bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact Of Electronic Health Record Interface Design On Unsafe Prescribing Of Ciclosporin, Tacrolimus and Diltiazem: A Cohort Study In English NHS Primary Care
Authors: MacKenna Brian , Bacon Seb , Walker Alex J , Curtis Helen J , Croker Richard , Goldacre Ben 
Published: November 2019

AbstractBackgroundIn England, national safety guidance recommends that ciclosporin, tacrolimus and diltiazem are prescribed by brand name due to their narrow therapeutic windows and, in the case of tacrolimus, to reduce the chance of organ transplantation rejection. Various small studies have shown that changes to electronic health records (EHR) interface can affect prescribing choices.ObjectivesOur objectives were to assess variation by EHR system in breaches of safety guidance around prescribing of ciclosporin, tacrolimus and diltiazem; and to conduct user-interface research into the causes of such breaches.MethodsWe carried out a retrospective cohort study using prescribing data in English primary care. Participants were English general practices and their respective electronic health records. The main outcome measures were (1) variation in ratio of breaching / adherent prescribing all practices (2) description of observations of EHR usage.ResultsA total of 2,575,411 prescriptions were issued in 2018 for ciclosporin, tacrolimus and diltiazem (over 60mg); of these, 316,119 prescriptions breached NHS guidance (12.3%). Breaches were most common amongst users of the EMIS EHR (in 23.2% of ciclosporin & tacrolimus prescriptions, and 22.7% of diltiazem prescriptions); but breaches were observed in all EHRs.ConclusionDesign choices in EHR strongly influence safe prescribing of ciclosporin, tacrolimus and diltiazem; and breaches are prevalent in general practices in England. We recommend that all EHR vendors review their systems to increase safe prescribing of these medicines in line with national guidance. Almost all clinical practice is now mediated through an EHR system: further quantitative research into the effect of EHR design on clinical practice is long overdue.
Is There a Health Inequality in Gambling Related Harms? A Systematic Review
Authors: Raybould J. N , Larkin M , Tunney R. J 
Published: November 2019

ABSTRACTObjectiveHere we present a systematic review of the existing research into gambling harms, in order to determine whether there are differences in the presentation of these across demographic groups such as age, gender, culture, and socioeconomic status, or gambling behaviour categories such as risk severity and play frequency.Primary and Secondary Outcome Measures: Inclusion criteria were: 1) focus on gambling harms; 2) focus on harms to the gambler rather than affected others; 3) discussion of specific listed harms and not just harms in general terms. Exclusion criteria were: 1) research of non-human subjects; 2) not written in English; 3) not an empirical study; 3) not available as a full article.SearchWe conducted a systematic search using the Web of Science and Scopus databases in February 2020. Assessment of quality took place using Standard Quality Assessment Criteria.Results56 studies published between 1994 and 2019 met the inclusion criteria. These were categorised into thematic groups for comparison and discussion. There were replicated differences found in groups defined by age, socioeconomic status, education level, ethnicity and culture, risk severity, and gambling behaviours.ConclusionHarms appear to be dependent on specific social, demographic and environmental conditions that suggests there is a health inequality in gambling related harms. Further investigation is required to develop standardised measurement tools and to understand confounding variables and co-morbidities. With a robust understanding of harms distribution in the population, Primary Care Workers will be better equipped to identify those who are at risk, or who are showing signs of Gambling Disorder, and to target prevention and intervention programmes appropriately.
Sarcomeres regulate cardiomyocyte maturation through MRTF-SRF signaling
Authors: Guo Yuxuan , Jardin Blake D. , Sethi Isha , Ma Qing , Moghadaszadeh Behzad , Troiano Emily C. , Trembley Michael A. , Small Eric M. , Yuan Guo-Cheng , Beggs Alan H. , Pu William T. 
Published: November 2019

