bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA-522-3p plays an oncogenic role in glioblastoma through activating Wnt/β-catenin signaling pathway via targeting SFRP2
Authors: Zhang Lingdang , Zhang Peng , Tan Yun , Feng Qinglin , Zhao Rui 
Published: January 2021

Background
Increasing studies have suggested that microRNAs (miRNAs) contribute to the occurrence and development of glioblastoma. MiR-522-3p is a novel miRNA, which has been found to modulate tumorigenesis and tumor progression. However, its pathological role and functional mechanism in glioblastoma remain elusive at present.

Method
The miR-522-3p expression in glioblastoma and adjacent normal tissues, human fetal astrocyte HA1800, and glioblastoma cell lines was detected by reverse transcription-PCR. The proliferation, migration, and invasion were detected through Cell Counting Kit-8 (CCK8) and Transwell assay, and apoptosis was calculated through flow cytometry. The downstream target of miR-522-3p was analyzed through bioinformatics, and the correlation between miR-522-3p and secreted frizzled-related protein 2 (SFRP2) was verified through dual-luciferase reporter assay and RNA immunoprecipitation (RIP) experiment. Besides, western blot was conducted to test the level of SFRP2 and the Wnt/β-catenin pathway.

Results
MiR-522-3p was overexpressed in glioblastoma tissues compared with that in normal tissues, and the inhibition of miR-522-3p reduced cell proliferation, migration, and invasion and promoted apoptosis in glioblastoma. Bioinformatics revealed that SFRP2 was an essential downstream target of miR-522-3p, and it inhibited the malignant biological behaviors induced by miR-522-3p and inactivated the Wnt/β-catenin pathway.

Conclusion
MiR-522-3p is an oncogene in glioblastoma by targeting SFRP2 through the Wnt/β-catenin pathway.
Upregulating miR-130a-5p relieves astrocyte over activation-induced neuropathic pain through targeting C-X-C motif chemokine receptor 12/C-X-C motif chemokine receptor 4 axis
Authors: Dong Jiacai , Xu Cheng , Xia Rui , Zhang Zhonggui 
Published: January 2021

Objectives
This study intends to explore the role and specific mechanism of miR-130a-5p in neuropathic pain through regulating the C-X-C motif chemokine receptor 12 (CXCL12)–C-X-C motif chemokine receptor 4 (CXCR4) pathway.

Methods
First, mouse neuropathic pain model was constructed by spinal nerve ligation. MiR-130a-5p mimics were used to upregulate miR-130a-5p in vivo. The behaviour and pain scores of the spinal cord injury (SCI) mice were assessed. In addition, astrocytic activation as well as inflammatory response in the spinal lesions was determined.

Results
The results manifested miR-130a-5p was notably downregulated in neuropathic pain model and reached the lowest point at 3 days after injury. Besides, tail vein injection of miR-130a-5p mimics inhibited the activation and inflammatory response of astrocytes, thus alleviating chronic constriction injury-induced neuropathic pain. Moreover, miR-130a-5p inactivated CXCR4 and its downstream Rac1, nuclear factor-κB (NF-κB) and extracellular regulated protein kinases signalling pathways by attenuating CXCL12.

Conclusion
MiR-130a-5p inactivated astrocytes by targeting CXCL12/CXCR4, thus alleviating SCI-induced neuropathic pain.
Emerging Therapies and challenges for individuals with Angelman syndrome
Authors: Heussler Helen S. 
Published: January 2021

Purpose of review
This review describes current understandings in the search for therapies to support children with Angelman syndrome. There is a rapid progression in particular in genetic therapies in this disorder supported by the Angelman community.

Recent findings
Recent papers shed light on the timing of therapies and novel genetic therapies coming to trial as well as potential therapies still in preclinical phases. Further understanding of UBE3A and its role in neuronal development and plasticity as well as other mechanisms contributing to the Angelman phenotype is offering an opportunity for novel therapeutics.

