bluuebunny/crossref_metadata_2025 huggingface dataset:
Al Rescate del amor pedagógico
Authors: Meléndez Soto Rosa María
Published: June 2021

Educar implica esfuerzo, orden, sistematización, buenos y malos ratos, sacrificio personal, saber esperar, aprovechar el momento oportuno y rectificar cuantas veces sea necesario, entre otras cosas. Aunque a nivel superior se nos olvide que los jóvenes con los que tenemos la oportunidad de emprender la aventura de buscar algunas respuestas, son seres humanos inacabados y nosotros también, la verdad es que nuestra misión va más allá de la instrucción técnica y debiera priorizar la formación para la vida. Esta educación sólo será humanista si provoca que la persona pueda integrarse a su realidad, siendo libre e independiente y también solidaria.
Importancia de la educación superior en el proyecto del envejecimiento saludable activo
Authors: Velasco Laura Macías
Published: June 2021

La educación del siglo XXI presenta diferentes retos entre los cuales se encuentran la urgente necesidad de vincular la escuela con el aparato productivo, los problemas sociales, el sector público y el diseño de sus programas. Un proyecto importante, que en la actualidad tienen diferentes países como tema de agenda, es el de la educación para la vida, el cual pretende que las personas tengan interés por estar en constante aprendizaje, esto con la finalidad de que su población se mantenga en la búsqueda de la mejora continua, lo cual permite tener sociedades con mejor calidad de vida y, por ello, la disminución de las problemáticas que se viven.

En este momento es apremiante considerar la educación de las personas mayores, pero no en el sentido que se ha realizado hasta el momento de “alfabetización”, sino como una educación que tiene la intención de ampliar las competencias para la vida adulta, debido a que presentan diferentes circunstancias que requieren apoyo, tales como la atención en salud física y emocional, la socialización (aceptación de todos los integrantes de su familia y de la comunidad en la que viven). En este sentido, el atender las diferentes necesidades de formación de las personas mayores puede favorecer el envejecimiento saludable activo.
La evaluación del desempeño musical y el uso de rúbricas
Authors: Capistrán Gracia Raúl W. , Correa Ortega Juan Pablo
Published: June 2021

Evaluar es una tarea permanente en cualquier proceso de enseñanza y de aprendizaje. Su objetivo principal es conocer qué tanto ha aprendido el estudiante, así como la calidad de lo aprendido.

Los resultados de la evaluación son de vital consideración; por un lado, proporcionan al maestro información importante para optimizar la labor docente y promover el aprendizaje y el espíritu de superación en los estudiantes; por otro, ofrecen retroalimentación al alumnado sobre sus fortalezas y áreas de oportunidad, lo que le da elementos para mejorar.
Recursos académicos digitales
Authors: Padilla Ornelas Patricia Janet
Published: June 2021

Este artículo tiene como propósito presentar algunas opciones de recursos digitales y multimedia para facilitar, así como enriquecer, el trabajo pedagógico y de investigación de cada docente a fin de propiciar experiencias constructivistas de aprendizaje. Debido a que la práctica docente actual demanda la búsqueda permanente de superación intelectual y excelencia académica, las condiciones competitivas así lo exigen.
El profesor de la Universidad Autónoma de Aguascalientes y las dimensiones de la formación integral
Authors: Pacheco González María de Lourdes
Published: June 2021

El ser humano cuenta con la capacidad para adquirir una serie de recursos que le permitirán dotar de sentido a su existencia, de conformarse de la manera más idónea, y una de las vías para lograrlo es la educación, que le permitirá desarrollar su personalidad, sus capacidades e insertarse en el mundo social que le tocó vivir.

A través de la educación, el sujeto, además de adquirir una gama de conocimientos específicos de las diversas ciencias, también desarrollará un sentido crítico, valoral y cívico; es decir, será formado integralmente, entendiendo por formación integral el desarrollo de todas las dimensiones del ser humano.
Ansiedad hacia las habilidades productivas del idioma Inglés
Authors: Velázquez  Macías Lorena Paulina
Published: June 2021

El siguiente escrito expone un apartado de los resultados de una investigación realizada en la Universidad Autónoma de Aguascalientes, cuyo objetivo es identificar la presencia de Ansiedad hacia el Aprendizaje del Idioma Extranjero (FLCA1) en estudiantes de inglés del Programa Institucional de Lenguas Extranjeras (PILE). El estudio se realiza mediante una adaptación del cuestionario Foreign Language Classroom Anxiety Scale2 (FLCAS), que mide los niveles de este tipo de ansiedad. Se exploraron los perfiles de aquellos estudiantes con niveles mayores, y se descubrió que los presentan debido a factores relacionados con su percepción del dominio y dificultad del idioma, primordialmente durante actividades comunicativas de manera oral. La información presentada documenta la potencial influencia que tiene la ansiedad sobre las habilidades productivas del idioma inglés.
Prevalence of T2 Diabetes Mellitus (DM) Among the Rural People of Selected villages Of Bangladesh
Authors: Ali Md Yunus , Begum Maksuda , Dipu Sultan Sobnam
Published: June 2021

Objectives: This cross-sectional study was conducted to find out the prevalence of type 2 diabetes and pre-diabetes ((PD) (Impaired fasting glucose-IFG, impaired glucose tolerance-IGT)) and to see the associations with risk factors.

Methods: Two villages were randomly selected from rural area of Mymensingh district. 125 study subjects (≥30 years) were selected with systematic procedure but 118 samples were participated in the study. Below 30 years, diagnosed case of diabetes and urban people were excluded from study. Socio-demographic data were collected on a pre-tested interview schedule through face to face interview. DM, PD were interpreted by estimating fasting blood glucose level and 2 hour after 75 gm glucose load. Obesity was assigned by BMI. SPSS program (version 11.5) used for data analysis.

