bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Horizons—Cognitive Dysfunction Associated With Type 2 Diabetes
Authors: Moran Chris , Than Stephanie , Callisaya Michele , Beare Richard , Srikanth Velandai 
Published: November 2021

AbstractThe prevalence of type 2 diabetes (T2D) and cognitive dysfunction increases with age. As society ages, clinicians will be increasingly tasked with managing older people who have both T2D and cognitive dysfunction. T2D is associated with an increased risk of cognitive dysfunction and hence there is increasing interest in whether T2D is a causal factor in the pathogenesis of cognitive decline and dementia. Recent advances in the use of sensitive measures of in vivo brain dysfunction in life-course studies can help understand potential mechanistic pathways and also help guide recommendations for clinical practice.In this article we will describe new horizons in the understanding of cognitive dysfunction associated with T2D. Coming from a clinical perspective, we discuss potential mechanisms and pathways linking the 2 conditions and the contribution of multimodal neuroimaging and study designs to advancing understanding in the field. We also highlight the important issues on the horizon that will need addressing in clinical identification, management, and risk reduction for people with coexistent T2D and cognitive dysfunction.
Optimizing the Timing of Highest Hydrocortisone Dose in Children and Adolescents With 21-Hydroxylase Deficiency
Authors: Schröder Mariska A M , van Herwaarden Antonius E , Span Paul N , van den Akker Erica L T , Bocca Gianni , Hannema Sabine E , van der Kamp Hetty J , de Kort Sandra W K , Mooij Christiaan F , Schott Dina A , Straetemans Saartje , van Tellingen Vera , van der Velden Janiëlle A , Sweep Fred C G J , Claahsen-van der Grinten Hedi L 
Published: November 2021

Abstract

Context
Hydrocortisone treatment of young patients with 21-hydroxylase deficiency (21OHD) is given thrice daily, but there is debate about the optimal timing of the highest hydrocortisone dose, either mimicking the physiological diurnal rhythm (morning), or optimally suppressing androgen activity (evening).

Objective
We aimed to compare 2 standard hydrocortisone timing strategies, either highest dosage in the morning or evening, with respect to hormonal status throughout the day, nocturnal blood pressure (BP), and sleep and activity scores.

Methods
This 6-week crossover study included 39 patients (aged 4-19 years) with 21OHD. Patients were treated for 3 weeks with the highest hydrocortisone dose in the morning, followed by 3 weeks with the highest dose in the evening (n = 21), or vice versa (n = 18). Androstenedione (A4) and 17-hydroxyprogesterone (17OHP) levels were quantified in saliva collected at 5 am; 7 am; 3 pm; and 11 pm during the last 2 days of each treatment period. The main outcome measure was comparison of saliva 17OHP and A4 levels between the 2 treatment strategies.

Results
Administration of the highest dose in the evening resulted in significantly lower 17OHP levels at 5 am, whereas the highest dose in the morning resulted in significantly lower 17OHP and A4 levels in the afternoon. The 2 treatment dose regimens were comparable with respect to averaged daily hormone levels, nocturnal BP, and activity and sleep scores.

Conclusion
No clear benefit for either treatment schedule was established. Given the variation in individual responses, we recommend individually optimizing dose distribution and monitoring disease control at multiple time points.
Recurrence of Papillary Thyroid Cancer: A Systematic Appraisal of Risk Factors
Authors: Nieto Hannah R , Thornton Caitlin E M , Brookes Katie , Nobre de Menezes Albert , Fletcher Alice , Alshahrani Mohammed , Kocbiyik Merve , Sharma Neil , Boelaert Kristien , Cazier Jean-Baptiste , Mehanna Hisham , Smith Vicki E , Read Martin L , McCabe Christopher J 
Published: November 2021

Abstract

Context
Thyroid cancer recurrence is associated with increased mortality and adverse outcomes. Recurrence risk is currently predicted using clinical tools, often restaging patients after treatment. Detailed understanding of recurrence risk at disease onset could lead to personalized and improved patient care.

