bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis of circular RNA profiling in AZD9291‐resistant non‐small cell lung cancer cell lines
Authors: Chen Tianxiang , Luo Jizhuang , Gu Yu , Huang Jia , Luo Qingquan , Yang Yunhai 
Published: March 2019

BackgroundOsimertinib (AZD9291), a third‐generation EGFR‐tyrosine kinase inhibitor, can effectively prolong survival in non‐small cell lung cancer (NSCLC) patients with EGFR mutations, particularly T790M mutations; however, acquired resistance to AZD9291 is inevitable, thus exploration of the targets of resistance is urgent.MethodsConsidering the important role of circular RNAs (circRNAs) in cancers, we established AZD9291‐resistant NSCLC cell lines (H1975/AZDR and HCC827/AZDR) and used microarray analysis to determine the circRNA expression profiles of the cells. The H1975/AZDR and HCC827/AZDR cell lines were induced by gradually increasing the drug concentration. CircRNA microarray expression profiles were obtained from H1975, HCC827, H1975/AZDR, and HCC827/AZDR cells and validated by quantitative reverse transcription PCR. Expression data were analyzed bioinformatically.ResultsThe H1975/AZDR and HCC827/AZDR cell lines were successfully established. The half‐maximal inhibitory concentration and the invasion ability of H1975/AZDR and HCC827/AZDR cells were significantly enhanced. The proliferation rates of H1975/AZDR and HCC827/AZDR were much lower than H1975 and HCC827. Microarray analysis identified 15 504 circRNAs differentially expressed in H1975, HCC827, H1975/AZDR, and HCC827/AZDR cells. Among them, 7966 were upregulated and 7538 were downregulated more than two‐fold. We predicted the possible miRNAs of the top dysregulated circRNAs. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the most modulated circRNAs regulate several cancers and cancer‐related pathways.ConclusionOur results reveal that circRNAs may play a role in NSCLC AZD9291 resistance and might be a promising molecular target candidate for gene therapy.
Phase locking of event‐related oscillations is decreased in both young adult humans and rats with a history of adolescent alcohol exposure
Authors: Ehlers Cindy L. , Phillips Evie , Wills Derek , Benedict Jessica , Sanchez‐Alavez Manuel 
Published: March 2019

AbstractAlcohol exposure typically begins in adolescence, and frequent binge drinking has been associated with health risk behaviors including alcohol use disorders (AUDs). Few studies have documented the effects of a history of adolescent binge drinking on neurophysiological consequences in young adulthood. Synchrony of phase (phase locking (PL)) of event‐related oscillations (EROs) within and between different brain areas reflects communication exchange between neural networks and is a sensitive measure of adolescent development in both rats and humans, and thus may be a good translational measure of the potential harmful effects of alcohol exposure during adolescence. In this study, EROs were collected from 1041 young adults of Mexican American and American Indian ancestry (age 18‐30 years) with and without a history of adolescent binge drinking (five drinks for boys and four for girls per occasion at least once per month) and in 74 young adult rats with and without a history of 5 weeks of adolescent alcohol vapor exposure. PL of theta and beta frequencies between frontal and parietal cortex were estimated using an auditory‐oddball paradigm in the rats and a visual facial expression paradigm in the humans. Significantly lower PL between frontal and parietal cortices in the theta frequencies was seen in both the humans and the rats with a history of adolescent alcohol exposure as compared with their controls. These findings suggest that alcohol exposure during adolescence may result in decreases in synchrony between cortical neuronal networks, suggesting a developmental delay, in young adult humans and in rats.
Decomposing social inequalities in alcohol consumption in Germany 1995–2015: an age–period–cohort analysis
Authors: Pabst Alexander , van der Auwera Sandra , Piontek Daniela , Baumeister Sebastian E. , Kraus Ludwig 
Published: March 2019