Summary
Greater understanding of the pathophysiology of the different phenotypes will offer an opportunity for novel therapeutics and may well change the course of this disorder over time where previously there has been minimal ability to intervene.
Animal models of neurodevelopmental disorders with behavioral phenotypes
Authors: Harris James C. 
Published: January 2021

Purpose of review
Genetic mutations in animals advance our understanding of disease mechanisms and treatments of neurodevelopmental disorders. Research with mutant mouse models is being extended to nonhuman primates whose brain development is closer to that of humans. This review summaries advances in mouse and nonhuman primate models.

Recent findings
Mutant mouse models recapitulate key symptoms in neurodevelopmental disorders. However, successful phenotypic reversal of symptoms in mouse models has not been replicated in human studies; this failure may be because of differences in the structure and physiology of the brain between rodents and humans. Rett syndrome MECP2 models and Phelan–McDermid syndrome where reduced expression of SH3 and multiple ankyrin repeat domains 3 (SHANK3) models have been introduced in nonhuman primates and are underway in other neurodevelopmental disorders.

Summary
Mutant mouse models in neurogenetic disorders continued to be pursued along with gene-edited and cell-based models in nonhuman primates. Established ethical guidelines are being followed and infrastructure being established to facilitate dissemination of primate transgenic models as they become available.
Urbanization and eating disorders: a scoping review of studies from 2019 to 2020
Authors: Hay Phillipa , Mitchison Deborah 
Published: January 2021

Purpose of review
This review scoped recent (2019–2020) literature investigating the association between urbanization and eating disorders, and the putative role of urbanization as a direct or indirect risk factor.

Recent findings
There are few epidemiological studies which investigated adequately direct or indirect association between urban domicile and eating disorders. Findings suggest that urbanization is a complex phenomenon and its effects on eating behaviour are indirect, for example, because of other important social and environmental features, such as the amount of ‘green’ space, ‘Western’ thin idealization, and poverty. The review also supports others indicating an increase of eating disorders in Africa and Asia. The majority of research includes only adolescent and young woman.

Summary
It does not seem likely that metropolitan dwelling in itself is a major risk factor for developing an eating disorder. However, when accompanied by other sociodemographic effects, there may well be an increase in eating disorder risk. There are opportunities for planners to design cities to be supportive of peoples’ eating and mental health in general. More research investigating moderating and mediating effects on the associations between urban dwelling and eating disorder is needed as well as studies of more sexually and age diverse populations.
Hypertension and Alzheimer's disease: is the picture any clearer?
Authors: Lennon Matthew J. , Koncz Rebecca , Sachdev Perminder S. 
Published: January 2021

Purpose of review
The relationship between hypertension and Alzheimer's disease (AD) is complex and varies across the lifespan. Studies have suggested that midlife hypertension is a risk factor for AD, although studies of late life hypertension have suggested that it either has no effect or a weak protective effect.

Recent findings
Animal models of induced and spontaneous hypertension have found that AD pathological change (β-amyloid plaques and tau tangles) occurs within weeks of a hypertensive insult. Human imaging and autopsy studies indicate that midlife and late life hypertension are associated with increased AD pathological change. Meta-analyses of longitudinal studies indicate that midlife rather than late life hypertension is a risk factor for AD. New areas of research have suggested that rather than mean blood pressure (BP), it is the negative BP trajectories or the variability of BP that contributes to AD. In a number of meta-analyses of antihypertensive medications and their effect on AD, there were weak associations between improved AD outcomes and treatment.

Summary
The combined analysis of animal, human clinical/pathological, epidemiological and drug trial data indicates that hypertension increases the risk of AD and treatment of hypertension may be an appropriate preventive measure.
Agitation in schizophrenia: origins and evidence-based treatment
Authors: Citrome Leslie 
Published: January 2021

Purpose of review
Agitation associated with schizophrenia remains an important clinical concern and if not managed effectively, can escalate into aggressive behavior. This is a review of the recent biomedical literature on agitation in individuals with schizophrenia.

