bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA let‐7c‐5p promotes osteogenic differentiation of dental pulp stem cells by inhibiting lipopolysaccharide‐induced inflammation via HMGA2/PI3K/Akt signal blockade
Authors: Yuan Hao , Zhao Hongyan , Wang Jiafeng , Zhang Hong , Hong Lihua , Li He , Che Hongze , Zhang Zhimin 
Published: December 2018

SummaryPulpitis suppressed the level of let‐7c‐5p that promotes osteogenesis and bone formation by repressing HMGA2. In the current study, the function of let‐7c‐5p in the inflammation and osteogenesis in dental pulp stem cells (DPSCs) was explored. The level of let‐7c‐5p in DPSCs was up‐regulated, and the cells were subjected to lipopolysaccharide (LPS) to induce inflammation. The effect of let‐7c‐5p on cell proliferation potential, osteogenic differentiation potential, and activity of HMGA2/PI3K/Akt pathway was detected. The administration of LPS suppressed the cell proliferation of DPSCs and suppressed calcium deposition, activity of alkaline phosphatase (ALP), and levels of OCN, OPN, OSX, MSX2, and RUNX2 in inflamed DPSCs. The impaired osteogenic differentiation of inflamed DPSCs was associated with the increased levels of HMGA2, p‐PI3K, and p‐Akt. In let‐7c‐5p‐overexpressed inflamed DPSCs, the proliferation and osteogenic differentiation potential of DPSCs were restored, and the activation of HMGA2/PI3K/Akt signalling was inhibited. In rat pulpitis models, the injection of let‐7c‐5p agomir restored the osteogenic differentiation potential of dental pulp cells and inhibited HMGA2/PI3K/Akt signalling. The findings demonstrated the anti‐inflammation and pro‐osteogenesis effect of let‐7c‐5p during the attack of pulpitis, which depended on the inhibition of HMGA2/PI3K/Akt signalling.
Dietary Exposures to Common Emulsifiers and Their Impact on the Gut Microbiota: Is There a Cause for Concern?
Authors: Vo Trung D. , Lynch Barry S. , Roberts Ashley 
Published: December 2018

AbstractEmulsifiers are commonly used in food processing for the technological purpose of altering the flavor or to improve the texture of foods. Due to their ubiquity, these substances are consumed daily at low levels in the human diet. Recently published in vitro and in vivo studies suggest dietary exposure to emulsifiers modulate the gut microbiota and contribute to the increasing prevalence of metabolic disease. A literature search was conducted which identified eight studies investigating the interaction of sodium carboxymethyl cellulose, polysorbate 80, gum arabic, carrageenan, and arabinogalactan with the gut microbiota in murine and in vitro models. Numerous inconsistent changes in various phyla and genera were identified. These studies were conducted at high doses that have no relevance to the current dietary levels consumed in the United States. Subtle changes in gut microbiota composition as a toxicological endpoint is not supported by established internationally recognized toxicology testing guidelines. Therefore, the results of these studies are difficult to interpret and extrapolate to humans and are not supported by previous safety conclusions of international food safety authorities. The current understanding of the gut microbiota is that the structure is highly dynamic and is heavily influenced by the diet. Thus, the results of these studies may not necessarily suggest a safety concern, but rather reflect an adaptive response of the gut microbiota to an external stressor. Future research will need to further elucidate the mechanisms of metabolic disease in rodents and humans and establish clinically relevant and reliable endpoints to assess changes in gut microflora.
Probiotic research in neonates with congenital gastrointestinal surgical conditions – Now is the time
Authors: Rao Shripada C. , Patole Sanjay K. 
Published: December 2018