Results: Mean age of participants was 46.68 with SD ± 12.698. Female participation (66.9%) was double compare to male, literacy rate was (64.4%) with female illiteracy of 29.67%. House wives (61.9%) were more than other professions. Middle class people were nearly 73%, Poor 14.4%, sedentary life style 11% and depressives 14.4% evident in study. A 20.3% people did laborious works. 17.8% had the family history of diabetes. Smokers (53.4%) were more than the non-smokers. Majority (89.0%) of rural people eat rice thrice a day. Normal BMI 61.0%, underweight 31.4% and 7.6% overweight observed.  Overall prevalence of T2 DM was 11.0% showing increase trend of diabetes compared to 8.6% estimated in 2000 and higher than several studies of home and abroad. Female showed higher prevalence (7.6%) compare to male (P>0.05). The overall prevalence of PD was 16.1% evident in this study. The prevalence of IFG and IGT were 8.5% and 7.6% respectively. Female showed higher prevalence of IFG (5.1%) and IGT (5.9%) than male (P>0.05). House wives showed higher prevalence (5.6%) of DM compare to other professions (P>0.05). Illiterates showed more PD (10.3%) and less DM (1.7%) but literates showed more (9.3%) DM (P >0.05). DM (6.7%) and PD (11.8%) more were among the middle class (P=0.018). A high prevalence of PD (13.6%) and DM (9.3%) noticed among non-sedentary lifestyle (P >0.05). Smoker showed higher DM (8.5%) and PD (11.8%). (P-0.071). Prevalence of PD and DM were high among the people with physically less active (P =0.795). Depressives showed more prevalence of DM (8.5%) and PD (13.5%), (P=0.345). increased frequency of rice eating (P=0.004), people with normal BMI (P=0.081) and family history of DM (P=0.000) showed positive association with diabetes mellitus.

CBMJ 2015 January: Vol. 04 No. 01 P: 22-29
Estimation of accumulated degree hours-based post-mortem intervals in mammalian and avian model
Authors: Mostafa Md Golam , Shobha Mst Shahanaz Parvin , Ara Anjuman , Ahmad Saadia
Published: June 2021

The post-mortem interval (PMI) of a jungle cat (Felis chaus) and a chicken (Gallus gallus domesticus) were estimated as a mammalian and an avian model, respectively. The estimations were performed adopting the Accumulated Degree Hours (ADH) method using blowfly, Lucilia sericata. The required developmental time from oviposition to the 3rd instar larvae of the blowfly species was considered for the determination of PMI in each of the study. The results revealed that the calculated PMI of jungle cat was 5.29 days. On the other hand, the estimated PMI of the chicken was 2.83 days. The difference of these two PMIs in two different models might be due to the variation of temperatures and other related factors in the development of the larvae of the blowfly species. This study might offer a new approach in the medico-legal investigations with a view to resolving homicide as well as other suspected death of animals including wildlife in Bangladesh.

Jahangirnagar University J. Biol. Sci. 9(1 & 2): 49-58, 2020 (June & December)
Korttelimaiset asumisen konseptit
Authors: Lappalainen Inka , Federley Maija
Published: June 2021

This paper analyses holistic urban housing concepts that combine spatial, social and digital solutions. The analysis is based on qualitative empirical case research, utilizing service-dominant logic approach and recent platform and sharing economy studies in residential context. The research focuses on 1) chosen service concepts to meet the diverse needs of residents, 2) related opportunities of platform and sharing economy, and 3) alternative network models considering life cycle perspective. The results indicate that value creation of housing expands from an apartment to a block providing sustainable base for all local ecosystem actors. While implementation models and applications of platform economy are still emergent, the conceptual frame is proposed for guiding further studies.
Simultaneous Treatment of Vestibular Schwannoma and Concurrent Middle Ear Disease Using the Enlarged Translabyrinthine Approach
Authors: Noh Hae Eun , Lee Ho Young , Na Gina , Moon In Seok
Published: June 2021

Unilateral presentation of vestibular schwannoma with concurrent chronic middle ear disease or cholesteatoma is rare. We report a series of patients with ipsilateral chronic middle ear disease and vestibular schwannoma, which were simultaneously removed via the enlarged translabyrinthine approach. All tumors were near-totally removed, and middle ear disease was completely excised; there were no major postoperative complications such as cerebrospinal fluid leakage, cholesteatoma recurrence, or meningitis. If hearing preservation of the affected ear is not necessary, simultaneous surgical removal of both pathologies is more convenient than staged treatment. The enlarged translabyrinthine approach can achieve complete treatment with one corridor.
Eventos adversos relacionados à assistência à saúde no Brasil: Estudo ecológico no período 2014-2018
Authors: Braga Cristina Spena , Cunha Karinne Cristinne da Silva , Pereira Quezia Vilela da Costa , Peixoto Eduardo Mesquita
Published: June 2021

