bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity in Medical Device Clinical Trials: Do We Know What Works for Which Patients?
Authors: FOX‐RAWLINGS STEPHANIE R. , GOTTSCHALK LAURA B. , DOAMEKPOR LAURÉN A. , ZUCKERMAN DIANA M. 
Published: September 2018

Policy Points:
A 1993 law required the National Institutes of Health to include women and racial and ethnic minorities in relevant research studies. Most federal health agencies adopted the same policy, but the US Food and Drug Administration (FDA) did not.
A 2012 law encouraged the FDA to ensure that new medical products be analyzed for safety and effectiveness for key demographic patient groups.
Our study of high‐risk medical devices reviewed by the FDA in 2014‐2017 found that due to lack of patient diversity and publicly available data, clinicians and patients often cannot determine which devices are safe and effective for specific demographic groups.
ContextDemographic differences can influence the safety and effectiveness of medical devices; however, clinical trials of devices for adults have historically underrepresented women, people of color, and patients over age 65. The US Food and Drug Administration (FDA) Safety and Innovation Act became law in 2012, encouraging greater diversity and subgroup analyses. In 2013, the FDA reported that there was diversity in clinical trials considered “pivotal” for approval decisions and that subgroup analyses were conducted for most applications for the highest‐risk medical devices. However, the FDA's report did not specify whether analyses included sufficient numbers to be meaningful, whether analyses were conducted for most major subgroups, or whether analyses included safety, effectiveness, or accuracy.MethodsWe examined publicly available documents for all 22 medical devices that the FDA designated “highest risk” or “novel,” were reviewed through the premarket approval pathway, and were scrutinized at FDA public meetings from 2014 to 2017. We evaluated patient demographics and subgroup analyses for all pivotal trials.FindingsOnly 3 (14%) of the devices provided subgroup analyses for both effectiveness and safety or both sensitivity and selectivity for gender, race, and age. However, 55% of the devices reported both of those subgroup analyses for at least 1 of the 3 subgroups. Whether analyses were reported or not, the number of patients in most subgroups was too small to draw meaningful conclusions. Subgroup analyses were more likely to be reported to the FDA's Advisory Committees than in the FDA's public reviews or labeling.ConclusionsDespite a law encouraging more diversity and subgroup analyses in pivotal trials used as the basis for FDA approval, the results of our study indicate relatively few subgroup analyses are publicly available for the highest‐risk and novel medical devices. The lack of subgroup analyses makes it impossible to inform patients or physicians as to whether many newly approved medical devices are safe and effective for specific demographic subgroups defined by gender, race, and age.
Finding Nemo’s Genes: A chromosome‐scale reference assembly of the genome of the orange clownfishAmphiprion percula
Authors: Lehmann Robert , Lightfoot Damien J. , Schunter Celia , Michell Craig T. , Ohyanagi Hajime , Mineta Katsuhiko , Foret Sylvain , Berumen Michael L. , Miller David J. , Aranda Manuel , Gojobori Takashi , Munday Philip L. , Ravasi Timothy 
Published: September 2018

AbstractThe iconic orange clownfish,Amphiprion percula, is a model organism for studying the ecology and evolution of reef fishes, including patterns of population connectivity, sex change, social organization, habitat selection and adaptation to climate change. Notably, the orange clownfish is the only reef fish for which a complete larval dispersal kernel has been established and was the first fish species for which it was demonstrated that antipredator responses of reef fishes could be impaired by ocean acidification. Despite its importance, molecular resources for this species remain scarce and until now it lacked a reference genome assembly. Here, we present a de novo chromosome‐scale assembly of the genome of the orange clownfishAmphiprion percula. We utilized single‐molecule real‐time sequencing technology from Pacific Biosciences to produce an initial polished assembly comprised of 1,414 contigs, with a contig N50 length of 1.86 Mb. Using Hi‐C‐based chromatin contact maps, 98% of the genome assembly were placed into 24 chromosomes, resulting in a final assembly of 908.8 Mb in length with contig and scaffold N50s of 3.12 and 38.4 Mb, respectively. This makes it one of the most contiguous and complete fish genome assemblies currently available. The genome was annotated with 26,597 protein‐coding genes and contains 96% of the core set of conserved actinopterygian orthologs. The availability of this reference genome assembly as a community resource will further strengthen the role of the orange clownfish as a model species for research on the ecology and evolution of reef fishes.
Does Family History of Alcohol Use Disorder Relate to Differences in Regional Brain Volumes? A Descriptive Review with New Data
Authors: McPhee Matthew D. , Claus Eric D. , Boileau Isabelle , Lee Andy C. H. , Graff‐Guerrero Ariel , Hendershot Christian S. 
Published: September 2018