Objective
We aimed to perform a comprehensive bioinformatic and experimental analysis of 3 levels of genetic change (mRNA, microRNA, and somatic mutation) apparent in recurrent tumors and construct a new combinatorial prognostic risk model.

Methods
We analyzed The Cancer Genome Atlas data (TCGA) to identify differentially expressed genes (mRNA/microRNA) in 46 recurrent vs 455 nonrecurrent thyroid tumors. Two exonic mutational pipelines were used to identify somatic mutations. Functional gene analysis was performed in cell-based assays in multiple thyroid cell lines. The prognostic value of genes was evaluated with TCGA datasets.

Results
We identified 128 new potential biomarkers associated with recurrence, including 40 mRNAs, 39 miRNAs, and 59 genetic variants. Among differentially expressed genes, modulation of FN1, ITGα3, and MET had a significant impact on thyroid cancer cell migration. Similarly, ablation of miR-486 and miR-1179 significantly increased migration of TPC-1 and SW1736 cells. We further utilized genes with a validated functional role and identified a 5-gene risk score classifier as an independent predictor of thyroid cancer recurrence.

Conclusion
Our newly proposed risk model based on combinatorial mRNA and microRNA expression has potential clinical utility as a prognostic indicator of recurrence. These findings should facilitate earlier prediction of recurrence with implications for improving patient outcome by tailoring treatment to disease risk and increasing posttreatment surveillance.
Regulation of AKT Signaling in Mouse Uterus
Authors: Sirohi Vijay K , Medrano Theresa I , Mesa Ana M , Kannan Athilakshmi , Bagchi Indrani C , Cooke Paul S 
Published: November 2021

Abstract
17β-estradiol (E2) treatment of ovariectomized adult mice stimulates the uterine PI3K-AKT signaling pathway and epithelial proliferation through estrogen receptor 1 (ESR1). However, epithelial proliferation occurs independently of E2/ESR1 signaling in neonatal uteri. Similarly, estrogen-independent uterine epithelial proliferation is seen in adulthood in mice lacking Ezh2, critical for histone methylation, and in wild-type (WT) mice treated neonatally with estrogen. The role of AKT in estrogen-independent uterine epithelial proliferation was the focus of this study. Expression of the catalytically active phosphorylated form of AKT (p-AKT) and epithelial proliferation were high in estrogen receptor 1 knockout and WT mice at postnatal day 6, when E2 concentrations were low, indicating that neither ESR1 nor E2 are essential for p-AKT expression and epithelial proliferation in these mice. However, p-AKT levels and proliferation remained estrogen responsive in preweaning WT mice. Expression of p-AKT and proliferation were both high in uterine luminal epithelium of mice estrogenized neonatally and ovariectomized during adulthood. Increased expression of phosphorylated (inactive) EZH2 was also observed. Consistent with this, Ezh2 conditional knockout mice show ovary-independent uterine epithelial proliferation and high epithelial p-AKT. Thus, adult p-AKT expression is constitutive and E2/ESR1 independent in both model systems. Finally, E2-induced p-AKT expression and normal uterine proliferation did not occur in mice lacking membrane (m)ESR1, indicating a key role for membrane ESR1 in AKT activation. These findings emphasize the importance of AKT activation in promoting uterine epithelial proliferation even when that proliferation is not E2/ESR1 dependent and further indicate that p-AKT can be uncoupled from E2/ESR1 signaling in several experimental scenarios.
In vivo proximity biotin ligation identifies the interactome of Egalitarian, a Dynein cargo adaptor
Authors: Baker Frederick C. , Neiswender Hannah , Veeranan-Karmegam Rajalakshmi , Gonsalvez Graydon B. 
Published: November 2021

