bluuebunny/crossref_metadata_2025 huggingface dataset:
Levels and sources of manganese on bone performance and resistance in broilers
Authors: Bassi Guilherme Santos , Lara Leonardo José Camargos , Araújo Itallo Conrado Sousa , Ferreira Vanusa Patrícia de Araújo , Barbosa Hítalo José Santos , Sousa Lorena Salim de , Costa Bruno Teixeira Antunes
Published: March 2021

O objetivo desse estudo foi determinar o nível ideal de suplementação de manganês (Mn) para frangos de corte. Foram realizados dois experimentos, um avaliando uma fonte quelatada (aminoacídico) e o outro uma fonte inorgânica (óxido) que garanta melhor desempenho e qualidade óssea necessária, para suportar o processo de crescimento, pega, transporte e abate. O período experimental foi de um a 35 dias de idade das aves, onde foram utilizados 1260 frangos de corte machos da linhagem Cobb®. Os tratamentos foram definidos pela suplementação de 0, 35, 70, 105 mg de Mn/kg de ração na forma inorgânica ou quelatada do mineral. A ocorrência de lesões ou fraturas ósseas foi observada desde a apanha das aves até a linha de abate e não foi observada nenhuma incidência de lesões ósseas. As estimativas da exigência de Mn para frangos de corte para a máxima concentração desse micromineral e do Ca no fêmur foram, respectivamente, 57,36 mg de Mn/kg e 81,07 mg/kg de suplementação na forma inorgânica. Para os níveis de suplementação do Mn quelatado, a estimativa da exigência foi de 73,13 mg de Mn/kg para a máxima concentração de Ca no fêmur, não apresentando diferenças para a concentração de Mn nesse mesmo tecido ósseo. Os demais parâmetros de desempenho e qualidade óssea avaliada não apresentaram diferenças para ambas as fontes estudadas. Portanto, não há necessidade de suplementação de Mn em uma dieta a base de milho e farelo de soja, para frangos de corte.
Padrões do sono na população pantaneira
Authors: Gaudioso Carlos Eduardo Vilela , Magna Luis Alberto , Souza José Carlos , Mônaco Daniela Vicimansa
Published: March 2021

Introdução: o sono é vital, caracterizado como um conjunto de alterações comportamentais e fisiológicas. A pesquisa foi realizada numa população rural, isolada, pantaneira, residente na maior planície alagada do planeta. Objetivos: Identificar os padrões do sono na população pantaneira. Método: Estudo quantitativo, descritivo, analítico, de corte transversal e comparativo, o total da amostra foi de 789 participantes, distribuídos em população rural (25%) e urbana (75%). Para a análise foi utilizado métodos de estatística descritiva, com estimativa de proporções e correspondente erro-padrão da média. A análise univariada consistiu em comparação de proporções pelo teste qui-quadrado e comparação de médias. O ajuste à distribuição normal foi aferido por teste não paramétrico. Resultados: Constatou-se aumento significativo da proporção de alteração do sono com o aumento da faixa etária, diminuindo com o aumento do nível de escolaridade. As alterações do sono ocorreram em maior proporção entre as mulheres, entre aquelas que têm escolaridade até o ensino médio, que possuem maior número de filhos. Conclusão: A divulgação destes achados é essencial para a promoção da saúde integral do pantaneiro, visando superar problemas relacionados ao sono e à qualidade de vida.
Grupos educativos sobre aleitamento: saberes de gestantes
Authors: Farias Ana Luiza Amancio de , Boller Carlos Eduardo Pessanha , Lopes Fernanda de Oliveira , Santos Priscila Barbosa dos , Ribeiro Antonio da Silva , Bento Paulo Alexandre de Souza São
Published: March 2021

Esta pesquisa objetivou identificar saberes prévios e avaliar os conhecimentos construídos considerando a participação em grupos educativos sobre aleitamento materno, assim como, analisar as interações, entre profissionais e gestantes, que propiciam a construção deste conhecimento a partir dos grupos. A pesquisa de avaliação diagnóstica, processual e somativa foi o método proposto e realizada com 90 gestantes participantes de um grupo educativo em um Banco de Leite Humano, no Rio de Janeiro. Os resultados analisados mostram que as gestantes construíram conhecimentos sobre o assunto (51,1%), algumas mantiveram saberes que já possuíam (36,6%) e na menor parte (12,2%) houve desconstrução de saberes. A complexidade do tema e as lacunas presentes na realização dos grupos orientaram a discussão. Como considerações finais propõe-se um deslocamento da educação bancária para a construtivista, priorizando uma pauta simplificada contendo informações elementares, permitindo que estes assuntos sejam tratados na medida em que são demandados.
As mídias alternativas ChanacomChana e Lampião da Esquina: uma trajetória de resistência, identidade e visibilidade
Authors: Eddine Eder Ahmad Charaf , Sena Aline de Jesus , Rodrigues José Eduardo de Azevedo Gomes , Lima Thamires Rosa Costa
Published: March 2021

