bluuebunny/crossref_metadata_2025 huggingface dataset:
PARASITOS INTESTINAIS DE Leopardus wiedii E Leopardus tigrinus (FELIDAE) DA FLORESTA NACIONAL DE TRÊS BARRAS, SC
Authors: Kusma Suellen Cristine , Wrublewski Derlise Maria , Teixeira Valéria Natacha , Holdefer Daniela Roberta
Published: April 2023

Os felí­deos apresentam diferenciados papéis ecológicos e enquanto predadores são importantes e benéficos para os ecossistemas, pois atuam no topo da cadeia alimentar. Quando infectados por algumas formas parasitárias pode ocorrer interferência na sua atividade alimentar atuando diretamente na estrutura e atribuindo um novo perfil a tal comunidade. Desta forma o objetivo deste estudo foi promover reconhecimento das parasitoses e o ní­vel de infestações nas espécies de Leopardus wiedii e Leopardus tigrinus acrescentando informações sobre a saúde destas espécies selvagens. O levantamento de amostras fecais foi realizado nos limites da Unidade de Conservação da Floresta Nacional de Três Barras (FLONA) no perí­odo de agosto a dezembro de 2013 e perfez 10 visitas ás trilhas e estradas existentes. As amostras coletadas foram submetidas à análise tricológica para confirmação das espécies de felí­deos e destinadas ao Laboratório de Parasitologia da PUC-PR para a realização dos exames coproparasitológicos. Os resultados indicaram que Leopardus wiedii apresentou dezessete formas parasitárias, sendo ovos de Spirometra sp. o mais frequente (85,7%), seguido de Capillaria sp. (71,4%) e larvas Aelurostrongylus sp. (38,10%). Em Leopardus tigrinus foram encontradas 12 formas parasitárias, sendo a mais frequente os ovos de Spirometra sp. em 100% das amostras, ovos de Ancylostomatidae, Trichuris sp., Paragonimus sp. (28,57%) e larvas Aelurostrongylus sp. (35,72%). Os resultados indicam que a FLONA apresenta condições ambientais favoráveis á infecção dos felí­deos silvestres com diversas formas de parasitos destacando uma grande frequência de nematoides.
AS POLÍTICAS ECONÔMICAS E SUAS IMPLICAÇÕES PARA O TRABALHO E A EDUCAÇÃO
Authors: De Aragão Mikolaiczyk Fernanda
Published: April 2023

O presente trabalho apresenta-se como uma tentativa de situar historicamente o trabalho na sociedade capitalista, por meio da análise das relações estabelecidas entre as polí­ticas de desenvolvimento econômico e a educação no Brasil, vislumbrando os limites e as possibilidades do trabalho constituir-se ou não como princí­pio educativo. O objeto de estudo são as relação existentes entre desenvolvimento e educação, estas, inseridas no contexto das polí­ticas desenvolvimentistas protagonizadas no Brasil a partir de 1930, na reforma dos Estados Nacionais a partir de 1980-1990 e em como a redefinição do papel dos Estados influenciou na prática da desregulamentação do mundo do trabalho e suas implicações recentes na educação pública do paí­s. Como referencial teórico e metodológico, o Materialismo Histórico Dialético possibilita por meio das categorias de desenvolvimento, Estado, trabalho e educação, analisar o Brasil e suas linhas gerais de desenvolvimento, tendo como referenciais centrais neste trabalho a concepção educacional de Antonio Gramsci e os trabalhos de autores marxistas. A partir desses, conclui-se que o trabalho como princí­pio educativo e como princí­pio metodológico, ainda é a forma em potência mais revolucionária de que dispõe o trabalhador.
Artigos Religiosos no(s) Pentecostalismo(s): Estudo das relações dos bens simbólicos na geração de economia local de Rio Grande da Serra, periferia urbana no Grande ABC Paulista
Authors: Scarpioni Marcos
Published: April 2023

Este artigo visa compreender como são ou estão estabelecidas algumas das relações dos bens simbólicos produzidos nas religiões cristã pentecostais com a economia local de Rio Grande da Serra - periferia urbana no Grande ABC. Embasado no sistema de fluxo de economia, nossa pergunta principal seria: Em que medida o capital simbólico gerado e distribuí­do nessas instituições, gerariam avanços culturais socioeconômicos, sociopolí­ticos no cotidiano dos indiví­duos na região central e periférica de Rio Grande da Serra? De que forma os bens simbólicos estariam condicionados ao Código de Defesa do Consumidor e assim concorreriam para melhoria da economia local? Para análise, servirmo-nos da observação empí­rica da distribuição desses bens materiais "consagrados" em reuniões cúlticas, verificação dos produtos religiosos disponí­veis nos estabelecimentos comerciais na região. E por fim, contatamos a Associação Comercial, Industrial e Agricola de Rio Grande da Serra para verificarmos a existência de dados sobre essas relações. Embora, os artigos religiosos gerem um capital social para os grupos religiosos que o produzem e os consomem, todavia, não contribuem para a geração de economia local.
Qualidade e técnica de curtimento em couros de linguados
Authors: Schwarz Katia Kalko , Agostinho Suelen Cunha , Pereira Nagila De Souza
Published: April 2023