AbstractCardiomyocyte maturation is essential for robust heart contraction throughout life. The signaling networks governing cardiomyocyte maturation remain poorly defined. Our prior studies established the transcription factor SRF as a key regulator of the assembly of sarcomeres, the contractile unit of cardiomyocytes. Whether sarcomeres regulate other aspects of maturation remains unclear. Here we generated mice with cardiomyocyte specific, mosaic mutation of α-actinin-2 (Actn2), a key organizer of sarcomeres, to study its cell-autonomous role in cardiomyocyte maturation. In addition to the expected structural defects,Actn2mutation triggered dramatic transcriptional dysregulation, which strongly correlated with transcriptional changes observed in SRF-depleted cardiomyocytes.Actn2mutation increased monomeric actin, which perturbed the nuclear localization of the SRF cofactor MRTFA. Overexpression of a dominant-negative MRTFA mutant was sufficient to recapitulate the transcriptional and morphological defects inActn2andSrfmutant cardiomyocytes. Together, we demonstrate that ACTN2-based sarcomere assembly and MRTF-SRF signaling establish a positive feedback loop that promotes cardiomyocyte maturation.
Caramel Dye IV Induces Oxidative Stress Damage In Liver And Kidney From Mice
Authors: Marins Emerson , da Silva Julia Spanhol , da Rosa Pâmela Carvalho , de Oliveira Vitor Antunes , Pasinato Aline Zuanazzi , Moretto Joana Grandó , Vargas José Eduardo , Soares Felix Alexandre Antunes , Barcelos Rômulo Pillon 
Published: November 2019

ABSTRACTCaramel dye IV (C-IV) is a synthetic organic product, does not present nutritional, ergogenic, or technological factors, but leads to reactive oxygen species (ROS), causing damage to a wide range of molecules, leading to cancer, cardiovascular and neurodegenerative diseases development. We aimed to verify the effects of different doses of C-IV dye on the markers of oxidative stress in the liver and kidneys from male Swiss CF-1 mice, divided into 4 experimental groups: control; C-IV 0.3g/kg; C-IV 1g/kg and C-IV 3g/kg. We found that 3 g/Kg of C-IV dye promote oxidative damage in liver and kidney homogenates, evidenced by the increase of lipid peroxidation, reduction of free SH groups, and higher ROS production. As a consequence, increased superoxide dismutase and acetylcholinesterase enzymes activities were detected. These damages were confirmed through histology images. These results indicate that daily doses might induce oxidative stress damages and possible lead to chronic diseases development.
Subarachnoid hemorrhage leads to early and persistent functional connectivity and behavioral changes in mice
Authors: Chung David Y , Oka Fumiaki , Jin Gina , Harriott Andrea , Kura Sreekanth , Aykan Sanem , Qin Tao , Edmiston William J , Lee Hang , Yaseen Mohammad A , Sakadžić Sava , Boas David A , Whalen Michael J , Ayata Cenk 
Published: November 2019

AbstractAneurysmal subarachnoid hemorrhage (SAH) leads to significant long-term cognitive deficits. Studies in survivors of SAH show an association between persistent cognitive deficits and alterations in resting state functional connectivity (RSFC). However, modalities commonly used to assess RSFC in humans, such as fMRI, have practical limitations in small animals. Therefore, we used non-invasive functional optical intrinsic signal imaging to determine the effect of SAH on measures of RSFC in mice at early (day 4), intermediate (1 month), and late (3 months) time points after prechiasmatic arterial blood injection. We assessed Morris water maze, open field test, Y-maze, and rotarod performance from approximately 2 weeks to 3 months after SAH induction. We found qualitative and quantitative differences in seed-based connectivity maps between sham and SAH mice. SAH reduced motor, retrosplenial and visual seed-based connectivity indices, which persisted in retrosplenial and visual cortex seeds at 3 months. Seed-to-seed connectivity analysis confirmed attenuation of correlation coefficients in SAH mice, which persisted in predominantly posterior network connections at later time points. Seed-independent global and interhemispheric indices of connectivity revealed decreased correlations following SAH for at least 1 month. SAH led to Morris water maze hidden platform and open field deficits at 2 weeks, and Y-maze deficits for at least 3 months, without altering rotarod performance. In conclusion, experimental SAH leads to early and persistent alterations both in hemodynamically-derived measures of RSFC and in cognitive performance.
DIMERBOW: exploring possible GPCR dimer interfaces
Authors: García-Recio Adrián , Navarro Gemma , Franco Rafael , Olivella Mireia , Guixà-González Ramon , Cordomí Arnau 
Published: November 2019

