Authors: He C , Xu S , Kang Z , Song S , Li C
Published: February 2021

Phaeocystis globosa blooms have become one of the major ecological issues in the Beibu Gulf, China, in recent years, resulting in a series of negative impacts on local fisheries and industry. While prokaryotes play key roles in nutrient cycling and energy flow during algal blooms, information regarding the response of the prokaryotic community during Phaeocystis blooms remains scarce. Thus, a comprehensive field study covering the onset and senescent phase of P. globosa blooms was conducted in the area from December 2016 to February 2017. The community composition was revealed with high-throughput sequencing of the 16S rRNA gene. A total of 7426 operational taxonomic units (OTUs) (97% similarity) were identified from 3132328 effective tags, with Proteobacteria, Cyanobacteria, Thaumarchaeota, Verrucomicrobia, Euryarchaeota, Actinobacteria, and Bacteroidetes being the predominant taxa. The composition and structure of particle-attached (PA) and free-living (FL) prokaryotic communities were significantly different: the PA fraction was more diverse and unstable temporally compared to the FL fraction. Variations in the composition and structure of the prokaryotic community were closely associated with major environmental variables, particularly dissolved oxygen (DO), NH4+, PO43-, and dissolved organic carbon (DOC). The presence of P. globosa may result in differences in the prokaryotic community; members of Rhodobacteraceae, Alteromonadales, Porticoccaceae, Vibrio, Flavobacteriales, and Verrucomicrobiae were the key taxa in the prokaryotic communities during the outbreak and senescent phases of P. globosa blooms. This study provides primary information on the response of prokaryotic communities during P. globosa blooms and will facilitate further study on biogeochemical processes of algal-derived organic matter in the tropical gulf.
Spel i förskolan stöttar förskolebarns lärande i matematik
Authors: Elofsson Jessica
Published: February 2021

I denna artikel presenteras resultatet från en studie i förskolan där barns lärande i matematik stått i fokus. Resultaten visar att förskolebarn som ges möjlighet att spela spel som innefattar siffror och tal stöttas i sitt lärande. Olika spel stöttar olika typer av förmågor hos barnen och kan med fördel användas i förskolans verksamhet för att stötta barns tidiga lärande i matematik.
Advances in the Microbial Synthesis of 5-Hydroxytryptophan
Authors: Liu Xin-Xin , Zhang Bin , Ai Lian-Zhong
Published: February 2021

5-Hydroxytryptophan (5-HTP) plays an important role in the regulation of emotion, behavior, sleep, pain, body temperature, and other physiological functions. It is used in the treatment of depression, insomnia, migraine, and other diseases. Due to a lack of effective biosynthesis methods, 5-HTP is mainly obtained by natural extraction, which has been unable to meet the needs of the market. Through the directed evolution of enzymes and the introduction of substrate supply pathways, 5-HTP biosynthesis and yield increase have been realized. This review provides examples that illustrate the production mode of 5-HTP and the latest progress in microbial synthesis.
Selection of the Optimal Candidate to MitraClip for Secondary Mitral Regurgitation: Beyond Mitral Valve Morphology
Authors: Salvatore Tanya , Ricci Fabrizio , Dangas George D. , Rana Bushra S. , Ceriello Laura , Testa Luca , Khanji Mohammed Y. , Caterino Anna Laura , Fiore Corrado , Popolo Rubbio Antonio , Appignani Marianna , Di Fulvio Maria , Bedogni Francesco , Gallina Sabina , Zimarino Marco
Published: February 2021

