bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced resting-state brain functional network connectivity and poor regional homogeneity in patients with CADASIL
Authors: Su Jingjing , Ban Shiyu , Wang Mengxing , Hua Fengchun , Wang Liang , Cheng Xin , Tang Yuping , Zhou Houguang , Zhai Yu , Du Xiaoxia , Liu Jianren 
Published: November 2019

Abstract

Background
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) manifests principally as a suite of cognitive impairments, particularly in the executive domain. Executive functioning requires the dynamic coordination of neural activity over large-scale networks. It remains unclear whether changes in resting-state brain functional network connectivity and regional homogeneities (ReHos) underly the mechanisms of executive dysfunction evident in CADASIL patients.

Methods
In this study, 22 CADASIL patients and 44 matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI). Independent component analysis (ICA) was used to measure functional brain network connectivity, and ReHos were calculated to evaluate local brain activities. We used seed-based functional connectivity (FC) analyses to determine whether dysfunctional areas (as defined by ReHos) exhibited abnormal FC with other brain areas. Relationships among the mean intra-network connectivity z-scores of dysfunctional areas within functional networks, and cognitive scores were evaluated using Pearson correlation analyses.

Results
Compared to the controls, CADASIL patients exhibited decreased intra-network connectivity within the bilateral lingual gyrus (LG) and the right cuneus (CU) (thus within the visual network [VIN)], and within the right precuneus (Pcu), inferior frontal gyrus (IFG), and precentral gyrus (thus within the frontal network [FRN]). Compared to the controls, patients also exhibited significantly lower ReHos in the right precuneus and cuneus (Pcu/CU), visual association cortex, calcarine gyri, posterior cingulate, limbic lobe, and weaker FC between the right Pcu/CU and the bilateral parahippocampal gyrus (PHG), and between the right Pcu/CU and the right postcentral gyrus. Notably, the mean connectivity z-scores of the bilateral LG and the right CU within the VIN were positively associated with compromised attention, calculation and delayed recall as revealed by tests of the various cognitive domains explored by the Mini-Mental State Examination.

Conclusions
The decreases in intra-network connectivity within the VIN and FRN and reduced local brain activity in the posterior parietal area suggest that patients with CADASIL may exhibit dysfunctional visuomotor behaviors (a hallmark of executive function), and that all visual information processing, visuomotor planning, and movement execution may be affected.
Genome-wide DNA methylation analysis of Metarhizium anisopliae during tick mimicked infection condition
Authors: Sbaraini Nicolau , Bellini Reinaldo , Penteriche Augusto Bartz , Guedes Rafael Lucas Muniz , Garcia Ane Wichine Acosta , Gerber Alexandra Lehmkuhl , Vainstein Marilene Henning , de Vasconcelos Ana Tereza Ribeiro , Schrank Augusto , Staats Charley Christian 
Published: November 2019

Abstract

Background
The Metarhizium genus harbors important entomopathogenic fungi. These species have been widely explored as biological control agents, and strategies to improve the fungal virulence are under investigation. Thus, the interaction between Metarhizium species and susceptible hosts have been explored employing different methods in order to characterize putative virulence determinants. However, the impact of epigenetic modulation on the infection cycle of Metarhizium is still an open topic. Among the different epigenetic modifications, DNA methylation of cytosine bases is an important mechanism to control gene expression in several organisms. To better understand if DNA methylation can govern Metarhizium-host interactions, the genome-wide DNA methylation profile of Metarhizium anisopliae was explored in two conditions: tick mimicked infection and a saprophytic-like control.

Results
Using a genome wide DNA methylation profile based on bisulfite sequencing (BS-Seq), approximately 0.60% of the total cytosines were methylated in saprophytic-like condition, which was lower than the DNA methylation level (0.89%) in tick mimicked infection condition. A total of 670 mRNA genes were found to be putatively methylated, with 390 mRNA genes uniquely methylated in the tick mimicked infection condition. GO terms linked to response to stimuli, cell wall morphogenesis, cytoskeleton morphogenesis and secondary metabolism biosynthesis were over-represented in the tick mimicked infection condition, suggesting that energy metabolism is directed towards the regulation of genes associated with infection. However, recognized virulence determinants known to be expressed at distinct infection steps, such as the destruxin backbone gene and the collagen-like protein gene Mcl1, were found methylated, suggesting that a dynamic pattern of methylation could be found during the infectious process. These results were further endorsed employing RT-qPCR from cultures treated or not with the DNA methyltransferase inhibitor 5-Azacytidine.