O presente estudo foi realizado com os objetivos de avaliar as caracterí­sticas histológicas das epidermes de linguado (Paralichthys spp.) e no desenvolvimento de técnica curtente com tanino vegetal de mimosa, avaliando a resistência do produto final totalmente isento de sais de cromo. Após o curtimento das peles foram retirados corpos-de-prova no sentido longitudinal e transversal em relação ao comprimento do peixe, submetendo-se ao teste de resistência. O couro do linguado-abaxial (pele branca) e linguado-axial (pele preta) apresentou diferenças morfológicas na flor da pele. Os testes de resistência à tração, alongamento e força máxima aplicada até a ruptura no sentido longitudinal foram significativos (P<0,05), porém no sentido transversal os valores não diferiram. O linguado-abaxial apresentou resultados de 18,10N/mm², 55,75 %e 104,84 N. Comparado ao linguado-axial, 20,97 N/mm², 44,25% e 145,2 N. Ambas as peles diferiram quanto à disposição das fibras colágenas e espessura dos couros. O couro do linguado-axial pode ser utilizado na confecção de cabedal de moda (vestuários) e o couro do linguado-abaxial para customizações, visto ser este de menor espessura. Estes estudos sugerem que a quantidade das fibras colágenas, bem como a sua disposição nas peles do linguado podem ter interferido na determinação da resistência após o curtimento.
Atividade anti-protozoário in vitro do p-Cimeno sobre Leishmania amazonensis
Authors: Beraldo-Borrazzo Jesieli , Dos Santos Adriana Oliveira , Abreu Filho Benício Alves de , Quintans-Júnior Lucindo José , Nakamura Celso Vataru
Published: April 2023

As doenças tropicais se constituem em um grave problema de saúde pública, por serem negligenciadas e atingirem especialmente as populações mais pobres. Entre os principais problemas mundiais de saúde, a leishmaniose se destaca por apresentar altas taxas de mortalidade. Grandes esforços tem sido empregados na busca por novos medicamentos nas ultimas décadas, sendo o uso da fitoterapia investigado com grande interesse, devido às plantas serem consideradas uma ampla fonte de compostos com potencial biomedicinal. A atividade anti-protozoário da substância p-Cimeno sobre formas promastigotas e amastigotas axênicas de Leishmania amazonensis, foi avaliado. Após 72 horas de cultivo, o p-Cimeno apresentou concentração inibitória de 50% (CI50) igual à 65,0 µg/mL e 55,0 µg/mL sobre as formas promastigotas e amastigotas axênicas, respectivamente. Análises de citotoxicidade do p-Cimeno, foram realizadas por meio do método colorimétrico da sulforodamina-B sobre macrófagos J774G8 e a concentração citotóxica para 50% das células (CC50) foi de 54,0 µg/mL. Os dados obtidos indicam efeito antiparasitário do p-Cimeno sobre Leishmania amazonensis, principalmente sobre sua forma amastigota, sendo considerado potencial candidato para novos estudos contra o parasito.
Primeiro registro de Nesomyrmex costatus (Emery, 1896) (Hymenoptera: Formicidae) para o estado do Paraná, Brasil
Authors: Iasczczaki Rafael Stempniak , Carneiro Gabriel Siqueira , Doline Fernando Rodrigo , Holdefer Daniela Roberta
Published: April 2023

O gênero Nesomyrmex é composto atualmente por cerca de 83 espécies válidas, distribuí­das nas regiões Neotropical e Afrotropical. No Brasil o gênero é representado por 12 espécies e entre elas Nesomyrmex costatus (Emery, 1896). Pouco se conhece sobre a biologia e ecologia dessa espécie em particular, sendo que somente quatro estados brasileiros registram sua ocorrência. No perí­odo compreendido entre setembro de 2018 e janeiro de 2021, durante coleta de formigas em São Mateus do Sul, Paraná, Brasil (25°44'30.59"S 50°25'59.48" O; 24º 46' 41.6''S 50º 24'1" O e 25º 44' 49.4''S 50º 25'42.9" O), observamos sua presença na captura direta e em pitfall arbóreo. Objetiva-se, portanto, cobrir uma lacuna na sua distribuição geográfica para o Sul do paí­s; auxiliar no reconhecimento da mirmecofauna do estado; e colaborar com informações sobre sua interação com espécies vegetais. A espécie foi registrada na primavera de 2018 e nos verões de 2019 e 2021, sobre Ilex paraguariensis e Mimosa scabrella, em área de silvicultura de erva mate, e sobre Senegalia sp. num fragmento de Ombrofila Mista. A captura direta foi responsável por seis exemplares e o pitfall arbóreo por três. Este estudo, além registrar N. costatus para o Estado do Paraná, reforça a observação de que esta espécie apresenta hábitos arborí­colas. Destaca ainda a importância dos agroecossistemas de cultivo de I. paraguariensis, assim como fragmentos de mata nativa, para conservação e manutenção da diversidade de formigas.
Bioprospecting endophytic Diaporthe species associated with Pachystachys lutea (Acanthaceae) with antagonistic effect against Sclerotinia sclerotiorum
Authors: Ferreira Ana Paula , Jenifer Mateus Natieli , Arthur dos Santos de Oliveira João , Alencar Pamphile João , Lucio Azevedo João
Published: April 2023

