bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic effect of Anakinra in the relapsing chronic phase of febrile infection–related epilepsy syndrome
Authors: Dilena Robertino , Mauri Eleonora , Aronica Eleonora , Bernasconi Pia , Bana Cristina , Cappelletti Cristina , Carrabba Giorgio , Ferrero Stefano , Giorda Roberto , Guez Sophie , Scalia Catenacci Stefano , Triulzi Fabio , Barbieri Sergio , Calderini Edoardo , Vezzani Annamaria 
Published: March 2019

SummaryFebrile infection–related epilepsy syndrome (FIRES) is a severe epileptic encephalopathy with presumed inflammatory origin and lacking effective treatments. Anakinra is the human recombinant interleukin 1 receptor antagonist clinically used in autoinflammatory or autoimmune conditions. We report a case of FIRES for which the spatial and temporal match between electroencephalography (EEG) and magnetic resonance imaging (MRI) focal alterations provides support for the detrimental synergic interplay between seizures and inflammation that may evolve to permanent focal lesions and progressive brain atrophy in weeks to months. Brain biopsy showed aspects of chronic neuroinflammation with scarce parenchymal lymphocytes. We report the novel evidence that anakinra reduces the relapse of highly recurrent refractory seizures at 1.5 years after FIRES onset. Our evidence, together with previously reported therapeutic effects of anakinra administered since the first days of disease onset, support the hypothesis that interleukin 1β and inflammation‐related factors play a crucial role in seizure recurrence in both the acute and chronic stages of the disease.
Neurochemical correlates of scene processing in the precuneus/posterior cingulate cortex: A multimodal fMRI and 1H‐MRS study
Authors: Costigan Alison G. , Umla‐Runge Katja , Evans C. John , Hodgetts Carl J. , Lawrence Andrew D. , Graham Kim S. 
Published: March 2019

AbstractPrecuneus/posterior cingulate cortex (PCu/PCC) are key components of a midline network, activated during rest but also in tasks that involve construction of scene or situation models. Despite growing interest in PCu/PCC functional alterations in disease and disease risk, the underlying neurochemical modulators of PCu/PCC's task‐evoked activity are largely unstudied. Here, a multimodal imaging approach was applied to investigate whether interindividual differences in PCu/PCC fMRI activity, elicited during perceptual discrimination of scene stimuli, were correlated with local brain metabolite levels, measured during resting‐state 1H‐MRS. Forty healthy young adult participants completed an fMRI perceptual odd‐one‐out task for scenes, objects and faces. 1H‐MRS metabolites N‐acetyl‐aspartate (tNAA), glutamate (Glx) and γ‐amino‐butyric acid (GABA+) were quantified via PRESS and MEGA‐PRESS scans in a PCu/PCC voxel and an occipital (OCC) control voxel. Whole brain fMRI revealed a cluster in right dorsal PCu/PCC that showed a greater BOLD response to scenes versus faces and objects. When extracted from an independently defined PCu/PCC region of interest, scene activity (vs. faces and objects and also vs. baseline) was positively correlated with PCu/PCC, but not OCC, tNAA. A voxel‐wise regression analysis restricted to the PCu/PCC 1H‐MRS voxel area identified a significant PCu/PCC cluster, confirming the positive correlation between scene‐related BOLD activity and PCu/PCC tNAA. There were no correlations between PCu/PCC activity and Glx or GABA+ levels. These results demonstrate, for the first time, that scene activity in PCu/PCC is linked to local tNAA levels, identifying a neurochemical influence on interindividual differences in the task‐driven activity of a key brain hub.
Functional and effective reorganization of the aging brain during unimanual and bimanual hand movements
Authors: Larivière Sara , Xifra‐Porxas Alba , Kassinopoulos Michalis , Niso Guiomar , Baillet Sylvain , Mitsis Georgios D. , Boudrias Marie‐Hélène 
Published: March 2019