AbstractG protein-coupled receptors (GPCRs) can form homo-, heterodimers and larger order oligomers that exert different functions than monomers. The pharmacological potential of such complexes is hampered by the limited information available on the type of complex formed and its quaternary structure. Several GPCR structures in the Protein Data Bank display crystallographic interfaces potentially compatible with physiological interactions. Here we present DIMERBOW, a database and web application aimed to visually browse the complete repertoire of potential GPCR dimers present in solved structures. The tool is suited to help finding the best possible structural template to model GPCR homomers. DIMERBOW is available at http://lmc.uab.es/dimerbow/.
First record of ‘plasticrusts’ and ‘pyroplastic’ from the European Mediterranean Sea
Authors: Ehlers Sonja M. , Ellrich Julius A. 
Published: November 2019

AbstractWe report the presence of ‘plasticrusts’ and ‘pyroplastic’ from coastal habitats in Giglio island, Tyrrhenian Sea, Italy. These novel plastic debris types have only recently been described for the first time from Madeira island (NE Atlantic Ocean) and the United Kingdom, respectively. While ‘plasticrusts’ are generated by sea waves smashing plastic debris against intertidal rocks, ‘pyroplastic’ derives from (un)deliberately burnt plastic waste. Using Fourier-transform infrared (FTIR) spectroscopy, we identified the ‘plasticrust’ material as polyethylene (PE) and the ‘pyroplastic’ material as polyethylene terephthalate (PET). These polymers are widely used in everyday products and, therefore, contribute heavily to plastic pollution in aquatic and terrestrial environments worldwide. Furthermore, our field surveys suggest that ‘plasticrust’ abundance is related to wave-exposure and that the ‘pyroplastic’ derived from beverage bottles which we frequently found along the Giglio coast. Overall, our findings corroborate the notion that ‘plasticrusts’ and ‘pyroplastic’ are common debris types in marine coastal habitats.
Transcriptional analysis of sodium valproate in a serotonergic cell line reveals gene regulation through both HDAC inhibition-dependent and independent mechanisms
Authors: Sinha Priyanka , Cree Simone , Miller Allison L. , Pearson John F. , Kennedy Martin A. 
Published: November 2019

AbstractSodium valproate (VPA) is a histone deacetylase (HDAC) inhibitor, widely prescribed in the treatment of bipolar disorder, and yet the precise modes of therapeutic action for this drug are not fully understood. After exposure of the rat serotonergic cell line RN46A to VPA, RNA-sequencing (RNA-Seq) analysis showed widespread changes in gene expression. Analysis by multiple pipelines revealed as many as 230 genes were significantly upregulated and 72 genes were significantly downregulated. A subset of 23 differentially expressed genes was selected for validation using the nCounter®platform, and of these we obtained robust validation forADAM23, LSP1, MAOB, MMP13, PAK3, SERPINB2, SNAP91, WNT6, andZCCHC12. We investigated the effect of lithium on this subset and found four genes,CDKN1C, LSP1, SERPINB2andWNT6co-regulated by lithium and VPA. We also explored the effects of other HDAC inhibitors and the VPA analogue valpromide on the subset of 23 selected genes. Expression of eight of these genes,CDKN1C, MAOB, MMP13, NGFR, SHANK3, VGF, WNT6andZCCHC12, was modified by HDAC inhibition, whereas others did not appear to respond to several HDAC inhibitors tested. These results suggest VPA may regulate genes through both HDAC-dependent and independent mechanisms. Understanding the broader gene regulatory effects of VPA in this serotonergic cell model should provide insights into how this drug works and whether other HDACi compounds may have similar gene regulatory effects, as well as highlighting molecular processes that may underlie regulation of mood.
An integrative approach to investigate natural variation in the accumulation of aliphatic glucosinolates in Arabidopsis thaliana
Authors: Sharma Suraj , Popa Ovidiu , Kopriva Stanislav , Ebenhoeh Oliver 
Published: November 2019