Background and aimsPrevious research indicates that compared with individuals with lower socio‐economic status (SES), individuals in higher SES groups are more often drinkers but those who drink report drinking smaller amounts more frequently. We aimed to decompose trends in self‐reported alcohol consumption in Germany into age, period and birth cohort effects and examine whether these effects varied by SES.DesignAge–period–cohort (APC) analysis using data from eight waves of the cross‐sectional German Epidemiological Survey of Substance Abuse (ESA) collected between 1995 and 2015.SettingGermany.ParticipantsThe analytical sample included n = 65 821 individuals aged 18–64 years reporting alcohol use within the last 30 days.MeasurementsAlcohol measures included drinking prevalence, alcohol volume and prevalence of episodic heavy drinking (EHD). Educational attainment was used as an indicator of SES. A series of generalized linear and logistic regression models, including both main and interaction effects of age, period and cohort with SES, were estimated.FindingsRegression models revealed significant interactions between APC effects and SES on two alcohol consumption measures. Higher SES was consistently associated with drinking prevalence across age (P < 0.001), period (P = 0.016) and cohort (P = 0.016), and with volume of drinking in younger cohorts (P = 0.002) and 50+‐year‐olds (P = 0.001). Model results were inconclusive as to whether or not APC effects on EHD prevalence differed by SES.ConclusionsIn Germany, there are positive associations between socio‐economic status and alcohol consumption during the life‐course, over time and among birth cohorts. Three groups appear vulnerable to risky drinking: high socio‐economic status young birth cohorts who drink high average quantities, low socio‐economic status young birth cohorts who show a risky drinking pattern and high socio‐economic status adults in their 50s and older who increase their drinking volume beyond that age.
The association between residential relocation and re‐incarceration among drug‐dependent former prisoners
Authors: Kirk David S. 
Published: March 2019

AimsTo assess whether residential relocation to a different geographic area by drug‐dependent former prisoners reduced their likelihood of re‐incarceration.DesignNon‐randomized observational study using Hurricane Katrina as a natural experiment to determine whether residential relocation induced by the hurricane affected the likelihood of re‐incarceration among drug‐dependent former prisoners. The study used data provided by the Louisiana Department of Public Safety and Corrections.SettingNew Orleans metropolitan area, Louisiana, USA.CasesThe pre‐Katrina cohort comprised individuals released from Louisiana prisons from September 2003 to February 2004 with a history of drug misuse, as determined by the Louisiana Risk/Needs Assessment (n = 796). The post‐Katrina cohort comprised prisoners released from a Louisiana prison immediately after the hurricane, from September 2005 to February 2006 (n = 677).MeasurementsRe‐incarceration, the dependent variable, was operationalized as a return to a Louisiana prison for a new criminal conviction or a parole violation within 1 year of prison release. Residential relocation was operationalized as a change in parish of residence from the location immediately prior to imprisonment to the location immediately upon release from prison.FindingsInstrumental variables probit analysis revealed that the probability of re‐incarceration was 0.10 lower for individuals who relocated to a new parish upon their exit from prison relative to individuals who returned to their home parish, with a 95% confidence interval ranging from −0.192 to −0.011. An estimated 10% of parolees who moved were re‐incarcerated within 1 year of their release from prison versus 20% of the stayers.ConclusionsResidential relocation of drug‐dependent former prisoners in Louisiana as a result of Hurricane Katrina was associated with reduced likelihood of re‐incarceration.
Complex Communication Dynamics: Exploring the Structure of an Academic Talk
Authors: Alviar Camila , Dale Rick , Galati Alexia 
Published: March 2019

AbstractCommunication is a multimodal phenomenon. The cognitive mechanisms supporting it are still understudied. We explored a natural dataset of academic lectures to determine how communication modalities are used and coordinated during the presentation of complex information. Using automated and semi‐automated techniques, we extracted and analyzed, from the videos of 30 speakers, measures capturing the dynamics of their body movement, their slide change rate, and various aspects of their speech (speech rate, articulation rate, fundamental frequency, and intensity). There were consistent but statistically subtle patterns in the use of speech rate, articulation rate, intensity, and body motion across the presentation. Principal component analysis also revealed patterns of system‐like covariation among modalities. These findings, although tentative, do suggest that the cognitive system is integrating body, slides, and speech in a coordinated manner during natural language use. Further research is needed to clarify the specific coordination patterns that occur between the different modalities.
Exposure–Response Analysis of Overall Survival for Tremelimumab in Unresectable Malignant Mesothelioma: The Confounding Effect of Disease Status
Authors: Baverel Paul , Roskos Lorin , Tatipalli Manasa , Lee Nancy , Stockman Paul , Taboada Maria , Vicini Paolo , Horgan Kevin , Narwal Rajesh 
Published: March 2019