AbstractMotor performance decline observed during aging is linked to changes in brain structure and function, however, the precise neural reorganization associated with these changes remains largely unknown. We investigated the neurophysiological correlates of this reorganization by quantifying functional and effective brain network connectivity in elderly individuals (n = 11; mean age = 67.5 years), compared to young adults (n = 12; mean age = 23.7 years), while they performed visually‐guided unimanual and bimanual handgrips inside the magnetoencephalography (MEG) scanner. Through a combination of principal component analysis and Granger causality, we observed age‐related increases in functional and effective connectivity in whole‐brain, task‐related motor networks. Specifically, elderly individuals demonstrated (i) greater information flow from contralateral parietal and ipsilateral secondary motor regions to the left primary motor cortex during the unimanual task and (ii) decreased interhemispheric temporo‐frontal communication during the bimanual task. Maintenance of motor performance and task accuracy in elderly was achieved by hyperactivation of the task‐specific motor networks, reflecting a possible mechanism by which the aging brain recruits additional resources to counteract known myelo‐ and cytoarchitectural changes. Furthermore, resting‐state sessions acquired before and after each motor task revealed that both older and younger adults maintain the capacity to adapt to task demands via network‐wide increases in functional connectivity. Collectively, our study consolidates functional connectivity and directionality of information flow in systems‐level cortical networks during aging and furthers our understanding of neuronal flexibility in motor processes.
Association of Appendicular Lean Mass, and Subcutaneous and Visceral Adipose Tissue With Mortality in Older Brazilians: The São Paulo Ageing & Health Study
Authors: de Santana Felipe M , Domiciano Diogo S , Gonçalves Michel A , Machado Luana G , Figueiredo Camille P , Lopes Jaqueline B , Caparbo Valéria F , Takayama Lilliam , Menezes Paulo R , Pereira Rosa MR 
Published: March 2019

ABSTRACT
Body composition changes as a result of ageing may impact the survival of older adults. However, its influence on mortality risk is uncertain. Currently, the best method for body composition analysis in clinical practice is DXA. Nonetheless, the few studies on body composition by DXA and mortality risk in the elderly have some limitations. We investigated the association between body composition by DXA and mortality in a cohort of elderly subjects. Eight hundred thirty-nine community-dwelling subjects (516 women, 323 men) ≥ 65 years of age were assessed by a questionnaire, clinical data, laboratory exams, and body composition by DXA at baseline. Total fat and its components (eg, visceral adipose tissue [VAT]) were estimated. Appendicular lean mass (ALM) adjusted for fat and ALM divided by height² was used to ascertain the presence of low muscle mass (LMM). Mortality was recorded during follow-up. Multivariate logistic regression was used to compute ORs for all-cause and cardiovascular mortality. Over a mean follow-up of 4.06 ± 1.07 years, there were 132 (15.7%) deaths. In men, after adjustment for relevant variables, the presence of LMM (OR, 11.36, 95% CI, 2.21 to 58.37, P = 0.004) and VAT (OR, 1.99, 95% CI, 1.38 to 2.87, P &lt; 0.001, for each 100-g increase) significantly increased all-cause mortality risk, whereas total fat, measured by the fat mass index, was associated with decreased mortality risk (OR, 0.48, 95% CI, 0.33 to 0.71, P &lt; 0.001). Similar results were observed for cardiovascular mortality. In women, only LMM was a predictor of all-cause (OR, 62.88, 95% CI, 22.59 to 175.0, P &lt; 0.001) and cardiovascular death (OR, 74.54, 95% CI, 9.72 to 571.46, P &lt; 0.001). LMM ascertained by ALM adjusted for fat and fat mass by itself are associated with all-cause and cardiovascular mortality risk in the elderly. Visceral and subcutaneous fat have opposite roles on mortality risk in elderly men. Thus, DXA is a promising tool to estimate risk of mortality in the elderly. © 2019 American Society for Bone and Mineral Research.
KDM5D inhibit epithelial‐mesenchymal transition of gastric cancer through demethylation in the promoter of Cul4A in male
Authors: Shen Xudong , Hu Kewei , Cheng Guilian , Xu Liming , Chen Zhengrong , Du Peng , Zhuang Zhixiang 
Published: March 2019

AbstractGastric cancer is one of the top causes of cancer‐related death around the world, and poor prognosis of gastric cancer is due to the lack of early detection and effective treatment especially in male. Here, we first revealed the role of histone lysine‐specific demethylase 5D (KDM5D) in gastric cancer in male. KDM5D was associated with the metastasis of gastric cancer because of its critical role in the epithelial‐mesenchymal transition of gastric cancer cells. Downregulation of KDM5D in gastric cancer cells significantly increase the number of migrated or invaded cells due to the increasing expressions of mesenchymal markers. Downregulation of KDM5D also promotes tumor formation of gastric cancer cell in vivo. For mechanism, downregulation of KDM5D could inhibit the demethylation in the promoter of CUL4A, which lead to the increasing expression of ZEB1 and decreasing expressions of p21 and p53. Collectively, KDM5D performed its role in metastasis of gastric cancer through demethylation in the promoter of CUL4A, and it suggested us a novel target in gastric cancer treatment in male.
Downregulation of circDYNC1H1 exhibits inhibitor effect on cell proliferation and migration in hepatocellular carcinoma through miR‐140‐5p
Authors: Wang Zheng‐Yang , Zhu Zhu , Wang Hua‐Fei , Qin Bo , Liu Jing , Yao Xiao‐Han , Li Wen‐Cai , Chen Kui‐Sheng 
Published: March 2019