Algumas mídias alternativas foram importantes instrumentos de resistência em um Brasil que estava em plena ditadura civil e militar (1964-1985). Vários grupos minoritários foram considerados subversivos e acusados de tentarem contra a moral e os bons costumes. Entre eles pode-se encontrar aqueles formados por gays, lésbicas, travestis e transexuais. Alguns grupos políticos compostos por populações excluídas foram criados para combater essas formas de opressão e para dar visibilidade a suas causas, como o GALF – Grupo de Ação Lésbico-Feminista e o grupo SOMOS. Esse período foi devastador para as questões de liberdades individuais, principalmente para a população e o movimento LGBT. A criação de mídias alternativas como o jornal Lampião da Esquina (1978-1981) e o boletim ChanacomChana (1981-1987), que apresentavam questões relacionadas ao cotidiano, às artes e a política, foi um passo importante na luta para o reconhecimento dessa população. O objetivo desse trabalho é fazer e analisar a revisão narrativa de literatura sobre os dois periódicos, para tanto realizamos a busca nos bancos de dados Scielo, BDTD e Periódicos Capes. Os descritores foram: Lampião da Esquina, Chana com Chana e Chanacomchana. Retornaram 20 teses e dissertações e 20 artigos baseados nesses descritores. Após quantificação e categorização dos resultados observa-se poucos os estudos sobre o boletim ChanacomChana, uma tese e um artigo. As pesquisas elencadas analisam os periódicos como processos de resistências, visibilidade/invisibilidade trans, gay e lésbica, identidades, corpo e literatura.
As estratégias para avaliação de aprendizagem empregadas em estudantes de enfermagem de ensino superior: revisão integrativa
Authors: Ribeiro Beatriz Queiroz , Tiroli Carla Fernanda , Bolorino Natacha , Souza Ana Beatriz Floriano de , González Alberto Durán , Dellaroza Mara Solange Gomes , Freitas Franciely Midori Bueno de , Ferreira Natalia Marciano de Araújo , Ribeiro Laís Cristina Gonçalves , Montanha Rafaela Marioto , Pereira Denise Andrade , Stieven Ariane Sabina , Pieri Flávia Meneguetti
Published: March 2021

Foi realizada uma revisão integrativa, com objetivo de identificar quais as estratégias para a avaliação de aprendizagem estão sendo empregadas aos estudantes de enfermagem de ensino superior. A pesquisa foi norteada pela estratégia PICO: qual a efetividade de intervenções avaliativas disponíveis na literatura científica sobre as estratégias para avaliação de aprendizagem aplicadas aos estudantes de enfermagem do nível superior? A busca por estudos foi realizada entre janeiro e fevereiro de 2019 nas seguintes bases de dados: LILACS, Medline, Scielo, BDENF, PubMed, CINAHL e Scopus.  Foram incluídas 24 referências e identificadas 8 estratégias de avaliação. A maioria citou avaliação em práticas, seguida de feedback, avaliação teórica, avaliação interpares, autoavaliação, avaliação de trabalho em grupo e por último avaliação qualitativa. Observou-se que 75% (n=18) dos estudos inclusos foram realizados fora do cenário brasileiro. Dos estudos internacionais, 20,8% estão concentrados no Reino Unido, 12,5% em Hong Kong e 12,5% na Irlanda. No Brasil, os estudos se concentraram na região sudeste, com 12,5% em São Paulo e 8,3% em Minas Gerais. Quanto ao método utilizado, 66% dos artigos foram de abordagem qualitativa, 20,8% utilizaram de método quantitativo e 20,8% empregaram método misto, com abordagem quantitativa e qualitativa. Por fim, este estudo identificou como os principais instrumentos de avaliação usados no ensino superior de enfermagem: avaliação em práticas, feedback, portfólio, avaliação teórica, avaliação interpares, autoavaliação, avaliação de trabalho em grupo e avaliação qualitativa. Sugere-se a realização de estudos nacionais, a fim de ampliar as discussões e aprimorar as técnicas de avaliações aplicadas.
Exhibiting Transformative Fashion: Digital Interventions to Enhance Display and Interpretation
Authors: Yeo Pearline
Published: March 2021

While the issues of displaying fashion in motion in museum exhibitions have been addressed with various interventions to animate displays, the challenge of successfully presenting transformative fashion in exhibitions has received less attention. With more contemporary designers creating conceptual fashion that is transformative and technological in nature, this article discusses a research project that proposes a series of digital interventions to best display these garments. With the use of digital technology in fashion exhibitions becoming commonplace, this article aims to explore this application and the ways in which it can be used to greater effect to enhance the performance of transformation in the presentation of fashion. The use of digital technology to improve and advance opportunities for inclusivity and accessibility in reading fashion in exhibitions will also be demonstrated.
Suggestion Theory Across the Disciplines: The History of Communication Research Before Communication Research
Authors: Pooley Jefferson
Published: March 2021

This is a solicited commentary on a forthcoming monograph by Patrick Parsons, "The Lost Doctrine: Suggestion Theory in Early Media Effects Research," to be published in Journalism & Mass Communication Monographs.
An Overview on the Therapeutics of Neglected Infectious Diseases—Leishmaniasis and Chagas Diseases
Authors: J Brindha , M Balamurali M. , Chanda Kaushik
Published: March 2021

Neglected tropical diseases (NTDs) as termed by WHO include twenty different infectious diseases that are caused by bacteria, viruses, and parasites. Among these NTDs, Chagas disease and leishmaniasis are reported to cause high mortality in humans and are further associated with the limitations of existing drugs like severe toxicity and drug resistance. The above hitches have rendered researchers to focus on developing alternatives and novel therapeutics for the treatment of these diseases. In the past decade, several target-based drugs have emerged, which focus on specific biochemical pathways of the causative parasites. For leishmaniasis, the targets such as nucleoside analogs, inhibitors targeting nucleoside phosphate kinases of the parasite’s purine salvage pathway, 20S proteasome of Leishmania, mitochondria, and the associated proteins are reviewed along with the chemical structures of potential drug candidates. Similarly, in case of therapeutics for Chagas disease, several target-based drug candidates targeting sterol biosynthetic pathway (C14-ademethylase), L-cysteine protease, heme peroxidation, mitochondria, farnesyl pyrophosphate, etc., which are vital and unique to the causative parasite are discussed. Moreover, the use of nano-based formulations towards the therapeutics of the above diseases is also discussed.
Helicobacter hepaticus Induce Colitis in Male IL-10−/− Mice Dependent by Cytolethal Distending Toxin B and via the Activation of Jak/Stat Signaling Pathway
Authors: Zhu Liqi , Zhu Chen , Cao Shuyang , Zhang Quan
Published: March 2021

