bluuebunny/crossref_metadata_2025 huggingface dataset:
Violência interpessoal contra a mulher no Estado do Ceará de 2009 a 2018: estudo ecológico
Authors: Leitão Paola Rachel Pinheiro , Batista Jefferson Felipe Calazans , Dantas Brenda Layssa Lima , Oliveira Ana Vitória do Nascimento , Quezado Silvia Rebeca Sabóia , Silva Juliana de Oliveira Musse
Published: August 2021

Objetivo: Analisar a tendência da violência interpessoal contra a mulher no Estado do Ceará de 2009 a 2018. Métodos: Trata-se de um estudo ecológico de série temporal, sobre os casos notificados e mortalidade por violência contra mulher. Foram selecionadas quatro grupos de variáveis para análise: perfil da vítima/caso, tipos de violência, mecanismos de ação e agressor. Para análise de tendência adotou-se o modelo de regressão linear simples. Resultados: De 2009 a 2018, foram 19.135 casos de violência contra a mulher. Ao longo dos anos observou-se um aumento de 95,1% no quantitativo de notificações. Verificou-se associação estatisticamente significativa entre as taxas de mortalidade e os anos do estudo (p= 0,0024), indigitando um incremento anual de 0,5885. O coeficiente de prevalência mostrou um aumento anual - relevante - de 11,5188 (p <0,001). Conclusão: No decorrer da série temporal os coeficientes de prevalência aumentaram, o que demonstra a efetividade de algumas políticas de saúde públicas direcionadas para esse aspecto.
Emprego de água biossalina na germinação de sementes de espécies florestais da Caatinga – uma revisão
Authors: Santos Agda Raiany Mota dos , Silva Monalisa Alves Diniz da , Sousa Lady Daiane Costa de , Araújo Ariana Veras de , Gonçalves Edilma Pereira
Published: August 2021

Com a redução das águas de boa qualidade e o aumento de águas biossalinas no mundo tornam-se necessários estudos voltados para a produção de mudas de espécies florestais, visto que há uma necessidade de recuperação de áreas degradadas e estas podem estar sujeitas a diversos estresses, sobretudo o salino. A presente revisão de literatura possui como objetivo avaliar artigos científicos sobre o emprego de águas biossalinas na germinação de sementes de espécies florestais da Caatinga, assim como averiguar as temáticas abordadas (salinidade, estresse salino, águas biossalinas, efeito dos sais na germinação de sementes, tolerância à salinidade, estratégias para uso de águas biossalinas, produção de mudas com águas biossalinas, sementes florestais submetidas à salinidade) nas publicações, idiomas adotados (português, inglês e espanhol) e o número de artigos por base de dados. Com as temáticas utilizadas abordadas foi possível encontrar um número muito elevado de artigos nas bases de dados (Scielo, Web of Science, Periódico Capes e Google Acadêmico) durante os 20 anos analisados, totalizando 217.477, entretanto com maior aprofundamento das temáticas para espécies florestais da Caatinga esse número reduziu drasticamente chegando a 183 artigos, com maior predominância na base de dados Google Acadêmico. Os resultados sugerem que são necessárias mais pesquisas com relação ao estresse salino, ao qual as espécies florestais da Caatinga estão sujeitas, pois a salinidade é uma realidade nesta floresta tropical seca.
Um inimigo invisível: Covid-19 e o seu impacto à saúde mental
Authors: Monteiro Raíssa Ester Maia , Luiz Cynthia Borges , Monteiro Emerson Serafim Galdino , Lopez Luiz Carlos Serramo
Published: August 2021

O COVID-19 trouxe diversos desafios para o Brasil e para o mundo. Além dos impactos biológicos, sociais e econômicos, o novo coronavírus vem comprometendo sobremaneira a saúde mental das pessoas, seja pela possibilidade de exposição ao contágio, pelo impacto advindo do distanciamento social ou pelo medo da morte. Esse estudo se trata de uma revisão narrativa de literatura mediante o uso da pesquisa bibliográfica, de pesquisa descritiva e natureza qualitativa, com o objetivo de apresentar conhecimentos relativos à saúde mental durante o COVID-19, especificamente sobre os impactos à saúde mental ocasionados pelo vírus. Buscou-se por materiais em diversas bases de dados (Google Scholar, SciELO, PubMed, Lilacs, entre outros), bem como se utilizou de alguns descritores para filtrar a busca pelo conteúdo, a exemplo de “Covid-19”, “Sars-Cov-2”, “pandemia”, “distanciamento social” e “saúde mental”. À guisa de conclusão, a literatura indica que boa parte da população foi afetada, desenvolvendo algum transtorno mental nesse período, com destaque para a ansiedade e a depressão.  Importa a criação de estratégias para promover qualidade de vida e bem-estar em tempos tão propícios para o adoecimento mental.
Flow instability effects related to purge through a gas turbine chute seal
Authors: Roy Arijit , Fridh Jens , Scobie James , Sangan Carl , Lock Gary
Published: August 2021