Endophytic microorganisms live inside the plant tissues symptomless. These microorganisma may present antagonistic activity against phytopathogens or produce metabolites with antifungal activity. We aimed to evaluate in vitro antagonism and competitive interactions between endophytic fungi of Diaporthe species and Sclerotinia sclerotiorum. We also carried out in vitro screening of antifungal activity of metabolic extracts of the two endophytes against the pathogen. The antagonism was performed by the paired-culture and two promising antagonists strains were selected for metabolic extraction from the fermented culture. Metabolic extracts were obtainment using two different organic solvents (Ethyl Acetate and Hexane) and their antifungal activity was carried out using the agar diffusion test. The in vitro antagonistic index ranged from 22.1 to 59.5%, with Diaporthe sp. PL03 (59.1%), D. schini PL40 (59.5%), D. infecunda PL63 (41.8%), D. anacardii PL64 (56.8%), with inhibition by mycelial contact. The endophytes PL01 (28.6%) and PL43 (28.5%), both D. anacardii, stood out blocking mycelial growth from a distance. In the antifungal assay, D. anacardii PL01 (31.7%) and D. schini PL40 (18.2%) acetate metabolite stood out. In summary, our results indicate a few Diaporthe endophytes able to antagonize a S. sclerotiorum pathogen under in vitro conditions.
Ferroptosis-associated circular RNAs: Opportunities and challenges in the diagnosis and treatment of cancer
Authors: Yang Ruotong , Ma Liwei , Wan Junhu , Li Zhuofang , Yang Zhengwu , Zhao Zhuochen , Ming Liang
Published: April 2023

Ferroptosis is an emerging form of non-apoptotic regulated cell death which is different from cell death mechanisms such as autophagy, apoptosis and necrosis. It is characterized by iron-dependent lipid peroxide accumulation. Circular RNA (circRNA) is a newly studied evolutionarily conserved type of non-coding RNA with a covalent closed-loop structure. It exhibits universality, conservatism, stability and particularity. At present, the functions that have been studied and found include microRNA sponge, protein scaffold, transcription regulation, translation and production of peptides, etc. CircRNA can be used as a biomarker of tumors and is a hotspot in RNA biology research. Studies have shown that ferroptosis can participate in tumor regulation through the circRNA molecular pathway and then affect cancer progression, which may become a direction of cancer diagnosis and treatment in the future. This paper reviews the molecular biological mechanism of ferroptosis and the role of circular RNA in tumors and summarizes the circRNA related to ferroptosis in tumors, which may inspire research prospects for the precise prevention and treatment of cancer in the future.
Genome diversity of Leishmania aethiopica
Authors: Hadermann Amber , Heeren Senne , Maes Ilse , Dujardin Jean-Claude , Domagalska Malgorzata Anna , Van den Broeck Frederik
Published: April 2023

Leishmania aethiopica is a zoonotic Old World parasite transmitted by Phlebotomine sand flies and causing cutaneous leishmaniasis in Ethiopia and Kenya. Despite a range of clinical manifestations and a high prevalence of treatment failure, L. aethiopica is one of the most neglected species of the Leishmania genus in terms of scientific attention. Here, we explored the genome diversity of L. aethiopica by analyzing the genomes of twenty isolates from Ethiopia. Phylogenomic analyses identified two strains as interspecific hybrids involving L. aethiopica as one parent and L. donovani and L. tropica respectively as the other parent. High levels of genome-wide heterozygosity suggest that these two hybrids are equivalent to F1 progeny that propagated mitotically since the initial hybridization event. Analyses of allelic read depths further revealed that the L. aethiopica - L. tropica hybrid was diploid and the L. aethiopica - L. donovani hybrid was triploid, as has been described for other interspecific Leishmania hybrids. When focusing on L. aethiopica, we show that this species is genetically highly diverse and consists of both asexually evolving strains and groups of recombining parasites. A remarkable observation is that some L. aethiopica strains showed an extensive loss of heterozygosity across large regions of the nuclear genome, which likely arose from gene conversion/mitotic recombination. Hence, our prospection of L. aethiopica genomics revealed new insights into the genomic consequences of both meiotic and mitotic recombination in Leishmania.
Case report: A rare case of anomalous origin of the left coronary artery from the pulmonary artery accompanied with unilateral absence of pulmonary artery in an adult patient
Authors: Yi Dong , Xia Juan , Zhou Xiang , Liu Chengwei , Liu Li , Yan Hua , Ma Xiaojing
Published: April 2023

Both the anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) and unilateral absence of the pulmonary artery (UAPA) are rare congenital malformations, ALCAPA accompanied with UAPA is extremely rare. Here, we reported a middle-aged man admitted to our department for evaluation of chest pain during exercise. Physical examination and lab tests did not unveil obvious abnormality; however, transthoracic echocardiogram (TTE) revealed multivessel myocardial collateral blood flow signals in the left ventricular wall and ventricular septum, a shunting flow from the left coronary artery into the pulmonary artery and dilated right coronary artery (RCA), which supported but did not confirm the diagnosis of ALCAPA. Coronary angiography (CAG) showed an absent left coronary ostium and a dilated RCA, with extensive collaterals supplying the left coronary system. Multidetector computed tomography angiography (MDCTA) was then performed and revealed the anomalous origin of the left main coronary artery (LMCA) arising from the pulmonary artery, and it incidentally unveiled another rare congenital malformation of UAPA. The patient underwent surgical correction of ALCAPA by reimplantation of the LMCA to the aorta, without surgical treatment of UAPA. The patient had been in good clinical condition and remained angina free with good exercise tolerance during follow-up (∼6 months so far). In this case, we discussed the diagnostic value of TTE, CAG, and MDCTA on rare abnormalities as ALCAPA and UAPA. We highlighted the role of multiple non-invasive imaging modalities in diagnosing rare causes of angina in adult patients, and the importance of careful examination in avoiding misdiagnosis. To our best knowledge, this is the first report of ALCAPA accompanied with UAPA in an adult patient.
Environmental contamination characteristics of heavy metals from abandoned lead–zinc mine tailings in China
Authors: Han Wei , Zhao Ruifeng , Liu Wanrong , Wang Yujing , Zhang Shuai , Zhao Kang , Nie Jinglei
Published: April 2023