It has been well documented that cytolethal distending toxin (CDT) from Helicobacter hepaticus (H. hepaticus), Campylobacter jejuni (C. jejuni) and other Gram-negative intestinal pathogens is linked to the inflammatory bowel disease (IBD). However, the mechanisms underlying the progression of H. hepaticus induced colitis remains unclear. In this study, male B6.129P2-IL10tm1Cgn/J mice were infected by H. hepaticus and ΔCdtB H. hepaticus for 6, 12, 18, and 24 weeks. Histopathology, H. hepaticus colonization levels, expression of inflammatory cytokines, signaling pathways, and content of NO in proximal colon were examined. We found that Cytolethal distending toxin subunit B (CdtB) deletion had no influence on colonization ability of H. hepaticus in colon of B6.129P2-IL10tm1cgn/J mice, and there was no significant difference in abundance of colonic H. hepaticus over infection duration. H. hepaticus aggravated rectocele and proximal colonic inflammation, especially at 24 WPI, while ΔCdtB H. hepaticus could not cause significant symptom. Furthermore, mRNA levels of Il-6, Tnf-α, Il-1β, and iNOS significantly increased in the proximal colon of H. hepaticus-infected mice compared to ΔCdtB H. hepaticus infected group from 12 WPI to 24 WPI. In addition, the elevated content of NO and activated Stat3 and Jak2 in colon were observed in H. hepaticus infected mice. These data demonstrated that CdtB promote colitis development in male B6.129P2-IL10tm1Cgn/J mice by induction of inflammatory response and activation of Jak-Stat signaling pathway.
The Association Between Metformin Treatment and Outcomes in Type 2 Diabetes Mellitus Patients With Heart Failure With Preserved Ejection Fraction: A Retrospective Study
Authors: Wang Jianfang , Lu Yi , Min Xinjia , Yuan Tan , Wei Jia , Cai Zhejun
Published: March 2021

Background: Metformin is the first-line antidiabetic medication for type 2 diabetes mellitus (T2DM). However, the association between metformin and outcomes in T2DM patients with heart failure with preserved ejection fraction (HFpEF) is still unknown. We aimed to explore the association between metformin and adverse outcome in T2DM patients with HFpEF.

Methods: A total of 372 T2DM patients with HFpEF hospitalized from January 1, 2013, to December 31, 2017, were included in this retrospective cohort study. There were 113 and 259 subjects in metformin and non-metformin group, respectively. Subjects were followed up for all-cause mortality, cardiovascular death, all-cause hospitalization, and heart failure hospitalization.

Results: The median follow-up period was 47 months. Eleven patients (2.49% per patient-year) in the metformin group and 56 patients (5.52% per patient-year) in the non-metformin group deceased during follow-up (P = 0.031). However, a multivariable Cox regression failed to show that metformin was an independent factor of all-cause mortality [HR (95% CI) = 0.682 (0.346–1.345); P = 0.269]. A subgroup analysis revealed a significant association between metformin and all-cause mortality in patients with a higher hemoglobin A1c (HbA1c) level (HbA1c ≥7%) [HR (95% CI) = 0.339 (0.117–0.997); P = 0.045]. The 4-year estimated number needed to treat (NNT) with metformin compared with non-metformin for all-cause mortality was 12 in all populations and 8 in the HbA1c ≥7% subgroup.

Conclusions: Metformin was not independently associated with clinical outcomes in patients with T2DM and HFpEF, but was associated with lower all-cause mortality in the subgroup of patients with poor glycemic control. Prospective, randomized controlled trials are needed to further verify these findings.
Long Noncoding RNA X-Inactive-Specific Transcript Promotes the Secretion of Inflammatory Cytokines in LPS Stimulated Astrocyte Cell Via Sponging miR-29c-3p and Regulating Nuclear Factor of Activated T cell 5 Expression
Authors: Zhang Mengqi , Yang Haojun , Chen Zhuohui , Hu Xinhang , Wu Tong , Liu Weiping
Published: March 2021

Background

Astrocyte activation promotes glutamate accumulation and secretion of inflammatory factors, mainly responsible for epilepsy. Long noncoding RNA (lncRNA) X-inactive-specific transcript (XIST) regulates inflammation; however, the biological role and regulatory mechanism of XIST during astrocyte activation remain unclear.

Methods

In the present study, rat epilepsy model and lipopolysaccharide (LPS)-treated CTX-TNA2 were established. XIST and miR-29c-3p expression were evaluated using quantitative real-time polymerase chain reaction. Nuclear factor of activated T cells 5 (NFAT5) was measured using western blot analysis. Interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and L-glutamate levels in the culture supernatants were assessed using enzyme-linked immunosorbent assay. The binding between XIST and miR-29c-3p and between miR-29c-3p and the 3′-UTR of NFAT5 was analyzed using dual-luciferase reporter, RNA-binding protein immunoprecipitation (RIP), and Biotin pull-down assay. The proliferation and apoptosis were evaluated using CCK8 and flow cytometry, respectively.

Results

XIST expression and NFAT5 protein level was increased, whereas miR-29c-3p expression was decreased in the epilepsy rat model and LPS-treated CTX-TNA2 cells. Silenced XIST expression, miR-29c-3p overexpression, or silenced NFAT5 expression inhibited the secretion of IL-1β, IL-6, and TNF-α and promoted glutamate transport in LPS-treated CTX-TNA2 cells. miR-29c-3p was the potential miRNA sponged by XIST. NFAT5 acted as a direct binding target of miR-29c-3p. Silenced miR-29c-3p expression or NFAT5 overexpression reversed the effect of silenced XIST expression on LPS-treated CTX-TNA2.XIST and miR-29c-3p treatment does not affect NFAT5 mRNA expression, but affects NFAT5 protein level. Furthermore, underexpressed XIST or overexpressed miR-29c-3p in LPS-stimulated CTX-TNA2 can attenuate neuronal apoptosis induced by LPS-stimulated CTX-TNA2.