Tremelimumab, an anti‐cytotoxic T‐lymphocyte antigen‐4 monoclonal antibody that enhances T‐cell activation, was evaluated in a randomized, double‐blind, placebo‐controlled, phase IIb study (NCT01843374) in patients with unresectable malignant mesothelioma. The study demonstrated no clinically meaningful differences in overall survival (OS). The objective of this analysis was to evaluate the relationship of exposure with OS. A population pharmacokinetic (PK) model adequately described the PK data. Three factors (sex, C‐reactive protein, and baseline tumor size) were identified as statistically significant PK predictors (P < 0.05 on clearance). A positive association between exposure and OS was observed. However, an association between key baseline factors with OS (regardless of treatment) and imbalances in prognostic factors favoring patients with higher exposure (upper vs. lower PK quartile) was seen. Taken together, these results suggest that the exposure OS relationship observed for tremelimumab in mesothelioma is likely spurious rather than a true association of exposure with efficacy.
Gene expression profiling of lichenoid dermatitis immune‐related adverse event from immune checkpoint inhibitors reveals increased CD14+ and CD16+ monocytes driving an innate immune response
Authors: Curry Jonathan L. , Reuben Alexandre , Szczepaniak‐Sloane Robert , Ning Jing , Milton Denái R. , Lee Chi H. , Hudgens Courtney , George Saira , Torres‐Cabala Carlos , Johnson Daniel , Subramanya Sandesh , Wargo Jennifer A. , Mudaliar Kumaran , Wistuba Ignacio I. , Prieto Victor G. , Diab Adi , Tetzlaff Michael T. 
Published: March 2019

BackgroundCancer patients receiving antibodies abrogating immune checkpoint pathways may develop a diverse array of immune‐related adverse events (irAEs), of which lichenoid dermatitis (LD) is the most common. The mechanism driving the emergence of these irAEs remain understudied, underscoring a critical need to determine the unique gene expression profiles and immune composition in LD—irAE.MethodsLD—irAE (n = 3) and benign lichenoid keratosis (BLK) control (n = 3) were profiled with NanoString nCounter PanCancer Immune Profiling Panel interrogating the mRNA levels of 770 genes. Immunohistochemical (IHC) studies (n = 14 samples) for CD14, CD16, T‐Bet, Gata‐3, and FoxP3 were further evaluated using Aperio digital image analysis.ResultsThe LD—irAE showed downregulation of 93 mRNA transcripts (P < 0.05) and upregulation of 74 mRNA transcripts (P < 0.04) including toll‐like receptor (TLR) 2 and TLR4 (P < 0.05). CD14+ and CD16+ monocytes quantified by IHC (H‐score) were higher in LD—irAE than in the BLK control (P < 0.05). The immune composition of LD—irAE exhibited higher numbers of T‐Bet+ (Th1) cells compared with Gata‐3+ (Th2) cells (P = 0.016) and lower numbers of FoxP3 (T regulatory) cells (P = 0.008).ConclusionsLD—irAE exhibited activation of CD14/TLR innate immune response with increased CD14+ and CD16+ monocytes compared with BLK control. CD14/TLR signaling may drive the development of LD—irAE.
Topische Therapie bei Psoriasis vulgaris – ein Behandlungspfad
Authors: Körber Andreas , Wilsmann‐Theis Dagmar , Augustin Matthias , von Kiedrowski Ralph , Mrowietz Ulrich , Rosenbach Thomas , Meller Stephan , Pinter Andreas , Sticherling Michael , Gerdes Sascha ,   on behalf of the PsoNet Förderverein
Published: March 2019