Secondary mitral regurgitation (MR) occurs despite structurally normal valve apparatus due to an underlying disease of the myocardium leading to disruption of the balance between tethering and closing forces with ensuing failure of leaflet coaptation. In patients with heart failure (HF) and left ventricular dysfunction, secondary MR is independently associated with poor outcome, yet prognostic benefits related to the correction of MR have remained elusive. Surgery is not recommended for the correction of secondary MR outside coronary artery bypass grafting. Percutaneous mitral valve repair (PMVR) with MitraClip implantation has recently evolved as a new transcatheter treatment option of inoperable or high-risk patients with severe MR, with promising results supporting the extension of guideline recommendations. MitraClip is highly effective in reducing secondary MR in HF patients. However, the derived clinical benefit is still controversial as two randomized trials directly comparing PMVR vs. optimal medical therapy in severe secondary MR yielded virtually opposite conclusions. We reviewed current evidence to identify predictors of PMVR-related outcomes in secondary MR useful to improve the timing and the selection of patients who would derive maximal benefit from MitraClip intervention. Beyond mitral valve anatomy, optimal candidate selection should rely on a comprehensive diagnostic workup and a fine-tuned risk stratification process aimed at (i) recognizing the substantial heterogeneity of secondary MR and its complex interaction with the myocardium, (ii) foreseeing hemodynamic consequences of PMVR, (iii) anticipating futility and (iv) improving symptoms, quality of life and overall survival.
Duration of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndrome Treated With New Generation Stents: A Meta-Analysis of Randomized Controlled Trials
Authors: Zhang Wen-Jiao , Qiao Xuan , Guo Wen-Fen , Liang Xi-Ying , Li Yan , Wang Zhi-Lu
Published: February 2021

Background and Objective: The optimum duration of dual antiplatelet therapy (DAPT) remains uncertain in patients with acute coronary syndrome treated with new generation stents. This meta-analysis was performed to investigate ischemia and bleeding outcomes with different DAPT strategies.

Methods: PubMed, Embase, Cochrane and Web of science from inception to May 27, 2020, were systematically searched. Randomized controlled trials were included to compare short-term (6 months or less) with standard (12 months) DAPT in patients with acute coronary syndrome treated with new generation stents. The primary endpoints were myocardial infarction, definite or probable stent thrombosis and major bleeding. The secondary endpoints included all-cause death, cardiovascular death, stroke, target vessel revascularization and net adverse clinical events. Random effect model and fixed effect model were used to calculate the odds ratio (OR) and 95% confidence interval (CI) of each endpoint.

Results: Four randomized controlled trials and seven subgroup analyses of larger randomized controlled trials, including a total of 21,344 patients with acute coronary syndrome, met our inclusion criteria. The shorter DAPT was associated with significantly lower major bleeding compared with the standard DAPT (OR 0.71, 95% CI 0.56–0.90, P = 0.005, I2 = 25%), while without increasing the risk of myocardial infarction (OR 1.18, 0.88–1.58, P = 0.28, I2 = 20%), definite or probable stent thrombosis (OR 1.60, 0.98–2.59, P = 0.06, I2 = 0%). No significantly difference was observed in the risk of all-cause death (OR 0.96, 0.72–1.27, P = 0.76, I2 = 2%), cardiovascular death (OR 0.91, 0.62–1.33, P = 0.62, I2 = 0%), stroke (OR 0.84, 0.54–1.30, P = 0.43, I2 = 0%), target vessel revascularization (OR 1.14, 0.84–1.55, P = 0.41, I2 = 8%), and net adverse clinical events (OR 0.93, 0.80–1.07, P = 0.3, I2 = 18%) between the two groups.

Conclusions: In patients with acute coronary syndrome treated with new generation stents, the shorter DAPT leads to a marked reduction in the risk of major bleeding compared with the standard DAPT. This benefit is achieved without increasing the risk of mortality or ischemic outcomes. The study protocol was registered in PROSPERO (CRD42020189871).
Immune Checkpoint Inhibitors: Cardiotoxicity in Pre-clinical Models and Clinical Studies
Authors: Xu Shirley , Sharma Umesh C. , Tuttle Cheyanna , Pokharel Saraswati
Published: February 2021