China holds large-scale lead–zinc mineral resources; however, mining activities often cause severe contamination by heavy metals. This study systemically assessed contamination by eight heavy metals (Cu, Zn, Cd, Pb, Cr, Hg, Ni, and As) in mine tailings, soil, and groundwater from 27 contaminated sites across China. Regarding mine tailings, 1% of the mine tailing samples were hazardous waste and 20% were class II non-hazardous waste. Regarding soil, Zn and Pb showed the highest mean concentrations, at 5574.67 mg/kg and 2034.88 mg/kg, respectively. The indexes of geo-accumulation (Igeo) of eight heavy metals ranged from −3.62 to 7.67, while Zn, Pb, and Cd showed the highest environmental risk levels as the priority pollutants. The contamination levels of these heavy metals in groundwater were generally in the order of Zn>As>Pb>Ni>Cd>Cu>Hg>Cr. In this study, 20% of the soil and 10% of the groundwater samples exceeded the corresponding quality limits. The content of heavy metals in soil, groundwater, and mine tailing were positively correlated, demonstrating the main pollution source and transport paths. The pollution levels of heavy metals in soil and groundwater were listed in the foremost and moderate positions compared with similar sites from other countries, respectively. These results may help determine the pollution levels of lead–zinc mining regions and direct the remediation activities of target sites to support the environmental management of abandoned mining and tailing waste in China.
System-thinking progress in engineering programs: A case for broadening the roles of students
Authors: Tamir Ram , Ben-Zvi Assaraf Orit , Maman Shimrit
Published: April 2023

Introduction

Complex systems are prevalent in many scientific and engineering disciplines, which makes system thinking important for students of these fields. Duchifat 3 is a unique engineering educational extracurricular program, where high school students designed, assembled, and tested a nano-satellite.

Methods

This study applied qualitative methods to explore how the participants’ systems-thinking developed during the program. Participants were interviewed using the repertory grid interview, and a semi structured interview at the beginning and at the end of the project, while various observations were conducted throughout.

Results

While the participants were initially assigned narrow roles, each dealing with a single sub-system of the satellite, some chose to be involved with other sub-systems and aspects of the project. Our findings show that the broader the participants’ involvement was, the greater the progress they experienced in their systems-thinking. Participants who stayed focused on a single subsystem did not show progress, while participants who involved themselves with several sub-systems exhibited a more meaningful progress.

Discussion

Although the program design aimed to assign students to a narrow role to enable them to achieve the educational goals, from the perspective of systems-thinking this was counterproductive. These findings shed light on the design of engineering programs such as the one examined here in terms of systems-thinking development. We discuss the implications of the findings for similar programs and make suggestions for improvement.
Comparative study between delivery modalities in higher education during emergency remote teaching due to COVID-19
Authors: Rodríguez-Hernández Carlos Felipe , Rincon-Flores Elvira G.
Published: April 2023

Despite the difficulties faced during Emergency Remote Teaching (ERT) because of the COVID-19 pandemic, it is also true that such a situation has left a series of learnings that educational institutions around the world should capitalize on. Under this scenario, interest arose in studying three delivery modalities (face-to-face, hybrid, and remote) at the university level, aiming to compare the students’ learning level and their perceptions of each delivery modality. The present study was developed in a private university in Mexico, following a quantitative methodological approach involving 360 students and 14 professors from various schools and geographical locations. Data were collected through pre-and post-tests and a perception questionnaire for students. Findings suggest that the students’ learning level in every modality varies by school and that students positively perceive the three delivery modalities, albeit identifying factors that foster and hinder their learning process in each one. The results of this study contribute to strengthening the research field on teaching during ERT, allowing educational institutions to make better decisions regarding the quality of the educational offer.
Association between triglyceride-glucose index and risk of end-stage renal disease in patients with type 2 diabetes mellitus and chronic kidney disease
Authors: Gao Yue-Ming , Chen Wei-Jia , Deng Zhen-Ling , Shang Zhi , Wang Yue
Published: April 2023

Aims

It has been suggested that the triglyceride-glucose (TyG) index is a novel and reliable surrogate marker of insulin resistance (IR). However, its relationship with the risk of end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) remains uncertain. Accordingly, we sought to examine the relationship between the TyG index and ESRD risk in patients with T2DM and CKD.

Methods

From January 2013 to December 2021, 1,936 patients with T2DM and CKD hospitalized at Peking University Third Hospital (Beijing, China) were enrolled into the study. The formula for calculating the TyG index was ln[fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. ESRD was defined as an estimated glomerular filtration rate of less than 15 mL/min/1.73 m2 or the commencement of dialysis or renal transplantation. The relationship between the TyG index and ESRD risk was analyzed using Cox proportional hazard regression.

Results

105 (5.42%) participants developed ESRD over a mean follow-up of 41 months. The unadjusted analysis revealed a 1.50-fold (95% confidence interval [CI] 1.17-1.93; P = 0.001) increased risk for ESRD per one unit rise in the TyG index, and the positive association remained stable in the fully adjusted model (hazard ratio, 1.49; 95% CI, 1.12-1.99; P = 0.006). Analysis using restricted cubic spline revealed a significant positive association between the TyG index and ESRD risk. In addition, Kaplan-Meier analysis revealed significant risk stratification with a TyG index cutoff value of 9.5 (P = 0.003).