This paper investigates flow instabilities inside the cavity formed between the stator and rotor disks of a high-speed turbine rig. The cavity rim seal is of chute seal design. The influence of flow coefficient on the sealing effectiveness at constant purge flow rate through the wheel-space is determined. The effectiveness at different radial positions over a range of purge flow conditions and flow coefficients is also studied. Unsteady pressure measurements have identified the frequency of instabilities that form within the rim seal, phenomena which have been observed in other studies. Frequencies of these disturbances, and their correlation in the circumferential direction have determined the strength and speed of rotation of the instabilities within the cavity. Large scale unsteady rotational structures have been identified, which show similarity to previous studies. These disturbances have been found to be weakly dependent on the purge flow and flow coefficients, although an increased purge reduced both the intensity and speed of rotation of the instabilities. Additionally, certain uncorrelated disturbances have been found to be inconsistent (discontinuous) with pitchwise variation.
A Starting Note: A Historical Perspective in Lasso
Authors: CANER Mehmet
Published: August 2021

we provide history of lasso, and see new ventures and talk about key concept of debiased lasso. Lasso provided a good fit through sparse regression but did not deliver standard errors. The debiased lasso delivers.
Two Novel Pathogenic Variants of TJP2 Gene and the Underlying Molecular Mechanisms in Progressive Familial Intrahepatic Cholestasis Type 4 Patients
Authors: Tang Jia , Tan Meihua , Deng Yihui , Tang Hui , Shi Haihong , Li Mingzhen , Ma Wei , Li Jia , Dai Hongzheng , Li Jianli , Zhou Shengmei , Li Xu , Wei Fengxiang , Ma Xiaofen , Luo Liangping
Published: August 2021

Progressive familial intrahepatic cholestasis (PFIC) is an autosomal recessive inherited disease that accounts for 10%–15% childhood cholestasis and could lead to infant disability or death. There are three well-established types of PFIC (1–3), caused by mutations in the ATP8B1, ABCB11, and ABCB4 genes. Biallelic pathogenic variants in the tight junction protein 2 gene (TJP2) were newly reported as a cause for PFIC type 4; however, only a limited number of patients and undisputable variants have been reported for TJP2, and the underlying mechanism for PFIC 4 remains poorly understood. To explore the diagnostic yield of TJP2 analysis in suspected PFIC patients negative for the PFIC1–3 mutation, we designed a multiplex polymerase chain reaction-based next-generation sequencing method to analyze TJP2 gene variants in 267 PFIC patients and identified biallelic rare variants in three patients, including three known pathogenic variants and two novel variants in three patients. By using CRISPR-cas9 technology, we demonstrated that TJP2 c.1202A > G was pathogenic at least partially by increasing the expression and nuclear localization of TJP2 protein. With the minigene assay, we showed that TJP2 c.2668-11A > G was a new pathogenic variant by inducing abnormal splicing of TJP2 gene and translation of prematurely truncated TJP2 protein. Furthermore, knockdown of TJP2 protein by siRNA technology led to inhibition of cell proliferation, induction of apoptosis, dispersed F-actin, and disordered microfilaments in LO2 and HepG2celles. Global gene expression profiling of TJP2 knockdown LO2 cells and HepG2 cells identified the dysregulated genes involved in the regulation of actin cytoskeleton. Microtubule cytoskeleton genes were significantly downregulated in TJP2 knockdown cells. The results of this study demonstrate that TJP2 c.1202A > G and TJP2 c.2668-11A > G are two novel pathogenic variants and the cytoskeleton-related functions and pathways might be potential molecular pathogenesis for PFIC.
How Different Albumin-Binders Drive Probe Distribution of Fluorescent RGD Mimetics
Authors: Höltke Carsten , Alsibai Wael , Grewer Martin , Stölting Miriam , Geyer Christiane , Eisenblätter Michel , Wildgruber Moritz , Helfen Anne
Published: August 2021

The biodistribution of medical imaging probes depends on the chemical nature of the probe and the preferred metabolization and excretion routes. Especially targeted probes, which have to reach a certain (sub)cellular destination, have to be guided to the tissue of interest. Therefore, small molecular probes need to exhibit a well-balanced polarity and lipophilicity to maintain an advantageous bioavailability. Labelled antibodies circulate for several days due to their size. To alter the biodistribution behavior of probes, different strategies have been pursued, including utilizing serum albumin as an inherent transport mechanism for small molecules. We describe here the modification of an existing fluorescent RGD mimetic probe targeted to integrin αvβ3 with three different albumin binding moieties (ABMs): a diphenylcyclohexyl (DPCH) group, a p-iodophenyl butyric acid (IPBA) and a fatty acid (FA) group with the purpose to identify an optimal ABM for molecular imaging applications. All three modifications result in transient albumin binding and a preservation of the target binding capability. Spectrophotometric measurements applying variable amounts of bovine serum albumin (BSA) reveal considerable differences between the compounds concerning their absorption and emission characteristics and hence their BSA binding mode. In vivo the modified probes were investigated in a murine U87MG glioblastoma xenograft model over the course of 1 wk by fluorescence reflectance imaging (FRI) and fluorescence mediated tomography (FMT). While the unmodified probe was excreted rapidly, the albumin-binding probes were accumulating in tumor tissue for at least 5 days. Considerable differences between the three probes in biodistribution and excretion characteristics were proved, with the DPCH-modified probe showing the highest overall signal intensities, while the FA-modified probe exhibits a low but more specific fluorescent signal. In conclusion, the modification of small molecular RGD mimetics with ABMs can precisely fine-tune probe distribution and offers potential for future clinical applications.
Expression Profiles and Potential Functions of Long Non-Coding RNAs in the Heart of Mice With Coxsackie B3 Virus-Induced Myocarditis
Authors: Nie Xiang , Li Huihui , Wang Jin , Cai Yuanyuan , Fan Jiahui , Dai Beibei , Chen Chen , Wang Dao Wen
Published: August 2021

Aims

Long non-coding RNAs (lncRNAs) are critical regulators of viral infection and inflammatory responses. However, the roles of lncRNAs in acute myocarditis (AM), especially fulminant myocarditis (FM), remain unclear.