Since the approval of the first immune checkpoint inhibitor (ICI) 9 years ago, ICI-therapy have revolutionized cancer treatment. Lately, antibodies blocking the interaction of programmed cell death protein (PD-1) and ligand (PD-L1) are gaining momentum as a cancer treatment, with multiple agents and cancer types being recently approved for treatment by the US Food and Drug Administration (FDA). Unfortunately, immunotherapy often leads to a wide range of immune related adverse events (IRAEs), including several severe cardiac effects and most notably myocarditis. While increased attention has been drawn to these side effects, including publication of multiple clinical observational data, the underlying mechanisms are unknown. In the event of IRAEs, the most widely utilized clinical solution is administration of high dose corticosteroids and in severe cases, discontinuation of these ICIs. This is detrimental as these therapies are often the last line of treatment options for many types of advanced cancer. In this review, we have systematically described the pathophysiology of the PD-1/PD-L1 axis (including a historical perspective) and cardiac effects in pre-clinical models, clinical trials, autoimmune mechanisms, and immunotherapy in combination with other cancer treatments. We have also reviewed the current challenges in the diagnosis of cardiac events and future directions in the field. In conclusion, this review will delve into this expanding field of cancer immunotherapy and the emerging adverse effects that should be quickly detected and prevented.
Association Between Lipoprotein(a) and Peri-procedural Myocardial Infarction in Patients With Diabetes Mellitus Who Underwent Percutaneous Coronary Intervention
Authors: Liu Yupeng , Wang Wenyao , Song Jingjing , Zhang Kuo , Xu Bo , Li Ping , Shao Chunli , Yang Min , Chen Jing , Tang Yi-Da
Published: February 2021

Background

High lipoprotein(a) (Lp[a]) levels are associated with increased risks of cardiovascular events in Percutaneous Coronary Intervention (PCI) patients with diabetes mellitus (DM). Peri-procedural myocardial infarction (PMI) occurs commonly during the PCI, whereas the relationship between Lp(a) and PMI remains unclear. Our study aimed to evaluate the association between Lp(a) value and the incidence of PMI in a larger-scale diabetic cohort undergoing PCI throughout 2013.

Methods

A total of 2,190 consecutive patients with DM were divided into two groups according to the median Lp(a) level of 175 mg/L: Low Lp(a) group (N = 1095) and high Lp(a) group (N = 1095). PMI was defined based on the 2018 universal definition of myocardial infarction.

Results

Patients with high Lp(a) levels exhibited higher rates of PMI compared to those with low Lp(a) levels (2.3% versus 0.8%, P = 0.006). The multivariable logistic analysis showed that PMI was independently predicted by Lp(a) as a dichotomous variable (OR 2.64, 95%CI 1.22–5.70) and as a continuous variable (OR 1.57, 95% CI 1.12–2.20). However, further investigation found that this association was only maintained in men, whose Lp(a) levels were significantly associated with the frequency of PMI, both as a dichotomous variable (OR 3.66, 95%CI 1.34–10.01) and as a continuous variable (OR 1.81, 95%CI 1.18–2.78). Lp(a) wasn’t a risk factor of PMI in women.

Conclusions

High Lp(a) levels had forceful correlations with the increased frequency of PMI in male diabetic patients undergoing PCI. Lp(a) might act as a marker of risk stratification and a therapeutic target to reduce PCI-related ischemic events.
Lek Territory Size and the Evolution of Leks: A Model and a Test Using an Ungulate With a Flexible Mating System
Authors: Isvaran Kavita
Published: February 2021