AbstractGlucosinolates are a fascinating class of specialised metabolites found in the plants of Brassicacea family. The variation in glucosinolate composition across different Arabidopsis ecotypes could be a result of allelic compositions at different biosynthetic loci. The contribution of methylthioalkylmalate synthase (MAM) genes to diversity of glucosinolate profiles across different Arabidopsis ecotypes has been confirmed by genetic analyses. Different MAM isoforms utilise different chain-elongated substrates for glucosinolate biosynthesis causing thus a variation in chain lengths across different Arabidopsis ecotypes. To further investigate the relationship between the genotype and the associated metabolic phenotype, we studied the diversity of genes and enzymes of glucosinolate biosynthesis. Using Shannon entropy as a measure we revealed that several genes of the pathway show a clear derivation from the expected behaviour, either accumulating non-synonymous SNPs or showing signs of purifying selection. We found that the genotype-phenotype relationship is much more complicated than inferred from the diversity of MAM synthases. We conclude therefore, that the ON/OFF feature of key QTLs is not enough to elucidate the diversity of glucosinolates across different Arabidopsis thaliana ecotypes and that glucosinolate profiles are determined also through the polymorphic residues along the coding regions of multiple metabolic genes.
Dynamic integration of forward planning and heuristic preferences during multiple goal pursuit
Authors: Ott Florian , Marković Dimitrije , Strobel Alexander , Kiebel Stefan J. 
Published: November 2019

AbstractSelecting goals and successfully pursuing them in an uncertain and dynamic environment is an important aspect of human behaviour. In order to decide which goal to pursue at what point in time, one has to evaluate the consequences of one’s actions over future time steps by forward planning. However, when the goal is still temporally distant, detailed forward planning can be prohibitively costly. One way to select actions at minimal computational costs is to use heuristics. It is an open question how humans mix heuristics with forward planning to balance computational costs with goal reaching performance. To test a hypothesis about dynamic mixing of heuristics with forward planning, we used a novel stochastic sequential two-goal task. Comparing participants’ decisions with an optimal full planning agent, we found that at the early stages of goal-reaching sequences, in which both goals are temporally distant and planning complexity is high, on average 42% (SD = 19%) of participants’ choices deviated from the agent’s optimal choices. Only towards the end of the sequence, participant’s behaviour converged to near optimal performance. Subsequent model-based analyses showed that participants used heuristic preferences when the goal was temporally distant and switched to forward planning when the goal was close.Author summaryWhen we pursue our goals, there is often a moment when we recognize that we did not make the progress that we hoped for. What should we do now? Persevere to achieve the original goal, or switch to another goal? Two features of real-world goal pursuit make these decisions particularly complex. First, goals can lie far into an unpredictable future and second, there are many potential goals to pursue. When potential goals are temporally distant, human decision makers cannot use an exhaustive planning strategy, rendering simpler rules of thumb more appropriate. An important question is how humans adjust the rule of thumb approach once they get closer to the goal. We addressed this question using a novel sequential two-goal task and analysed the choice data using a computational model which arbitrates between a rule of thumb and accurate planning. We found that participants’ decision making progressively improved as the goal came closer and that this improvement was most likely caused by participants starting to plan ahead.
Genome Repository of Oiled Systems (GROS): an interactive and searchable database that expands the catalogued diversity of crude oil-associated microbes
Authors: Karthikeyan Smruthi , Rodriguez-R Luis M. , Heritier-Robbins Patrick , Hatt Janet K. , Huettel Markus , Kostka Joel E. , Konstantinidis Konstantinos T. 
Published: November 2019

ABSTRACTIndigenous microbial communities ultimately control the fate of petroleum hydrocarbons (PHCs) that enters the natural environment through natural seeps or accidental oil spills, but the interactions among microbes and with their chemical environment during oil biodegradation are highly complex and poorly understood. Genome-resolved metagenomics have the potential to help in unraveling these complex interactions. However, the lack of a comprehensive database that integrates existing genomic/metagenomic data from oiled environments with physicochemical parameters known to regulate the fate of PHCs currently limits data analysis and interpretations. Here, we present a curated, comprehensive, and searchable database that documents microbial populations in oiled ecosystems on a global scale, along with underlying physicochemical data, geocoded via GIS to reveal geographic distribution patterns of the populations. Analysis of the ~2,000 metagenome-assembled genomes (MAGs) available in the database revealed strong ecological niche specialization within habitatse.g., specialization to coastal sediments vs. water-column vs. deep-sea sediments. Over 95% of the recovered MAGs represented novel and uncultured species underscoring the limited representation of cultured organisms from oil-contaminated and oil reservoir ecosystems. The majority of MAGs linked to oiled ecosystems are members of the rare biosphere in non-oiled samples, except for the Gulf of Mexico (GoM) which appears to be primed for oil biodegradation. GROS should facilitate future work toward a more predictive understanding of the microbial taxa and their activities that control the fate of oil spills as well as serve as a model approach for building similar resources for additional environmental processes and omic data of interest.
ERBB2 is a Key Mediator in Hearing Restoration in Noise-Deafened Young Adult Mice
Authors: Zhang Jingyuan , Na Daxiang , Beaulac Holly J. , Dilts Miriam , Henry Kenneth S. , Bullen Anwen , White Patricia M. 
Published: November 2019