AbstractCircular RNAs have been found to be aberrantly expressed in tumors and their significance in tumorigenesis has been focused on. The role of circDYNC1H1 in hepatocellular carcinoma (HCC) pathogenesis and its relationship with miR‐140‐5p were explored. The expression of circDYNC1H1, miR‐140‐5p, and SULT2B1 in HCC tissues and cells was measured, and Pearson's analysis was used to analyze their expression correlation. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and Transwell assays were performed to determine cell proliferation and migration. Binding between circDYNC1H1 and miR‐140‐5p was evaluated with RNA pull‐down assay. A luciferase reporter assay was conducted to assess the interaction between circDYNC1H1 and miR‐140‐5p and between miR‐140‐5p and SULT2B1. circDYNC1H1 was highly expressed in HCC tissues (n = 20), and it was negatively associated with the expression of miR‐140‐5p but positively correlated with SULT2B1 messenger RNA expression. circDYNC1H1 was upregulated in cell lines of HCC. Interference of circDYNC1H1 suppressed cell proliferation and migration of HCC. circDYNC1H1 acted as a sponge of miR‐140‐5p. miR‐140‐5p controlled SULT2B1 expression by targeting its 3′‐untranslated region. circDYNC1H1 enhanced SULT2B1 expression via sponging miR‐140‐5p. Downregulation of circDYNC1H1 disturbed cell proliferation and migration of HCC through miR‐140‐5p/SULT2B1 pathway. Silencing of circDYNC1H1 delayed tumor growth in HCC mouse model. Acting like a sponge of miR‐140‐5p, silenced circDYNC1H1 downregulated SULT2B1 to restrain HCC cell proliferation and migration, which is adverse to HCC growth and progression.
Flip‐flops of natural killer cells in autoimmune diseases versus cancers: Immunologic axis
Authors: Shahrabi Saeid , Zayeri Zeinab D. , Ansari Narges , Hadad Elham H. , Rajaei Elham 
Published: March 2019

AbstractNatural killer (NK) cells play an essential role in the immune response to infections, inflammations, and malignancies. Recent studies suggest that NK cell surface receptors and cytokines are the key points of the disease development and protection. We hypothesized that the interactions between NK cell receptors and targeted cells construct an eventual niche, and this niche has an eventual profile in various autoimmune diseases and cancers. The NK cells preactivated with cytokines, such as interleukin‐2 (IL‐2), IL‐12, IL‐15, and IL‐18 can have higher cytotoxicity; however, the toxic side effect of IL‐2 should be considered. The vicissitudes of NK cell profile and its receptors obey the environmental communications and cell interactions. Our vision around the NK cells as an immune axis remained dual, and we still cannot judge the immune responses based on the NK cell flip‐flop. A design of eventual niche to monitor the NK cell and targeted cell interaction is needed to strengthen our ability in diagnosis and treatment approaches based on the NK cells. Here, we have reviewed the shifts in the NK cells and their surface receptors in autoimmune diseases, solid tumors, and leukemia, and also discussed the effective chemokines that affect NK cell activation and proliferation. The main aim of this review is to present a broader vision of the NK cell changes in autoimmune disease and cancers.
Monoclonal Antibodies and Fc‐Fusion Proteins for Pediatric Use: Dosing, Immunogenicity, and Modeling and Simulation in Data Submitted to the US Food and Drug Administration
Authors: Liu Xiaomei I. , Dallmann André , Wang Yow‐Ming , Green Dionna J. , Burnham Janelle M. , Chiang Beatrice , Wu Perry , Sheng Mark , Lu Kelley , van den Anker John N. , Burckart Gilbert J. 
Published: March 2019