Conclusions
The set of genes here analyzed focused on secondary metabolites associated genes, known to be involved in several processes, including virulence. The BS-Seq pipeline and RT-qPCR analysis employing 5-Azacytidine led to identification of methylated virulence genes in M. anisopliae. The results provided evidences that DNA methylation in M. anisopliae comprises another layer of gene expression regulation, suggesting a main role of DNA methylation regulating putative virulence determinants during M. anisopliae infection cycle.
Isolation, purification and characterization of an ascorbate peroxidase from celery and overexpression of the AgAPX1 gene enhanced ascorbate content and drought tolerance in Arabidopsis
Authors: Liu Jie-Xia , Feng Kai , Duan Ao-Qi , Li Hui , Yang Qing-Qing , Xu Zhi-Sheng , Xiong Ai-Sheng 
Published: November 2019

Abstract

Background
Celery is a widely cultivated vegetable abundant in ascorbate (AsA), a natural plant antioxidant capable of scavenging free radicals generated by abiotic stress in plants. Ascorbate peroxidase (APX) is a plant antioxidant enzyme that is important in the synthesis of AsA and scavenging of excess hydrogen peroxide. However, the characteristics and functions of APX in celery remain unclear to date.

Results
In this study, a gene encoding APX was cloned from celery and named AgAPX1. The transcription level of the AgAPX1 gene was significantly upregulated under drought stress. AgAPX1 was expressed in Escherichia coli BL21 (DE3) and purified. The predicted molecular mass of rAgAPX1 was 33.16 kDa, which was verified by SDS-PAGE assay. The optimum pH and temperature for rAgAPX1 were 7.0 and 55 °C, respectively. Transgenic Arabidopsis hosting the AgAPX1 gene showed elevated AsA content, antioxidant capacity and drought resistance. Less decrease in net photosynthetic rate, chlorophyll content, and relative water content contributed to the high survival rate of transgenic Arabidopsis lines after drought.

Conclusions
The characteristics of APX in celery were different from that in other species. The enhanced drought resistance of overexpressing AgAPX1 in Arabidopsis may be achieved by increasing the accumulation of AsA, enhancing the activities of various antioxidant enzymes, and promoting stomatal closure. Our work provides new evidence to understand APX and its response mechanisms to drought stress in celery.
PdWND3A, a wood-associated NAC domain-containing protein, affects lignin biosynthesis and composition in Populus
Authors: Yang Yongil , Yoo Chang Geun , Rottmann William , Winkeler Kimberly A. , Collins Cassandra M. , Gunter Lee E. , Jawdy Sara S. , Yang Xiaohan , Pu Yunqiao , Ragauskas Arthur J. , Tuskan Gerald A. , Chen Jin-Gui 
Published: November 2019

Abstract

Background
Plant secondary cell wall is a renewable feedstock for biofuels and biomaterials production. Arabidopsis VASCULAR-RELATED NAC DOMAIN (VND) has been demonstrated to be a key transcription factor regulating secondary cell wall biosynthesis. However, less is known about its role in the woody species.

Results
Here we report the functional characterization of Populus deltoides WOOD-ASSOCIATED NAC DOMAIN protein 3 (PdWND3A), a sequence homolog of Arabidopsis VND4 and VND5 that are members of transcription factor networks regulating secondary cell wall biosynthesis. PdWND3A was expressed at higher level in the xylem than in other tissues. The stem tissues of transgenic P. deltoides overexpressing PdWND3A (OXPdWND3A) contained more vessel cells than that of wild-type plants. Furthermore, lignin content and lignin monomer syringyl and guaiacyl (S/G) ratio were higher in OXPdWND3A transgenic plants than in wild-type plants. Consistent with these observations, the expression of FERULATE 5-HYDROXYLASE1 (F5H1), encoding an enzyme involved in the biosynthesis of sinapyl alcohol (S unit monolignol), was elevated in OXPdWND3A transgenic plants. Saccharification analysis indicated that the rate of sugar release was reduced in the transgenic plants. In addition, OXPdWND3A transgenic plants produced lower amounts of biomass than wild-type plants.