Methods

FM and non-fulminant myocarditis (NFM) were induced by coxsackie B3 virus (CVB3) in different mouse strains. Then, the expression profiles of the lncRNAs in the heart tissues were detected by sequencing. Finally, the patterns were analyzed by Pearson/Spearman rank correlation, Kyoto Encyclopedia of Genes and Genomes, and Cytoscape 3.7.

Results

First, 1,216, 983, 1,606, and 2,459 differentially expressed lncRNAs were identified in CVB3-treated A/J, C57BL/6, BALB/c, and C3H mice with myocarditis, respectively. Among them, 88 lncRNAs were commonly dysregulated in all four models. Quantitative real-time polymerase chain reaction analyses further confirmed that four out of the top six commonly dysregulated lncRNAs were upregulated in all four models. Moreover, the levels of ENSMUST00000188819, ENSMUST00000199139, and ENSMUST00000222401 were significantly elevated in the heart and spleen and correlated with the severity of cardiac inflammatory infiltration. Meanwhile, 923 FM-specific dysregulated lncRNAs were detected, among which the levels of MSTRG.26098.49, MSTRG.31307.11, MSTRG.31357.2, and MSTRG.32881.28 were highly correlated with LVEF.

Conclusion

Expression of lncRNAs is significantly dysregulated in acute myocarditis, which may play different roles in the progression of AM.
Natural Entrapments of Killer Whales (Orcinus orca): A Review of Cases and Assessment of Intervention Techniques
Authors: Jourdain Eve , Barrett-Lennard Lance G. , Ellis Graeme M. , Ford John K. B. , Karoliussen Richard , Towers Jared R. , Vongraven Dag
Published: August 2021

Identifying mortality sources and mitigation solutions is crucial in species management and conservation. In killer whales (Orcinus orca), mortality events may pose a serious concern for the conservation of small discrete populations, especially if they involve entire groups. This study investigated 19 incidents involving 116 killer whales from a minimum of five populations becoming naturally entrapped in inshore areas of the North Pacific (n= 12) and North Atlantic (n= 7) oceans between 1949 and 2019. Here, we aim to provide an assessment of possible causal factors, lethality and human responses to these events. Site characteristics and group size identified three categories of entrapments. InCategory 1, nine cases involved small groups of killer whales (median = 5, range: 1–9) at sites characterized by severe geographic and food constraints. Four cases inCategory 2included larger groups (median= 14, range: 6–19) and entrapment sites with no obvious geographic constraints but at which man-made structures could have acted as deterrents. Five cases assigned toCategory 3involved lone, often young individuals settling in a restricted home range and engaging in interactions with people and boats. Overall, all or some of the killer whales swam out on their own after a mean of 36 d of entrapment (range: 1–172, SD = 51,n= 9 cases), died of nutritional/physiological stress after 58 d (range: 42–90, SD = 21,n= 3 cases) or of injury after ~5 years of daily interactions with boat traffic (n= 1 case). Indication of the killer whales' declining condition or being at risk of injury, and of poor habitat quality, led to the decision to intervene in seven cases where a variety of methods were used to guide or relocate remaining individuals back to open waters after 39 d (SD = 51, range = 8–150). Monitoring protocols, which aided in identifying entrapment situations, and intervention methods which enhanced the health and survival of entrapped killer whales, are discussed.
Practical Decision Algorithms for the Use of the Cardiovascular Polypill in Secondary Prevention in Europe
Authors: Grigorian-Shamagian Lilian , Edel Klaus , Esteve-Pastor María Asunción , Aceña Álvaro , Silva Claudia , Delgado-Silva Joana , Ntaios Georges , Demerouti Eftychia , Brotons Carlos
Published: August 2021

The main objective of cardiovascular disease (CVD) prevention is to reduce morbidity and mortality. Despite recommendations on evidence-based pharmacological treatment and lifestyle changes, the control of CV risk factors such as hypertension or dyslipidaemia is not optimal. The use of a CV polypill, including guideline-recommended drugs, as a baseline therapy, may contribute to improving risk factors control either by improving the treatment adherence or by the synergistic effect of its components. The CNIC-Polypill is the first CV polypill approved in Europe as an effective strategy for secondary prevention, which contains acetylsalicylic acid, atorvastatin (in two optional doses), and ramipril (in three optional doses) in a single pill. The present practical clinical document aims to provide a guide for patient management after an acute coronary syndrome (ACS) or with chronic CVD (CCVD) with a strategy based on the CNIC-Polypill, also considering the need to add other therapies for a personalized treatment. The most suitable clinical scenarios for the CNIC-Polypill use are discussed: (a) in patients after an ACS at discharge, (b) in patients with CCVD (chronic coronary syndrome, stroke, or peripheral artery disease) with uncontrolled low-density lipoprotein cholesterol (LDL-c) and/or blood pressure levels and (c) in patients with CCVD with well-controlled risk factors to simplify treatment and reduce polypharmacy in the context of CCVD prevention.
Social and Emotional Learning in Preschool Settings: A Systematic Map of Systematic Reviews
Authors: Djamnezhad Dariush , Koltcheva Nadia , Dizdarevic Alma , Mujezinovic Amila , Peixoto Carla , Coelho Vera , Achten Mart , Kolumbán Erika , Machado Francisco , Hofvander Björn
Published: August 2021