Objetivos: Identificar os tipos de incidentes mais notificados no Brasil desde a implantação dos núcleos de segurança do paciente. Método: Estudo epidemiológico ecológico com base nos dados obtidos nos Boletins Informativos de Segurança do Paciente e Qualidade em Serviços de Saúde relacionados a assistência à Saúde emitidos pela ANVISA e do Cadastro Nacional de Estabelecimentos de Saúde (CNES) dos anos de 2014 a 2018.  Resultados: Os dados foram submetidos a teste de normalidade de Kolmogorov-smirnovi, sendo escolhida uma abordagem não-paramétrica (Sperman, Wilcox, Kruskal-Wallis) com nível de significância de 5%. Os resultados evidenciaram que nos biênios 2015-2016 e 2017-2018 os tipos de incidentes mais prevalentes foram: falha durante a assistência (27,8%/22,2%); lesão por pressão (17%/18,6%); queda (11,1%/11%); falha na identificação do paciente (6,3%/8%); perda ou obstrução de sonda (7,5%/ 6,5%) e flebite (5,4% /4,9%). Conclusão: Diferente de outros países onde as falhas mais prevalentes estiveram relacionadas a infecção, medicamentos e procedimentos cirúrgicos, os eventos adversos no Brasil estão mais relacionados aos cuidados de enfermagem. Apesar dos avanços alcançados, há muito a ser feito para estabelecimento da cultura da segurança do paciente nas instituições de saúde e na transposição das barreiras existentes quanto a notificação destes eventos, sendo o sistema de notificação de incidente uma importante estratégia na identificação de problemas na área de segurança do paciente, promovendo o aprendizado e melhoria dos processos assistenciais.
Hipodermoclise em cuidados paliativos oncológicos
Authors: Lemos Allan Carlos Mazzoni , Araujo Fabio Machado , Silva Andreia de Oliveira da , Ribeiro Rafaela Guingo , Santos Juliane Everton
Published: June 2021

O presente trabalho tem como objetivo: Compreender a hipodermoclise em cuidados paliativos oncológicos: uma técnica de infusão que é aplicada quando o paciente fica impossibilitado de usar a rede venosa e a via oral em casos oncológicos de doenças crônicas. Metodologia: Realizou-se um estudo descritivo de caráter exploratório com abordagem qualitativa. Discussão e resultados: Apresenta-se como uma técnica utilizada para administração de medicações e eletrólitos, vantagem, desvantagem, técnica de instalação, material utilizado para punção, tempo de permanência, manutenção de curativos. Considerações finais: Sendo assim, mostra-se como uma técnica de fácil aplicabilidade, baixo custo, segura, eficaz, reduz o sofrimento do paciente na hora de ser puncionado e diminuindo a dor e sintomas ocasionados pela patologia. Porém a prática ainda é pouco reconhecida entre os profissionais da área de saúde e necessita de mais divulgação e de investimento com manuais e protocolos institucionais sobre hipodermoclise. Dessa forma irá favorecer ao reconhecimento da técnica cientificamente para enfermeiros, acadêmicos e médicos.
Análise de tendências nas séries históricas de precipitação e curva de permanência de vazão no município Cachoeira do Piriá, Pará
Authors: Silva Gabriela Rousi Abdon da , Silva Fabiola Souza da , Duarte Juliana Maia , Tavares Aliny Ricarda Furtado
Published: June 2021

O Norte do Brasil apresenta altos índices pluviométricos, o que está relacionado a presença da floresta Amazônica. Em vista disso é necessário que estudos que analisem o comportamento hidrológico em bacias hidrográficas desta região sejam desenvolvidos, para que estes possam ser utilizados, posteriormente, como ferramentas e bases pra outras tipologias de estudos ou para análise de viabilidades de obras de modo geral. Dois dos principais componentes do ciclo hidrológico são as precipitações e as vazões dos corpos hídricos. Desta forma a presente pesquisa realizou uma análise acerca da estação pluviométrica de código (146008) e fluviométrica de código (32620000), ambas localizadas no munícipio de Cachoeira do Piriá, estado do estado do Pará, com o objetivo de  analisar a influência das precipitações nas vazões do rio da bacia hidrográfica através da construção de um hietograma, realizando também a avaliação de normal climatologia e tendência para a série histórica dos dados de chuva, utilizando os métodos Linear, Mann Kendall e Sen´s Slope. Além disso, para os dados de vazão foi elaborado a curva de permanência. Por fim, foi observado, a partir dos dados pluviométricos, que a precipitação no município não apresenta tendência e, a partir dos dados fluviométricos, foi possível observar que sua vazão em 95% dos casos é de, aproximadamente, 200 m³/s.
Benefícios da posição de prona em pacientes com COVID-19 não-intubados
Authors: Bigaran Larissa Toloy , Meira Layssa Delgado , Silva Juliana Valões Alencar da , Graça Rêgo Vítor , Barbosa Talita Costa , Paula Elenberg Chaves de
Published: June 2021

O objetivo do estudo foi evidenciar os benefícios da posição de prona em pacientes com COVID-19 não-intubados. Trata-se de uma revisão integrativa da literatura, usando os descritores “prone position” and “coronavirus” not “respiration, artificial”, usando as bases de dados PubMed, o Google Scholar, a Biblioteca Virtual em Saúde (BVS), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS). Após aplicação dos critérios de inclusão e exclusão, utilizou-se o fluxograma PRISMA para elucidar a seleção dos artigos e uma tabela mostrando os resultados que compõem a revisão. A posição de prona em pacientes acometidos pelo SARS-COV-2 em ventilação não-invasiva trouxe principalmente uma redução do esforço respiratório e com isso foi relatado que a mesma levou a uma menor incidência de intubação. Ainda, a mesma pode melhorar a homogeneidade pulmonar, a redistribuição pulmonar, a complascência pulmonar, a proporção de recrutamento para infiltração e o recrutamento de pulmão. Conclui-se, que a posição de prona proporciona diversos benefícios para os pacientes não-intubados com COVID-19, proporcionando melhora da saturação e redução da mortalidade, além de prevenir a intubação.
The effect of warm compresses on perineal tear and pain intensity during the second stage of labor: A randomized controlled trial
Authors: Modoor Soumaya , Fouly Howieda , Rawas Hawazen
Published: June 2021