Conclusion

In individuals with T2DM and CKD, a significant and positive association was shown between an elevated TyG index and the risk of ESRD. This conclusion provides evidence for the clinical importance of the TyG index for evaluating renal function decline in individuals with T2DM and CKD.
A bibliometric and visualized research on global trends of immune checkpoint inhibitors related complications in melanoma, 2011–2021
Authors: Zhang Hongyi , Shi Yanlong , Ying Jianghui , Chen Yi , Guo Rong , Zhao Xin , Jia Lingling , Xiong Jiachao , Jiang Fei
Published: April 2023

Background

Melanoma is a malignant tumor that originates from the canceration of melanocytes with a high rate of invasiveness and lethality. Immune escape has been regarded as an important mechanism for tumor development, while the treatment of immune checkpoint inhibitors (ICIs) is beneficial in restoring and enhancing the body’s anti-tumor immune response to kill tumor cells. To date, ICIs therapy has achieved remarkable efficacy in treating melanoma patients. Despite the significant clinical benefits of ICIs, multiple complications such as rashes, thyroiditis, and colitis occur in melanoma patients. In this study, we aim to explore the development process and trends in the field of ICIs-related complications in melanoma, analyze current hot topics, and predict future research directions.

Methods

We screened the most relevant literatures on ICIs-related complications in melanoma from 2011 to 2021 in the Web of Science Core Collection (WoSCC). Using VOSviewer, CiteSpace and R language packages, we analyzed the research trends in this field.

Results

A total of 1,087 articles were screened, and the USA had the highest number of publications (publications = 454, citations = 60,483), followed by Germany (publications = 155, citations = 27,743) and Italy (publications = 139, citations = 27,837). The Memorial Sloan Kettering Cancer Center had the most publications, but the Angeles Clinic and Research Institute had the highest average citation rate. Lancet oncology (IF, 2021 = 54.43) was the most prominent of all journals in terms of average citation rate. Reference and keyword cluster analysis revealed that anti-tumor efficacy, adjuvant treatment, clinical response, clinical outcome, etc. were the hotspots and trends of research in recent years.

Conclusions

This study offers a comprehensive summary and analysis of global research trends on ICIs-related complications in melanoma. Over the past decade, there has been a significant increase in the number of publications on this topic. However, the safety and benefits of retreatment after the recovery of ICIs-related complications remain unknown. Therefore,the establishment of related prediction models, as well as the immunotherapy of melanoma with ICIs in combination with other adjuvant therapies, are future research hotspots.
Non-alcoholic fatty liver disease is associated with a worse prognosis in patients with heart failure: A pool analysis
Authors: Qiu Min , Li Jiahuan , Hao Shali , Zheng Haoxiao , Zhang Xiaojie , Zhu Hailan , Zhu Xiaolin , Hu Yunzhao , Cai Xiaoyan , Huang Yuli
Published: April 2023

Background and aims

Non-alcoholic fatty liver disease (NAFLD) is associated with a higher risk of heart failure (HF) than those without NAFLD. However, the prognostic impact of NAFLD in HF is still controversial. This meta-analysis aimed to explore the association between NAFLD and the risk of adverse outcomes in patients with HF.

Methods

We searched multiple electronic databases (Embase, PubMed, and Google Scholar) for potentially related studies up to June 30, 2022. Cohort studies reported multivariable adjusted relative risks and 95% confidence intervals (CIs) of adverse outcomes in HF patients with NAFLD comparing those without NAFLD were included for analysis.

Results

A total of six studies involving 12,374 patients with HF were included for analysis, with a median follow-up duration of 2.5 years. The pooled analysis showed that HF patients with NAFLD were associated with a significantly increased risk of major composite adverse outcomes (HR 1.61, 95% CI 1.25-2.07), all-cause mortality (HR 1.66, 95% CI 1.39-1.98), and HF hospitalization or re-hospitalization (HR 1.71, 95% CI 1.03-2.86).

Conclusion

NAFLD is associated with a worse prognosis in patients with HF. Effective screening and treatment strategies are needed to improve the prognosis in HF patients with NAFLD.
Concurrent and lagged effects of drought on grassland net primary productivity: a case study in Xinjiang, China
Authors: Liu Yujia , Zheng Jianghua , Guan Jingyun , Han Wanqiang , Liu Liang
Published: April 2023

Xinjiang grasslands play a crucial role in regulating the regional carbon cycle and maintaining ecosystem stability, and grassland net primary productivity (NPP) is highly vulnerable to drought. Drought events are frequent in Xinjiang due to the impact of global warming. However, there is a lack of more systematic research results on how Xinjiang grassland NPP responds to drought and how its heterogeneity is characterized. In this study, the CASA (Carnegie Ames Stanford Application) model was used to simulate the 1982–2020 grassland NPP in Xinjiang, and the standardized Precipitation Evapotranspiration Index (SPEI) was calculated using meteorological station data to characterize drought. The spatial and temporal variability of NPP and drought in Xinjiang grasslands from 1982 to 2020 were analyzed by the Sen trend method and the Mann-Kendall test, and the response characteristics of NPP to drought in Xinjiang grasslands were investigated by the correlation analysis method. The results showed that (1) the overall trend of NPP in Xinjiang grassland was increasing, and its value was growing season > summer > spring > autumn. Mild drought occurred most frequently in the growing season and autumn, and moderate drought occurred most frequently in spring. (2) A total of 64.63% of grassland NPP had a mainly concurrent effect on drought, and these grasslands were primarily located in the northern region of Xinjiang. The concurrent effect of drought on NPP was strongest in plain grassland and weakest in alpine subalpine grassland. (3) The lagged effect is mainly in the southern grasslands, the NPP of alpine subalpine meadows, meadows, and alpine subalpine grasslands showed mainly a 1-month time lag effect to drought, and desert grassland NPP showed mainly a 3-month time lag effect to drought. This research can contribute to a reliable theoretical basis for regional sustainable development.
Recruitment mechanisms and therapeutic implications of tumor-associated macrophages in the glioma microenvironment
Authors: Zhou Xianzhe , Jin Guishan , Zhang Junwen , Liu Fusheng
Published: April 2023