AbstractThe experience with the use of monoclonal antibodies and Fc‐fusion proteins (mAb/Fc) in the pediatric population is limited. The objective of this study is to review those factors impacting the clinical efficacy and product safety of mAb/Fc products in pediatric patients during drug development. We reviewed the list of biologic products in the US Food and Drug Administration's Purple Book as of March 2018 with a focus on mAb/Fc products that are indicated for use in both adults and pediatric patients. Of 68 mAb/Fc products in the Purple Book (excluding biosimilars), 20 products have approved indications in both adults and children. Thirteen products had concurrent approval for both adult and pediatric populations. The sample size of pediatric studies generally ranged from approximately 2% to 70% of the sample size of adult studies with the same indication. In general, pediatric dosing regimens were found to be more based on body weight and weight tiered than the regimens for adults. Modeling and simulation techniques comprised mainly population pharmacokinetic and pharmacodynamic models. A review of the immunogenicity incidence did not reveal any notable difference in the 5 products having data on both pediatric and adult patients. In conclusion, most of the mAb/Fc products have a different weight‐based dosing regimen for pediatric patients versus adults. An understanding of the comparative experience in drug development for mAb/Fc products between adult and pediatric patients coupled with the application of advanced modeling and simulation methods should assist future development of new mAb/Fc products for pediatric patients.
Organelle interplay—peroxisome interactions in health and disease
Authors: Schrader Michael , Kamoshita Maki , Islinger Markus 
Published: March 2019

AbstractPeroxisomes are multifunctional, dynamic, membrane‐bound organelles with important functions in cellular lipid metabolism, rendering them essential for human health and development. Important roles for peroxisomes in signaling and the fine‐tuning of cellular processes are emerging, which integrate them in a complex network of interacting cellular compartments. Like many other organelles, peroxisomes communicate through membrane contact sites. For example, peroxisomal growth, positioning, and lipid metabolism involves contacts with the endoplasmic reticulum (ER). Here, we discuss the most recent findings on peroxisome‐organelle interactions including peroxisome‐ER interplay at membrane contacts sites, and functional interplay with mitochondria, lysosomes, and lipid droplets in mammalian cells. We address tether proteins, metabolic cooperation, and the impact of peroxisome interactions on human health and disease.
Early response assessment of glioma patients to definitive chemoradiotherapy using chemical exchange saturation transfer imaging at 7 T
Authors: Meissner Jan‐Eric , Korzowski Andreas , Regnery Sebastian , Goerke Steffen , Breitling Johannes , Floca Ralf Omar , Debus Jürgen , Schlemmer Heinz‐Peter , Ladd Mark Edward , Bachert Peter , Adeberg Sebastian , Paech Daniel 
Published: March 2019

BackgroundPatients with newly diagnosed inoperable glioma receive chemoradiotherapy (CRT). Standard Response Assessment in Neuro‐Oncology (RANO) takes a minimum of 4 weeks after the end of treatment.Purpose/HypothesisTo investigate whether chemical exchange saturation transfer (CEST) MRI enables earlier assessment of response to CRT in glioma patients.Study TypeLongitudinal prospective study.PopulationTwelve brain tumor patients who underwent definitive CRT were included in this study. Three longitudinal CEST MRI measurements were performed for each patient at 7T: first before, second immediately after completion of CRT, and a third measurement as a 6‐week follow‐up.Field Strength/SequenceConventional MRI (contrast‐enhanced, T2w and diffusion‐weighted imaging) at 3T and T2w and CEST MRI at 7T was performed for all patients.AssessmentThe mean relaxation‐compensated relayed nuclear‐Overhauser‐effect CEST signal (rNOE) and the mean downfield‐rNOE‐suppressed amide proton transfer (dns‐APT) CEST signal were investigated. Additionally, choline‐to‐N‐acetyl‐aspartate ratios (Cho/NAA) were evaluated using single‐voxel 1H‐MRS in six of these patients. Performance of obtained contrasts was analyzed in assessing treatment response as classified according to the updated RANO criteria.Statistical TestUnpaired Student's t‐test.ResultsThe rNOE signal significantly separated stable and progressive disease directly after the end of therapy (post‐treatment normalized to pre‐treatment mean ± SD: rNOEresponder = 1.090 ± 0.110, rNOEnon‐responder = 0.808 ± 0.155, P = 0.015). In contrast, no significant difference was observed between either group when assessing the normalized dns‐APT (dns‐APTresponder = 0.953 ± 0.384, dns‐APTnon‐responder = 0.972 ± 0.477, P = 0.95). In the smaller MRS subcohort, normalized Cho/NAA decreased in therapy responders (Cho/NAAresponder = 0.632 ± 0.007, Cho/NAAnon‐responder = 0.946 ± 0.124, P = 0.070).Data ConclusionrNOE mediated CEST imaging at 7T allowed for discrimination of responders and non‐responders immediately after the end of CRT, additionally supported by 1H‐MRS data. This is at least 4 weeks earlier than the standard clinical evaluation according to RANO. Therefore, CEST MRI may enable early response assessment in glioma patients.Level of Evidence: 1Technical Efficacy Stage: 5J. Magn. Reson. Imaging 2019;50:1268–1277.
Genetic diversity of influenza A(H3N2) viruses in Northern Cameroon during the 2014‐2016 influenza seasons
Authors: Njifon Hermann Landry Munshili , Monamele Chavely Gwladys , Vernet Marie‐Astrid , Njankouo Mohamadou Ripa , Deweerdt Louis , Nono Raphael , Kenmoe Sebastien , Mbacham Wilfred , Njouom Richard 
Published: March 2019