Conclusion

LncRNA XIST promotes the secretion of inflammatory cytokines in LPS- treated CTX-TNA2 via sponging miR-29c-3p and regulating NFAT5 expression.
Motivational Interviewing and Glycemic Control in Adolescents With Poorly Controlled Type 1 Diabetes: A Randomized Controlled Pilot Trial
Authors: Tuomaala Anna-Kaisa , Hero Matti , Tuomisto Martti T. , Lähteenmäki Maria , Miettinen Päivi J. , Laine Tiina , Wehkalampi Karoliina , Kiiveri Sanne , Ahonen Pekka , Ojaniemi Marja , Kaunisto Kari , Tossavainen Päivi , Lapatto Risto , Sarkola Taisto , Pulkkinen Mari-Anne
Published: March 2021

A multicenter randomized controlled pilot trial investigated whether motivational interviewing (MI) by diabetes physicians improves glycemic control and variability in the context of follow-up for adolescent patients with poorly controlled type 1 diabetes. Patients (n = 47) aged 12 to 15.9 years who showed poor glycemic control (HbA1c >75 mmol/mol/9.0%) were randomized to standard education (SE) only or MI+SE, with study physicians randomized to employ MI+SE (N = 24 patients) or SE only (N = 23). For one year of follow-up, the main outcome measurements were obtained at three-month visits (HbA1c) or six-monthly: time in range (TIR) and glycemic variability (CV). Mean adjusted 12-month change in HbA1c was similar between the MI+SE and SE-only group (-3.6 vs. -1.0 mmol/mol), and no inter-group differences were visible in the mean adjusted 12-month change in TIR (-0.8 vs. 2.6%; P = 0.53) or CV (-0.5 vs. -6.2; P = 0.26). However, the order of entering the study correlated significantly with the 12-month change in HbA1c in the MI+SE group (r = -0.5; P = 0.006) and not in the SE-only group (r = 0.2; P = 0.4). No link was evident between MI and changes in quality of life. The authors conclude that MI’s short-term use by diabetes physicians managing adolescents with poorly controlled type 1 diabetes was not superior to SE alone; however, improved skills in applying the MI method at the outpatient clinic may produce greater benefits in glycemic control.
Participatory Use of a Tool to Assess Governance for Sustainable Landscapes
Authors: Peteru Swetha , Duchelle Amy E. , Stickler Claudia , Durbin Joanna , Luque Cecilia , Komalasari Mella
Published: March 2021

Sustainable management of resources is crucial for balancing competing livelihood, economic, and environmental goals. Since forests and other systems do not exist in isolation, comprehensive jurisdictional approaches to forest, and land-use governance can help promote sustainability. The ability of jurisdictions to provide evidence of progress toward sustainability is essential for attracting public and private sector investments and maintaining local stakeholder involvement. The Sustainable Landscapes Rating Tool (SLRT) provides a way to assess enabling conditions for jurisdictional sustainability through an evidence-based rating system. We applied this rating tool in 19 states and provinces across six countries (Brazil, Ecuador, Indonesia, Cote d'Ivoire, Mexico, Peru) that are members of the Governors' Climate and Forests Task Force (GCF TF). Each SLRT assessment was completed using publicly available information, interviews with stakeholders in the jurisdiction, and a multi-stakeholder workshop to validate the indicator ratings. This paper explores the effects of stakeholder involvement in the validation process, along with stakeholder perceptions of the tool's usefulness. Our analysis shows that the validation workshops often led to modifications of the indicator ratings, even for indicators originally assessed using publicly available data, highlighting the gap between existence of a policy and its implementation. Also, a more diverse composition of stakeholders at the workshops led to more changes in indicator ratings, which indicates the importance of including different perspectives in compiling and validating the assessments. Overall, most participants agreed that the tool is useful for self-assessment of the jurisdiction and to address coordination gaps. Further, the validation workshops provided a space for discussions across government agencies, civil society organizations (CSOs), producer organizations, indigenous peoples and local community representatives, and researchers about improving policy and governance conditions. Our findings from the analysis of a participatory approach to collecting and validating data can be used to inform future research on environmental governance and sustainability.
RRM2B Is Frequently Amplified Across Multiple Tumor Types: Implications for DNA Repair, Cellular Survival, and Cancer Therapy
Authors: Iqbal Waleed , Demidova Elena V. , Serrao Samantha , ValizadehAslani Taha , Rosen Gail , Arora Sanjeevani
Published: March 2021

RRM2B plays a crucial role in DNA replication, repair and oxidative stress. While germline RRM2B mutations have been implicated in mitochondrial disorders, its relevance to cancer has not been established. Here, using TCGA studies, we investigated RRM2B alterations in cancer. We found that RRM2B is highly amplified in multiple tumor types, particularly in MYC-amplified tumors, and is associated with increased RRM2B mRNA expression. We also observed that the chromosomal region 8q22.3–8q24, is amplified in multiple tumors, and includes RRM2B, MYC along with several other cancer-associated genes. An analysis of genes within this 8q-amplicon showed that cancers that have both RRM2B-amplified along with MYC have a distinct pattern of amplification compared to cancers that are unaltered or those that have amplifications in RRM2B or MYC only. Investigation of curated biological interactions revealed that gene products of the amplified 8q22.3–8q24 region have important roles in DNA repair, DNA damage response, oxygen sensing, and apoptosis pathways and interact functionally. Notably, RRM2B-amplified cancers are characterized by mutation signatures of defective DNA repair and oxidative stress, and at least RRM2B-amplified breast cancers are associated with poor clinical outcome. These data suggest alterations in RR2MB and possibly the interacting 8q-proteins could have a profound effect on regulatory pathways such as DNA repair and cellular survival, highlighting therapeutic opportunities in these cancers.
Long Non-coding RNA GAS5 Regulates T Cell Functions via miR21-Mediated Signaling in People Living With HIV
Authors: Nguyen Lam Ngoc Thao , Nguyen Lam Nhat , Zhao Juan , Schank Madison , Dang Xindi , Cao Dechao , Khanal Sushant , Chand Thakuri Bal Krishna , Lu Zeyuan , Zhang Jinyu , Li Zhengke , Morrison Zheng D. , Wu Xiao Y. , El Gazzar Mohamed , Ning Shunbin , Wang Ling , Moorman Jonathan P. , Yao Zhi Q.
Published: March 2021