Recent findings
Themes in the recent literature include consideration of comorbidities such as cigarette smoking and cannabis use. Surveys reveal that pharmacological approaches to manage agitation have changed little, with haloperidol remaining in common use and intramuscular administration of antipsychotics and/or benzodiazepines being frequently administered to more severely agitated/aggressive individuals. Of note, ketamine has been recently adopted for use in severe agitation in medical emergency departments, but the risk of this medication for people with schizophrenia is unclear. At present, inhaled loxapine remains the only rapidly acting noninjectable FDA-approved treatment for agitation associated with schizophrenia. In development is an intranasal formulation for olanzapine (a well characterized atypical antipsychotic already approved to treat agitation) and a sublingual film for dexmedetomidine (an α2-adrenergic agonist used as an anesthetic and now being repurposed).

Summary
Comorbidities can contribute to agitation and can make an accurate differential diagnosis challenging. The ongoing development of rapidly acting novel formulations of antiagitation medications, if successful, may facilitate clinical treatment by providing additional options.
Noninvasive brain stimulation for the treatment of neurocognitive disorders: right for prime time?
Authors: Rajji Tarek K. 
Published: January 2021

Purpose of review
Neurocognitive disorders are associated with tremendous burden at the level of the individual, the care giver, and society at large. No effective treatments have been discovered to date.

Recent findings
Noninvasive brain stimulation (NIBS) comprises several promising interventions that have been studied in Alzheimer's disease and related dementias. Most recent studies have tested transcranial direct current stimulation or repetitive transcranial magnetic stimulation on their own or in combination with other interventions, particularly cognitive training. While most studies were proof-of-principle studies with small sample sizes, combination and long-duration protocols seem to be promising approaches to pursue. Some studies also investigated novel neurophysiological markers as predictors of response to NIBS.

Summary
NIBS presents several interventional options that are ready to be evaluated using well powered, long-duration trials. These future studies should build on the promising leads from the current literature, including the potential advantage of combining NIBS with other interventions; the delivery of interventions for long durations to assess long-term impact; and the use of neurophysiological markers that could optimize the personalization and efficacy of NIBS.
The high infectivity of SARS-CoV-2 B.1.1.7 is associated with increased interaction force between Spike-ACE2 caused by the viral N501Y mutation
Authors: Santos Jadson C. , Passos Geraldo A. 
Published: January 2021

AbstractThe Spike glycoprotein receptor-binding domain (RBD) of SARS-CoV-2 mediates the viral particle’s binding to the angiotensin-converting enzyme 2 (ACE2) receptor on the surface of human cells. Therefore, Spike-ACE2 interaction is a crucial determining factor for viral infectivity. A new phylogenetic group of SARS-CoV-2 (lineage B.1.1.7) has been recently identified in the COVID-19 Genomics UK Consortium dataset, which features an amino acid substitution in the Spike RBD (N501Y mutation). Infections with the SARS-CoV-2 lineage B.1.1.7 have been overgrowing in recent weeks in the United Kingdom, indicating an even greater spread capacity than that seen with previous strains of the novel coronavirus. We hypothesized that this rapid spreading/infectivity of the B.1.1.7 lineage might be due to changes in the interaction force between the mutant Spike RBD and ACE2. This study employedin silicomethods involving mutagenesis (N501Y mutation) and interface analysis focusing on the Spike RDB-ACE2 interaction. The results showed that the SARS-CoV-2 N501Y mutant (lineage B.1.1.7) establishes a more significant number of interactions relating to the mutant residue Y501 (Spike RDB) with residues Y41 and K353 (ACE2). This finding shows that the increased infectivity of SARS-CoV-2 lineage B.1.1.7 is associated with the interaction force between the Spike RBD Y501 mutant residue with the ACE2 receptor, which in this strain is increased.
MVA Vector Vaccines Inhibit SARS CoV-2 Replication in Upper and Lower Respiratory Tracts of Transgenic Mice and Prevent Lethal Disease
Authors: Liu Ruikang , Americo Jeffrey L. , Cotter Catherine A. , Earl Patricia L. , Erez Noam , Peng Chen , Moss Bernard 
Published: January 2021