Despite many decades of research, the evolution of the rare and unusual lek-mating system continues to be debated. The key question is: why do males defend tiny territories clustered together in an aggregation when the costs of doing so are so high? Theory and empirical work on lek evolution typically focus on why males cluster their territories. Surprisingly, the other characteristic feature of classical leks, which is the unusually small size of lek-territories, has received very little attention. Here, I argue that understanding the factors favoring the reduced size of lek-territories can provide fresh insights into the evolution of leks. I used the variable mating system of an Indian antelope, the blackbuck (Antilope cervicapra), to investigate lek territory size. Because there are few quantitative models of mating territory size, I first constructed a spatial simulation model of territory size based on male competition costs and on mating benefits generated by a female bias for mating on central lek-territories, the processes most likely to influence lek-territory size. The model generated much systematic variation in territory size within a territory-cluster and also across territory-clusters varying in the number of territorial males. I tested predictions from the model using comparative data on territory size from six blackbuck populations, and detailed spatial and temporal data from an intensively-studied population. Empirical analyses strongly supported model predictions and assumptions. Based on these findings, I present a novel hypothesis for the small size of classical lek-territories. I suggest that much of the variation in the size of lek-territories can be explained by the competition that arises from a female bias for mating on central territories and that is intensified by the number of territorial males in an aggregation. Thus, the reduced size of classical lek-territories is likely a consequence of a central mating advantage in large aggregations. I present a framework for the evolution of leks that explicitly incorporates the evolution of reduced territory size alongside the evolution of male clustering. This framework can also help explain other forms of mating systems that are based on the defense of mating territories by males.
Human Ubiquitin-Specific Peptidase 18 Is Regulated by microRNAs via the 3'Untranslated Region, A Sequence Duplicated in Long Intergenic Non-coding RNA Genes Residing in chr22q11.21
Authors: Rubino Erminia , Cruciani Melania , Tchitchek Nicolas , Le Tortorec Anna , Rolland Antoine D. , Veli Önay , Vallet Leslie , Gaggi Giulia , Michel Frédérique , Dejucq-Rainsford Nathalie , Pellegrini Sandra
Published: February 2021

Ubiquitin-specific peptidase 18 (USP18) acts as gatekeeper of type I interferon (IFN) responses by binding to the IFN receptor subunit IFNAR2 and preventing activation of the downstream JAK/STAT pathway. In any given cell type, the level of USP18 is a key determinant of the output of IFN-stimulated transcripts. How the baseline level of USP18 is finely tuned in different cell types remains ill defined. Here, we identified microRNAs (miRNAs) that efficiently target USP18 through binding to the 3’untranslated region (3’UTR). Among these, three miRNAs are particularly enriched in circulating monocytes which exhibit low baseline USP18. Intriguingly, the USP18 3’UTR sequence is duplicated in human and chimpanzee genomes. In humans, four USP18 3’UTR copies were previously found to be embedded in long intergenic non-coding (linc) RNA genes residing in chr22q11.21 and known as FAM247A-D. Here, we further characterized their sequence and measured their expression profile in human tissues. Importantly, we describe an additional lincRNA bearing USP18 3’UTR (here linc-UR-B1) that is expressed only in testis. RNA-seq data analyses from testicular cell subsets revealed a positive correlation between linc-UR-B1 and USP18 expression in spermatocytes and spermatids. Overall, our findings uncover a set of miRNAs and lincRNAs, which may be part of a network evolved to fine-tune baseline USP18, particularly in cell types where IFN responsiveness needs to be tightly controlled.
Community Metabolic Interactions, Vitamin Production and Prebiotic Potential of Medicinal Herbs Used for Immunomodulation
Authors: Peterson Christine T. , Iablokov Stanislav N. , Uchitel Sasha , Chopra Deepak , Perez-Santiago Josue , Rodionov Dmitry A. , Peterson Scott N.
Published: February 2021

Historically, the health benefits and immunomodulatory potential of medicinal herbs have been considered an intrinsic quality of the herb itself. We have hypothesized that the health benefits of medicinal herbs may be partially due to their prebiotic potential that alter gut microbiota leading to changes in short chain fatty acids and vitamin production or biotransformation of herb encoded molecules and secondary metabolites. Accumulating studies emphasize the relationship between the gut microbiota and host immune function. While largely unknown, these interactions are mediated by secreted microbial products that activate or repress a variety of immune cell types. Here we evaluated the effect of immunomodulatory, medicinal Ayurvedic herbs on gut microbiota in vitro using 16S rRNA sequencing to assess changes in community composition and functional potential. All immunomodulatory herbs displayed substantial prebiotic potential, targeting unique taxonomic groups. Application of genome reconstruction and analysis of biosynthetic capacity of herb selected communities suggests that many of the 11 herbs tested altered the community metabolism as the result of differential glycan harvest and sugar utilization and secreted products including multiple vitamins, butyrate, and propionate that may impact host physiology and immune function. Taken together, these results provide a useful framework for the further evaluation of these immunomodulatory herbs in vivo to maintain immune homeostasis or achieve desired regulation of immune components in the context of disease.
Accurate, Efficient and User-Friendly Mutation Calling and Sample Identification for TILLING Experiments
Authors: Gil Juanita , Andrade-Martínez Juan Sebastian , Duitama Jorge
Published: February 2021