SummaryNeonates with congenital gastrointestinal surgical conditions (CGISC) receive parenteral nutrition, get exposed to multiple courses of antibiotics, undergo invasive procedures, and are nursed in intensive care units. They do not receive early enteral feeding and have limited opportunities for skin to skin contact with their mothers. Many of these infants receive gastric acid suppression therapies. All these factors increase the risk of gut dysbiosis in these infants. Gut dysbiosis is known to be associated with increased risk of infections and other morbidities in ICU patients. Experimental studies have shown that probiotics inhibit gut colonization with pathogenic bacteria, enhance gut barrier function, facilitate colonization with healthy commensals, protect from enteropathogenic infection through production of acetate, reduce antimicrobial resistance, enhance innate immunity, and increase the maturation of the enteric nervous system and promote gut peristalsis. Through these mechanisms, probiotics have the potential to decrease the risk of sepsis and inflammation, improve feed tolerance and minimise cholestasis in neonates with CGISC. Among preterm non‐surgical infants, evidence from more than 35 RCTs and multiple observational studies have shown probiotics to be safe and beneficial. A RCT in neonates (N=24) with gastroschisis found that probiotic supplementation partially attenuated gut dysbiosis. Two ongoing RCTs (total N=168) in neonates with gastrointestinal surgical conditions are expected to provide feasibility data to enable the conduct of large RCTs. Rigorous quality assurance of the probiotic product, ongoing microbial surveillance and clinical vigilance are warranted while conducting such RCTs.
Discovering millions of plankton genomic markers from the Atlantic Ocean and the Mediterranean Sea
Authors: Arif Majda , Gauthier Jérémy , Sugier Kevin , Iudicone Daniele , Jaillon Olivier , Wincker Patrick , Peterlongo Pierre , Madoui Mohammed‐Amin 
Published: December 2018

AbstractComparison of the molecular diversity in all plankton populations present in geographically distant water columns may allow for a holistic view of the connectivity, isolation and adaptation of organisms in the marine environment. In this context, a large‐scale detection and analysis of genomic variants directly in metagenomic data appeared as a powerful strategy for the identification of genetic structures and genes under natural selection in plankton. Here, we used discosnp++, a reference‐free variant caller, to produce genetic variants from large‐scale metagenomic data and assessed its accuracy on the copepod Oithona nana in terms of variant calling, allele frequency estimation and population genomic statistics by comparing it to the state‐of‐the‐art method. discosnp ++ produces variants leading to similar conclusions regarding the genetic structure and identification of loci under natural selection. discosnp++ was then applied to 120 metagenomic samples from four size fractions, including prokaryotes, protists and zooplankton sampled from 39 tara Oceans sampling stations located in the Atlantic Ocean and the Mediterranean Sea to produce a new set of marine genomic markers containing more than 19 million of variants. This new genomic resource can be used by the community to relocate these markers on their plankton genomes or transcriptomes of interest. This resource will be updated with new marine expeditions and the increase of metagenomic data (availability: http://bioinformatique.rennes.inria.fr/taravariants/).
Polyneuropathy associated with chronic hemodialysis: Clinical and electrophysiological study
Authors: Ezzeldin Nillie , Abdel Galil Sahar Mahfouz , Said Dina , Kamal Nafesa Mohamed , Amer Mona 
Published: December 2018

AbstractAimTo estimate the frequency and pattern of peripheral polyneuropathy (PNP) that may affect patients maintained on hemodialysis.Patients and methodsThe study was carried out on 60 middle‐aged male patients attending the Internal Medicine Department for maintenance hemodialysis. All were subjected to a complete neurological examination. Motor and sensory nerve conduction studies of both lower limbs (the tibial, peroneal and sural nerves) and both upper limbs (median and ulnar nerves), as well as F‐wave measurements of both tibial and median nerves, were done. The patients were subdivided clinically into two groups, clinically apparent neuropathy and inapparent groups. Then they were divided according to the types of peripheral neuropathy detected by electrophysiological studies into axonal, demyelinated and mixed polyneuropathy. In addition, they were divided into motor, sensory and sensorimotor groups.ResultsPolyneuropathy was found clinically presented in 33 (55%) cases, while evident by electrophysiological examination in 100% of the clinically apparent group (33 patients) and evident in 92.5% of the clinically inapparent group (27 patients). The frequency of pathologic electrophysiological parameters was significantly higher in patients with longer duration of hemodialysis. Axonal polyneuropathy is the most prevalent type in those patients.ConclusionPeripheral polyneuropathy is a common presentation in patients maintained on hemodialysis. The longer the duration of hemodialysis, the more liability to develop PNP that can be detected earlier by electrodiagnostic studies in the subclinical cases.
House dust mite drives proinflammatory eicosanoid reprogramming and macrophage effector functions
Authors: Henkel Fiona D. R. , Friedl Antonie , Haid Mark , Thomas Dominique , Bouchery Tiffany , Haimerl Pascal , de los Reyes Jiménez Marta , Alessandrini Francesca , Schmidt‐Weber Carsten B. , Harris Nicola L. , Adamski Jerzy , Esser‐von Bieren Julia 
Published: December 2018