The preschool years presents an important opportunity to support children’s social and emotional development. Social and emotional learning (SEL) programs in early childhood education and care (ECEC) have gained an increased interest due to its potential to improve child health and educational outcomes. We aimed to identify existing systematic reviews on universal, curriculum-based SEL interventions in ECEC settings (children aged 0 to 7 years), assess their risk of bias, synthesize the findings and identify knowledge gaps. We undertook a systematic literature search in seven different databases. Reviews of studies without control groups were excluded. Each abstract and full text article was assessed independently, and disagreements were solved in consensus. Relevant reviews were assessed for bias using the ROBIS tool. Of 4912 records identified through database searches, two systematic reviews met the inclusion criteria. Both reviews were assessed as having a high risk of bias. The results were used to summarize existing knowledge and knowledge gaps. In conclusion, SEL interventions in preschool settings must be considered knowledge gaps. There is a need for more high-quality primary studies and further systematic reviews that adhere to strict scientific methods and address the overwhelming heterogeneity in field, in terms of interventions, settings and outcomes.
Mathematical Problem-Solving Through Cooperative Learning—The Importance of Peer Acceptance and Friendships
Authors: Klang Nina , Karlsson Natalia , Kilborn Wiggo , Eriksson Pia , Karlberg Martin
Published: August 2021

Mathematical problem-solving constitutes an important area of mathematics instruction, and there is a need for research on instructional approaches supporting student learning in this area. This study aims to contribute to previous research by studying the effects of an instructional approach of cooperative learning on students’ mathematical problem-solving in heterogeneous classrooms in grade five, in which students with special needs are educated alongside with their peers. The intervention combined a cooperative learning approach with instruction in problem-solving strategies including mathematical models of multiplication/division, proportionality, and geometry. The teachers in the experimental group received training in cooperative learning and mathematical problem-solving, and implemented the intervention for 15 weeks. The teachers in the control group received training in mathematical problem-solving and provided instruction as they would usually. Students (269 in the intervention and 312 in the control group) participated in tests of mathematical problem-solving in the areas of multiplication/division, proportionality, and geometry before and after the intervention. The results revealed significant effects of the intervention on student performance in overall problem-solving and problem-solving in geometry. The students who received higher scores on social acceptance and friendships for the pre-test also received higher scores on the selected tests of mathematical problem-solving. Thus, the cooperative learning approach may lead to gains in mathematical problem-solving in heterogeneous classrooms, but social acceptance and friendships may also greatly impact students’ results.
“Fold the Eggs … Fold the Eggs … ”: Experiences of Educational Stakeholders During COVID-19
Authors: Bharaj Pavneet Kaur , Singh Anisha
Published: August 2021

As the world experienced the COVID-19 outbreak, education was one of the multiple systems that were hit hard. We explored the consequences of the reconfiguration of schooling based on the experiences of the educational stakeholders caught up in the sudden transition to virtual schooling during COVID-19. Using Bronfenbrenner’s (1976) Ecological Systems framework, we underscored the complexity of the individual’s socio-cultural world and the myriad influences that impact the individual’s growth to examine how agents involved in the educational system have dealt with this unanticipated crisis academically, personally, socially, and emotionally. People can endorse contradictory positions on the same policy. Recognizing that multiplicity of voices might bring a different perspective, we captured various voices—an administrator leading the teachers’ professional development, a public-school elementary teacher, and a parent with two kids. Using unstructured interviews, we unpacked the narratives and counter-narratives of the participants to unpack “what worked” and “what did not work” during virtual learning and teaching environment. The voices centered in this article offer a rich source of insight into challenges faced by those who are at the forefront of the educational crisis—teachers and parents. The results showed how various communities cooperated to deal with such unprecedented times while maintaining the responsibility of educating children. The key trends that emerged from our qualitative investigation were: 1) development of collaboration among teachers as they transitioned into virtual teaching, 2) flexibility of the school leaders to assist the teachers in this new instructional modality, and 3) parents’ acknowledgment of the teachers’ efforts to assist their children.
Vasopressinergic Activity of the Suprachiasmatic Nucleus and mRNA Expression of Clock Genes in the Hypothalamus-Pituitary-Gonadal Axis in Female Aging
Authors: Nicola Angela Cristina , Ferreira Larissa Brazoloto , Mata Milene Mantovani , Vilhena-Franco Tatiane , Leite Cristiane Mota , Martins Andressa Busetti , Antunes-Rodrigues José , Poletini Maristela Oliveira , Dornelles Rita Cássia Menegati
Published: August 2021

