bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Next Generation Connectivity Map: L1000 Platform And The First 1,000,000 Profiles
Authors: Subramanian Aravind , Narayan Rajiv , Corsello Steven M. , Peck David D. , Natoli Ted E. , Lu Xiaodong , Gould Joshua , Davis John F. , Tubelli Andrew A. , Asiedu Jacob K. , Lahr David L. , Hirschman Jodi E. , Liu Zihan , Donahue Melanie , Julian Bina , Khan Mariya , Wadden David , Smith Ian , Lam Daniel , Liberzon Arthur , Toder Courtney , Bagul Mukta , Orzechowski Marek , Enache Oana M. , Piccioni Federica , Berger Alice H. , Shamji Alykhan , Brooks Angela N. , Vrcic Anita , Flynn Corey , Rosains Jacqueline , Takeda David , Davison Desiree , Lamb Justin , Ardlie Kristin , Hogstrom Larson , Gray Nathanael S. , Clemons Paul A. , Silver Serena , Wu Xiaoyun , Zhao Wen-Ning , Read-Button Willis , Wu Xiaohua , Haggarty Stephen J. , Ronco Lucienne V. , Boehm Jesse S. , Schreiber Stuart L. , Doench John G. , Bittker Joshua A. , Root David E. , Wong Bang , Golub Todd R. 
Published: May 2017

SUMMARYWe previously piloted the concept of a Connectivity Map (CMap), whereby genes, drugs and disease states are connected by virtue of common gene-expression signatures. Here, we report more than a 1,000-fold scale-up of the CMap as part of the NIH LINCS Consortium, made possible by a new, low-cost, high throughput reduced representation expression profiling method that we term L1000. We show that L1000 is highly reproducible, comparable to RNA sequencing, and suitable for computational inference of the expression levels of 81% of non-measured transcripts. We further show that the expanded CMap can be used to discover mechanism of action of small molecules, functionally annotate genetic variants of disease genes, and inform clinical trials. The 1.3 million L1000 profiles described here, as well as tools for their analysis, are available athttps://clue.io.HIGHLIGHTSA new gene expression profiling method, L1000, dramatically lowers costThe Connectivity Map database now includes 1.3 million publicly accessible L1000 perturbational profilesThis expanded Connectivity Map facilitates discovery of small molecule mechanism of action and functional annotation of genetic variantsThe work establishes feasibility and utility of a truly comprehensive Connectivity Map
Classification of gene signatures for their information value and functional redundancy
Authors: Cantini Laura , Calzone Laurence , Martignetti Loredana , Rydenfelt Mattias , Blüthgen Nils , Barillot Emmanuel , Zinovyev Andrei 
Published: May 2017

ABSTRACTLarge collections of gene signatures play a pivotal role in interpreting results of omics data analysis but suffer from compositional (large overlap) and functional (redundant read-outs) redundancy, and many gene signatures rarely pop-up in statistical tests. Based on pan-cancer data analysis, here we define a restricted set of 962 so called informative signatures and demonstrate that they have more chances to appear highly enriched in cancer biology studies. We show that the majority of informative signatures conserve their weights for the composing genes (eigengenes) from one cancer type to another. We construct InfoSigMap, an interactive online map showing the structure of compositional and functional redundancies between informative signatures and charting the territories of biological functions accessible through transcriptomic studies. InfoSigMap can be used to visualize in one insightful picture the results of comparative omics data analyses and suggests reconsidering existing annotations of certain reference gene set groups.
The AAA Protein Msp1 Mediates Clearance of Excess Tail-Anchored Proteins from the Peroxisomal Membrane
Authors: Weir Nicholas R. , Kamber Roarke A. , Martenson James S. , Denic Vladimir 
Published: May 2017