Background: Warm compress is believed to reduce perineal tear occurrence and decrease pain intensity during the second stage of childbirth.Objective: This study aimed to determine the effect of warm compresses on perineal tear and pain intensity during the second stage of labor. Methods: A randomized controlled trial was conducted between 28 September 2018 to 30 October 2018 in King Khaled Hospital (KKH), affiliated with the Ministry of National Guard Hospital Affairs, King Abdul-Aziz Medical City Western Region, Saudi Arabia. According to eligibility criteria, the sample randomly recruited through lottery included 100 primigravida pregnant women, with 50 in each intervention and control group. Data were presented in the form of frequency and percentages, standard deviation, and mean. Chi-square test was used for data analysis, with p-value significance at ˂ 0.05.Results: Sociodemographic data revealed no statistically significant difference in the age, education, occupation, and residence of both the control and experimental group. The perineum area’s pain intensity after birth showed a statistically significant difference between the intervention and the control groups (p = 0.001). The perineal tear was also significantly different between both groups (p = 0.001).  Conclusion: The applied warm compresses on the perineum area positively reduce second and third-degree perineal tear and pain intensity during the second stage of labor and after childbirth. Therefore, midwives and nurses are expected to actively provide effective planned in-service training programs regarding warm compresses' advantages in the second stage of labor and apply this procedure actively.
Measuring the delivery of children’s rights to protection, care and development: Promoting improved understanding of mental health support for looked after children and children in care
Authors: Feinstein Leon
Published: June 2021

The vulnerability framework of measurement and voice was developed by the office of the Children’s Commissioner for England between 2017 and 2020 to provide a general approach to understanding levels of need, vulnerability and risk amongst children and young people. We developed a taxonomy drawn from systematic and multi-disciplinary literature review and identified 70 indicators that were our best fit to 7 categories of need, vulnerability and risk. For each we reviewed information for England on numbers of children indicated (demography), their views and experiences (voice), and what they receive by way of public services expenditure (finance). This work should be nested within a wider framework of measurement of capabilities. Particular areas of concern identified include children in mental health detention and other unofficial secure settings and children with insecure immigration status. We identified substantial gaps in measurement across most indicators in the domains of demography, voice and financial information.
Introduction to Cambridge Public Health Annual Showcase 2021
Authors: Harold Gordon
Published: June 2021

Cambridge Public Health's first Annual Showcase aimed to introduce new research and innovations for supporting young people’s mental health, and took place on May 18th, 2021. The showcase offered an impressive programme of speakers and contributors who seek to influence the nation’s approach to promoting mental health for children and adolescents.
Study of Pyrroloquinoline Quinine From Phosphate-Solubilizing Microbes Responsible for Plant Growth: In silico Approach
Authors: Bhanja Eeshita , Das Renuka , Begum Yasmin , Mondal Sunil Kanti
Published: June 2021

Plants cannot uptake the insoluble form of phosphate from soil. Phosphate-solubilizing microbes (PSMs) release gluconic acid (C6H12O7) that is synthesized by the interaction between co-factor pyrroloquinoline quinine (PQQ) and glucose dehydrogenase within themselves and hence convert the insoluble phosphate into a soluble form. Phylogenetic analyses based on individual sequences of PqqA–PqqE proteins involved in the PQQ biosynthetic pathway manifested clear clustering formation of the selected species according to their respective genera such asPantoea, Rouxiella, Rahnella, Kosakonia, Mixta, Cronobacter, andSerratia. In multiple sequence alignment (MSA), numerous semi-conserved sites were identified that indicate acquired mutation during evolution. The selectedpqqgenes that appeared within an operon system sustain a specified order viz.pqqABCDEfor both positive and negative strands. The nucleotide composition of the encoding genes displayed higher content of GCs at different positions of the codons and has also been properly reflected in relative synonymous codon usage (RSCU) values of the codons with few exceptions. The correspondence analysis (COA) based on RSCU proclaimed that thepqqBgenes prefer A/U-ending codons over G/C, while for thepqqEgene, G/C-ending codons are comparatively more preferable (except CGU). Mutational pressure contributes to shaping the codon usage pattern for the selectedpqqgenes evinced from the COAs, while the ENc and neutrality plot gives attestation of natural selection. The higher values of CAI indicate the gene adaptability and codon usage bias. These comprehensive computational studies can be beneficial for further research in molecular phylogenetics, genomics, and proteomics and to better understand the evolutionary dynamics of PQQ.
The Mathematical Structure of Integrated Information Theory
Authors: Kleiner Johannes , Tull Sean
Published: June 2021

Integrated Information Theory is one of the leading models of consciousness. It aims to describe both the quality and quantity of the conscious experience of a physical system, such as the brain, in a particular state. In this contribution, we propound the mathematical structure of the theory, separating the essentials from auxiliary formal tools. We provide a definition of a generalized IIT which has IIT 3.0 of Tononi et al., as well as the Quantum IIT introduced by Zanardi et al. as special cases. This provides an axiomatic definition of the theory which may serve as the starting point for future formal investigations and as an introduction suitable for researchers with a formal background.
Comparative Transcriptome Analysis Demonstrates the Positive Effect of the Cyclic AMP Receptor Protein Crp on Daptomycin Biosynthesis in Streptomyces roseosporus
Authors: Wu Jiequn , Chen Danqing , Wu Jinrong , Chu Xiaohe , Yang Yongmei , Fang Lina , Zhang Wei
Published: June 2021