AbstractIn Cameroon, genome characterization of influenza virus has been performed only in the Southern regions meanwhile genetic diversity of this virus varies with respect to locality. The Northern region characterized by a Sudan tropical climate might have distinct genetic characterization. This study aimed to better understand the genetic diversity of influenza A(H3N2) viruses circulating in Northern Cameroon. Sequences of three gene segments (hemagglutinin (HA), neuraminidase (NA) and matrix (M) genes) were obtained from 16 A(H3N2) virus strains collected during the 2014 to 2016 influenza seasons in Garoua. The HA gene segments were analysed with respect to reference strains while the NA and M gene was analysed for reported genetic markers of resistance to antivirals. Analysis of the HA sequences revealed that majority of the virus strains grouped together with the 2016‐2017 vaccine strain (3C.2a‐A/Hong Kong/4801/2014) while 3/5 (60%) of the 2015 viral strains grouped together with the 2015‐2016 vaccine strain 3C.3a‐A/Switzerland/9715293/2013. Within clade 3C.2a, Northern Cameroon sequences mostly grouped in sub‐clade A3 (10/16). Analysis of the coding regions of the NA and M genes showed that none had genetic markers of resistance to neuraminidase inhibitors but all strains possessed the S31N substitution of resistance to amantadine. Due to some discrepancies observed in this region with respect to the Southern regions of Cameroon, there is necessity of including all regions within a country in the sentinel surveillance of influenza. These data will enable to track changes in influenza viruses in Cameroon.
A 28‐year study of human parainfluenza in Rio Grande do Sul, Southern Brazil
Authors: Gregianini Tatiana Schäffer , Seadi Claudete Farina , Zavarize Neto Luiz Domingos , Martins Letícia Garay , Muller Guilherme Cerutti , Straliotto Selir Maria , Veiga Ana Beatriz Gorini da 
Published: March 2019

AbstractProblemHuman parainfluenza virus (hPIV) is an important pathogen in respiratory infections, however the health burden of hPIV is underestimated. This study describes the infections by hPIV1‐3 in Rio Grande do Sul, Brazil, from 1990 to 2017, providing data of the frequency and seasonality of cases and associated clinical symptoms.Method of studyNasopharyngeal samples of patients with respiratory infection were collected, clinical data were analyzed, and immunofluorescence was used to detect hPIV.ResultsRespiratory viruses were detected in 33.63% of respiratory infections. In a total of 11 606 cases of viral respiratory infection, 781 were positive for hPIV; hPIV prevalence ranged from 2.14% to 27% of viral respiratory infections. hPIV1 circulates mainly during fall; hPIV3 circulation, in turn, starts in fall and peaks during spring; and cases of hPIV2 are reported along the year, with peaks in fall and early spring. The most affected age group was children, with hPIV prevalence of 74.23% in patients for less than 1 year. A higher proportion of girls were infected than boys, however, no difference by sex was observed considering all age groups. The most frequent type was hPIV3, especially in hospitalized patients. Both hPIV1 and 3 were associated with dyspnea, while hPIV2 caused mild symptoms mainly in nonhospitalized patients. Nineteen fatalities occurred, 89.5% of them associated with risk factors (prematurity; chronic diseases; age, <1 or >60 years).ConclusionhPIV causes a high number of respiratory infections, leading to hospitalization especially in children; epidemiological and surveillance studies are important for the control and management of respiratory infections.