SUMMARYMsp1 is a conserved AAA ATPase in budding yeast localized to mitochondria where it prevents accumulation of mistargeted tail-anchored (TA) proteins, including the peroxisomal TA protein Pex15. Msp1 also resides on peroxisomes but it remains unknown how native TA proteins on mitochondria and peroxisomes evade Msp1 surveillance. We used live-cell quantitative cell microscopy tools and drug-inducible gene expression to dissect Msp1 function. We found that a small fraction of peroxisomal Pex15, exaggerated by overexpression, is turned over by Msp1. Kinetic measurements guided by theoretical modeling revealed that Pex15 molecules at mitochondria display age-independent Msp1 sensitivity. By contrast, Pex15 molecules at peroxisomes are rapidly converted from an initial Msp1-sensitive to an Msp1-resistant state. Lastly, we show that Pex15 interacts with the peroxisomal membrane protein Pex3, which shields Pex15 from Msp1-dependent turnover. In sum, our work argues that Msp1 selects its substrates on the basis of their solitary membrane existence.
The Investment Approach to Public Service Provision
Authors: Mintrom Michael , Luetjens Joannah 
Published: May 2017

AbstractThe investment approach to public service provision is now receiving considerable attention worldwide. By promoting data‐intensive assessments of baseline conditions and how government action can improve on them, the approach holds the potential to transform policy development, service implementation, and program evaluation. Recently, variations on the investment approach have been applied in Australia to explore the effectiveness of specific programs in employment training, criminal justice, and infrastructure development. This article reviews the investment approach, presents a Public Investment Checklist to guide such work, and discusses three examples. It concludes by considering the implications of investment thinking for the work of policy designers and public managers.
Hospital and Health Insurance Markets Concentration and Inpatient Hospital Transaction Prices in the U.S. Health Care Market
Authors: Dauda Seidu 
Published: May 2017

ObjectiveTo examine the effects of hospital and insurer markets concentration on transaction prices for inpatient hospital services.Data SourcesMeasures of hospital and insurer markets concentration derived from American Hospital Association and HealthLeaders‐InterStudy data are linked to 2005–2008 inpatient administrative data from Truven Health MarketScan Databases.Study DesignUses a reduced‐form price equation, controlling for cost and demand shifters and accounting for possible endogeneity of market concentration using instrumental variables (IV) technique.Principal FindingsThe findings suggest that greater hospital concentration raises prices, whereas greater insurer concentration depresses prices. A hypothetical merger between two of five equally sized hospitals is estimated to increase hospital prices by about 9 percent (p < .001). A similar merger of insurers would depress prices by about 15.3 percent (p < .001). Over the 2003–2008 periods, the estimates imply that hospital consolidation likely raised prices by about 2.6 percent, while insurer consolidation depressed prices by about 10.8 percent. Additional analysis using longer panel data and applying hospital fixed effects confirms the impact of hospital concentration on prices.ConclusionThe findings provide support for strong antitrust enforcement to curb rising hospital service prices and health care costs.
Using Photocatalyst Metal Oxides as Antimicrobial Surface Coatings to Ensure Food Safety—Opportunities and Challenges
Authors: Yemmireddy Veerachandra K. , Hung Yen‐Con 
Published: May 2017

AbstractCross‐contamination of foods with pathogenic microorganisms such as bacteria, viruses, and parasites may occur at any point in the farm to fork continuum. Food contact and nonfood contact surfaces are the most frequent source of microbial cross‐contamination. In the wake of new and emerging food safety challenges, including antibiotic‐resistant human pathogens, conventional sanitation and disinfection practices may not be sufficient to ensure safe food processing, proper preparation, and also not be environmentally friendly. Nanotechnology‐enabled novel food safety interventions have a great potential to mitigate the risk of microbial cross‐contamination in the food chain. Especially engineered nanoparticles (ENPs) are increasingly finding novel applications as antimicrobial agents. Among various ENPs, photocatalyst metal oxides have shown great promise as effective nontargeted disinfectants over a wide range of microorganisms. The present review provides an overview of antimicrobial properties of various photocatalyst metal oxides and their potential applications as surface coatings. Further, this review discusses the most common approaches to developing antimicrobial coatings, methods to characterize, test, and evaluate antimicrobial efficacy as well as the physical stability of the coatings. Finally, regulations and challenges concerning the use of these novel photocatalytic antimicrobial coatings are also discussed.
DNA Identification of Commingled Human Remains from the Cemetery Relocated by Flooding in Central Bosnia and Herzegovina
Authors: Čakar Jasmina , Pilav Amela , Džehverović Mirela , Ahatović Anesa , Haverić Sanin , Ramić Jasmin , Marjanović Damir 
Published: May 2017