Daptomycin, which is produced by Streptomyces roseosporus, has been characterized as a novel cyclic lipopeptide antibiotic that is effective against Gram-positive bacteria. The biosynthesis of daptomycin is regulated by various factors. In the present study, we demonstrated that the cyclic AMP receptor protein (Crp) plays an important role in producing daptomycin in the S. roseosporus industrial strain. We found that daptomycin production from the crp deletion strain decreased drastically, whereas production from the crp overexpression strain increased by 22.1%. Transcriptome and qPCR analyses showed that some genes related to the daptomycin biosynthetic gene cluster (dpt) and the pleiotropic regulator (adpA) were significantly upregulated. RNA-seq also shows Crp to be a multifunctional regulator that modulates primary metabolism and enhances precursor flux to secondary metabolite biosynthesis. These results provide guidance for the development and improvement of potential natural products.
Oxytocin Receptor Exon III Methylation in the Umbilical Cord Blood of Newborns With Prenatal Exposure to Crack Cocaine
Authors: Baptista Talita , de Azeredo Lucas Araújo , Zaparte Aline , Viola Thiago Wendt , Coral Sayra Catalina , Nagai Maria Aparecida , Mangone Flávia Rotea , Pavanelli Ana Carolina , Schuch Jaqueline B. , Mardini Victor , Szobot Claudia M. , Grassi-Oliveira Rodrigo
Published: June 2021

Background

Prenatal cocaine exposure (PCE) is associated with behavioral, cognitive, and social consequences in children that might persist into later development. However, there are still few data concerning epigenetic mechanisms associated with the effects of gestational cocaine exposure, particularly in human newborns.

Aims

We investigated the effects of PCE on DNA methylation patterns of the Oxytocin Receptor (OXTR) gene in the umbilical cord blood (UCB). The relationship between UCB DNA methylation levels and the severity of the mother’s cocaine use during pregnancy was also evaluated.

Methods

In this cross-sectional study, 28 UCB samples of newborns with a history of crack cocaine exposure in utero and 30 UCB samples of non-exposed newborns (NEC) were compared for DNA methylation levels at two genomic loci located in exon III of the OXTR gene (OXTR1 and OXTR2) through pyrosequencing. Maternal psychopathology was investigated using the Mini International Neuropsychiatric Interview, and substance use characteristics and addiction severity were assessed using the Smoking and Substance Involvement Screening Test (ASSIST).

Results

No differences between newborns with a history of PCE and NEC were observed in OXTR1 or OXTR2 DNA methylation levels. However, regression analyses showed that maternal addiction severity for crack cocaine use predicted OXTR1 DNA methylation in newborns.

Conclusion

These data suggest that OXTR methylation levels in the UCB of children are affected by the severity of maternal crack cocaine usage. Larger studies are likely to detect specific changes in DNA methylation relevant to the consequences of PCE.
Overexpression of Interferon-Inducible Protein 16 Promotes Progression of Human Pancreatic Adenocarcinoma Through Interleukin-1β-Induced Tumor-Associated Macrophage Infiltration in the Tumor Microenvironment
Authors: Chen Jing-Xian , Cheng Chien-Shan , Gao Hong-Fang , Chen Zi-Jie , Lv Ling-Ling , Xu Jia-Yue , Shen Xiao-Heng , Xie Jing , Zheng Lan
Published: June 2021

Activation of inflammasomes has been reported in human pancreatic adenocarcinoma (PAAD); however, the expression pattern and functional role of inflammasome-related proteins in PAAD have yet to be identified. In this study, we systemically examined the expression and role of different inflammasome proteins by retrieving human expression data. Several genes were found to be differentially expressed; however, only interferon-inducible protein 16 (IFI16) expression was found to be adversely correlated with the overall survival of PAAD patients. Overexpression of IFI16 significantly promoted tumor growth, increased tumor size and weight in the experimental PAAD model of mice, and specifically increased the population of tumor-associated macrophages (TAMs) in the tumor microenvironment. Depletion of TAMs by injection of liposome clodronate attenuated the IFI16 overexpression-induced tumor growth in PAAD. In vitro treatment of conditioned medium from IFI16-overexpressing PAAD cells induced maturation, proliferation, and migration of bone marrow-derived monocytes, suggesting that IFI16 overexpression resulted in cytokine secretion that favored the TAM population. Further analysis suggested that IFI16 overexpression activated inflammasomes, thereby increasing the release of IL-1β. Neutralization of IL-1β attenuated TAM maturation, proliferation, and migration induced by the conditioned medium from IFI16-overexpressing PAAD cells. Additionally, knockdown of IFI16 could significantly potentiate gemcitabine treatment in PAAD, which may be associated with the reduced infiltration of TAMs in the tumor microenvironment. The findings of our study shed light on the role of IFI16 as a potential therapeutic target for PAAD.
Targeting Bruton’s Tyrosine Kinase in Inflammatory and Autoimmune Pathologies
Authors: Neys Stefan F. H. , Hendriks Rudi W. , Corneth Odilia B. J.
Published: June 2021

Bruton’s tyrosine kinase (BTK) was discovered due to its importance in B cell development, and it has a critical role in signal transduction downstream of the B cell receptor (BCR). Targeting of BTK with small molecule inhibitors has proven to be efficacious in several B cell malignancies. Interestingly, recent studies reveal increased BTK protein expression in circulating resting B cells of patients with systemic autoimmune disease (AID) compared with healthy controls. Moreover, BTK phosphorylation following BCR stimulationin vitrowas enhanced. In addition to its role in BCR signaling, BTK is involved in many other pathways, including pattern recognition, Fc, and chemokine receptor signaling in B cells and myeloid cells. This broad involvement in several immunological pathways provides a rationale for the targeting of BTK in the context of inflammatory and systemic AID. Accordingly, numerousin vitroandin vivopreclinical studies support the potential of BTK targeting in these conditions. Efficacy of BTK inhibitors in various inflammatory and AID has been demonstrated or is currently evaluated in clinical trials. In addition, very recent reports suggest that BTK inhibition may be effective as immunosuppressive therapy to diminish pulmonary hyperinflammation in coronavirus disease 2019 (COVID-19). Here, we review BTK’s function in key signaling pathways in B cells and myeloid cells. Further, we discuss recent advances in targeting BTK in inflammatory and autoimmune pathologies.
Roles of Melatonin in Goat Hair Follicle Stem Cell Proliferation and Pluripotency Through Regulating the Wnt Signaling Pathway
Authors: Zhang Weidong , Wang Niu , Zhang Tongtong , Wang Meng , Ge Wei , Wang Xin
Published: June 2021