TILLING (Targeting Induced Local Lesions IN Genomes) is a powerful reverse genetics method in plant functional genomics and breeding to identify mutagenized individuals with improved behavior for a trait of interest. Pooled high throughput sequencing (HTS) of the targeted genes allows efficient identification and sample assignment of variants within genes of interest in hundreds of individuals. Although TILLING has been used successfully in different crops and even applied to natural populations, one of the main issues for a successful TILLING experiment is that most currently available bioinformatics tools for variant detection are not designed to identify mutations with low frequencies in pooled samples or to perform sample identification from variants identified in overlapping pools. Our research group maintains the Next Generation Sequencing Experience Platform (NGSEP), an open source solution for analysis of HTS data. In this manuscript, we present three novel components within NGSEP to facilitate the design and analysis of TILLING experiments: a pooled variants detector, a sample identifier from variants detected in overlapping pools and a simulator of TILLING experiments. A new implementation of the NGSEP calling model for variant detection allows accurate detection of low frequency mutations within pools. The samples identifier implements the process to triangulate the mutations called within overlapping pools in order to assign mutations to single individuals whenever possible. Finally, we developed a complete simulator of TILLING experiments to enable benchmarking of different tools and to facilitate the design of experimental alternatives varying the number of pools and individuals per pool. Simulation experiments based on genes from the common bean genome indicate that NGSEP provides similar accuracy and better efficiency than other tools to perform pooled variants detection. To the best of our knowledge, NGSEP is currently the only tool that generates individual assignments of the mutations discovered from the pooled data. We expect that this development will be of great use for different groups implementing TILLING as an alternative for plant breeding and even to research groups performing pooled sequencing for other applications.
Nontrivial Replication of Loci Detected by Multi-Trait Methods
Authors: Ning Zheng , Tsepilov Yakov A. , Sharapov Sodbo Zh. , Wang Zhipeng , Grishenko Alexander K. , Feng Xiao , Shirali Masoud , Joshi Peter K. , Wilson James F. , Pawitan Yudi , Haley Chris S. , Aulchenko Yurii S. , Shen Xia
Published: February 2021

The ever-growing genome-wide association studies (GWAS) have revealed widespread pleiotropy. To exploit this, various methods that jointly consider associations of a genetic variant with multiple traits have been developed. Most efforts have been made concerning improving GWAS discovery power. However, how to replicate these discovered pleiotropic loci has yet to be discussed thoroughly. Unlike a single-trait scenario, multi-trait replication is not trivial considering the underlying genotype-multi-phenotype map of the associations. Here, we evaluate four methods for replicating multi-trait associations, corresponding to four levels of replication strength. Weak replication cannot justify pleiotropic genetic effects, whereas strong replication using our developed correlation methods can inform consistent pleiotropic genetic effects across the discovery and replication samples. We provide a protocol for replicating multi-trait genetic associations in practice. The described methods are implemented in the free and open-source R package MultiABEL.
TGF-β Signaling Promotes Glioma Progression Through Stabilizing Sox9
Authors: Chao Min , Liu Nan , Sun Zhichuan , Jiang Yongli , Jiang Tongtong , Xv Meng , Jia Lintao , Tu Yanyang , Wang Liang
Published: February 2021

Gliomas are brain and spinal cord malignancies characterized by high malignancy, high recurrence and poor prognosis, the underlying mechanisms of which remain largely elusive. Here, we found that the Sry-related high mobility group box (Sox) family transcription factor, Sox9, was upregulated and correlated with poor prognosis of clinical gliomas. Sox9 promotes migration and invasion of glioma cells and in vivo development of xenograft tumors from inoculated glioma cells. Sox9 functions downstream of the transforming growth factor-β (TGF-β) pathway, in which TGF-β signaling prevent proteasomal degradation of the Sox9 protein in glioma cells. These findings provide novel insight into the wide interplay between TGF-β signaling and oncogenic transcription factors, and have implications for targeted therapy and prognostic assessment of gliomas.
Virus Infections and Host Metabolism—Can We Manage the Interactions?
Authors: Sumbria Deepak , Berber Engin , Mathayan Manikannan , Rouse Barry T.
Published: February 2021