As one of the main components of the glioma immune microenvironment, glioma-associated macrophages (GAMs) have increasingly drawn research interest. Primarily comprised of resident microglias and peripherally derived mononuclear macrophages, GAMs are influential in a variety of activities such as tumor cell resistance to chemotherapy and radiotherapy as well as facilitation of glioma pathogenesis. In addition to in-depth research of GAM polarization, study of mechanisms relevant in tumor microenvironment recruitment has gradually increased. Suppression of GAMs at their source is likely to produce superior therapeutic outcomes. Here, we summarize the origin and recruitment mechanism of GAMs, as well as the therapeutic implications of GAM inhibition, to facilitate future glioma-related research and formulation of more effective treatment strategies.
The immunomodulatory effect of IL-4 accelerates bone substitute material-mediated osteogenesis in aged rats via NLRP3 inflammasome inhibition
Authors: Li Duchenhui , Li Xiao , Zhang Jie , Tang Zhenglong , Tian Ai
Published: April 2023

Background

Bone defect repair by implanting bone substitute materials has been a common clinical treatment. With the understanding of substance–immune system interactions and increasing evidence indicating that the post-implantation immune response determines the fate of bone substitute materials, active modulation of host macrophage polarization is considered a promising strategy. However, whether the same regulatory effects exist when an individual immune system is altered with aging is unclear.

Methods

In this study, we mechanistically investigated the effect of immunosenescence on the active regulation of macrophage polarization by establishing a cranial bone defect model in young and aged rats implanted with Bio-Oss®. Forty-eight young and 48 aged specific pathogen-free (SPF) male SD rats were randomly divided into two groups. In the experimental group, 20 μL of IL-4 (0.5 μg/mL) was injected locally on the third to seventh postoperative days, while an equal volume of PBS was injected in the control group. Specimens were collected at 1, 2, 6, and 12 weeks postoperatively, and bone regeneration at the defect site was evaluated by micro-CT, histomorphometry, immunohistochemistry, double-labeling immunofluorescence, and RT–qPCR.

Results

The application of exogenous IL-4 reduced activation of NLRP3 inflammasomes by promoting the polarization of M1 macrophages to M2 macrophages, thus promoting bone regeneration at the site of bone defects in aged rats. However, this effect was gradually weakened after the IL-4 intervention was discontinued.

Conclusion

Our data confirmed that a strategy to regulate macrophage polarization is also feasible under conditions of immunosenescence, i.e., the local inflammatory microenvironment can be regulated by reducing M1-type macrophages. However, further experiments are needed to determine an exogenous IL-4 intervention that can maintain a more sustained effect.
Inflammatory bowel diseases, interleukin-6 and interleukin-6 receptor subunit alpha in causal association with cerebral cortical structure: a Mendelian randomization analysis
Authors: Liu Chunlong , Zhu Shijie , Zhang Jian , Ren Kuiwu , Li Kangkang , Yu Jiangtao
Published: April 2023

Background

Neurological involvement and psychiatric manifestations have been documented in clinical cases of inflammatory bowel disease (IBD); however, the presence of a causal relationship remains elusive. The objective of this study is to investigate the modifications occurring in the cerebral cortex as a result of IBD.

Methods

A compendium of data extracted from a genome-wide association study (GWAS) involving a maximum of 133,380 European subjects. A series of Mendelian random analyses were applied to exclude heterogeneity and pleiotropy, ensuring the stability of the results.

Results

Neither IBDs nor inflammatory cytokines (IL-6/IL-6Rα) were found to have a significant causality with surface area (SA) and thickness (TH) at the global level. At the regional functional brain level, Crohn’s disease (CD) significantly decreased the TH of pars orbitalis (β=-0.003mm, Se=0.001mm, pivw =4.85×10-4). IL-6 was observed to reduce the SA of middle temporal (β=-28.575mm2, Se=6.482mm2, pivw=1.04×10-5) and increase the TH of fusiform (β=0.008mm, Se=0.002mm, pivw=8.86×10-5) and pars opercularis (β=0.009mm, Se=0.002mm, pivw=2.34×10-4). Furthermore, a causal relationship between IL-6Rα and an increase in the SA of superior frontal (β=21.132mm2, Se=5.806mm2, pivw=2.73×10-4) and the TH of supramarginal (β=0.003mm, Se=0.0002mm, pivw=7.86×10-37). All results passed sensitivity analysis and no heterogeneity and pleiotropy were detected.

Conclusion

The correlation between IBD and changes in cerebral cortical structures implies the existence of a gut-brain axis at the organismal level. It is recommended that clinical patients with IBD prioritize long-term management of inflammation, as changes at the organismal level can lead to functional pathologies. Magnetic resonance imaging (MRI) may be considered as an additional screening option for IBD.
Alterations in immunophenotype and metabolic profile of mononuclear cells during follow up in children with multisystem inflammatory syndrome (MIS-C)
Authors: Kopitar Andreja Nataša , Repas Jernej , Janžič Larisa , Bizjak Maša , Vesel Tina Tajnšek , Emeršič Nina , Avramovič Mojca Zajc , Ihan Alojz , Avčin Tadej , Pavlin Mojca
Published: April 2023

Introduction

Although children seem to be less susceptible to COVID-19, some of them develop a rare but serious hyperinflammatory condition called multisystem inflammatory syndrome in children (MIS-C). While several studies describe the clinical conditions of acute MIS-C, the status of convalescent patients in the months after acute MIS-C is still unclear, especially the question of persistence of changes in the specific subpopulations of immune cells in the convalescent phase of the disease.