ABSTRACT
Numerous motors of the Kinesin family contribute to plus-end-directed microtubule transport. However, almost all transport towards the minus-end of microtubules involves Dynein. Understanding the mechanism by which Dynein transports this vast diversity of cargo is the focus of intense research. In selected cases, adaptors that link a particular cargo with Dynein have been identified. However, the sheer diversity of cargo suggests that additional adaptors must exist. We used the Drosophila egg chamber as a model to address this issue. Within egg chambers, Egalitarian is required for linking mRNA with Dynein. However, in the absence of Egalitarian, Dynein transport into the oocyte is severely compromised. This suggests that additional cargoes might be linked to Dynein in an Egalitarian-dependent manner. We therefore used proximity biotin ligation to define the interactome of Egalitarian. This approach yielded several novel interacting partners, including P body components and proteins that associate with Dynein in mammalian cells. We also devised and validated a nanobody-based proximity biotinylation strategy that can be used to define the interactome of any GFP-tagged protein.
Perfluorooctanesulfonic acid modulates barrier function and systemic T-cell homeostasis during intestinal inflammation
Authors: Diaz Oscar E. , Sorini Chiara , Morales Rodrigo A. , Luo Xinxin , Frede Annika , Krais Annette M. , Chávez Myra N. , Wincent Emma , Das Srustidhar , Villablanca Eduardo J. 
Published: November 2021

ABSTRACT
The intestinal epithelium is continuously exposed to deleterious environmental factors that might cause aberrant immune responses leading to inflammatory disorders. However, what environmental factors might contribute to disease are poorly understood. Here, to overcome the lack of in vivo models suitable for screening of environmental factors, we used zebrafish reporters of intestinal inflammation. Using zebrafish, we interrogated the immunomodulatory effects of polyfluoroalkyl substances, which have been positively associated with ulcerative colitis incidence. Exposure to perfluorooctanesulfonic acid (PFOS) during 2,4,6-trinitro-benzene sulfonic acid (TNBS)-induced inflammation enhanced the expression of proinflammatory cytokines as well as neutrophil recruitment to the intestine of zebrafish larvae, which was validated in the TNBS-induced colitis mouse model. Moreover, PFOS exposure in mice undergoing colitis resulted in neutrophil-dependent increased intestinal permeability and enhanced PFOS translocation into the circulation. This was associated with a neutrophil-dependent expansion of systemic CD4+ T cells. Thus, our results indicate that PFOS worsens inflammation-induced intestinal damage with disruption of T-cell homeostasis beyond the gut and provides a novel in vivo toolbox to screen for pollutants affecting intestinal homeostasis.
Crosstalk between the calcineurin and cell wall integrity pathways prevents chitin overexpression in Candida albicans
Authors: da Silva Dantas Alessandra , Nogueira Filomena , Lee Keunsook K. , Walker Louise A. , Edmondson Matt , Brand Alexandra C. , Lenardon Megan D. , Gow Neil A. R. 
Published: November 2021

ABSTRACT
Echinocandins such as caspofungin are frontline antifungal drugs that compromise β-1,3 glucan synthesis in the cell wall. Recent reports have shown that fungal cells can resist killing by caspofungin by upregulation of chitin synthesis, thereby sustaining cell wall integrity (CWI). When echinocandins are removed, the chitin content of cells quickly returns to basal levels, suggesting that there is a fitness cost associated with having elevated levels of chitin in the cell wall. We show here that simultaneous activation of the calcineurin and CWI pathways generates a subpopulation of Candida albicans yeast cells that have supra-normal chitin levels interspersed throughout the inner and outer cell wall, and that these cells are non-viable, perhaps due to loss of wall elasticity required for cell expansion and growth. Mutations in the Ca2+-calcineurin pathway prevented the formation of these non-viable supra-high chitin cells by negatively regulating chitin synthesis driven by the CWI pathway. The Ca2+-calcineurin pathway may therefore act as an attenuator that prevents the overproduction of chitin by coordinating both chitin upregulation and negative regulation of the CWI signaling pathway.
This article has an associated First Person interview with the first author of the paper.
Mobile banking adoption and usage among Generation Y Malaysians
Authors: Tarawneh Momen , Nguyen Lan Thi Phuong , Fie Yong 
Published: November 2021