AbstractBackgroundEicosanoid lipid mediators play key roles in type 2 immune responses, for example in allergy and asthma. Macrophages represent major producers of eicosanoids and they are key effector cells of type 2 immunity. We aimed to comprehensively track eicosanoid profiles during type 2 immune responses to house dust mite (HDM) or helminth infection and to identify mechanisms and functions of eicosanoid reprogramming in human macrophages.MethodsWe established an LC‐MS/MS workflow for the quantification of 52 oxylipins to analyze mediator profiles in human monocyte‐derived macrophages (MDM) stimulated with HDM and during allergic airway inflammation (AAI) or nematode infection in mice. Expression of eicosanoid enzymes was studied by qPCR and western blot and cytokine production was assessed by multiplex assays.ResultsShort (24 h) exposure of alveolar‐like MDM (aMDM) to HDM suppressed 5‐LOX expression and product formation, while triggering prostanoid (thromboxane and prostaglandin D2 and E2) production. This eicosanoid reprogramming was p38‐dependent, but dectin‐2‐independent. HDM also induced proinflammatory cytokine production, but reduced granulocyte recruitment by aMDM. In contrast, high levels of cysteinyl leukotrienes (cysLTs) and 12‐/15‐LOX metabolites were produced in the airways during AAI or nematode infection in mice.ConclusionOur findings show that a short exposure to allergens as well as ongoing type 2 immune responses are characterized by a fundamental reprogramming of the lipid mediator metabolism with macrophages representing particularly plastic responder cells. Targeting mediator reprogramming in airway macrophages may represent a viable approach to prevent pathogenic lipid mediator profiles in allergy or asthma.
Genetics of ncHH: from a peculiar inheritance of a novel GNRHR mutation to a comprehensive review of the literature
Authors: Cioppi F. , Riera‐Escamilla A. , Manilall A. , Guarducci E. , Todisco T. , Corona G. , Colombo F. , Bonomi M. , Flanagan C. A. , Krausz C. 
Published: December 2018

AbstractBackgroundNormosmic congenital hypogonadotropic hypogonadism (ncHH) is caused by the deficient production, secretion, or action of gonadotropin‐releasing hormone (GnRH). Its typical clinical manifestation is delayed puberty and azoospermia. Homozygous and compound heterozygous mutations in the GNRHR gene (4q13.2) are the most frequent genetic causes of ncHH.Objectives(i) Characterization at the molecular level (genetic origin and functional effect) of a unique homozygous mutation (p.Gly99Glu) in a ncHH man; (ii) to provide a comprehensive catalog of GNRHR mutations with genotype–phenotype correlation and comparison of in vitro studies vs. in silico prediction tools.Material and MethodsA ncHH man and his parents, in whom we performed the following: (i) Sanger sequencing, qPCR of the GNRHR gene; (ii) chromosome 4 SNP array; and (iii) competition binding assay and inositol phosphate signaling assay. PubMed and Human Genome Mutation Database (HGMD) search for GNRHR mutations. Bioinformatic analysis of 55 reported variants.ResultsqPCR showed two GNRHR copies in the index case. SNP array revealed the inheritance of two homologous chromosomes 4 from the mother (maternal heterodisomy; hUPD) with two loss of heterozygosity regions, one of them containing the mutated gene (maternal isodisomy; iUPD). Functional studies for the p.Gly99Glu mutation demonstrated a right‐shifted GnRH‐stimulated signaling response. Bioinformatic tools show that commonly used in silico tools are poor predictors of the function of ncHH‐associated GNRHR variants.DiscussionFunctional analysis of the p.Gly99Glu mutation is consistent with severely decreased GnRH binding affinity (a severe partial loss‐of‐function mutation). Complete LOF variants are associated with severe and severe/moderate phenotype, whereas partial LOF variants show wide range of clinical manifestations.ConclusionThis is the first ncHH patient carrying a novel causative missense mutation of GNRHR with proven ‘severe pLOF’ due to maternal hUPD/iUPD of chromosome 4. Our literature review shows that functional studies remain essential both for diagnostic and potential therapeutic purposes.
Fiction in Fact: Ernest Callenbach’sEcotopiaand the Creation of a Green Culture with Anthropological Ingredients
Authors: Lohmann Roger Ivar 
Published: December 2018