ZusammenfassungDie topische Behandlung der Psoriasis und ihrer Sonderformen hat einen hohen Stellenwert im Praxisalltag. Sie ist Therapiestandard bei leichter Psoriasis und wird unterstützend auch bei mittelschwerer bis schwerer Psoriasis eingesetzt. Bei der Optimierung der Behandlung der Psoriasis spielt neben den geeigneten Wirkstoffen auch die Wahl der Galenik eine entscheidende Rolle. Die Weiterentwicklungen in diesem Bereich wurden in der 2017 publizierten Aktualisierung der S3‐Leitlinie nicht berücksichtigt. Der vorliegende Behandlungspfad wurde im Rahmen der PsoNet‐­Sprecherkonferenz erarbeitet und durch die nationale Versorgungskonferenz Psoriasis bestätigt. Er stellt eine Illustration der aktuellen Optionen dar. Die Fachinformationen der genannten Präparate sind dabei stets zu berücksichtigen.Die Festlegung von Therapiezielen mit dem Patienten ist obligat und adhärenzsteigernd. Dabei sollten die persönlichen Präferenzen und Vorerfahrungen des Patienten berücksichtigt werden. Goldstandard in der Initialphase ist die Fixkombination aus Calcipotriol (Cal) 50 μg/g und Betamethason‐Dipropionat (Bet) 0,5 mg/g 1x täglich über vier bis acht Wochen. Als Darreichungsform ist der Schaum am effektivsten, wobei die individuelle Wahl der Grundlage auch nach Patientenpräferenz erfolgen sollte.In der Erhaltungsphase hat sich die 1–2x wöchentliche (proaktive) Anwendung dieser Fixkombination bewährt. In zweiter Linie können auch Vitamin D3 Analoga (Calcipotriol, Tacalcitol) und topische Corticosteroide als Monotherapie zur Anwendung kommen. Eine begleitende wirkstofffreie topische Basistherapie sollte regelhaft empfohlen werden. Bei besonderen Therapiesituationen werden spezifische Empfehlungen gegeben. Reicht eine alleinige Lokaltherapie nicht aus, sollte eine Therapieeskalation analog der S3‐Leitlinie zur Therapie der Psoriasis erfolgen.
Platelet reactivity patterns in patients treated with dual antiplatelet therapy
Authors: Winter Max‐Paul , Schneeweiss Theresia , Cremer Rolf , Biesinger Benedikt , Hengstenberg Christian , Prüller Florian , Wallner Markus , Kolesnik Ewald , von Lewinski Dirk , Lang Irene M. , Siller‐Matula Jolanta M. 
Published: March 2019

AbstractAimThe aim of the present study was to investigate the patterns of platelet reactivity and discriminators of therapeutic response to dual antiplatelet therapy (DAPT) with aspirin and ticagrelor or prasugrel in patients with acute coronary syndrome (ACS).DesignIn this multicentre prospective observational study, 492 patients with ACS were enrolled. Platelet aggregation was determined by multiple electrode aggregometry after stimulation with adenosine diphosphate (ADP) or arachidonic acid (AA) as agonists in the maintenance phase of treatment with prasugrel or ticagrelor.ResultsAge emerged as the strongest variable influencing aspirin response status: The mean AA‐induced platelet aggregation in patients <49 years of age was 49% higher than in those >49 years (13.1 U vs 8.8 U; P = 0.011). The second strongest discriminator of aspirin response was sex: Male patients had a 40% higher AA‐induced platelet aggregation values than female patients (9.5 U vs 6.8 U; P = 0.026). Platelet count emerged as the only variable influencing ADP antagonists response status showing that patients with platelet count >320 g/L displayed higher ADP‐induced platelet aggregation. About 12% of patients had high on‐treatment platelet reactivity (HTPR) to aspirin, 3% and 4% a HTPR to prasugrel and ticagrelor, respectively, and only 2% displayed HTPR to dual antiplatelet therapy.ConclusionWhen potent platelet inhibitors as prasugrel and ticagrelor are administered with aspirin, HTPR to DAPT plays only a marginal role.
Urogenital symptoms in mitochondrial disease: overlooked and undertreated
Authors: Poole O. V. , Uchiyama T. , Skorupinska I. , Skorupinska M. , Germain L. , Kozyra D. , Holmes S. , James N. , Bugiardini E. , Woodward C. , Quinlivan R. , Emmanuel A. , Hanna M. G. , Panicker J. N. , Pitceathly R. D. S. 
Published: March 2019