The important involvement of the suprachiasmatic nucleus (SCN) and the activity of vasopressinergic neurons in maintaining the rhythmicity of the female reproductive system depends on the mRNA transcription-translation feedback loops. Therefore, circadian clock function, like most physiological processes, is involved in the events that determine reproductive aging. This study describes the change of mRNA expression of clock genes, Per2, Bmal1, and Rev-erbα, in the hypothalamus-pituitary-gonadal axis (HPG) of female rats with regular cycle (RC) and irregular cycle (IC), and the vasopressinergic neurons activity in the SCN and kisspeptin neurons in the arcuate nucleus (ARC) of these animals. Results for gonadotropins and the cFos/AVP-ir neurons in the SCN of IC were higher, but kisspeptin-ir was minor. Change in the temporal synchrony of the clock system in the HPG axis, during the period prior to the cessation of ovulatory cycles, was identified. The analysis of mRNA for Per2, Bmal1, and Rev-erbα in the reproductive axis of adult female rodents shows that the regularity of the estrous cycle is guaranteed by alternation in the amount of expression of Bmal1 and Per2, and Rev-erbα and Bmal1 between light and dark phases, which ceases to occur and contributes to determining reproductive senescence. These results showed that the desynchronization between the central and peripheral circadian clocks contributes to the irregularity of reproductive events. We suggest that the feedback loops of clock genes on the HPG axis modulate the spontaneous transition from regular to irregular cycle and to acyclicity in female rodents.
When Leptin Is Not There: A Review of What Nonsyndromic Monogenic Obesity Cases Tell Us and the Benefits of Exogenous Leptin
Authors: Salum Kaio Cezar Rodrigues , Rolando Jônatas de Mendonça , Zembrzuski Verônica Marques , Carneiro João Regis Ivar , Mello Cicero Brasileiro , Maya-Monteiro Clarissa Menezes , Bozza Patrícia Torres , Kohlrausch Fabiana Barzotto , da Fonseca Ana Carolina Proença
Published: August 2021

Obesity is a pandemic condition of complex etiology, resulting from the increasing exposition to obesogenic environmental factors combined with genetic susceptibility. In the past two decades, advances in genetic research identified variants of the leptin-melanocortin pathway coding for genes, which are related to the potentiation of satiety and hunger, immune system, and fertility. Here, we review cases of congenital leptin deficiency and the possible beneficial effects of leptin replacement therapy. In summary, the cases presented here show clinical phenotypes of disrupted bodily energy homeostasis, biochemical and hormonal disorders, and abnormal immune response. Some phenotypes can be partially reversed by exogenous administration of leptin. With this review, we aim to contribute to the understanding of leptin gene mutations as targets for obesity diagnostics and treatment strategies.
Path Dependency and Future Adaptation of Coastal Cities: Examples From the Asia-Pacific
Authors: Nunn Patrick D. , Smith Timothy F. , Elrick-Barr Carmen
Published: August 2021

The need for Asia-Pacific coastal cities to adapt effectively and sustainably to accelerating (relative) sea-level rise is growing. If such adaptation does not occur in a timely manner, then it could result in socio-economic problems that will reverberate throughout the region. Using examples of coastal Asia-Pacific cities that are characterised by contrasting geographical settings and cultural contexts, this study argues that the main barrier to such adaptation is path dependency. In this sense, path dependency is a legacy of past decisions that have been influenced by topography, economic goals, and the cultural-political characteristics of key decision-making groups. These path dependencies manifest as various adaptation preferences, which to date have been dominated by hard engineering solutions. In an era of accelerating climate change there is now a need to seek alternatives to in-situ urban growth. This paper argues that an understanding of a city’s path dependency is key to optimizing the effectiveness of future adaptation.
Elevated Fibronectin Levels in Profibrotic CD14+ Monocytes and CD14+ Macrophages in Systemic Sclerosis
Authors: Rudnik Michał , Hukara Amela , Kocherova Ievgeniia , Jordan Suzana , Schniering Janine , Milleret Vincent , Ehrbar Martin , Klingel Karin , Feghali-Bostwick Carol , Distler Oliver , Błyszczuk Przemysław , Kania Gabriela
Published: August 2021

Background

Systemic sclerosis (SSc) is an autoimmune disease characterized by overproduction of extracellular matrix (ECM) and multiorgan fibrosis. Animal studies pointed to bone marrow-derived cells as a potential source of pathological ECM-producing cells in immunofibrotic disorders. So far, involvement of monocytes and macrophages in the fibrogenesis of SSc remains poorly understood.

Methods and Results

Immunohistochemistry analysis showed accumulation of CD14+ monocytes in the collagen-rich areas, as well as increased amount of alpha smooth muscle actin (αSMA)-positive fibroblasts, CD68+ and mannose-R+ macrophages in the heart and lungs of SSc patients. The full genome transcriptomics analyses of CD14+ blood monocytes revealed dysregulation in cytoskeleton rearrangement, ECM remodeling, including elevated FN1 (gene encoding fibronectin) expression and TGF-β signalling pathway in SSc patients. In addition, single cell RNA sequencing analysis of tissue-resident CD14+ pulmonary macrophages demonstrated activated profibrotic signature with the elevated FN1 expression in SSc patients with interstitial lung disease. Peripheral blood CD14+ monocytes obtained from either healthy subjects or SSc patients exposed to profibrotic treatment with profibrotic cytokines TGF-β, IL-4, IL-10, and IL-13 increased production of type I collagen, fibronectin, and αSMA. In addition, CD14+ monocytes co-cultured with dermal fibroblasts obtained from SSc patients or healthy individuals acquired a spindle shape and further enhanced production of profibrotic markers. Pharmacological blockade of the TGF-β signalling pathway with SD208 (TGF-β receptor type I inhibitor), SIS3 (Smad3 inhibitor) or (5Z)-7-oxozeaenol (TGF-β-activated kinase 1 inhibitor) ameliorated fibronectin levels and type I collagen secretion.