SummaryEcotopia is a quasi‐ethnographic novel influenced by anthropology. Some of its fictional practices have been adopted in the actual world since publication in 1975. Set two decades after Green secessionists achieve national independence for the U.S. Northwest, an American journalist‐fieldworker describes Ecotopians’ strange new ecological customs. Author Callenbach constructively criticized and inflenced his unsustainable culture by comparing it to an invented alternative. The case illustrates that a dialectic between cultural fact and fiction drives innovation.“So a light went on in my head: if a country doesn’t exist that gets its bleep together, maybe it’s time to start thinking about inventing one.”—Ernest Callenbach (Smith 2010)
Effect of wood kraft pulp feed on digestibility, ruminal characteristics, and milk production performance in lactating dairy cows
Authors: Nishimura Keiko , Kurosu Kazuhiro , Terada Fuminori , Mizuguchi Hitoshi , Sato Shigeru , Kushibiki Shiro 
Published: December 2018

AbstractThe effect of wood kraft pulp (KP) feed on dietary digestibility, ruminal fluid pH, rumen fermentation characteristics, and milk production performance in lactating dairy cows was examined. Four lactating dairy cows were used for the feeding experiment by the cross‐over design. The control group and KP group were set up as treatments. The control group was fed total mixed ration (TMR) (40% roughage and 60% concentrate) and the KP group was fed TMR containing 12% KP that replaced half of the rolled corn in the control diet. The dry matter intake, digestibility of the feed components, and milk yield were not significantly different between control group and KP group. The number of times that the ruminal fluid pH was below 6.1 tended to decrease in the KP group compared to the control group (p < 0.10). The acetic acid ratio in the ruminal fluid of the KP group increased compared to the control group (p < 0.05) and the propionic acid ratio in the ruminal fluid of the KP group decreased compared to the control group (p < 0.05). The acetate:propionate acid ratio was increased in the KP group compared with the control group (p < 0.05). Lipopolysaccharide levels in the ruminal fluid of the KP group tended to decrease compared to the control group (p < 0.10). Based on these results, it was indicated that the use of KP feed for lactating dairy cows induced the same rumen fermentation characteristics as those in cows given a large amount of roughage without depressing milk productivity. Therefore, KP could be a valuable feed resource substitute for grains, which would also reduce the risk for subacute rumen acidosis.
Atrial fibrillation and human immunodeficiency virus type‐1 infection: a systematic review. Implications for anticoagulant and antiarrhythmic therapy
Authors: Pastori Daniele , Mezzaroma Ivano , Pignatelli Pasquale , Violi Francesco , Lip Gregory Y. H. 
Published: December 2018

AbstractThe prevalence and incidence of atrial fibrillation/flutter (AF/AFL) in patients with human immunodeficiency virus type‐1 (HIV‐1) infection have been poorly investigated. We performed a systematic review using PubMed and Cochrane Database of Systematic Reviews, and screening of references, searching for clinical studies reporting on the association between HIV‐1 infection and AF/AFL. We also summarized the main interactions of antiretroviral agents with antithrombotic and antiarrhythmic drugs. We found a prevalence of AF/AFL ranging from 2.0% to 5.13% in patients with HIV‐1, with an incidence rate of 3.6/1000 person‐years. Low CD4+ count (<200–250 cells ml−1) and high viral load were predictors of AF/AFL. Regarding drugs interactions, nucleoside reverse transcriptase inhibitors, integrase inhibitor and maraviroc have the lowest interactions with oral anticoagulants. Among anticoagulants, dabigatran presents the most favourable profile. Most of antiarrhythmic drugs interact with protease inhibitors, with beta blockers and diltiazem having fewer interactions. The few studies available suggest a non‐negligible prevalence of AF/AFL in patients with HIV‐1 infection. Awareness of potential interactions with anticoagulation and antiarrhythmic drugs is needed to offer optimal management in this population.
Paleogene evolution and demise of the proto‐Paratethys Sea in Central Asia (Tarim and Tajik basins): Role of intensified tectonic activity at ca. 41 Ma
Authors: Kaya Mustafa Y. , Dupont‐Nivet Guillaume , Proust Jean‐Noël , Roperch Pierrick , Bougeois Laurie , Meijer Niels , Frieling Joost , Fioroni Chiara , Özkan Altıner Sevinç , Vardar Ezgi , Barbolini Natasha , Stoica Marius , Aminov Jovid , Mamtimin Mehmut , Zhaojie Guo 
Published: December 2018