When viruses infect cells, they almost invariably cause metabolic changes in the infected cell as well as in several host cell types that react to the infection. Such metabolic changes provide potential targets for therapeutic approaches that could reduce the impact of infection. Several examples are discussed in this review, which include effects on energy metabolism, glutaminolysis and fatty acid metabolism. The response of the immune system also involves metabolic changes and manipulating these may change the outcome of infection. This could include changing the status of herpesviruses infections from productive to latency. The consequences of viral infections which include coronavirus disease 2019 (COVID-19), may also differ in patients with metabolic problems, such as diabetes mellitus (DM), obesity, and endocrine diseases. Nutrition status may also affect the pattern of events following viral infection and examples that impact on the pattern of human and experimental animal viral diseases and the mechanisms involved are discussed. Finally, we discuss the so far few published reports that have manipulated metabolic eventsin-vivoto change the outcome of virus infection. The topic is expected to expand in relevance as an approach used alone or in combination with other therapies to shape the nature of virus induced diseases.
The Role of the Z-DNA Binding Domain in Innate Immunity and Stress Granules
Authors: Chiang De Chen , Li Yan , Ng Siew Kit
Published: February 2021

Both DNA and RNA can maintain left-handed double helical Z-conformation under physiological condition, but only when stabilized by Z-DNA binding domain (ZDBD). After initial discovery in RNA editing enzyme ADAR1, ZDBD has also been described in pathogen-sensing proteins ZBP1 and PKZ in host, as well as virulence proteins E3L and ORF112 in viruses. The host-virus antagonism immediately highlights the importance of ZDBD in antiviral innate immunity. Furthermore, Z-RNA binding has been shown to be responsible for the localization of these ZDBD-containing proteins to cytoplasmic stress granules that play central role in coordinating cellular response to stresses. This review sought to consolidate current understanding of Z-RNA sensing in innate immunity and implore possible roles of Z-RNA binding within cytoplasmic stress granules.
A Multi-Sensor and Modeling Approach for Mapping Light Under Sea Ice During the Ice-Growth Season
Authors: Stroeve Julienne , Vancoppenolle Martin , Veyssiere Gaelle , Lebrun Marion , Castellani Giulia , Babin Marcel , Karcher Michael , Landy Jack , Liston Glen E. , Wilkinson Jeremy
Published: February 2021

Arctic sea ice is shifting from a year-round to a seasonal sea ice cover. This substantial transformation, via a reduction in Arctic sea ice extent and a thinning of its thickness, influences the amount of light entering the upper ocean. This in turn impacts under-ice algal growth and associated ecosystem dynamics. Field campaigns have provided valuable insights as to how snow and ice properties impact light penetration at fixed locations in the Arctic, but to understand the spatial variability in the under-ice light field there is a need to scale up to the pan-Arctic level. Combining information from satellites with state-of-the-art parameterizations is one means to achieve this. This study combines satellite and modeled data products to map under-ice light on a monthly time-scale from 2011 through 2018. Key limitations pertain to the availability of satellite-derived sea ice thickness, which for radar altimetry, is only available during the sea ice growth season. We clearly show that year-to-year variability in snow depth, along with the fraction of thin ice, plays a key role in how much light enters the Arctic Ocean. This is particularly significant in April, which in some regions, coincides with the beginning of the under-ice algal bloom, whereas we find that ice thickness is the main driver of under-ice light availability at the end of the melt season in October. The extension to the melt season due to a warmer Arctic means that snow accumulation has reduced, which is leading to positive trends in light transmission through snow. This, combined with a thinner ice cover, should lead to increased under-ice PAR also in the summer months.
Efficacy and Tolerability of Nintedanib in Idiopathic-Inflammatory-Myopathy-Related Interstitial Lung Disease: A Pilot Study
Authors: Liang Junyu , Cao Heng , Yang Yang , Ke Yini , Yu Ye , Sun Chuanyin , Yue Lihuan , Lin Jin
Published: February 2021

Objectives: To initially clarify the efficacy and tolerability of nintedanib in patients with idiopathic-inflammatory-myopathy-related interstitial lung disease (IIM-ILD).