Conclusions

Our findings identified activated profibrotic signature with elevated production of profibrotic fibronectin in CD14+ monocytes and CD14+ pulmonary macrophages in SSc and highlighted the capability of CD14+ monocytes to acquire a profibrotic phenotype. Taking together, tissue-infiltrating CD14+ monocytes/macrophages can be considered as ECM producers in SSc pathogenesis.
Investigation of the Inherent Variability of the Mediterranean Sea Under Contrasting Extreme Climatic Conditions
Authors: Sampatakaki Angeliki , Zervakis Vassilis , Mamoutos Ioannis , Tragou Elina , Gogou Alexandra , Triantaphyllou Maria , Skliris Nikolaos
Published: August 2021

The internal variability of the thermohaline circulation of the Mediterranean Sea is examined under contrasting extreme thermal and mass atmospheric forcing conditions. Three millennium-long numerical simulation experiments were performed under: (a) the current climatology, (b) a strong buoyancy forcing (SBF) scenario due to cold and dry conditions resembling the Younger Dryas event, and (c) a weak buoyancy forcing (WBF) scenario due to S1a sapropel deposition-like conditions (warm and wet). To isolate the inherent variability of the system, independent of interannual atmospheric forcing variability, the latter was defined as a perpetual year pertinent to each experiment. Self-diagnosed heat and salt fluxes, consistent to sea-surface characteristics of the above periods, forced three millenium-long, relaxation-free numerical experiments. These simulations were preceded by initial spin-up periods. The inherent spatiotemporal variability of the Mediterranean Sea was analyzed using the empirical orthogonal function (EOF) and spectral analysis on the simulated density fields. Our results revealed that the Mediterranean Sea exhibits high sensitivity to climatic conditions, allowing its circulation to change from anti-estuarine (for the SBF scenario, leading to a buoyancy loss to the atmosphere) to estuarine (for the WBF scenario, corresponding to a buoyancy gain from the atmosphere). In all three experiments, the interannual and decennial variabilities dominate in upper layers, and the decennial variability dominates in the Gibraltar and Sicily Straits. Under current climatic conditions the first two EOF modes express only 60% of the density variability in the deep layers. This contribution exceeds 90% under more extreme conditions. Moreover, the first EOF modes correspond to a basin-wide in-phase variability of the deep layers under the reference and WBF conditions. During SBF conditions the first modes reveal a vertical buoyancy exchange between upper and deeper layers. The second EOF mode of deep waters under both extreme scenarios showed that the western and eastern basins exchange buoyancy in decennial (for the cold/dry) and interdecennial (for the warm/humid) timescales. The residence time of the Eastern Mediterranean deep water was diagnosed to be centennial, semicentennial, and intercentennial for the cases of current period, SBF, and WBF, respectively.
Clearing a Path to Commercialization of Marine Renewable Energy Technologies Through Public–Private Collaboration
Authors: Chang Grace , Harker-Klimeš Genevra , Raghukumar Kaustubha , Polagye Brian , Haxel Joseph , Joslin James , Spada Frank , Staines Garrett
Published: August 2021

Governments are increasingly turning toward public–private partnerships to bring industry support to improving public assets or services. Here, we describe a unique public–private collaboration where a government entity has developed mechanisms to support public and private sector advancement and commercialization of monitoring technologies for marine renewable energy. These support mechanisms include access to a range of skilled personnel and test facilities that promote rapid innovation, prove reliability, and inspire creativity in technology development as innovations move from concept to practice. The ability to iteratively test hardware and software components, sensors, and systems can accelerate adoption of new methods and instrumentation designs. As a case study, we present the development of passive acoustic monitoring technologies customized for operation in energetic waves and currents. We discuss the value of testing different systems together, under the same conditions, as well as the progression through different test locations. The outcome is multiple, complementary monitoring technologies that are well suited to addressing an area of high environmental uncertainty and reducing barriers to responsible deployment of low-carbon energy conversion systems, creating solutions for the future.
Impact of Ovarian Yield—Number of Total and Mature Oocytes Per Antral Follicular Count—On Live Birth Occurrence After IVF Treatment
Authors: Poulain Marine , Younes Rodine , Pirtea Paul , Trichereau Julie , Ziegler Dominique de , Benammar Achraf , Ayoubi Jean Marc
Published: August 2021

To assess the relation between oocytes yield including total retrieved oocytes (O)c and total mature oocytes (MII) relative to the antral follicular count (AFC) (3–9 mm in diameter) and relative to anti-müllerian hormone (AMH) ng/mL level: Oc/AFC, MII/AFC, Oc/AMH, and MII/AMH, respectively, and ART outcomes. We included retrospectively 264 IVF cycles after the first embryo transfer (ET) and after the cumulative ET (CET). The implantation rate (IR) and the live birth rate (LBR) after first ET were 31 ± 39% and 32.6%, respectively, and after CET 35 ± 38% and 45.1%, respectively. There was a significantly higher average of Oc/AFC and MII/AFC when live birth (LB) occurred after the first ET (0.82 ± 0.4 vs. 0.71 ± 0.35 and 0.57 ± 0.4 vs. 0.68 ± 0.3, respectively, P < 0.05). We reported a significantly higher average of MII/AFC when LB occurred after CET (0.66 ± 0.3 vs. 0.56 ± 0.30, P = 0.02) in comparison to the group where no LB was obtained. Increased Oc/AFC and MII/AFC ratios were associated with the occurrence of LB and increased IR after first ET (P < 0.05). Increased MII/AFC ratio was associated with the occurrence of LB and IR after CET (P = 0.02 and P = 0.04, respectively). After age-adjusted multivariate analyses, all these trends were confirmed (P < 0.05) except for the effect of MII/AFC ratio on IR after CET. In conclusion, Oc/AMH and MII/AMH ratios have no effect on the occurrence of LBR or on IR after first ET or CET at either age grouping. Ratios Oc/AFC and MII/AFC seem promising indicators to assess ovarian response.
Structural Comparisons of Cefotaximase (CTX-M-ase) Sub Family 1
Authors: Shurina Ben A. , Page Richard C.
Published: August 2021