Conclusions
PdWND3A affects lignin biosynthesis and composition and negatively impacts sugar release and biomass production.
Incidence and risk factors for recurrent cardiovascular disease in middle-eastern adults: a retrospective study
Authors: Govender Romona D. , Al-Shamsi Saif , Soteriades Elpidoforos S. , Regmi Dybesh 
Published: November 2019

Abstract

Background
Individuals with established cardiovascular disease (CVD) and risk factors such as age, smoking, hypertension, and diabetes mellitus are at an increased risk of recurrent cardiovascular events and death. The incidence rate of recurrent CVD events varies between countries and populations. The United Arab Emirates (UAE) has one of the highest age-standardized death rates for CVD worldwide. The aim of our study was to estimate the incidence rates and determine the predictors of recurrent CVD events among UAE nationals.

Methods
We investigated an outpatient-based cohort of patients with a history of CVD visiting Tawam Hospital between April 1, 2008 and December 31, 2008. They were followed-up until July 31, 2018. Univariable and multivariable Cox proportional hazards regression models were used to determine the association between major CVD risk factors and the risk of CVD recurrence.

Results
A total of 216 patients (167 males, 49 females) with a history of CVD were included. They were followed for a median (interquartile range) of 8.1 (5.5–9.3) years, with a total of 1184 patient-years of follow-up. The overall incidence rate of recurrent CVD events was 92.1 per 1000 patient-years. The 8-year cumulative incidence was 73.7%. Age, female sex, and diabetes mellitus were significant predictors of recurrent CVD events, where females had a 1.96 times higher risk of recurrent CVD events than males.

Conclusion
Significant predictors of recurrent CVD events are older age, female sex, and diabetes mellitus. The incidence rate of recurrent CVD events was 92.1 per 1000 patient-years. Preventive measures, based on international guidelines for CVD management, may improve CVD morbidity and mortality in the UAE population.
Concordance between physiotherapists and physicians for care of patients with musculoskeletal disorders presenting to the emergency department
Authors: Matifat E. , Perreault K. , Roy J.-S. , Aiken A. , Gagnon E. , Mequignon M. , Lowry V. , Décary S. , Hamelin B. , Ambrosio M. , Farley N. , Pelletier D. , Carlesso L. , Desmeules F. 
Published: November 2019

Abstract

Background
Overcrowding in emergency departments (ED) is a major concern worldwide. To answer increasing health care demands, new models of care including advanced practice physiotherapists (APP) have been implemented in EDs. The purpose of this study was to assess diagnostic, treatment and discharge plan concordance between APPs and ED physicians for patients consulting to the ED for minor musculoskeletal disorders (MSKD).

Methods
Patients presenting to two EDs in Montréal (Canada) with a minor MSKD were recruited and independently assessed by an APP and ED physician. Both providers had to formulate diagnosis, treatment and discharge plans. Cohen’s kappa (κ) and Prevalence and Bias Adjusted Kappas (PABAK) with associated 95%CI were calculated. Chi Square and t-tests were used to compare treatment, discharge plan modalities and patient satisfaction between providers.

Results
One hundred and thirteen participants were recruited, mean age was 50.3 ± 17.4 years old and 51.3% had an atraumatic MSKD. Diagnostic inter-rater agreement between providers was very good (κ = 0.81; 95% CI: 0.72–0.90). In terms of treatment plan, APPs referred significantly more participants to physiotherapy care than ED physicians (κ = 0.27; PABAK = 0.27; 95% CI: 0.07–0.45; p = 0.003). There was a moderate inter-rater agreement (κ = 0.46; PABAK = 0.64; 95% CI: 0.46–0.77) for discharge plans. High patient satisfaction was reported with no significant differences between providers (p = 0.57).