AbstractNoise-induced hearing loss (NIHL) affects over ten million adults in the United States, and has no biological treatment. We hypothesized that activation of signaling from ERBB2 receptors in cochlear supporting cells could mitigate cochlear damage. We adopted a new timeline for assessing mitigation that parallels hearing recovery from damage in avians. We drove expression of a constitutively active variant of ERBB2 (CA-ERBB2) in cochlear supporting cells three days after permanent noise damage in young adult mice. Between 100-200 supporting cells in the apical cochlea expressed a lineage marker, indicating competence to express CA-ERBB2. Hearing thresholds were assessed with auditory brainstem response tests, and hearing recovery was assessed over a ninety-day period. Mice harboring CA-ERBB2 capability had similar hearing thresholds to control littermates prior to noise exposure, immediately after, and 30-days after. Sixty and ninety days after noise exposure, CA-ERBB2+ mice demonstrated a partial but significant reversal of NIHL threshold shifts at one in five frequencies tested, which was in the region of CA-ERBB2 expression. We evaluated inner and outer hair cell (IHC and OHC) survival, synaptic preservation, stereociliary morphology, and IHC cytoskeletal alterations with histological techniques. Improved IHC and OHC survival were observed in the basal cochlea. No differences were seen in synaptic numbers or IHC cytoskeletal alterations, but more stereocilia may have been preserved. These data indicate, for the first time, that ERBB2 signaling in supporting cells can promote hair cell survival and partial functional recovery, and that permanent threshold shifts from noise may be partially reversed in mice.
A/T/N polygenic risk score for cognitive decline in old age
Authors: Moore Annah M. , Filshtein Teresa J. , Dumitrescu Logan , Harrati Amal , Elahi Fanny , Mormino Elizabeth C. , Deming Yuetiva , Kunkle Brian W. , Mungas Dan M. , Hedden Trey , Apostolova Liana G. , Saykin Andrew J. , Chasioti Danai , Lu Qiongshi , Dennis Jessica , Sealock Julia , Davis Lea K. , Fardo David W. , Buckley Rachel , Hohman Timothy J. 
Published: November 2019

AbstractINTRODUCTIONWe developed a novel polygenic risk score (PRS) based on the A/T/N (amyloid plaques (A), phosphorylated tau tangles (T), and neurodegeneration (N)) framework and compared a PRS based on clinical AD diagnosis to assess which was a better predictor of cognitive decline.METHODSWe used summary statistics from genome wide association studies of cerebrospinal fluid amyloid-β (Aβ42) and phosphorylated-tau (ptau181), left hippocampal volume (LHIPV), and late-onset AD dementia to calculate PRS for 1181 participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Individual PRS were averaged to generate a composite A/T/N PRS. We assessed the association of PRS with baseline and longitudinal cognitive composites of executive function and memory.RESULTSThe A/T/N PRS showed superior predictive performance on AD biomarkers and executive function decline compared to the clinical AD PRS.DISCUSSIONResults suggest that integration of genetic risk across AD biomarkers may improve prediction of disease progression.Research in ContextSystematic ReviewAuthors reviewed relevant literature using PubMed and Google Scholar. Key studies that generated and validated polygenic risk scores (PRS) for clinical and pathologic AD were cited. PRS scores have been increasingly used in the literature but clinical utility continues to be questioned.InterpretationIn the current research landscape concerning PRS clinical utility in the AD space, there is room for model improvement and our hypothesis was that a PRS with integrated risk for AD biomarkers could yield a better model for cognitive decline.Future DirectionsThis study serves as proof-of-concept that encourages future study of integrated PRS across disease markers and utility in taking an A/T/N (amyloidosis, tauopathy and neurodegeneration) focused approach to genetic risk for cognitive decline and AD.