The cefotaximase or CTX-M, family of serine-β-lactamases represents a significant clinical concern due to the ability for these enzymes to confer resistance to a broad array of β-lactam antibiotics an inhibitors. This behavior lends CTX-M-ases to be classified as extended spectrum β-lactamases (ESBL). Across the family of CTX-M-ases most closely related to CTX-M-1, the structures of CTX-M-15 with a library of different ligands have been solved and serve as the basis of comparison within this review. Herein we focus on the structural changes apparent in structures of CTX-M-15 in complex with diazabicyclooctane (DABCO) and boronic acid transition state analog inhibitors. Interactions between a positive surface patch near the active site and complementary functional groups of the bound inhibitor play key roles in the dictating the conformations of active site residues. The insights provided by analyzing structures of CTX-M-15 in complex with DABCO and boronic acid transition state analog inhibitors and analyzing existing structures of CTX-M-64 offer opportunities to move closer to making predictions as to how CTX-M-ases may interact with potential drug candidates, setting the stage for the further development of new antibiotics and β-lactamase inhibitors.
Spring Accumulation Rates in North Atlantic Phytoplankton Communities Linked to Alterations in the Balance Between Division and Loss
Authors: Mojica Kristina D. A. , Behrenfeld Michael J. , Clay Megan , Brussaard Corina P. D.
Published: August 2021

For nearly a century, phytoplankton spring blooms have largely been explained in the context of abiotic factors regulating cellular division rates (e.g., mixed-layer light levels). However, the accumulation of new phytoplankton biomass represents a mismatch between phytoplankton division and mortality rates. The balance between division and loss, therefore, has important implications for marine food webs and biogeochemical cycles. A large fraction of phytoplankton mortality is due to the combination of microzooplankton grazing and viral lysis, however, broad scale simultaneous measurements of these mortality processes are scarce. We applied the modified dilution assay along a West-to-East diagonal transect in the North Atlantic during spring. Our results demonstrate positive accumulation rates with losses dominated by microzooplankton grazing. Considering the dynamic light environment phytoplankton experience in the mixed surface layer, particularly in the spring, we tested the potential for incubation light conditions to affect observed rates. Incubations acted as short-term ‘light’ perturbations experiments, in which deeply mixed communities are exposed to elevated light levels. These “light perturbations” increased phytoplankton division rates and resulted in proportional changes in phytoplankton biomass while having no significant effect on mortality rates. These results provide experimental evidence for the Disturbance-Recovery Hypothesis, supporting the tenet that biomass accumulation rates co-vary with the specific rate of change in division.
A Murine Model of Mycobacterium kansasii Infection Reproducing Necrotic Lung Pathology Reveals Considerable Heterogeneity in Virulence of Clinical Isolates
Authors: Mussi Vinicius O. , Simão Thatiana L. B. V. , Almeida Fabrício M. , Machado Edson , de Carvalho Luciana D. , Calixto Sanderson D. , Sales Guilherme A. M. , Carvalho Eulógio C. Q. , Vasconcellos Sidra E. G. , Catanho Marcos , Suffys Philip N. , Lasunskaia Elena B.
Published: August 2021

Among non-tuberculous mycobacteria, Mycobacterium kansasii is one of the most pathogenic, able to cause pulmonary disease indistinguishable from tuberculosis in immunocompetent susceptible adults. The lack of animal models that reproduce human-like lung disease, associated with the necrotic lung pathology, impairs studies of M. kansasii virulence and pathogenicity. In this study, we examined the ability of the C57BL/6 mice, intratracheally infected with highly virulent M. kansasii strains, to produce a chronic infection and necrotic lung pathology. As a first approach, we evaluated ten M. kansasii strains isolated from Brazilian patients with pulmonary disease and the reference strain M. kansasii ATCC 12478 for virulence-associated features in macrophages infected in vitro; five of these strains differing in virulence were selected for in vivo analysis. Highly virulent isolates induced progressive lung disease in mice, forming large encapsulated caseous granulomas in later stages (120–150 days post-infection), while the low-virulent strain was cleared from the lungs by day 40. Two strains demonstrated increased virulence, causing premature death in the infected animals. These data demonstrate that C57BL/6 mice are an excellent candidate to investigate the virulence of M. kansasii isolates. We observed considerable heterogeneity in the virulence profile of these strains, in which the presence of highly virulent strains allowed us to establish a clinically relevant animal model. Comparing public genomic data between Brazilian isolates and isolates from other geographic regions worldwide demonstrated that at least some of the highly pathogenic strains isolated in Brazil display remarkable genomic similarities with the ATCC strain 12478 isolated in the United States 70 years ago (less than 100 SNPs of difference), as well as with some recent European clinical isolates. These data suggest that few pathogenic clones have been widely spread within M. kansasii population around the world.
Coarse-Grained Modeling and Molecular Dynamics Simulations of Ca2+-Calmodulin
Authors: Nde Jules , Zhang Pengzhi , Ezerski Jacob C. , Lu Wei , Knapp Kaitlin , Wolynes Peter G. , Cheung Margaret S.
Published: August 2021