Methods: A retrospective, real-world analysis was conducted in IIM-ILD patients who regularly received outpatient visit or hospitalization from January 2018 to March 2020 in three centers. And the patients were divided into two groups depending on presence or absence of nintedanib therapy. Comparisons, Kaplan-Meier survival analysis and propensity score matching were made to identify difference in time to death from any cause, incidence of rapidly progressive interstitial lung disease (RP-ILD) and comorbidity of pulmonary infection between the two groups. The following logistic regression analyses and Cox proportional-hazard regression analyses were used to verify the therapeutic value of nintedanib as well as clinical significance of other factors. Adverse events were descriptively recorded.

Results: Thirty-six patients receiving nintedanib therapy and 115 patients without use of nintedanib were included. Before and after propensity score matching, the primary comparisons revealed better survival (P = 0.015, P = 0016, respectively) and lower incidence of RP-ILD (P = 0.017, P = 0.014, respectively) in patients with nintedanib therapy. Logistic regression analysis identified that disease activity (P < 0.001), percent-predicted diffusing capacity of the lung for carbon monoxide (DLCO%, P = 0.036), nintedanib therapy (P = 0.004, OR value = 0.072) and amyopathic dermatomyositis (ADM, P = 0.012) were significantly correlated with RP-ILD. Cox proportional hazards regression analysis suggested that disease activity (P < 0.001), anti-MDA5 antibody (P < 0.001) and nintedanib therapy (P = 0.013, HR value=0.268) were significantly associated with survival of IIM-ILD patients. Similar results can also be seen in analyses after propensity score matching. In the 36 patients with nintedanib therapy, diarrhea was the most common adverse event (44.4%) and hepatic insufficiency contributed to most dosage reduction (44.4% of nine patients) or therapy discontinuation (60.0% of five patients).

Conclusions: Nintedanib was found to reduce incidence of RP-ILD and improve survival in IIM-ILD patients in a real-world setting. Anti-MDA5 antibody could be taken as a risk factor for unfavorable outcome. ADM was significantly correlated with occurrence of RP-ILD. In addition to the most frequent diarrhea, hepatic insufficiency was closely related to dosage reduction or therapy discontinuation.
Mycobacterium smegmatis GlnR Regulates the Glyoxylate Cycle and the Methylcitrate Cycle on Fatty Acid Metabolism by Repressing icl Transcription
Authors: Qi Nan , She Guo-Lan , Du Wei , Ye Bang-Ce
Published: February 2021

Mycobacterium smegmatis (Msm), along with its pathogenic counterpart Mycobacterium tuberculosis (Mtb), utilizes fatty acids and cholesterol as important carbon and energy sources during the persistence within host cells. As a dual-functional enzyme in the glyoxylate cycle and the methylcitrate cycle, isocitrate lyase (ICL, encoded by icl or MSMEG_0911) is indispensable for the growth of Msm and Mtb on short-chain fatty acids. However, regulation of icl in mycobacteria in response to nutrient availability remains largely unknown. Here, we report that the global nitrogen metabolism regulator GlnR represses icl expression by binding to an atypical binding motif in the icl promoter region under nitrogen-limiting conditions. We further show that GlnR competes with PrpR, a transcriptional activator of icl, and dominantly occupies the co-binding motif in the icl promoter region. In the absence of GlnR or in response to the excess nitrogen condition, Msm cells elongate and exhibit robust growth on short-chain fatty acids due to the PrpR-mediated activation of icl, thereby inducing enhanced apoptosis in infected macrophages. Taken together, our findings reveal the GlnR-mediated repression of icl on fatty acid metabolism, which might be a general strategy of nutrient sensing and environmental adaptation employed by mycobacteria.
Computational Ways to Enhance Protein Inhibitor Design
Authors: Jernigan Robert L. , Sankar Kannan , Jia Kejue , Faraggi Eshel , Kloczkowski Andrzej
Published: February 2021