BackgroundDifferences in regional brain volumes as a function of family history (FH) of alcohol use disorder (AUD) have been reported, and it has been suggested that these differences might index genetic risk for AUD. However, results have been inconsistent. The aims of the current study were (i) to provide an updated descriptive review of the existing literature and (ii) to examine the association of FH with indices of subcortical volumes and cortical thickness in a sample of youth recruited based on FH status.MethodsTo address aim 1, a literature search located 15 published studies comprising 1,735 participants. Studies were characterized according to population, analytic methods, regions of interest, and primary findings. To address the second aim, we examined volumetric and cortical thickness in a sample of 69 youth (mean age = 19.71 years, SD = 0.79) recruited based on FH status and matched on drinking variables. Associations of sex and alcohol use with volumetric outcomes were also examined.ResultsOur descriptive review revealed an inconsistent pattern of results with respect to the presence, direction, and regional specificity of volumetric differences across FH groups. The most consistent finding, significantly smaller amygdala volumes in FH+ participants, was not replicated in all studies. In the current sample of youth, measures of subcortical volumes and cortical thickness did not significantly differ as a function of FH, sex, or their interaction.ConclusionsEvidence for FH group differences in regional brain volumes is inconsistent, and the current study failed to detect any group differences. Further research is needed to confirm the reproducibility of FH group differences and implications for AUD risk.
Reduction in Nonabstinent WHO Drinking Risk Levels and Change in Risk for Liver Disease and Positive AUDIT‐C Scores: Prospective 3‐Year Follow‐Up Results in the U.S. General Population
Authors: Knox Justin , Wall Melanie , Witkiewitz Katie , Kranzler Henry R. , Falk Daniel , Litten Raye , Mann Karl , O'Malley Stephanie S. , Scodes Jennifer , Anton Raymond , Hasin Deborah S. ,   For the Alcohol Clinical Trials (ACTIVE) Workgroup
Published: September 2018

BackgroundAbstinence is often the treatment aim for alcohol use disorders (AUD), but this may deter individuals who prefer drinking reduction goals from entering treatment, and be an overly restrictive end point in alcohol clinical trials. Nonabstinent drinking reductions that predict improvement in how individuals feel or function may be useful clinical trial outcomes, for example, reductions in the 4‐category World Health Organization (WHO) drinking risk levels. To investigate the clinical relevance of these reductions, we examined their relationship with 2 outcomes of interest to medical providers: liver disease, and positive scores on an alcohol screening measure.MethodsCurrent drinkers in a U.S. national survey (n = 21,925) were interviewed in 2001 to 2002 (Wave 1) and re‐interviewed 3 years later (Wave 2). WHO drinking risk levels, liver disease, and the Alcohol Use Disorders Identification Test‐Consumption (AUDIT‐C) were assessed at both waves. Adjusted odds ratios (aORs) were used to indicate the association of change in WHO drinking risk levels with Wave 2 liver disease and AUDIT‐C scores.ResultsWave 1 very‐high‐risk drinkers who reduced 1, 2, or 3 WHO drinking risk levels had significantly lower odds of Wave 2 liver disease (aORs = 0.34, 0.23, 0.17) and positive AUDIT‐C scores (aORs = 0.27, 0.09, 0.03). Wave 1 high‐risk drinkers who reduced 1 or 2 WHO risk levels had significantly lower odds of positive AUDIT‐C scores (aORs = 0.61, 0.25). Adjusting for alcohol dependence or AUDIT‐C scoring variations did not affect results.ConclusionsIn the highest‐risk drinkers, reductions in WHO drinking risk levels predicted lower likelihood of liver disease and positive AUDIT‐C scores. Results add to findings that reductions in the 4‐category WHO drinking risk levels are a meaningful indicator of how individuals feel and function, and could serve as nonabstinent end points in clinical trials. Results also connect the WHO risk drinking levels to commonly used alcohol screening questions, which may be more familiar to healthcare providers.
Social media and its relationship with mood, self‐esteem and paranoia in psychosis
Authors: Berry N. , Emsley R. , Lobban F. , Bucci S. 
Published: September 2018