AbstractThe floods in Bosnia and Herzegovina in May 2014 caused landslides all over the country. In the small village of Šerići, near the town of Zenica, a landslide destroyed the local cemetery, relocated graves, and commingled skeletal remains. As the use of other physical methods of identification (facial recognition, fingerprint analysis, dental analysis, etc.) was not possible, DNA analysis was applied. DNA was isolated from 20 skeletal remains (bone and tooth samples) and six reference samples (blood from living relatives) and amplified using PowerPlex® Fusion and PowerPlex®Y23 kits. DNA profiles were generated for all reference samples and 17 skeletal remains. A statistical analysis (calculation of paternity, maternity, and sibling indexes and matching probabilities) resulted in 10 positive identifications. In this study, 5 individuals were identified based on one reference sample. This has once again demonstrated the significance of DNA analysis in resolving the most complicated cases, such as the identification of commingled human skeletal remains.
Effect of Different Extrusion Parameters on Dietary Fiber in Wheat Bran and Rye Bran
Authors: Andersson Annica A.M. , Andersson R. , Jonsäll Anette , Andersson Jörgen , Fredriksson Helena 
Published: May 2017

AbstractWheat bran and rye bran are mostly used as animal feed today, but their high content of dietary fiber and bioactive components are beneficial to human health. Increased use of bran as food raw material could therefore be desirable. However, bran mainly contains unextractable dietary fiber and deteriorates the sensory properties of products. Processing by extrusion could increase the extractability of dietary fiber and increase the sensory qualities of bran products. Wheat bran and rye bran were therefore extruded at different levels of moisture content, screw speed and temperature, in order to find the optimal setting for increased extractability of dietary fiber and positive sensory properties. A water content of 24% for wheat bran and 30% for rye bran, a screw speed of 400 rpm, and a temperature of 130 °C resulted in the highest extractability of total dietary fiber and arabinoxylan. Arabinoxylan extractability increased from 5.8% in wheat bran to 9.0% in extruded wheat bran at those settings, and from 14.6% to 19.2% for rye bran. Total contents of dietary fiber and arabinoxylan were not affected by extrusion. Content of β‐glucan was also maintained during extrusion, while its molecular weight decreased slightly and extractability increased slightly. Extrusion at these settings is therefore a suitable process for increasing the use of wheat bran and rye bran as a food raw material.
Single‐cell genomics reveals pyrrolysine‐encoding potential in members of uncultivated archaeal candidate division MSBL1
Authors: Guan Yue , Haroon Mohamed F. , Alam Intikhab , Ferry James G. , Stingl Ulrich 
Published: May 2017

SummaryPyrrolysine (Pyl), the 22nd canonical amino acid, is only decoded and synthesized by a limited number of organisms in the domains Archaea and Bacteria. Pyl is encoded by the amber codon UAG, typically a stop codon. To date, all known Pyl‐decoding archaea are able to carry out methylotrophic methanogenesis. The functionality of methylamine methyltransferases, an important component of corrinoid‐dependent methyltransfer reactions, depends on the presence of Pyl. Here, we present a putative pyl gene cluster obtained from single‐cell genomes of the archaeal Mediterranean Sea Brine Lakes group 1 (MSBL1) from the Red Sea. Functional annotation of the MSBL1 single cell amplified genomes (SAGs) also revealed a complete corrinoid‐dependent methyl‐transfer pathway suggesting that members of MSBL1 may possibly be capable of synthesizing Pyl and metabolizing methylated amines.
Feasibility of an endotracheal tube‐mounted camera for percutaneous dilatational tracheostomy
Authors: Grensemann J. , Eichler L. , Hopf S. , Jarczak D. , Simon M. , Kluge S. 
Published: May 2017