Background: By 2018, Malaysian mobile banking services made the third-largest amount of banking transactions, following credit card and Internet banking. In addition, it significantly contributes to the banking industry by providing easier transactions to banking consumers. This study examined factors affecting the intention to use, and the actual use of mobile banking services in Malaysia. Methods: Two main theories of the unified theory of acceptance and use of technology (extended version, UTAUT2), and the model of perceived risk, were used to propose a modified framework. Based on the non-probability sampling method, the data were collected from 504 respondents. The data vas analyzed using SPSS and PLS-SEM to derive the findings. Results: The study's findings revealed that the independent variables could explain 55.3% of the variance in mobile banking use and 60.3% of variance in intention to use variables. Moreover, it demonstrated that common factors that have significantly affected the actual use and intention to use mobile banking were habit, facilitating condition, and interface design quality. In contrast, perceived risk and intention to use were found to only have significant impacts on the use of mobile banking, while effort expectancy was found to only have a significant impact on the intention to use. Conclusions: The findings of this study provide significant new knowledge on mobile banking, from which mobile banking providers and interface designers can develop potential solutions to increase the usage of mobile banking services in Malaysia. However, using a qualitative method, the proposed model could only explain 55% of actual use and 60% of intentional use. Thus, additional variables and qualitative techniques may help increase the understanding on the actual use and intention to use.
O referencji innych
Authors: Wołk Mariola 
Published: November 2021

On the Reference of inni
The study focuses on the adjective inny [other] which appears in sentences in a noun position, yet with the noun absent, e.g. Nie porównuj się do innych; Inni dołączą do nas po 18 [literally in English: Do not compare yourself to others; Others will join as after 6 p.m.]. The analysis focuses on plural (masculine and non-masculine) forms of the adjective, which is related to the assumption that single and plural forms of the expression in question are differentiated functionally. The aim of the analysis is to determine the specificity of the unit as an exponent of reference. The main research issues concerned with the analyzed adjective include an attempt to refute the hypothesis of its substantivization, as well as answering the question whether the unit in its analyzed index (referential) function exhibits features of dictum. The solutions suggested in the study require further investigation, including addressing analyses of referential exponents of synonymous expressions.
Prozodia, semantyka, styl – o hierarchii poziomów ekwiwalencji w tłumaczeniu piosenki kabaretowej (studium przypadku: polskojęzyczne warianty Money… Freda Ebba)
Authors: Wysocka Aneta 
Published: November 2021

Prosody, Semantics and Style. On the Hierarchy of Levels of Equivalence in the Translation of Cabaret Songs (Case Study: Polish Versions of Fred Ebb's Money…)
The article is a case study and contains a comparative analysis of four variants of the Polish translation of Fred Ebb and John Kander’s song Money… from the musical “Cabaret”. The author of the translation is Wojciech Młynarski, one of the most respected Polish songwriters of the second half of the twentieth century. In the study, an assumption is made that Młynarski, who repeatedly changed versions of his translation, sought to create the most faithful rendition of the songs from the musical for the needs of the Polish stage. His efforts can be observed at four levels of text organization. The translator aimed mainly for sound equivalence, i.e. conformity with the original song in terms of rhythm (word stress), rhyme (consonance) and voice instrumentation and, to a lesser extent, sound imitation. He also cared about pragmatic equivalence by rendering into Polish the original intentions, with particular emphasis on the modes of indirect communication, such as irony and satire. However, other aspects of equivalence remained in the background. Not everywhere the translator managed to keep the cognitive equivalence, i.e. convergence of imagery, by translating scenes and scenarios that were part of cultural knowledge into parallel ones and, more broadly, by trying to evoke similar images in the mind of the reader and listener. His efforts to achieve the effect of broadly understood stylistic equivalence were also noteworthy; only to a small extent they consisted in giving the right stylistic coloring to the individual lexical items which had their English equivalents, and they mainly boiled down to translating stylistic games that did not necessarily cover the same fragments of the song, though were usually based on the same mechanism (a clash between low and high style, absurdity). The analysis shows that the translator adopted tabular rather than linear approach to the original.
Regionalismos e Cooperação em Saúde: a experiência da Unasul | Regionalism and Health Cooperation: the Unasur experience
Authors: Santos Lima Maria Isabel , Villarreal Villamar María del Carmen 
Published: November 2021