Emerging studies show that melatonin promotes cashmere development through hypodermic implantation. However, the impact and underlying mechanisms are currently unknown. In vitro study has previously demonstrated that melatonin induces cashmere growth by regulating the proliferation of goat secondary hair follicle stem cells (gsHFSCs), but there is limited information concerning the effects of melatonin on cell pluripotency. It is also known that Wnt signaling may actively participate in regulating cell proliferation and stem cell pluripotency. Therefore, in the current investigation, goat hair follicle stem cells were exposed to multiple concentrations of melatonin and different culture times to reveal the relationship between melatonin and the activation of Wnt signaling. A proportionally high Catenin beta-1 (CTNNB1) response was induced by 500 ng/L of melatonin, but it was then suppressed with the dosages over 1,000 ng/L. Greater amounts of CTNNB1 entered the cell nuclei by extending the exposure time to 72 h, which activated transcription factor 4/lymphoid enhancer-binding factor 1 and promoted the expression of the proliferation-related genes C-MYC, C-JUN, and CYCLIND1. Moreover, nuclear receptor ROR-alpha (RORα) and bone morphogenetic protein 4 (BMP4) were employed to analyze the underlying mechanism. RORα presented a sluggish concentration/time-dependent rise, but BMP4 was increased dramatically by melatonin exposure, which revealed that melatonin might participate in regulating the pluripotency of hair follicle stem cells. Interestingly, NOGGIN, which is a BMP antagonist and highly relevant to cell stemness, was also stimulated by melatonin. These findings demonstrated that melatonin exposure and/or NOGGIN overexpression in hair follicle stem cells might promote the expression of pluripotency markers Homeobox protein NANOG, Organic cation/carnitine transporter 4, and Hematopoietic progenitor cell antigen CD34. Our findings here provided a comprehensive view of Wnt signaling in melatonin stimulated cells and melatonin mediated stemness of gsHFSCs by regulating NOGGIN, which demonstrates a regulatory mechanism of melatonin enhancement on the growth of cashmere.
Preparation and DFT Study for New Three-Ring Supramolecular H-Bonded Induced Liquid Crystal Complexes
Authors: Mohammady Sayed Z. , Aldhayan Daifallah M. , Hagar Mohamed
Published: June 2021

Supramolecular three-ring Schiff base novel liquid crystal complexes have been prepared and investigated. Schiff bases of para-substituted aniline derivatives and para-pyridine carbaldehyde have been prepared and then mixed in equimolar quantities with para-alkoxy benzoic acids. On one side, the alkoxy chain length varies from 8 to 16 carbon atoms. On the other side, terminal small compact groups substituting aniline with various polarities are used. Hydrogen-bonding interaction was elucidated by FTIR spectroscopy. The mesomorphic thermal and optical characteristics of the samples were obtained by differential scanning calorimetry (DSC) and polarized optical microscopy (POM). All samples exhibit enantiotropic mesophases. Experimental results obtained for the induced mesophases were correlated with density functional theory (DFT) theoretical calculations. The results revealed that both the polar compact groups’ polarity and the alkoxy chain lengths contribute strongly to mesomorphic characteristics and thermal stabilities of the mesophases. Surprisingly, the observed values of enthalpy changes associated with the crystalline mesomorphic transitions lie in the range of 2.2–12.5 kJ/mol. However, the enthalpy changes corresponding to the mesomorphic–isotropic transitions vary from 0.9 to 13.9 kJ/mol, depending on the polarity of para-attached groups to the aniline moiety.
Impacts of Heart Failure and Physical Performance on Long-Term Mortality in Old Patients With Chronic Kidney Disease
Authors: Weng Shuo-Chun , Chen Yu-Chi , Hsu Chiann-Yi , Lin Chu-Sheng , Tarng Der-Cherng , Lin Shih-Yi
Published: June 2021

Background: In patients with chronic kidney disease (CKD), physical functional limitations and heart failure (HF) are common, and each is associated with adverse outcomes. However, their joint effects on mortality are not clear.

Design and Methods: Using administration data from the geriatric department in a tertiary hospital, retrospective longitudinal analyses of patients aged ≥65 years with CKD were consecutively enrolled from February 2010 to November 2015. Baseline CKD stages, HF with reduced and preserved ejection fraction (HFrEF and HFpEF), Rockwood frailty index, handgrip strength (HGS), 6-m walking speed, and timed up-and-go test were used to predict the prevalence of frailty, physical disability, and all-cause mortality.