T cells are critical for the control of viral infections and T cell responses are regulated by a dynamic network of non-coding RNAs, including microRNAs (miR) and long non-coding RNAs (lncRNA). Here we show that an activation-induced decline of lncRNA growth arrest-specific transcript 5 (GAS5) activates DNA damage response (DDR), and regulates cellular functions and apoptosis in CD4 T cells derived from people living with HIV (PLHIV) via upregulation of miR-21. Notably, GAS5-miR21-mediated DDR and T cell dysfunction are observed in PLHIV on antiretroviral therapy (ART), who often exhibit immune activation due to low-grade inflammation despite robust virologic control. We found that GAS5 negatively regulates miR-21 expression, which in turn controls critical signaling pathways involved in DNA damage and cellular response. The sustained stimulation of T cells decreased GAS5, increased miR-21 and, as a result, caused dysfunction and apoptosis in CD4 T cells. Importantly, this inflammation-driven T cell over-activation and aberrant apoptosis in ART-controlled PLHIV and healthy subjects (HS) could be reversed by antagonizing the GAS5-miR-21 axis. Also, mutation of the miR-21 binding site on exon 4 of GAS5 gene to generate a GAS5 mutant abolished its ability to regulate miR-21 expression as well as T cell activation and apoptosis markers compared to the wild-type GAS5 transcript. Our data suggest that GAS5 regulates TCR-mediated activation and apoptosis in CD4 T cells during HIV infection through miR-21-mediated signaling. However, GAS5 effects on T cell exhaustion during HIV infection may be mediated by a mechanism beyond the GAS5-miR-21-mediated signaling. These results indicate that targeting the GAS5-miR-21 axis may improve activity and longevity of CD4 T cells in ART-treated PLHIV. This approach may also be useful for targeting other infectious or inflammatory diseases associated with T cell over-activation, exhaustion, and premature immune aging.
Evaluation of Immune and Vaccine Competence in Steroid-Sensitive Nephrotic Syndrome Pediatric Patients
Authors: Colucci Manuela , Piano Mortari Eva , Zotta Federica , Corrente Francesco , Concato Carlo , Carsetti Rita , Emma Francesco , Vivarelli Marina
Published: March 2021

Idiopathic nephrotic syndrome is a childhood renal disease characterized by a damage of the glomerular filtration barrier leading to an intense leakage of proteins into the urine. This severe proteinuria causes a transient but strong reduction of serum IgG. Therefore, evaluation of vaccine competence by measuring serum levels of protective antibodies can be misleading in nephrotic syndrome, especially during the active phase of disease. To overcome this issue, in parallel to measuring serum antigen-specific IgG, we quantified by ELISPOT the number of antigen-specific memory B cells induced by previous immunization with tetanus and hepatitis B virus (HBV) in 11 steroid-sensitive nephrotic syndrome (SSNS) pediatric patients at onset before any immunosuppressive treatment (mean age 5.1±0.9 years). Five age-matched children with non-immunomediated nephro-urologic disorders were also enrolled as controls (mean age 6.9±2.3 years). Low total serum IgG levels (<520 mg/dl) were found in all the analyzed SSNS patients. In parallel, median levels of anti-tetanus and anti-HBV IgG were significantly reduced compared to controls [0.05 (0.03–0.16) vs. 0.45 (0.29–3.10) IU/ml and 0.0 (0.0–0.5) vs. 30.3 (5.5–400.8) mIU/ml, respectively; p = 0.02 for both], with serum IgG titers below protective threshold in 7/11 SSNS patients for tetanus and in 9/11 SSNS patients for HBV. In contrast, all SSNS patients had a competent B-cell response, showing an amount of total IgG-secreting B cells >1,000 counts/106 stimulated cells. The amount of anti-tetanus and anti-HBV IgG-secreting B cells was also comparable to that of controls (p = 0.24, p = 0.32, respectively), with a frequency of memory anti-tetanus and anti-HBV IgG secreting B cells >0.1% of total IgG secreting B cells. In conclusion, SSNS children at disease onset pre-immunosuppressive therapy showed a competent immune and vaccine response against tetanus and HBV, which can be correctly evaluated by quantification of antigen-specific memory B cells rather than by measuring serum IgG levels. This approach allows early identification of the impairment of immune and vaccine competence, which may derive from protracted use of different immunosuppressive drugs during disease course.
Deep Phenotyping of CD11c+ B Cells in Systemic Autoimmunity and Controls
Authors: Rincon-Arevalo Hector , Wiedemann Annika , Stefanski Ana-Luisa , Lettau Marie , Szelinski Franziska , Fuchs Sebastian , Frei Andreas Philipp , Steinberg Malte , Kam-Thong Tony , Hatje Klas , Keller Baerbel , Warnatz Klaus , Radbruch Andreas , Lino Andreia C. , Schrezenmeier Eva , Dörner Thomas
Published: March 2021