O objetivo deste trabalho é analisar a Unasul-saúde visando compreender suas características, seu legado e os elementos que a diferenciam de outras experiências regionais de cooperação no âmbito da saúde. A partir de uma pesquisa qualitativa, nosso trabalho evidencia que, no marco do regionalismo pós-liberal, a Unasul aprofundou a cooperação política e social e adotou uma perspectiva baseada na promoção do desenvolvimento, da autonomia e da soberania regional. Apesar de diversas limitações, este enfoque permitiu que a Unasul-saúde fosse além das experiências prévias para se tornar o exemplo de cooperação e diplomacia da saúde mais avançado a nível regional.Palavras-chave: Regionalismos, saúde, Unasul. ABSTRACTThe aim of this paper is to analyze the Unasur-health in order to understand its characteristics, its legacy and the elements that differentiate it from other regional experiences of cooperation in health. Based on qualitative research, our work shows that, within the framework of post-liberal regionalism, Unasur has deepened political and social cooperation and adopted a perspective based on the promotion of development, autonomy, and regional sovereignty. Despite several limitations, this approach allowed Unasur-health to go beyond previous experiences to become the most advanced example of health cooperation and diplomacy at the regional level.Keywords: regionalism, health, Unasul. Recebido em: 20 abr. 2021 | Aceito em: 22 set. 2021.
Alterações na Política Externa da Arábia Saudita: uma análise a partir do modelo de Hermann | Changes in Saudi Arabia’s Foreign Policy: an analysis under the Hermann’s model
Authors: Hendler Bruno , Porta Felipe 
Published: November 2021

O presente artigo busca analisar quais foram os graus de mudança percebidos na política externa da Arábia Saudita nas suas relações com China e Estados Unidos. Para a realização desta análise, utilizamos os conceitos cunhados por Charles Hermann (1990), que explicam as alterações em política externa de um país a partir de quatro graus de mudança e quatro fontes geradoras destas mudanças. Não obstante, a utilização de livros, artigos, notícias e documentos oficiais dos governos foram essenciais para o desenvolvimento deste trabalho. Assim, argumentamos que há um gradual deslocamento dos Estados Unidos para a China como parceiro prioritário do referido país a partir de 2010, tendência esta acelerada pelos choques externos, como a Primavera Árabe, a queda nos preços internacionais do petróleo e o afastamento dos Estados Unidos do Oriente Médio, e pela ascensão de Mohammed bin Salman ao poder executivo do Reino. Tal deslocamento está associado ao aumento na intensidade e à alteração dos meios pelos quais o país se relaciona com a China. Entretanto, reforçamos que esta tendência não significa um abandono, pela Arábia Saudita, de sua histórica relação com os Estados Unidos.Palavras-chave: Arábia Saudita; Política Externa; Hermann.ABSTRACTThe aim of this research is to analyze the levels of changes identified in Saudi Arabia's foreign policy in its relations with China and the United States. To carry out this analysis, we used the concepts formulated by Charles Hermann (1990) about levels and sources of change in a country's foreign policy. Nevertheless, the use of books, articles, news and official government documents were essential for the development of this article. Hence, we argue that there is a gradual shift from the United States to China as a priority partner of Saudi Arabia since 2010, a trend that has been accelerated by external shocks from the International System, such as the Arab Spring, the fall of the international oil prices and the United States withdraw from the Middle East politics and by the rise of Mohammed bin Salman to the executive power. Such a shift is associated with an increase in intensity and a change in the means by which the country relates to China. Notwithstanding, this trend does not mean that Saudi Arabia abandoned its historic relationship with the United States. Keywords: Saudi Arabia; Foreign Policy; Hermann. Recebido em: 28 abr. 2021 | Aceito em: 30 set. 2021.