Calmodulin (CaM) is a calcium-binding protein that transduces signals to downstream proteins through target binding upon calcium binding in a time-dependent manner. Understanding the target binding process that tunes CaM’s affinity for the calcium ions (Ca2+), or vice versa, may provide insight into how Ca2+-CaM selects its target binding proteins. However, modeling of Ca2+-CaM in molecular simulations is challenging because of the gross structural changes in its central linker regions while the two lobes are relatively rigid due to tight binding of the Ca2+ to the calcium-binding loops where the loop forms a pentagonal bipyramidal coordination geometry with Ca2+. This feature that underlies the reciprocal relation between Ca2+ binding and target binding of CaM, however, has yet to be considered in the structural modeling. Here, we presented a coarse-grained model based on the Associative memory, Water mediated, Structure, and Energy Model (AWSEM) protein force field, to investigate the salient features of CaM. Particularly, we optimized the force field of CaM and that of Ca2+ ions by using its coordination chemistry in the calcium-binding loops to match with experimental observations. We presented a “community model” of CaM that is capable of sampling various conformations of CaM, incorporating various calcium-binding states, and carrying the memory of binding with various targets, which sets the foundation of the reciprocal relation of target binding and Ca2+ binding in future studies.
Mirror Mechanism Behind Visual–Auditory Interaction: Evidence From Event-Related Potentials in Children With Cochlear Implants
Authors: Wang Junbo , Liu Jiahao , Lai Kaiyin , Zhang Qi , Zheng Yiqing , Wang Suiping , Liang Maojin
Published: August 2021

The mechanism underlying visual-induced auditory interaction is still under discussion. Here, we provide evidence that the mirror mechanism underlies visual–auditory interactions. In this study, visual stimuli were divided into two major groups—mirror stimuli that were able to activate mirror neurons and non-mirror stimuli that were not able to activate mirror neurons. The two groups were further divided into six subgroups as follows: visual speech-related mirror stimuli, visual speech-irrelevant mirror stimuli, and non-mirror stimuli with four different luminance levels. Participants were 25 children with cochlear implants (CIs) who underwent an event-related potential (ERP) and speech recognition task. The main results were as follows: (1) there were significant differences in P1, N1, and P2 ERPs between mirror stimuli and non-mirror stimuli; (2) these ERP differences between mirror and non-mirror stimuli were partly driven by Brodmann areas 41 and 42 in the superior temporal gyrus; (3) ERP component differences between visual speech-related mirror and non-mirror stimuli were partly driven by Brodmann area 39 (visual speech area), which was not observed when comparing the visual speech-irrelevant stimulus and non-mirror groups; and (4) ERPs evoked by visual speech-related mirror stimuli had more components correlated with speech recognition than ERPs evoked by non-mirror stimuli, while ERPs evoked by speech-irrelevant mirror stimuli were not significantly different to those induced by the non-mirror stimuli. These results indicate the following: (1) mirror and non-mirror stimuli differ in their associated neural activation; (2) the visual–auditory interaction possibly led to ERP differences, as Brodmann areas 41 and 42 constitute the primary auditory cortex; (3) mirror neurons could be responsible for the ERP differences, considering that Brodmann area 39 is associated with processing information about speech-related mirror stimuli; and (4) ERPs evoked by visual speech-related mirror stimuli could better reflect speech recognition ability. These results support the hypothesis that a mirror mechanism underlies visual–auditory interactions.
Current Therapies for Neonatal Hypoxic–Ischaemic and Infection-Sensitised Hypoxic–Ischaemic Brain Damage
Authors: Tetorou Konstantina , Sisa Claudia , Iqbal Arzo , Dhillon Kim , Hristova Mariya
Published: August 2021

Neonatal hypoxic–ischaemic brain damage is a leading cause of child mortality and morbidity, including cerebral palsy, epilepsy, and cognitive disabilities. The majority of neonatal hypoxic–ischaemic cases arise as a result of impaired cerebral perfusion to the foetus attributed to uterine, placental, or umbilical cord compromise prior to or during delivery. Bacterial infection is a factor contributing to the damage and is recorded in more than half of preterm births. Exposure to infection exacerbates neuronal hypoxic–ischaemic damage thus leading to a phenomenon called infection-sensitised hypoxic–ischaemic brain injury. Models of neonatal hypoxia–ischaemia (HI) have been developed in different animals. Both human and animal studies show that the developmental stage and the severity of the HI insult affect the selective regional vulnerability of the brain to damage, as well as the subsequent clinical manifestations. Therapeutic hypothermia (TH) is the only clinically approved treatment for neonatal HI. However, the number of HI infants needed to treat with TH for one to be saved from death or disability at age of 18–22 months, is approximately 6–7, which highlights the need for additional or alternative treatments to replace TH or increase its efficiency. In this review we discuss the mechanisms of HI injury to the immature brain and the new experimental treatments studied for neonatal HI and infection-sensitised neonatal HI.