Conclusion
There was significant agreement between APPs and ED physicians in terms of diagnosis and discharge plans, but more discrepancies regarding treatment plans. These results tend to support the integration of APPs in ED settings, but further prospective evaluation of the efficiency of these types of models is warranted.
Towards developing a consensus assessment framework for global emergency medicine fellowships
Authors: Jahn Haiko Kurt , Kwan James , O’Reilly Gerard , Geduld Heike , Douglass Katherine , Tenner Andrea , Wallis Lee , Tupesis Janis , Mowafi Hani O. 
Published: November 2019

Abstract

Background
The number of Global Emergency Medicine (GEM) Fellowship training programs are increasing worldwide. Despite the increasing number of GEM fellowships, there is not an agreed upon approach for assessment of GEM trainees.

Main body
In order to study the lack of standardized assessment in GEM fellowship training, a working group was established between the International EM Fellowship Consortium (IEMFC) and the International Federation for Emergency Medicine (IFEM). A needs assessment survey of IEMFC members and a review were undertaken to identify assessment tools currently in use by GEM fellowship programs; what relevant frameworks exist; and common elements used by programs with a wide diversity of emphases. A consensus framework was developed through iterative working group discussions. Thirty-two of 40 GEM fellowships responded (80% response). There is variability in the use and format of formal assessment between programs. Thirty programs reported training GEM fellows in the last 3 years (94%). Eighteen (56%) reported only informal assessments of trainees. Twenty-seven (84%) reported regular meetings for assessment of trainees. Eleven (34%) reported use of a structured assessment of any sort for GEM fellows and, of these, only 2 (18%) used validated instruments modified from general EM residency assessment tools. Only 3 (27%) programs reported incorporation of formal written feedback from partners in other countries. Using these results along with a review of the available assessment tools in GEM the working group developed a set of principles to guide GEM fellowship assessments along with a sample assessment for use by GEM fellowship programs seeking to create their own customized assessments.

Conclusion
There are currently no widely used assessment frameworks for GEM fellowship training. The working group made recommendations for developing standardized assessments aligned with competencies defined by the programs, that characterize goals and objectives of training, and document progress of trainees towards achieving those goals. Frameworks used should include perspectives of multiple stakeholders including partners in other countries where trainees conduct field work. Future work may evaluate the usability, validity and reliability of assessment frameworks in GEM fellowship training.
Novel EIF2AK4 mutations in histologically proven pulmonary capillary hemangiomatosis and hereditary pulmonary arterial hypertension
Authors: Abou Hassan Ossama K. , Haidar Wiam , Arabi Mariam , Skouri Hadi , Bitar Fadi , Nemer Georges , Akl Imad Bou 
Published: November 2019

Abstract

Background
Pulmonary hypertension (PH) remains one of the rarest and deadliest diseases. Pulmonary Capillary Hemangiomatosis (PCH) is one of the sub-classes of PH. It was identified using histological and molecular tools and is characterized by the proliferation of capillaries into the alveolar septae. Mutations in the gene encoding the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) have recently been linked to this particular subgroup of PH.

Methods
In our effort to unveil the genetic basis of idiopathic and familial cases of PH in Lebanon, we have used whole exome sequencing to document known and/or novel mutations in genes that could explain the underlying phenotype.

Results
We showed bi-allelic mutations in EIF2AK4 in two non-consanguineous families: a novel non-sense mutation c.1672C > T (p.Q558*) and a previously documented deletion c.560_564drlAAGAA (p.K187Rfs9*). Our histological analysis coupled with the CT-scan results showed that the two patients with the p.Q558* mutation have PH. In contrast, only one of the individuals harboring the p.K187Rfs9* variant has a documented PCH while his older brother remains asymtomatic. Differential analysis of the variants in the genes of the neighboring network of EIF2AK4 between the two siblings identified a couple of interesting missense mutations that could account for this discrepancy.