Methods

We therefore analyzed peripheral blood of 14 children with MIS-C at the onset of the disease (acute phase) and 2 to 6 months after disease onset (post-acute convalescent phase) for lymphocyte subsets and antigen-presenting cell (APC) phenotype. The results were compared with six healthy age-matched controls.

Results

All major lymphocyte populations (B cells, CD4 + and CD8+ T cells, and NK cells) were decreased in the acute phase and normalized in the convalescent phase. T cell activation was increased in the acute phase, followed by an increased proportion of γ/δ-double-negative T cells (γ/δ DN Ts) in the convalescent phase. B cell differentiation was impaired in the acute phase with a decreased proportion of CD21 expressing, activated/memory, and class-switched memory B cells, which normalized in the convalescent phase. The proportion of plasmacytoid dendritic cells, conventional type 2 dendritic cells, and classical monocytes were decreased, while the proportion of conventional type 1 dendritic cells was increased in the acute phase. Importantly the population of plasmacytoid dendritic cells remained decreased in the convalescent phase, while other APC populations normalized. Immunometabolic analysis of peripheral blood mononuclear cells (PBMCs) in the convalescent MIS-C showed comparable mitochondrial respiration and glycolysis rates to healthy controls.

Conclusions

While both immunophenotyping and immunometabolic analyzes showed that immune cells in the convalescent MIS-C phase normalized in many parameters, we found lower percentage of plasmablasts, lower expression of T cell co-receptors (CD3, CD4, and CD8), an increased percentage of γ/δ DN Ts and increased metabolic activity of CD3/CD28-stimulated T cells. Overall, the results suggest that inflammation persists for months after the onset of MIS-C, with significant alterations in some immune system parameters, which may also impair immune defense against viral infections.
Design and selection of optimal ErbB-targeting bispecific antibodies in pancreatic cancer
Authors: Rabia Emilia , Garambois Véronique , Dhommée Christine , Larbouret Christel , Lajoie Laurie , Buscail Yoan , Jimenez-Dominguez Gabriel , Choblet-Thery Sylvie , Liaudet-Coopman Emmanuelle , Cerutti Martine , Jarlier Marta , Ravel Patrice , Gros Laurent , Pirot Nelly , Thibault Gilles , Zhukovsky Eugene A. , Gérard Pierre-Emmanuel , Pèlegrin André , Colinge Jacques , Chardès Thierry
Published: April 2023

The ErbB family of receptor tyrosine kinases is a primary target for small molecules and antibodies for pancreatic cancer treatment. Nonetheless, the current treatments for this tumor are not optimal due to lack of efficacy, resistance, or toxicity. Here, using the novel BiXAb™ tetravalent format platform, we generated bispecific antibodies against EGFR, HER2, or HER3 by considering rational epitope combinations. We then screened these bispecific antibodies and compared them with the parental single antibodies and antibody pair combinations. The screen readouts included measuring binding to the cognate receptors (mono and bispecificity), intracellular phosphorylation signaling, cell proliferation, apoptosis and receptor expression, and also immune system engagement assays (antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity). Among the 30 BiXAbs™ tested, we selected 3Patri-1Cetu-Fc, 3Patri-1Matu-Fc and 3Patri-2Trastu-Fc as lead candidates. The in vivo testing of these three highly efficient bispecific antibodies against EGFR and HER2 or HER3 in pre-clinical mouse models of pancreatic cancer showed deep antibody penetration in these dense tumors and robust tumor growth reduction. Application of such semi-rational/semi-empirical approach, which includes various immunological assays to compare pre-selected antibodies and their combinations with bispecific antibodies, represents the first attempt to identify potent bispecific antibodies against ErbB family members in pancreatic cancer.
Environment and time drive the links between the species richness and ecosystem multifunctionality from multitrophic freshwater mesocosms
Authors: Xu Zhiyan , Yang Hui , Mao Hongzhi , Peng Qiutong , Yang Shiwen , Chou Qingchuan , Yang Yujing , Li Zhongqiang , Wei Lifei
Published: April 2023

Understanding the link between biodiversity and ecosystem functioning is imperative for ecosystem-based management. The role of multitrophic diversity in sustaining multifunctionality remains unclear, especially in highly diverse aquatic ecosystems. We performed a species-addition experiment consisting of one, two, three, and five species in simulated multitrophic ecosystems to evaluate biodiversity and ecosystem functioning relationships within and across trophic levels. Our results showed that there are positive species richness–productivity relationships within and across trophic levels. We found significant negative correlations between species richness and the cumulative variation of total phosphorus, and between species richness and ecosystem multifunctionality across trophic levels. Also, we found that the relationships between ecosystem multifunctionality and species richness within and across the trophic levels are mediated by a combination of environmental factors, including water temperature, dissolved oxygen, pH, irradiance, and time, rather than by species richness. Our results imply that species richness–ecosystem functioning relationships vary for different ecological functions; the individual ecosystem functions selected and the way multifunctionality calculated are critical when examining links between biodiversity and ecosystem multifunctionality. Our study highlights that multitrophic richness, such as for consumers, is crucial for driving ecosystem multifunctionality. Furthermore, our study implies that management practices for restoring the diversity of aquatic macrophytes in wetlands should consider not only macrophyte richness but also different functional groups and life-forms.
Situation analysis on the regulation of nanomedicines in Southern Africa
Authors: Mudyiwenyama Linda G. , Khoza Star , Dube Admire
Published: April 2023