ObjectiveAn evidence‐base is emerging indicating detrimental and beneficial effects of social media. Little is known about the impact of social media use on people who experience psychosis.MethodForty‐four participants with and without psychosis completed 1084 assessments of social media use, perceived social rank, mood, self‐esteem and paranoia over a 6‐day period using an experience sampling method (ESM).ResultsSocial media use predicted low mood, but did not predict self‐esteem and paranoia. Posting about feelings and venting on social media predicted low mood and self‐esteem and high paranoia, whilst posting about daily activities predicted increases in positive affect and self‐esteem and viewing social media newsfeeds predicted reductions in negative affect and paranoia. Perceptions of low social rank when using social media predicted low mood and self‐esteem and high paranoia. The impact of social media use did not differ between participants with and without psychosis; although, experiencing psychosis moderated the relationship between venting and negative affect. Social media use frequency was lower in people with psychosis.ConclusionFindings show the potential detrimental impact of social media use for people with and without psychosis. Despite few between‐group differences, overall negative psychological consequences highlight the need to consider use in clinical practice.
Correlation between handheld digital device use and asthenopia in Chinese college students: a Shanghai study
Authors: Xu Yupeng , Deng Guoying , Wang Weiheng , Xiong Shuyu , Xu Xun 
Published: September 2018

AbstractPurposeThe purpose of this study was to investigate the use of handheld digital devices and the prevalence of self‐reported asthenopia among college students in China and their potential relationship.MethodsFive thousand students were randomly assessed using a self‐reported asthenopia questionnaire. The students’ demographic characteristics and habits regarding digital device use were recorded. Univariate analysis was performed to select potential risk factors, and multivariate logistic regression was used to estimate the odds ratios for the selected risk factors of interest.ResultsAmong the 4786 students who completed the survey, the prevalence of asthenopia was 53.3%. Multivariate analysis revealed significant relationships between asthenopia and each of the following: level of digital reliance (OR 1.350, 95%CI: 1.230–1.481), workload, time spent on computer per day, sex and time spent on handheld digital devices in bed and at desk. Aerobic exercise duration (OR 0.912, 95%CI: 0.839–0.990) was found to be strong predictor of less asthenopia complaints.ConclusionAsthenopia appears to be common among college students in China. Preventative measures against asthenopia include limiting the amount of time spent using digital devices in bed (<0.5 h), adopting a posture of lying on one's back while doing so and engaging in aerobic exercise for more than one hour per day. Furthermore, studies on this topic are needed.
Can the flipped classroom model improve students’ academic performance and training satisfaction in Higher Education instructional media design courses?
Authors: Kazanidis Ioannis , Pellas Nikolaos , Fotaris Panagiotis , Tsinakos Avgoustos 
Published: September 2018

AbstractWhile “flipping” a classroom has gained attention in K‐12 and Secondary school programs, there has been relatively no explicit focus on its effectiveness as a teaching method for instructional media design courses in Higher Education. The purpose of this quasi‐experimental study was to determine the effectiveness of the flipped classroom approach to teaching instructional media design subjects by comparing students’ academic performance and training satisfaction in traditional lecture‐based instruction with those in a flipped classroom. A total of 128 undergraduate students participated voluntarily and were divided into a control (n = 62) and an experimental (n = 66) group, respectively. The study findings indicated substantial differences in both academic performance and training satisfaction between the two groups, with the students in the experimental group performing significantly better. Specifically, the results showed some determining factors associated with training satisfaction that explain why students in flipped classes achieved notably higher mastery in the learning objectives than their control group peers. This study adds to the literature by providing evidence on how a flipped classroom can potentially benefit students’ academic performance, leading to higher training satisfaction and deeper disciplinary understanding in instructional media design courses.
Anticoagulation in the cardiac patient: A concise review
Authors: Larson Elise A. , German David M. , Shatzel Joseph , DeLoughery Thomas G. 
Published: September 2018