AbstractThe proto‐Paratethys Sea covered a vast area extending from the Mediterranean Tethys to the Tarim Basin in western China during Cretaceous and early Paleogene. Climate modelling and proxy studies suggest that Asian aridification has been governed by westerly moisture modulated by fluctuations of the proto‐Paratethys Sea. Transgressive and regressive episodes of the proto‐Paratethys Sea have been previously recognized but their timing, extent and depositional environments remain poorly constrained. This hampers understanding of their driving mechanisms (tectonic and/or eustatic) and their contribution to Asian aridification. Here, we present a new chronostratigraphic framework based on biostratigraphy and magnetostratigraphy as well as a detailed palaeoenvironmental analysis for the Paleogene proto‐Paratethys Sea incursions in the Tajik and Tarim basins. This enables us to identify the major drivers of marine fluctuations and their potential consequences on Asian aridification. A major regional restriction event, marked by the exceptionally thick (≤ 400 m) shelf evaporites is assigned a Danian‐Selandian age (ca. 63–59 Ma) in the Aertashi Formation. This is followed by the largest recorded proto‐Paratethys Sea incursion with a transgression estimated as early Thanetian (ca. 59–57 Ma) and a regression within the Ypresian (ca. 53–52 Ma), both within the Qimugen Formation. The transgression of the next incursion in the Kalatar and Wulagen formations is now constrained as early Lutetian (ca. 47–46 Ma), whereas its regression in the Bashibulake Formation is constrained as late Lutetian (ca. 41 Ma) and is associated with a drastic increase in both tectonic subsidence and basin infilling. The age of the final and least pronounced sea incursion restricted to the westernmost margin of the Tarim Basin is assigned as Bartonian–Priabonian (ca. 39.7–36.7 Ma). We interpret the long‐term westward retreat of the proto‐Paratethys Sea starting at ca. 41 Ma to be associated with far‐field tectonic effects of the Indo‐Asia collision and Pamir/Tibetan plateau uplift. Short‐term eustatic sea level transgressions are superimposed on this long‐term regression and seem coeval with the transgression events in the other northern Peri‐Tethyan sedimentary provinces for the 1st and 2nd sea incursions. However, the 3rd sea incursion is interpreted as related to tectonism. The transgressive and regressive intervals of the proto‐Paratethys Sea correlate well with the reported humid and arid phases, respectively in the Qaidam and Xining basins, thus demonstrating the role of the proto‐Paratethys Sea as an important moisture source for the Asian interior and its regression as a contributor to Asian aridification.
Fluid flow and pore pressure development throughout the evolution of a trough mouth fan, western Barents Sea
Authors: Llopart Jaume , Urgeles Roger , Forsberg Carl Fredrik , Camerlenghi Angelo , Vanneste Maarten , Rebesco Michele , Lucchi Renata Giulia , Rüther Denise Christina , Lantzsch Hendrik 
Published: December 2018

AbstractUsing a combination of geophysical and geotechnical data from Storfjorden Trough Mouth Fan off southern Svalbard, we investigate the hydrogeology of the continental margin and how this is affected by Quaternary glacial advances and retreats over the continental shelf. The geotechnical results show that plumites, deposited during the deglaciation, have high porosities, permeabilities and compressibilities with respect to glacigenic debris flows and tills. These results together with margin stratigraphic models obtained from seismic reflection data were used as input for numerical finite element models to understand focusing of interstitial fluids on glaciated continental margins. The modelled evolution of the Storfjorden TMF shows that tills formed on the shelf following the onset of glacial sedimentation (ca. 1.5 Ma) acted as aquitards and therefore played a significant role in decreasing the vertical fluid flow towards the sea floor and diverting it towards the slope. The model shows that high overpressure ratios (up to λ ca. 0.6) developed below the shelf edge and on the middle slope. A more detailed model for the last 220 kyrs accounting for ice loading during glacial maxima shows that the formation of these aquitards on the shelf focused fluid flow towards the most permeable plumite sediments on the slope. The less permeable glacigenic debris flows that were deposited during glacial maxima on the slope hinder fluid evacuation from plumites allowing high overpressure ratios (up to λ ca. 0.7) to develop in the shallowest plumite layers. These high overpressures likely persist to the Present and are a critical precondition for submarine slope failure.