Background and purposeBowel symptoms are well documented in mitochondrial disease. However, data concerning other pelvic organs is limited. A large case–control study has therefore been undertaken to determine the presence of lower urinary tract symptoms (LUTS) and sexual dysfunction in adults with genetically confirmed mitochondrial disease.MethodsAdults with genetically confirmed mitochondrial disease and control subjects were recruited from a specialist mitochondrial clinic. The presence and severity of LUTS and their impact on quality of life, in addition to sexual dysfunction and bowel symptoms, were captured using four validated questionnaires. Subgroup analysis was undertaken in patients harbouring the m.3243A>G MT‐TL1 mitochondrial DNA mutation. A subset of patients underwent urodynamic studies to further characterize their LUTS.ResultsData from 58 patients and 19 controls (gender and age matched) were collected. Adults with mitochondrial disease had significantly more overactive bladder (81.5% vs. 56.3%, P = 0.039) and low stream (34.5% vs. 5.3%, P = 0.013) urinary symptoms than controls. Urodynamic studies in 10 patients confirmed that bladder storage symptoms predominate. Despite high rates of LUTS, none of the patient group was receiving treatment. Female patients and those harbouring the m.3243A>G MT‐TL1 mutation experienced significantly more sexual dysfunction than controls (53.1% vs. 11.1%, P = 0.026, and 66.7% vs. 26.3%, P = 0.011, respectively).ConclusionsLower urinary tract symptoms are common but undertreated in adult mitochondrial disease, and female patients and those harbouring the m.3243A>G MT‐TL1 mutation experience sexual dysfunction. Given their impact on quality of life, screening for and treating LUTS and sexual dysfunction in adults with mitochondrial disease are strongly recommended.
Conduction block in immune‐mediated neuropathy: paranodopathy versus axonopathy
Authors: Garg N. , Park S. B. , Howells J. , Vucic S. , Yiannikas C. , Mathey E. K. , Nguyen T. , Noto Y. , Barnett M. H. , Krishnan A. V. , Spies J. , Bostock H. , Pollard J. D. , Kiernan M. C. 
Published: March 2019

Background and purposeConduction block is a pathognomonic feature of immune‐mediated neuropathies. The aim of this study was to advance understanding of pathophysiology and conduction block in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN).MethodsA multimodal approach was used, incorporating clinical phenotyping, neurophysiology, immunohistochemistry and structural assessments.ResultsOf 49 CIDP and 14 MMN patients, 25% and 79% had median nerve forearm block, respectively. Clinical scores were similar in CIDP patients with and without block. CIDP patients with median nerve block demonstrated markedly elevated thresholds and greater threshold changes in threshold electrotonus, whilst those without did not differ from healthy controls in electrotonus parameters. In contrast, MMN patients exhibited marked increases in superexcitability. Nerve size was similar in both CIDP groups at the site of axonal excitability. However, CIDP patients with block demonstrated more frequent paranodal serum binding to teased rat nerve fibres. In keeping with these findings, mathematical modelling of nerve excitability recordings in CIDP patients with block support the role of paranodal dysfunction and enhanced leakage of current between the node and internode. In contrast, changes in MMN probably resulted from a reduction in ion channel density along axons.ConclusionsThe underlying pathologies in CIDP and MMN are distinct. Conduction block in CIDP is associated with paranodal dysfunction which may be antibody‐mediated in a subset of patients. In contrast, MMN is characterized by channel dysfunction downstream from the site of block.
Multi‐decadal climate and fishing predictors of abundance for U.S. South Atlantic coastal fishes and invertebrates
Authors: Stratton Mark A. , Nesslage Geneviève M. , Latour Robert J. 
Published: March 2019

AbstractAbundance of marine stocks fluctuates in response to both internal processes (e.g., density dependence) and exogenous drivers, including the physical environment, fishing, and trophodynamic interactions. In the United States, research investigating ecosystem drivers has been focused in data‐rich systems, primarily in the North Atlantic and North Pacific. To develop a more holistic understanding of important ecosystem drivers in the Southeast U.S. continental shelf Large Marine Ecosystem, we applied generalized linear and dynamic linear modeling to investigate the effects of climate and fishing covariates on the relative abundance trends of 71 demersal fish and invertebrate species sampled by a coastal trawl survey during 1990–2013. For the assemblage as a whole, fishing effects predominated over climate effects. In particular, changes in trawling effort within the penaeid shrimp fishery governed abundance trends of bony fishes, invertebrates, and elasmobranchs, a likely result of temporal changes in bycatch mortality. Changes in trawling intensity induced changes in overall community composition and appear to have altered trophic interactions among particular species. Among climate indices investigated, the Pacific Decadal Oscillation and the Western Bermuda High Index were most prevalent in well‐supported dynamic linear models. Observed annual abundance trends were synchronous among some taxonomically related species, highlighting similar responses to exogenous influences based on life history. This study strengthens the foundation for generating hypotheses and advancing ecosystem‐based fisheries research within the region.