Results: Among 331 old patients with CKD, their mean age was 81.3 ± 6.6 years. CKD stages showed the following distributions: stage 3, 74.9%; stage 4, 15.7%; stage 5, 9.4%. The prevalence of HF was 23.3%, and Rockwood frailty was 74.3%. Rockwood frailty and HF were both significantly associated with CKD stages. After a mean follow-up period of 3.1 ± 2.1 years, 44 patients died, and a crude analysis showed that stage 4, stage 5 CKD, low HGS, and Rockwood frailty index were associated with mortality. Regarding the survival of these patients, the adjusted mortality hazard ratio for CKD stage 5 was 3.84 against stage 3A [95% confidence interval (CI) 1.51–9.75], 1.04 (95% CI 1.01–1.07) for higher Rockwood frailty score, 4.78 (95% CI 1.26–18.11) for HFrEF, and 3.47 (95% CI 1.15–10.42) for low HGS. Survival analysis using Kaplan–Meier survival plots showed that patients with both HF and poor HGS had the poorest survival.

Conclusions: Our study shows that both low physical performance and HF were common in old CKD patients and were associated with CKD stages. HF, frailty, and HGS all independently predicted the mortality of these CKD patients. The mortality is especially high amongst individuals with both HF and decreased HGS.
Weight Change and Mortality Risk in Heart Failure With Preserved Ejection Fraction
Authors: Huang Peisen , Guo Zejun , Liang Weihao , Wu Yuzhong , Zhao Jingjing , He Xin , Zhu Wengen , Liu Chen , Dong Yugang , Yu Yuan , Dong Bin
Published: June 2021

Aims: The aim of the study was to determine the associations of weight loss or gain with all-cause mortality risk in heart failure with preserved ejection fraction (HFpEF).

Methods and Results: Non-lean patients from the Americas from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist study were analyzed (n = 1,515). Weight loss and weight gain were defined as a decrease or increase in weight ≥5% between baseline and 1 year. To determine the associations of weight change and mortality risk, we used adjusted Cox proportional hazards models and restricted cubic spline models. The mean age was 71.5 (9.6) years. Weight loss and gain were witnessed in 19.3 and 15.9% patients, respectively. After multivariable adjustment, weight loss was associated with higher risk of mortality (HR 1.42, 95% CI 1.06–1.89, P = 0.002); weight gain had similar risk of mortality (HR 0.98, 95% CI 0.68–1.42, P = 0.932) compared with weight stability. There was linear relationship between weight change and mortality risk. The association of weight loss and mortality was different for patients with and without diabetes mellitus (interaction p = 0.009).

Conclusion: Among patients with HFpEF, weight loss was independently associated with higher risk of all-cause mortality, and weight gain was not associated with better survival.

Clinical Trial Registration:https://clinicaltrials.gov, Identifier: NCT00094302.
A Novel Homozygous Variant in GJA1 Causing a Hallermann-Streiff/Oculodentodigital Dysplasia Overlapping Phenotype: A Clinical Report
Authors: Jimenez-Armijo Alexandra , Oumensour Khadja , Bousfiha Bouchra , Rey Tristan , Laugel-Haushalter Virginie , Bloch-Zupan Agnès , El Arabi Samira
Published: June 2021

This paper reports the case of a Moroccan girl with a phenotype within the clinical spectrum of both Hallermann-Streiff (HSS, OMIM 234100) and Oculodentodigital Dysplasia (ODDD, OMIM 164200) syndromes. The patient presented with repeated dental abscesses and severe early childhood caries. She had no learning deficit nor psychomotor regression; however, a language delay was noted. She also presented with obstructive sleep apnea syndrome and specific craniofacial features pathognomonic of HSS. Radiographic examination showed enamel and dentin defects, giving a ghost-like tooth appearance. Several clinical features of ODDD overlap those of HSS and may confuse diagnosis, considering that the inheritance of HSS is not described yet. The diagnostic odyssey of this patient ended with the identification by exome sequencing of a novel homozygous alteration in the GJA1 gene. A missense substitution in exon 2 [Chr6(GRCh37): g.121768554C>G NM_000165.4: c.561C>G p.Cys187Trp] was identified by whole-exome sequencing (WES), suggesting a diagnosis of ODDD. This is the first report of a homozygous mutation affecting the second extracellular loop of the CX43 protein.
Evidence That Non-Syndromic Familial Tall Stature Has an Oligogenic Origin Including Ciliary Genes
Authors: Weiss Birgit , Eberle Birgit , Roeth Ralph , de Bruin Christiaan , Lui Julian C. , Paramasivam Nagarajan , Hinderhofer Katrin , van Duyvenvoorde Hermine A. , Baron Jeffrey , Wit Jan M. , Rappold Gudrun A.
Published: June 2021

Human growth is a complex trait. A considerable number of gene defects have been shown to cause short stature, but there are only few examples of genetic causes of non-syndromic tall stature. Besides rare variants with large effects and common risk alleles with small effect size, oligogenic effects may contribute to this phenotype. Exome sequencing was carried out in a tall male (height 3.5 SDS) and his parents. Filtered damaging variants with high CADD scores were validated by Sanger sequencing in the trio and three other affected and one unaffected family members. Network analysis was carried out to assess links between the candidate genes, and the transcriptome of murine growth plate was analyzed by microarray as well as RNA Seq. Heterozygous gene variants in CEP104, CROCC, NEK1, TOM1L2, and TSTD2 predicted as damaging were found to be shared between the four tall family members. Three of the five genes (CEP104, CROCC, and NEK1) belong to the ciliary gene family. All genes are expressed in mouse growth plate. Pathway and network analyses indicated close functional connections. Together, these data expand the spectrum of genes with a role in linear growth and tall stature phenotypes.
From Endoderm to Progenitors: An Update on the Early Steps of Thyroid Morphogenesis in the Zebrafish
Authors: Marelli Federica , Rurale Giuditta , Persani Luca
Published: June 2021