Conclusion
These findings represent a novel documentation of the involvement of EIF2AK4 in the different aspects of pulmonary hypertension. The absence of a molecular mechanism that relates the abrogated function of the protein to the phenotype is still a major hurdle in our understanding of the disease.
Effects of a lifestyle intervention in routine care on prenatal physical activity – findings from the cluster-randomised GeliS trial
Authors: Hoffmann Julia , Günther Julia , Geyer Kristina , Stecher Lynne , Rauh Kathrin , Kunath Julia , Meyer Dorothy , Sitzberger Christina , Spies Monika , Rosenfeld Eva , Kick Luzia , Oberhoffer Renate , Hauner Hans 
Published: November 2019

Abstract

Background
Excessive gestational weight gain (GWG) is associated with an increased risk of pregnancy and obstetric complications. The “healthy living in pregnancy” (GeliS) study was performed in a routine care setting with the aim of limiting excessive GWG. The purpose of this secondary analysis is to evaluate the effect of the intervention on physical activity (PA) behaviour and to assess the impact of PA intensities on GWG.

Methods
The cluster-randomised, multicentre GeliS trial was performed in a routine care setting alongside scheduled prenatal visits. Pregnant women with a pre-pregnancy BMI between 18.5 and 40.0 kg/m2 were either assigned to the control group receiving usual care or to the intervention group. Participants in the intervention group attended three antenatal counselling sessions on diet and PA and one additional postpartum session. Data on PA behaviour were collected twice, before the end of the 12th (baseline) and after the 29th week of gestation using the Pregnancy Physical Activity Questionnaire.

Results
PA data were available for 1061 (93%) participants in the intervention and 1040 (93%) in the control group. Women in the intervention group reported significant improvements in the levels of total PA (p < 0.001), total PA of light intensity and above (p < 0.001), moderate-intensity (p = 0.024) and vigorous-intensity activities (p = 0.002) as well as sport activities (p < 0.001) in late pregnancy compared to the control group. The proportion of women meeting the international PA recommendations in late pregnancy was significantly higher in the intervention (64%) versus the control group (49%, p < 0.001). Activities of light-intensity and above (p = 0.006), light-intensity (p = 0.002) and vigorous-intensity (p = 0.014) in late pregnancy were inversely associated with total GWG.

Conclusion
We found significant evidence of improvements in the PA pattern of pregnant women receiving lifestyle counselling within the framework of routine care. Most PA intensities were inversely associated with total GWG which indicates that PA across different intensities should be promoted.

Trial registration
NCT01958307, ClinicalTrials.gov, retrospectively registered 9 October, 2013.
Novel HDGF/HIF-1α/VEGF axis in oral cancer impacts disease prognosis
Authors: Lin Yu-Wei , Huang Shih-Tsung , Wu Jian-Ching , Chu Tian-Huei , Huang Shih-Chung , Lee Ching-Chih , Tai Ming-Hong 
Published: November 2019

AbstractBackgroundHepatoma-derived growth factor (HDGF) participates in angiogenesis and represents a negative prognostic factor in oral cancer. The current study was designed to elucidate the regulatory mechanism between HDGF and vascular endothelial growth factor (VEGF) and the clinical impact of oral cancer.MethodsTCGA data and surgical samples from oral cancer patients were used for the clinicopathological parameter and survival analysis. Human oral cancer SCC4 and SAS cells were treated with recombinant HDGF protein. VEGF gene expression and protein level were analyzed by RT-PCR, Western blotting, and enzyme-linked immunosorbent assay. The signaling pathways for regulating VEGF expression were investigated. The nucleolin neutralizing antibody and HIF-1α inhibitor were applied to SCC4 cells to investigate their effects on the HDGF-stimulated VEGF pathways.ResultsTCGA and immunohistochemical analysis revealed a positive correlation between HDGF and VEGF expression in oral cancer tissues. Recombinant HDGF significantly increased VEGF gene and protein expression in oral cancer SCC4 cells in a dose-dependent manner. HDGF enhanced the phosphorylation levels of AKT and IkB and the protein level of HIF-1α and NF-κB. The nucleolin-neutralizing antibody abolished HDGF-stimulated HIF-1α, NF-κB and VEGF protein expression in SCC4 cells. The HIF-1α inhibitor antagonized the HDGF-induced VEGF gene expression. High VEGF expression was strongly correlated with HDGF expression, advanced disease, and poor survival.ConclusionThis study postulated a new pathway in which HDGF activated HIF-1α and then induced VEGF expression through binding to membrane nucleolin under normoxic conditions, leading to poor disease control. The HDGF/HIF-1α/VEGF axis is important for developing future therapeutic strategies.