AbstractReplication-restricted modified vaccinia virus Ankara (MVA) is a licensed smallpox vaccine and numerous clinical studies investigating recombinant MVAs (rMVAs) as vectors for prevention of other infectious diseases have been completed or are in progress. Two rMVA COVID-19 vaccine trials are at an initial stage, though no animal protection studies have been reported. Here, we characterize rMVAs expressing the S protein of CoV-2. Modifications of full length S individually or in combination included two proline substitutions, mutations of the furin recognition site and deletion of the endoplasmic retrieval signal. Another rMVA in which the receptor binding domain (RBD) flanked by the signal peptide and transmembrane domains of S was also constructed. Each modified S protein was displayed on the surface of rMVA-infected human cells and was recognized by anti-RBD antibody and by soluble hACE2 receptor. Intramuscular injection of mice with the rMVAs induced S-binding and pseudovirus-neutralizing antibodies. Boosting occurred following a second homologous rMVA but was higher with adjuvanted purified RBD protein. Weight loss and lethality following intranasal infection of transgenic hACE2 mice with CoV-2 was prevented by one or two immunizations with rMVAs or by passive transfer of serum from vaccinated mice. One or two rMVA vaccinations also prevented recovery of infectious CoV-2 from the lungs. A low amount of virus was detected in the nasal turbinates of only one of eight rMVA-vaccinated mice on day 2 and none later. Detection of subgenomic mRNA in turbinates on day 2 only indicated that replication was abortive in immunized animals.SignificanceVaccines are required to control COVID-19 during the pandemic and possibly afterwards. Recombinant nucleic acids, proteins and virus vectors that stimulate immune responses to the CoV-2 S protein have provided protection in experimental animal or human clinical trials, though questions remain regarding their ability to prevent spread and the duration of immunity. The present study focuses on replication-restricted modified vaccinia virus Ankara (MVA), which has been shown to be a safe, immunogenic and stable smallpox vaccine and a promising vaccine vector for other infectious diseases and cancer. In a transgenic mouse model, one or two injections of recombinant MVAs that express modified forms of S inhibited CoV-2 replication in the upper and lower respiratory tracts and prevented severe disease.
A phylogenetic and functional perspective on the origin and evolutionary shifts of growth ring anatomical markers in seed plants
Authors: Silva Marcelo dos S. , Funch Ligia S. , da Silva Lazaro B. , Cardoso Domingos 
Published: January 2021

ABSTRACTWe reconstruct the evolutionary changes in different anatomical markers in order to understand the evolution and functional aspects of growth rings during the diversification of seed plants (spermatophytes), one of the largest and most diverse lineages of the tree of life. We carried out a wide revision of the anatomy of secondary xylem in spermatophytes and reconstructed the evolution of the different anatomical markers in a time‐calibrated phylogeny. By embodying a functionally and evolutionarily significant concept in growth rings we reveal a new panorama for their frequency and show how common they are in diverse lineages of tropical plants. In this context, the principal anatomical markers of growth rings are identified in the evolutionary history of plants and their association with climate‐related ecological characteristics. We discuss the function of these anatomical markers, especially for thick‐walled and/or radially flattened latewood fibres, fibre zone and dilated rays. Despite the high evolutionary lability of the anatomical markers evidenced by our analyses, they appear to represent deep homologies.
Ultrastructural studies of the neurovascular unit reveal enhanced endothelial transcytosis in hyperglycemia‐enhanced hemorrhagic transformation after stroke
Authors: Xu Xiaomin , Zhu Liuqi , Xue Ke , Liu Jiayi , Wang Jian , Wang Guohua , Gu Jin‐hua , Zhang Yunfeng , Li Xia 
Published: January 2021