AbstractAnticoagulation has multiple roles in the treatment of cardiovascular disease, including in management of acute myocardial infarction, during percutaneous coronary intervention, as stroke prophylaxis in patients with atrial arrhythmias, and in patients with mechanical heart valves. Clinical anticoagulation choices in the aforementioned diseases vary widely, due to conflicting data to support established agents and the rapid evolution of evidence‐based practice that parallels more widespread use of novel oral anticoagulants. This review concisely summarizes evidence‐based guidelines for anticoagulant use in cardiovascular disease, and highlights new data specific to direct oral anticoagulants.
Clinical implications of molecular markers in acute myeloid leukemia
Authors: Kayser Sabine , Levis Mark J. 
Published: September 2018

AbstractThe recently updated World Health Organization (WHO) Classification of myeloid neoplasms and leukemia reflects the fact that research in the underlying pathogenic mechanisms of acute myeloid leukemia (AML) has led to remarkable advances in our understanding of the disease. Gene mutations now allow us to explore the enormous diversity among cytogenetically defined subsets ofAML, particularly the large subset of cytogenetically normalAML. Despite the progress in unraveling the tumor genome, only a small number of recurrent mutations have been incorporated into risk‐stratification schemes and have been proven to be clinically relevant, targetable lesions. We here discuss the utility of molecular markers inAMLin prognostication and treatment decision making, specifically highlighting the aberrations included in the currentWHOclassification.
Insular‐limbic dissociation to intra‐epidermal electrical Aδ activation: A comparative study with thermo‐nociceptive laser stimulation
Authors: Hagiwara Koichi , Perchet Caroline , Frot Maud , Bastuji Hélène , Garcia‐Larrea Luis 
Published: September 2018

AbstractIntra‐epidermal electrical stimulation (IEES) has been shown to activate selectively Aδ fibers subserving spinothalamic‐mediated sensations. Owing to electrically induced highly synchronous afferent volleys, IEES induces Aδ‐mediated evoked potentials at nonpainful intensities, contrasting with thermo‐nociceptive laser pulses which entail painful pricking sensations. Here, we recorded intracortical responses from sensory and limbic‐cognitive regions of human subjects in response to IEE and laser stimuli, in order to test the hypothesis that IEES could dissociate the sensory from nonsensory networks of nociceptive processing. Intracortical evoked potentials were obtained in 11 epileptic patients with stereotactically implanted electrodes in sensory regions receiving spinothalamic afferents (posterior insula), limbic regions receiving spino‐parabrachial input (amygdalar nucleus), and high‐order affective‐cognitive regions (anteromedial frontal cortex, including perigenual anterior cingulate and rostromedial prefrontal areas). Responses in the sensory posterior insula were of similar amplitude and latency to IEE and laser stimuli (after accounting for heat‐transduction time of laser), and consistent in both cases with spinothalamic activation. However, responses to IEES in the amygdala and the anteromedial frontal regions were inconsistent and significantly smaller compared to those evoked to the laser stimulation. Thus, IEES can effectively activate the spinothalamic‐sensory system with little recruitment of affective‐motivational networks, including those triggered by spino‐parabrachio‐amygdalar projections. The fact that identical sensory responses were associated to either painful or nonpainful percepts underscores that subjective pain perception is not solely dependent on the sensory recruitment, but rather on the combined activation of sensory, limbic and cognitive areas with precise spatiotemporal relations.
Helicobacter pylori and extragastric diseases
Authors: Ražuka‐Ebela Danute , Giupponi Bianca , Franceschi Francesco 
Published: September 2018

AbstractMany studies have been performed in the last year concerning the potential role of Helicobacter pylori in different extragastric diseases, reinforcing the idea that specific microorganisms may cause diseases even far from the primary site of infection. While the role of H. pylori on idiopathic thrombocytopenic purpura, sideropenic anemia, and vitamin B12 deficiency has been well established, there is a growing interest in other conditions, such as cardiovascular, neurologic, dermatologic, obstetric, immunologic, and metabolic diseases. Concerning neurologic diseases, there is a great interest in cognitive impairment and neurodegeneration. The aim of this review was to summarize the results of the most relevant studies published over the last year on this fascinating topic.
Gastric cancer: Basic aspects
Authors: Duarte Henrique O. , Gomes Joana , Machado José C. , Reis Celso A. 
Published: September 2018