Two new computational approaches are described to aid in the design of new peptide-based drugs by evaluating ensembles of protein structures from their dynamics and through the assessing of structures using empirical contact potential. These approaches build on the concept that conformational variability can aid in the binding process and, for disordered proteins, can even facilitate the binding of more diverse ligands. This latter consideration indicates that such a design process should be less restrictive so that multiple inhibitors might be effective. The example chosen here focuses on proteins/peptides that bind to hemagglutinin (HA) to block the large-scale conformational change for activation. Variability in the conformations is considered from sets of experimental structures, or as an alternative, from their simple computed dynamics; the set of designe peptides/small proteins from the David Baker lab designed to bind to hemagglutinin, is the large set considered and is assessed with the new empirical contact potentials.
Cholesterols Work as a Molecular Regulator of the Antimicrobial Peptide-Membrane Interactions
Authors: Li Jia , Lu Xuemei , Ma Wendong , Chen Zhonglan , Sun Shuqing , Wang Qinghui , Yuan Bing , Yang Kai
Published: February 2021

The existing cholesterols (Chols) in animal cell membranes play key roles in many fundamental cellular processes, which also promise the possibility to modulate the bioactivity of various membrane-active biomacromolecules. Here, combining dynamic giant unilamellar vesicle leakage experiments and molecular dynamics simulations, the inhibitory effect of Chols on the membrane poration activity of melittin (Mel), a typical natural antimicrobial peptide, is demonstrated. Molecular details of the Mel-Chol interactions in membrane show that, for a Chol-contained lipid membrane, Mel exposure would perturb the symmetric bilayer structure of the membrane and specifically influence the location and orientation distributions of Chol molecules to an asymmetric state between the two leaflets; moreover, the Mel-Chol interactions are significantly influenced by the membrane environment such as unsaturation degree of the lipid components. Such inhibitory effect is normally ascribed to an accumulation of Chol molecules around the membrane-bound peptide chains and formation of Chol-Mel complexes in the membrane, which hinder the further insertion of peptides into the membrane. This work clarifies the molecular interactions between membrane-active peptides and Chol-contained membranes, and suggest the possibility to develop targeted drugs due to the membrane component specificity between bacterial and animal cells.
Cerebral Metabolite Concentrations Are Associated With Cortical and Subcortical Volumes and Cognition in Older Adults
Authors: Williamson John B. , Lamb Damon G. , Porges Eric C. , Bottari Sarah , Woods Adam J. , Datta Somnath , Langer Kailey , Cohen Ronald A.
Published: February 2021

Background

Cerebral metabolites are associated with different physiological processes in brain aging. Cortical and limbic structures play important roles in cognitive aging; however, the relationship between these structures and age remains unclear with respect to physiological underpinnings. Regional differences in metabolite levels may be related to different structural and cognitive changes in aging.

Methods

Magnetic resonance imaging and spectroscopy were obtained from 117 cognitively healthy older adults. Limbic and other key structural volumes were measured. Concentrations of N-acetylaspartate (NAA) and choline-containing compounds (Cho) were measured in frontal and parietal regions. Neuropsychological testing was performed including measures of crystallized and fluid intelligence and memory.

Results

NAA in the frontal voxel was associated with limbic and cortical volumes, whereas Cho in parietal cortex was negatively associated with hippocampal and other regional volumes. Hippocampal volume was associated with forgetting, independent of age. Further, parietal Cho and hippocampal volume contributed independent variance to age corrected discrepancy between fluid and crystallized abilities.

Conclusion

These findings suggest that physiological changes with age in the frontal and parietal cortices may be linked to structural changes in other connected brain regions. These changes are differentially associated with cognitive performance, suggesting potentially divergent mechanisms.