AbstractAimsPre‐existing hyperglycemia (HG) aggravates the breakdown of blood–brain barrier (BBB) and increases the risk of hemorrhagic transformation (HT) after acute ischemic stroke in both animal models and patients. To date, HG‐induced ultrastructural changes of brain microvascular endothelial cells (BMECs) and the mechanisms underlying HG‐enhanced HT after ischemic stroke are poorly understood.MethodsWe used a mouse model of mild brain ischemia/reperfusion to investigate HG‐induced ultrastructural changes of BMECs that contribute to the impairment of BBB integrity after stroke. Adult male mice received systemic glucose administration 15 min before middle cerebral artery occlusion (MCAO) for 20 min. Ultrastructural characteristics of BMECs were evaluated using two‐dimensional and three‐dimensional electron microscopy and quantitatively analyzed.ResultsMice with acute HG had exacerbated BBB disruption and larger brain infarcts compared to mice with normoglycemia (NG) after MCAO and 4 h of reperfusion, as assessed by brain extravasation of the Evans blue dye and microtubule‐associated protein 2 immunostaining. Electron microscopy further revealed that HG mice had more endothelial vesicles in the striatal neurovascular unit than NG mice, which may account for their deterioration of BBB impairment. In contrast with enhanced endothelial transcytosis, paracellular tight junction ultrastructure was not disrupted after this mild ischemia/reperfusion insult or altered upon HG. Consistent with the observed increase of endothelial vesicles, transcytosis‐related proteins caveolin‐1, clathrin, and hypoxia‐inducible factor (HIF)‐1α were upregulated by HG after MCAO and reperfusion.ConclusionOur study provides solid structural evidence to understand the role of endothelial transcytosis in HG‐elicited BBB hyperpermeability. Enhanced transcytosis occurs prior to the physical breakdown of BMECs and is a promising therapeutic target to preserve BBB integrity.
Reflections on Non‐Imperialist, Feminist Values
Authors: Meyers Diana Tietjens 
Published: January 2021

AbstractThis paper clarifies and reflects on the four values that Serene Khader argues feminism can do without in Decolonizing Universalism: independence individualism, personhood individualism, Enlightenment freedom, and gender‐role eliminativism. Persuaded by her condemnation of the view Khader calls “headship complementarianism” and her defense of a different form of gender complementarianism, the paper leaves the question of gender role eliminativism aside. It starts by presenting some concerns about her treatment of Enlightenment freedom, independence individualism, and personhood individualism. It agrees that Enlightenment freedom and independence individualism have no place in feminism. Contrary to Khader, however, it maintains that personhood individualism is necessarily a feminist value. It then shows why the value of women’s autonomy is more central to non‐imperialist feminism than Khader acknowledges. Ultimately, it agrees with Khader that feminism can be both universalist and non‐imperialist provided that these qualifications are adopted.
Guava with an institutional supplementary meal improves iron status of preschoolers: a cluster‐randomized controlled trial
Authors: Roy Choudhury Dripta , Nair Krishnapillai Madhavan , Nagalla Balakrishna , Vijaya Kankipati Radhakrishna , Ghosh Sudip , Buwade Jagdish , Fernandez‐Rao Sylvia 
Published: January 2021

AbstractThe Integrated Child Development Services of India provides Supplementary Nutrition Program (SNP) to preschoolers. Using this platform, the current study examined the impact of diversifying a cereal/pulse–based SNP‐meal with guava on iron status and cognitive development among 24–48 months old children. A three‐arm, nonblinded, cluster‐randomized controlled trial (CTRI/2014/09/004983) included 399 beneficiaries from 28 preschools in 16 villages in Telangana state, India. The villages were randomly assigned to receive 25 g of guava (guava group (GG)), banana (banana group (BG)), or cucumber (cucumber group (CG)) along with a SNP meal for 140 days. Nutrient biomarkers (iron status, plasma vitamin C, vitamin B12, and folate), cognitive development, anthropometric indicators (WAZ, HAZ, and WHZ), and morbidity were assessed at baseline and endline. A linear mixed model and a generalized estimating equation were applied to compare changes in outcomes across the groups. All outcome variables were comparable across groups at baseline. The iron to vitamin C molar ratio improved in the GG from 1:1.4 to 1:12 but remained unaltered in control groups. Higher hemoglobin (P = 0.002), serum ferritin (SF; P < 0.001), vitamin C (P = 0.047), and lower soluble transferrin receptor (sTfR; P < 0.001) causing decreased prevalence of iron deficiency (ID) (P = 0.003) were observed in the GG compared with BG and CG. Prevalence of acute respiratory infection (ARI) was lower in the GG (P = 0.035) versus controls. No impact was observed on cognitive development or growth. Thus, diversifying a cereal/pulse–based meal with guava increased meal vitamin C content, thereby reducing ID and ARI‐related morbidity. This approach represents a valid and scalable strategy to address ID among young children.