AbstractDespite major breakthroughs in the field of personalized medicine, gastric cancer (GC) remains a clinically challenging disease, characterized by scarce effective treatment options and the lack of reliable molecular tools for the prediction of patient outcome and response to therapy. The pronounced molecular heterogeneity that dictates the phenotypical aggressiveness of gastric neoplasms severely limits the antitumor efficacy of targeted agents brought to clinical trials, and constitutes a favorable setting for the emergence of refractory tumors exhibiting multidrug resistance. We will review the most recent advances in our understanding of GC biology, which are underlying the development and clinical testing of novel targeted therapeutic agents. We will also emphasize how their efficacy and acquired resistance relate to the aberrant molecular signatures that drive gastric malignancy.
Medium‐temperature sintering efficiency of ZrB2 ceramics using polymer‐derived SiBCN as a sintering aid
Authors: Feng Bo , Zhang Yue , Li Bingyang , Hu Shujuan 
Published: September 2018

AbstractPolymer‐derived SiBCN, with superior thermal stability and amorphous activity, was introduced into ZrB2 powders. This sintering aid highly improved the sintering efficiency of ZrB2 ceramics at medium temperature (1000‐1600°C), which showed a different service temperature range from that of traditional crystal additives. The microstructure and densification behavior of ZrB2–SiBCN samples were mainly studied. The polymer structural evolution including construction, rearrangement, and crystallization of the amorphous SiBCN network, made a large contribution to the densification of ZrB2 ceramics. The carbothermal reduction of pyrolysis carbon with oxide impurities could not only decrease the oxygen content, but also develop the activity of chemical bonds in SiBCN network. Diffusions and reactions at the interface also benefited the microstructure and consolidation of ZrB2–SiBCN ceramics.
Essential role of ryanodine receptor 2 phosphorylation in the effect of azumolene on ventricular arrhythmia vulnerability in a rabbit heart model
Authors: Si Daoyuan , Azam Mohammed Ali , Lai Patrick F. H. , Zamiri Nima , Kichigina Galina , Asta John , Massé Stéphane , Bokhari Mahmoud M. , Porta‐Sánchez Andreu , Labos Christopher , Sun Huan , Yang Ping , Nanthakumar Kumaraswamy 
Published: September 2018

AbstractIntroductionFollowing long‐duration ventricular fibrillation (LDVF), reinitiation of ventricular fibrillation (VF) poses a major challenge during resuscitation. Ryanodine receptor 2 (RyR2) becomes dysfunctional following VF. The relationship between LDVF, RyR2 modulation, and ventricular refibrillation, as well as the role of RyR2 phosphorylation, remains unknown.MethodsLangendorff‐perfused rabbit hearts were subjected to global ischemia and treated with azumolene (or vehicle alone in controls) upon reperfusion. After electrical induction of an initial LDVF episode, each heart was further stimulated electrically to assess reinducibility of VF. Myocardial calcium dynamics were assessed by optical mapping. RyR2 phosphorylation in left ventricular tissue extracts was analyzed by Western blot analysis.ResultsFewer episodes of refibrillation (lasting ≥ 10 seconds) were induced in azumolene‐treated hearts than in controls (P = 0.01); however, this reduction in refibrillation was abrogated in the presence of the protein kinase A inhibitor H89. Spontaneous calcium elevation was significantly lower in azumolene‐treated hearts than in control hearts (
P = 0.002) and in hearts pretreated with H89 before azumolene (
P = 0.01). RyR2 phosphorylation at Ser2808 was higher in hearts subjected to LDVF than in non‐VF hearts (
P = 0.029), while no significant difference was found at Ser2814. Pretreatment with H89 led to significantly less RyR2 phosphorylation at Ser2808 (
P = 0.04) after LDVF, while pretreatment with KN93 or azumolene alone showed no effects on RyR2 phosphorylation.ConclusionVentricular refibrillation following LDVF was reduced by azumolene, which also improves calcium dynamics. RyR2 phosphorylation at Ser2808 is a prerequisite for the beneficial effects of azumolene.