Circulating CD11c+ B cells are a key phenomenon in certain types of autoimmunity but have also been described in the context of regular immune responses (i.e., infections, vaccination). Using mass cytometry to profile 46 different markers on individual immune cells, we systematically initially confirmed the presence of increased CD11c+ B cells in the blood of systemic lupus erythematosus (SLE) patients. Notably, significant differences in the expression of CD21, CD27, and CD38 became apparent between CD11c− and CD11c+ B cells. We observed direct correlation of the frequency of CD21−CD27− B cells and CD21−CD38− B cells with CD11c+ B cells, which were most pronounced in SLE compared to primary Sjögren's syndrome patients (pSS) and healthy donors (HD). Thus, CD11c+ B cells resided mainly within memory subsets and were enriched in CD27−IgD−, CD21−CD27−, and CD21−CD38− B cell phenotypes. CD11c+ B cells from all donor groups (SLE, pSS, and HD) showed enhanced CD69, Ki-67, CD45RO, CD45RA, and CD19 expression, whereas the membrane expression of CXCR5 and CD21 were diminished. Notably, SLE CD11c+ B cells showed enhanced expression of the checkpoint molecules CD86, PD1, PDL1, CD137, VISTA, and CTLA-4 compared to HD. The substantial increase of CD11c+ B cells with a CD21− phenotype co-expressing distinct activation and checkpoint markers, points to a quantitative increased alternate (extrafollicular) B cell activation route possibly related to abnormal immune regulation as seen under the striking inflammatory conditions of SLE which shows a characteristic PD-1/PD-L1 upregulation.
Mini Review Immunological Consequences of Immunization With COVID-19 mRNA Vaccines: Preliminary Results
Authors: Lombardi Andrea , Bozzi Giorgio , Ungaro Riccardo , Villa Simone , Castelli Valeria , Mangioni Davide , Muscatello Antonio , Gori Andrea , Bandera Alessandra
Published: March 2021

Background:BNT162b2 and mRNA-1273 are the two recently approved mRNA-based vaccines against COVID-19 which has shown excellent safety and efficacy. Preliminary data about specific and neutralizing antibodies is available covering the first 100 days after vaccination.

Methods:We reviewed all the publications regarding the immunologic consequences of BNT162b2 and mRNA-1273 vaccination. A summary of specific antibodies concentration and neutralizing antibodies titers elicited by each vaccine is provided.

Results:BNT162b2 and mRNA-1273 displayed a reassuring safety and efficacy profile, with the latter above 94%. They can elicit specific antibodies titers and neutralizing antibodies concentrations that are far superior from those observed among COVID-19 human convalescent serum, across a wide span of age, for at least 100 days after vaccination. Moreover, the vaccine-induced T cellular response is oriented toward a TH1 response and no evidence of vaccine-enhanced disease have been reported.

Discussion:BNT162b2 and mRNA-1273 can elicit specific antibodies titers and neutralizing antibodies concentrations above those observed among COVID-19 human convalescent serum in the first 100 days after vaccination. Data about vaccine efficacy in those with previous COVID-19 or immunocompromised is still limited.
Think of the Early Career Researchers! Saving the Oceans Through Collaborations
Authors: Cosentino Mel , Souviron-Priego Lucrecia
Published: March 2021

Oceans are complex systems and problems preventing a sustainable future require complex solutions. This can be achieved through innovative blends of natural and social sciences, with input from stakeholders. There is growing expectation that early career researchers (ECR), especially conservationists, should be more than natural scientists. ECR are expected to have skills in several domains, not all important to the quality of their work. Scientific skills range from knowledge of complex statistics to programming, and experience in different scientific fields. It is not only impossible to master all such tasks in a lifetime, much less as an ECR, but most importantly, attempting to do so means an ECR cannot master any single skill. This is especially true for minorities, non-native English speakers, and those who must juggle doing science with little or no funding, while having other jobs and family commitments. ECR are also expected to participate in activities that, while important for conservation, do not necessarily improve their scientific skills. These are social skills and range from policy engagement to science communication. This can contribute to developing mental health issues as it hinders having a healthy work-life balance. This expectation of engaging in extracurricular activities can overwhelm people with social anxiety and other difficulties with social interactions (e.g., people in the autism spectrum). Through collaborations, we can effectively draw on the more specialized skills of various people. Building an inclusive scientific community for ECR, therefore, calls for seeing diversity of skills, thoughts, and personality traits as its strength.
Spatio-Temporal Variation in Growth Performance and Condition of the Winged Pearl Oyster Pteria penguin
Authors: Gordon Sophie E. , Wingfield Max , Smallhorn-West Patrick F. , Malimali Siola’a , Halafihi Tu’ikologahau , Schoeman David S. , Southgate Paul C.
Published: March 2021

Environmental conditions can strongly influence the growth performance of pearl oysters and affect pearl farm production schedules. Growth and condition index (CI) of two age cohorts ofPteria penguinwere measured for 13 months to investigate differences in growth performance between four culture sites within the northern (Vava’u) and southern (Tongatapu) island groups of the Kingdom of Tonga. Environmental conditions were also measured at culture sites and used to explore potential effects on oyster growth and condition. Between island groups, growth performance ofP. penguinwas superior at northern sites and was most strongly related to higher water temperatures at these sites. Within the southern island group, growth performance varied significantly between sites and may be driven by differences in wave energy. Monthly growth rates (GM) ofP. penguinalso showed significant temporal variation related to age and environmental conditions. This study demonstrated significant variation in the growth performance ofP. penguinat latitudinal and local scales and suggests that in oligotrophic marine environments with minimal terrestrial inputs, such as Tonga, water temperature and wave exposure may be the primary environmental conditions influencing the growth performance ofP. penguin.This study therefore recommends that optimal culture sites forP. penguinin Tonga are characterized primarily by warmer water temperatures (25–30°C) and low wave exposure (<15 joules m2day–1). Culture ofP. penguinat sites with more suitable environmental conditions enables pearl production to begin up to 34.2 % (6.5 months) earlier than at less-suitable sites and this may greatly influence mabé pearl farm profitability and feasibility.
Long-Term Changes in the Water Mass Properties in the Balearic Channels Over the Period 1996–2019
Authors: Vargas-Yáñez Manuel , Juza Mélanie , García-Martínez M. Carmen , Moya Francina , Balbín Rosa , Ballesteros Enrique , Muñoz María , Tel Elena , Pascual Josep , Vélez-Belchí Pedro , Salat Jordi
Published: March 2021