The mechanisms underlying thyroid gland development have a central interest in biology and this review is aimed to provide an update on the recent advancements on the early steps of thyroid differentiation that were obtained in the zebrafish, because this teleost fish revealed to be a suitable organism to study the early developmental stages. Physiologically, the thyroid precursors fate is delineated by the appearance among the endoderm cells of the foregut of a restricted cell population expressing specific transcription factors, including pax2a, nkx2.4b, and hhex. The committed thyroid primordium first appears as a thickening of the pharyngeal floor of the anterior endoderm, that subsequently detaches from the floor and migrates to its final location where it gives rise to the thyroid hormone-producing follicles. At variance with mammalian models, thyroid precursor differentiation in zebrafish occurs early during the developmental process before the dislocation to the eutopic positioning of thyroid follicles. Several pathways have been implicated in these early events and nowadays there is evidence of a complex crosstalk between intrinsic (coming from the endoderm and thyroid precursors) and extrinsic factors (coming from surrounding tissues, as the cardiac mesoderm) whose organization in time and space is probably required for the proper thyroid development. In particular, Notch, Shh, Fgf, Bmp, and Wnt signaling seems to be required for the commitment of endodermal cells to a thyroid fate at specific developmental windows of zebrafish embryo. Here, we summarize the recent findings produced in the various zebrafish experimental models with the aim to define a comprehensive picture of such complicated puzzle.
Precision Medicine in Graves’ Disease: CD40 Gene Variants Predict Clinical Response to an Anti-CD40 Monoclonal Antibody
Authors: Faustino Larissa C. , Kahaly George J. , Frommer Lara , Concepcion Erlinda , Stefan-Lifshitz Mihaela , Tomer Yaron
Published: June 2021

Background

CD40, a key co-stimulatory molecule expressed on antigen-presenting cells, is genetically associated with a number of autoimmune diseases including Graves’ disease (GD). Therefore, recent therapies targeting CD40 have been developed, including the anti-CD40 monoclonal antibody Iscalimab. In a recent pilot study, Iscalimab was shown to induce clinical remission in ~ 50% of GD patients, but the reason why only 50% of GD patients responded is not known. The aim of our study was to test the hypothesis that specific CD40 single nucleotide polymorphism (SNP) genotypes and haplotypes are associated with clinical response of GD patients to Iscalimab.

Methods

We extracted genomic DNA from the whole blood of 13 GD patients treated with Iscalimab, and genotyped seven CD40 single nucleotide polymorphisms (SNPs) associated with autoimmunity. Additionally, we analyzed CD40 mRNA expression levels in whole blood. The patients’ CD40 SNP genotypes and mRNA levels were tested for association with clinical response to Iscalimab.

Results

Three common haplotypes, designated haplotypes A, B, and C, were identified. Haplotypes B and C were associated with higher CD40 mRNA levels and clinical response to Iscalimab (i.e., patients achieving euthyroidism without need for additional medications), while haplotype A was associated with decreased CD40 mRNA levels and no response to Iscalimab.

Conclusion

Our data suggest that genetic polymorphisms in the CD40 gene drive its expression levels and response to Iscalimab. Polymorphisms associated with higher CD40 levels are also associated with clinical response to CD40-targeted therapies. These results set the stage to implementing precision medicine in the therapeutic approach to GD.
Evaluating the Role of Social Norms in Fostering Pro-Environmental Behaviors
Authors: Perry George L.W. , Richardson Sarah J. , Harré Niki , Hodges Dave , Lyver Phil O’B. , Maseyk Fleur J.F. , Taylor Riki , Todd Jacqui H. , Tylianakis Jason M. , Yletyinen Johanna , Brower Ann
Published: June 2021

Human activity is changing the biosphere in unprecedented ways, and addressing this challenge will require changes in individual and community patterns of behavior. One approach to managing individual behaviors is “top-down” and involves imposing sanctions through legislative frameworks. However, of itself, a top-down framework does not appear sufficient to encourage the changes required to meet environmental sustainability targets. Thus, there has been interest in changing individual-level behavior from the “bottom-up” by, for example, fostering desirable pro-environmental behaviors via social norms. Social norms arise from expectations about how others will behave and the consequences of conforming to or departing from them. Meta-analyses suggest that social norms can promote pro-environmental behavior. Environmental social norms that appear to have changed in recent decades and have themselves promoted change include recycling, include nascent behavioral shifts such as the move away from single-use plastics and flight shaming (flygskam). However, whether the conditions under which pro-environmental social norms emerge and are adhered to align with environmental systems’ features is unclear. Furthermore, individuals might feel powerless in a global system, which can limit the growth and influence of pro-environmental norms. We review the conditions believed to promote the development of and adherence to social norms, then consider how those conditions relate to the environmental challenges of the Anthropocene. While promoting social norms has a valuable role in promoting pro-environmental actions, we conclude that norms are most likely to be effective where individual actions are immediately evident and have an obvious and local effect.
Leveraging Biodiversity Action From Plural Values: Transformations of Governance Systems
Authors: Leventon Julia , Duşe Ioana A. , Horcea-Milcu Andra-Ioana
Published: June 2021

In this paper, we argue that leveraging plural values into action for biodiversity requires a focus on transforming the biodiversity governance system. We draw on Donella Meadows’ concept of Leverage Points, which outlines the “depth” of intervention in order to shift a system toward sustainability. Engaging with deep leverage points (system intent and goals) is argued to lead to greater transformation than engaging with shallow leverage points (system design and materials). We outline how embracing plural values of biodiversity requires changes at deeper systems properties within governance systems to create space to reflect diversity in values and knowledge systems, and move away from a focus on commodification of nature’s contributions to people. We point toward political and policy sciences to highlight frameworks and concepts for understanding governance system transformation. We conclude with a call for meaningful engagement with such sciences in ongoing research.