Background

Medical products incorporating nanoparticle drug delivery systems (nanomedicines) are therapeutic or imaging agents, which comprise a delivery system within the nanometer size range (1 – 1000 nm). As medical products, nanomedicines meet definitions of medicines according to various national legislations for regulation of medicines. However, for the regulation of nanomedicines, additional assessments including toxicological issues have to be considered. These complexities require extra regulatory effort. In the resource-limited context of low- and middle-income countries, many National Medicines Regulatory Authorities (NMRAs) lack resources and capacities to effectively assure the quality of medicinal products in their countries. With emerging trends in innovative technologies, including nanotechnology, this burden is worsened. The need to overcome regulatory challenges drove the formation of a work sharing initiative in the Southern African Development Community (SADC), ZaZiBoNA in 2013. Regulatory agencies participating in this initiative cooperate in the assessment of applications for registration of medicines.

Methods

A cross-sectional exploratory study design with qualitative techniques was used to investigate the status of the regulation of nanomedicines in Southern African countries in particular those participating in the ZaZiBoNA initiative.

Results

The study found that in general, NMRAs are aware of the existence of nanomedicines and they apply legislation applicable to other medical products. The NMRAs however neither have specific definition for nanomedicines and technical guidance documents, nor technical committees specific for consideration of nanomedicines. Collaboration with external experts or organisations in the regulation of nanomedicines was also found to be lacking.

Discussion

Capacity building and collaboration in the area of regulation of nanomedicines is strongly encouraged.
Inflammatory bowel disease and risk of Parkinson’s disease: evidence from a meta-analysis of 14 studies involving more than 13.4 million individuals
Authors: Li Hong-xing , Zhang Cui , Zhang Kai , Liu Yi-zhe , Peng Xiao-xiao , Zong Qiang
Published: April 2023

Background

The relationship between inflammatory bowel disease (IBD) and the risk of Parkinson’s Disease (PD) has been investigated in several epidemiological studies. However, the results of these studies were inconclusive and inconsistent. We evaluated the potential relationship between IBD and PD risk by a meta-analysis.

Methods

Search the electronic databases PubMed, Embase and Cochrane databases from inception to November 30, 2022, to identify relevant studies that assess the risk of PD in patients with IBD. The cohort, cross-sectional, mendelian randomization and case-control studies that reported risk estimates of PD and IBD were included in our analysis. The random-effect model and fixed-effects model were used to calculate the summary relative risks (RRs) with 95% confidence intervals (CIs).

Results

In total, 14 studies (nine cohort studies, two cross-sectional studies, two mendelian randomization studies and one case-control study) involving more than 13.4 million individuals were analyzed in our analysis. Our results suggested that the risk of PD in IBD patients is moderately increased, with the pooled RR was 1.17 (95% CI: 1.03–1.33, P = 0.019). Omit of any single study from this analysis had little effect on the combined risk estimate. No evidence of publication bias was found. In the subgroup analysis, the combined RR was 1.04 (95% CI: 0.96, 1.12, P = 0.311) for Crohn’s disease (CD), and 1.18 (95% CI: 1.06, 1.31, P = 0.002) for ulcerative colitis (UC). In addition, a significant association was identified in patients with IBD aged ≥ 60 years (RR = 1.22; 95% CI: 1.06–1.41, P = 0.007), but not in age < 60 years (RR = 1.19; 95% CI: 0.58–2.41, P = 0.639). Meanwhile, the meta-analysis results suggested a protective role for IBD medication use against PD development, with the RR was 0.88 (95% CI: 0.74, 1.04, P = 0.126).

Conclusion

Our results indicated that patients with IBD had a moderately higher risk of PD compared to non-IBD individuals. Patients with IBD should be aware of the potential risks for PD, especially who were ≥ 60 years old.
Influence of Voxelotor–hemoglobin complexes in the estimation of hemoglobin S levels by the current standard of care laboratory evaluation techniques
Authors: Alkindi Salam , Al Subhi Ahmed , Ali Abubakr E. H. , Pathare Anil V.
Published: April 2023

Background

Sickle cell disease is an inherited disorder characterized by the presence of sickle hemoglobin (HbS). The process of Hb molecule polymerization is a pivotal step in the sickling process. Voxelotor, a recently approved novel therapeutic agent, is known to interfere with polymerization. We aim to study the impact of Voxelotor on Hb variants analysis using high performance liquid chromatography (HPLC).

Material and methods

We are reporting the impact of Voxelotor on Hb variants analysis using HPLC after an informed consent and medical research committee approval. Data was collected from eight patients who are enrolled in the GBT440-034OL study using electronic medical records, to evaluate the Hb levels, hemolytic markers and the clinical response.

Results

Our patients were well-balanced for gender, with a mean age of 31.1 years (19–50). Six patients showed a significant improvement in the Hb level, with reduced reticulocytes, bilirubin, LDH and an improved clinical outcome. Interestingly, these patients showed the appearance of a split band of Hb S and D on HPLC impacting significantly on HbS level. Two patients did not show any improvement on laboratory parameters, and no changes on their HPLC analysis.

Conclusions

We report here eight patients on Voxelotor therapy, six of which showed improved hemolytic markers and anemia and demonstrated the appearance of HbD peak on the HPLC chromatogram. Therefore, the absence of HbD on HPLC or other laboratory methods for estimating HbS in patients on Voxelotor therapy, gives the clinician a possible hint regarding the patient's compliance with the drug.