The analysis of a 24-year time series of Conductivity-Temperature-Depth (CTD) casts collected in the Balearic Channels (1996–2019) has allowed detecting and quantifying long-term changes in water mass properties in the Western Mediterranean. For the complete period, the intermediate waters have experienced warming and salting at rates of 1.4°C/100yr and 0.3–0.6/100yr for the Western Intermediate Water, and 1°C/100yr and 0.3–0.4/100yr for the Levantine Intermediate Water. The density of these two water masses has not changed. The deep waters, defined as those denser than 29.1 kg/m3, showed positive trends in temperature, salinity, and density (0.8°C/100yr, 0.2/100yr, and 0.02 kg.m–3/100yr, respectively). The high temporal variability of the upper layer makes the detection of long-term changes more difficult. Nevertheless, combining CTD data with temperature data from the oceanographic station at L’Estartit and simulated data from the NCEP/NCAR reanalysis, it can be established that the Atlantic Water increased its temperature at a rate of 2.1–2.8°C/100yr and likely its salinity at a rate of 0.6/100yr. The water column absorbed heat at a rate equivalent to 1–1.2 W/m2. All these trends are much higher than those reported in previous works (more than double in some cases). The warming of the water column produced an increase in the thermosteric component of sea level. However, this increase was compensated by the decrease in the halosteric component. Besides these changes, other alterations related to the Western Mediterranean Transition have been observed over shorter periods. The temperature and salinity of the intermediate waters increased before the winter of 2004/2005 and then the temperature and salinity of the deep waters increased dramatically in 2005. The density of the deep water reached values unprecedented before 2005. Deep and intermediate waters were uplifted by the presence of such dense deep waters. The arrival of warmer and saltier intermediate waters from the Eastern Mediterranean is also observed, mainly after 2010.
Expression and Characterization of a Thermostable Carrageenase From an Antarctic Polaribacter sp. NJDZ03 Strain
Authors: Gui Yuanyuan , Gu Xiaoqian , Fu Liping , Zhang Qian , Zhang Peiyu , Li Jiang
Published: March 2021

The complete genome of Polaribacter sp. NJDZ03, which was isolated from the surface of Antarctic macroalgae, was analyzed by next-generation sequencing, and a putative carrageenase gene Car3206 was obtained. Car3206 was cloned and expressed in Escherichia coli BL21(DE3). After purification by Ni-NTA chromatography, the recombinant Car3206 protein was characterized and the antioxidant activity of the degraded product was investigated. The results showed that the recombinant plasmid pet-30a-car3206 was highly efficiently expressed in E. coli BL21(DE3). The purified recombinant Car3206 showed a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with an apparent molecular weight of 45 kDa. The optimum temperature of the recombinant Car3206 was 55°C, and it maintain 60–94% of its initial activity for 4–12 h at 55°C. It also kept almost 70% of the initial activity at 30°C, and more than 40% of the initial activity at 10°C. These results show that recombinant Car3206 had good low temperature resistance and thermal stability properties. The optimum pH of recombinant Car3206 was 7.0. Car3206 was activated by Na+, K+, and Ca2+, but was significantly inhibited by Cu2+ and Cr2+. Thin-layer chromatographic analysis indicated that Car3206 degraded carrageenan generating disaccharides as the only products. The antioxidant capacity of the degraded disaccharides in vitro was investigated and the results showed that different concentrations of the disaccharides had similar scavenging effects as vitamin C on O2•-, •OH, and DPPH•. To our knowledge, this is the first report about details of the biochemical characteristics of a carrageenase isolated from an Antarctic Polaribacter strain. The unique characteristics of Car3206, including its low temperature resistance, thermal stability, and product unity, suggest that this enzyme may be an interesting candidate for industrial processes.
Crop Rotation With Cress Increases Cucumber Yields by Regulating the Composition of the Rhizosphere Soil Microbial Community
Authors: Gong Xiaoya , Shi Jibo , Zhou Xingang , Yuan Tao , Gao Danmei , Wu Fengzhi
Published: March 2021

Paddy-upland rotation is an effective agricultural management practice for alleviating soil sickness. However, the effect of varying degrees of flooding on the soil microbial community and crop performance remains unclear. We conducted a pot experiment to determine the effects of two soil water content (SWC) and two flooding durations on the soil microbial community attributes and yield in cucumber. In the pot experiment, cucumber was rotated with cress single (45 days) or double (90 days) under 100 or 80% SWC. Then, the soil microbial were inoculated into sterilized soil to verified the relationship between cucumber growth and microorganisms. The results indicated single cress rotation resulted in a higher cucumber yield than double cress rotation and control. Cress rotation under 80% SWC had higher soil microbial diversity than cress rotation under 100% SWC and control. Flooding duration and SWC led to differences in the structure of soil microbial communities. Under 80% SWC, single cress rotation increased the relative abundance of potentially beneficial microorganisms, including Roseiflexus and Pseudallescheria spp., in cucumber rhizosphere. Under 100% SWC, single cress rotation increased the relative abundance of potentially beneficial bacteria, such as Haliangium spp., and decreased potential pathogenic fungi, such as Fusarium and Monographella spp., compared with double cress rotation and control. Varying degrees of flooding were causing the difference in diversity, structure and composition of soil microbial communities in the cucumber rhizosphere, which have a positive effect on cucumber growth and development.
Anti-aquaporin 4 IgG Is Not Associated With Any Clinical Disease Characteristics in Neuromyelitis Optica Spectrum Disorder
Authors: Schmetzer Oliver , Lakin Elisa , Roediger Ben , Duchow Ankelien , Asseyer Susanna , Paul Friedemann , Siebert Nadja
Published: March 2021

Background:Neuromyelitis optica spectrum disorder (NMOSD) is a clinically defined, inflammatory central nervous system (CNS) disease of unknown cause, associated with humoral autoimmune findings such as anti-aquaporin 4 (AQP4)-IgG. Recent clinical trials showed a benefit of anti-B cell and anti-complement-antibodies in NMOSD, suggesting relevance of anti-AQP4-IgG in disease pathogenesis.

Objective:AQP4-IgG in NMOSD is clearly defined, yet up to 40% of the patients are negative for AQP4-IgG. This may indicate that AQP4-IgG is not disease-driving in NMOSD or defines a distinct patient endotype.

Methods:We established a biobank of 63 clinically well-characterized NMOSD patients with an extensive annotation of 351 symptoms, patient characteristics, laboratory results and clinical scores. We used phylogenetic clustering, heatmaps, principal component and longitudinal causal interference analyses to test for the relevance of anti-AQP4-IgG.

Results:Anti-AQP4-IgG was undetectable in 29 (46%) of the 63 NMOSD patients. Within anti-AQP4-IgG-positive patients, anti-AQP4-IgG titers did not correlate with clinical disease activity. Comparing anti-AQP4-IgG-positive vs. -negative patients did not delineate any clinically defined subgroup. However, anti-AQP4-IgG positive patients had a significantly (p= 0.022) higher rate of additional autoimmune diagnoses.

Conclusion:Our results challenge the assumption that anti-AQP4-IgG alone plays a disease-driving role in NMOSD. Anti-AQP4-IgG might represent an epiphenomenon associated with NMOSD, may represent one of several immune mechanisms that collectively contribute to the pathogenesis of this disease or indeed, anti-AQP4-IgG might be the relevant factor in only a subgroup of patients.
MicroRNA Dysregulation in Epilepsy: From Pathogenetic Involvement to Diagnostic Biomarker and Therapeutic Agent Development
Authors: Wang Jialu , Zhao Jiuhan
Published: March 2021

Epilepsy is the result of a group of transient abnormalities in brain function caused by an abnormal, highly synchronized discharge of brain neurons. MicroRNA (miRNA) is a class of endogenous non-coding single-stranded RNA molecules that participate in a series of important biological processes. Recent studies demonstrated that miRNAs are involved in a variety of central nervous system diseases, including epilepsy. Although the exact mechanism underlying the role of miRNAs in epilepsy pathogenesis is still unclear, these miRNAs may be involved in the inflammatory response in the nervous system, neuronal necrosis and apoptosis, dendritic growth, synaptic remodeling, glial cell proliferation, epileptic circuit formation, impairment of neurotransmitter and receptor function, and other processes. Here, we discuss miRNA metabolism and the roles of miRNA in epilepsy pathogenesis and evaluate miRNA as a potential new biomarker for the diagnosis of epilepsy, which enhances our understanding of disease processes.
Evaluating and Balancing the Risk of Breast Cancer-Specific Death and Other Cause-Specific Death in Elderly Breast Cancer Patients
Authors: Peng Yuan , Hu Taobo , Cheng Lin , Tong Fuzhong , Cao Yingming , Liu Peng , Zhou Bo , Liu Miao , Liu Hongjun , Guo Jiajia , Xie Fei , Yang Houpu , Wang Siyuan , Wang Chaobin , Wang Shu
Published: March 2021

Purpose: The dilemma of undertreatment and overtreatment of elderly breast cancer patients is common. This study aimed to investigate clinicopathological features, treatment modalities, and survival in women diagnosed with breast cancer at age 70 years or over, and to assist clinicians in developing individualized treatment plans by balancing the risks of breast cancer-specific death (BCSD) and other cause-specific death (OCSD).

Methods: This retrospective study included 420 women who were diagnosed with pathologically confirmed invasive breast cancer at age 70 years or older from January 2008 to December 2015 at Peking University People's Hospital (PKUPH). We collected baseline health status, tumor characteristics, treatment choices, and outcomes and created nomograms for clinicians to estimate individualized BCSD and OCSD risk directly.

Results: During a median follow-up of 71.5 months (range 2 to 144 months) in patients with stage I–III tumors, breast cancer specific survival (BCSS) was 92.4% (376/407) and overall survival (OS) was 78.1% (318/407). There were 89 deaths, and 65.2% (58/89) were non-breast cancer related. Upon multivariate analysis by Cox regression model, tumor size, positive lymph nodes, Ki-67, and surgery were independent predictors of BCSS, and comorbidities, positive lymph nodes, Ki-67, surgery, and endocrine therapy were independent predictors of OS. Propensity score weighted (PSW) was applied to analyze therapeutic efficacy, and there was BCSS and OS benefit with surgery (both p < 0.001), BCSS benefit with chemotherapy (p = 0.029), BCSS and OS benefit with endocrine therapy (p = 0.006 and 0.004), and neither BCSS nor OS benefit with radiotherapy (RT) (p = 0.348 and 0.289). Competing-risk nomograms were developed to estimate cumulative mortality probabilities for BCSD and OCSD for individual patients according to clinicopathologic characteristics and treatments. The calibration curves displayed exceptionally, with C-indexes 0.714 for BCSD and 0.717 for OCSD.

Conclusions: Older patients had greater risk of dying from non-breast cancer causes. Surgery, chemotherapy, and endocrine therapy were associated with improved survival. Competing risk nomograms allowed individual assessment of BCSD and OCSD, based on clinicopathological characteristics and treatment options, and can be used as a tool to help in choosing appropriate treatment strategies.

This study was approved by the Peking University People's Hospital Research Ethics Board on September 4, 2018.