BackgroundPercutaneous dilatational tracheostomy (PDT) in critically ill patients is often led by optical guidance with a bronchoscope. This is not without its disadvantages. Therefore, we aimed to study the feasibility of a recently introduced endotracheal tube‐mounted camera (VivaSight™‐SL, ET View, Misgav, Israel) in the guidance of PDT.MethodsWe studied 10 critically ill patients who received PDT with a VivaSight‐SL tube that was inserted prior to tracheostomy for optical guidance. Visualization of the tracheal structures (i.e., identification and monitoring of the thyroid, cricoid, and tracheal cartilage and the posterior wall) and the quality of ventilation (before puncture and during the tracheostomy) were rated on four‐point Likert scales. Respiratory variables were recorded, and blood gases were sampled before the interventions, before the puncture and before the insertion of the tracheal cannula.ResultsVisualization of the tracheal landmarks was rated as ‘very good’ or ‘good’ in all but one case. Monitoring during the puncture and dilatation was also rated as ‘very good’ or ‘good’ in all but one. In the cases that were rated ‘difficult’, the visualization and monitoring of the posterior wall of the trachea were the main concerns. No changes in the respiratory variables or blood gases occurred between the puncture and the insertion of the tracheal cannula.ConclusionPercutaneous dilatational tracheostomy with optical guidance from a tube‐mounted camera is feasible. Further studies comparing the camera tube with bronchoscopy as the standard approach should be performed.
Validation of the No Objective Testing Rule and Comparison to the HEART Pathway
Authors: Stopyra Jason P. , Miller Chadwick D. , Hiestand Brian C. , Lefebvre Cedric W. , Nicks Bret A. , Cline David M. , Askew Kim L. , Riley Robert F. , Russell Gregory B. , Hoekstra James W. , Mahler Simon A. 
Published: May 2017

AbstractBackgroundThe no objective testing rule (NOTR) is a decision aid designed to safely identify emergency department (ED) patients with chest pain who do not require objective testing for coronary artery disease.ObjectivesThe objective was to validate the NOTR in a cohort of U.S. ED patients with acute chest pain and compare its performance to the HEART Pathway.MethodsA secondary analysis of 282 participants enrolled in the HEART Pathway randomized controlled trial was conducted. Each patient was classified as low risk or at risk by the NOTR. Sensitivity for major adverse cardiac events (MACE) at 30 days was calculated in the entire study population. NOTR and HEART Pathways were compared among patients randomized to the HEART Pathway in the parent trial using McNemar's test and the net reclassification improvement (NRI).ResultsMajor adverse cardiac events occurred in 22/282 (7.8%) participants, including no deaths, 16/282 (5.6%) with myocardial infarction (MI), and 6/282 (2.1%) with coronary revascularization without MI. NOTR was 100% (95% confidence interval [CI] = 84.6%–100%) sensitive for MACE and identified 78/282 patients (27.7%, 95% = CI 22.5–33.3%) as low risk. In the HEART Pathway arm (n = 141), both NOTR and HEART Pathway identified all patients with MACE as at risk. Compared to NOTR, the HEART Pathway was able to correctly reclassify 27 patients without MACE as low risk, yielding a NRI of 20.8% (95% CI = 11.3%–30.2%).ConclusionsWithin a U.S. cohort of ED patients with chest pain, the NOTR and HEART Pathway were 100% sensitive for MACE at 30 days. However, the HEART Pathway identified more patients suitable for early discharge than the NOTR.
Nalmefene Prevents Alcohol‐Induced Neuroinflammation and Alcohol Drinking Preference in Adolescent Female Mice: Role of TLR4
Authors: Montesinos Jorge , Gil Anabel , Guerri Consuelo 
Published: May 2017

BackgroundWe previously showed that, by activating innate immune receptors Toll‐like 4 (TLR4), adolescent intermittent ethanol (EtOH) exposure causes neuroinflammation, myelin damage, and behavioral dysfunctions. Recent findings reveal that clinically used opioid antagonists naltrexone (NT) and naloxone (NX) inhibit opioid‐induced TLR4 signaling and that NT, NX, and nalmefene (NF), the 6‐methylene derivative of NX, are able to reduce alcohol drinking escalation.MethodsNF (0.1 mg/kg, intraperitoneally) was injected 1 hour prior to EtOH (3 g/kg, intraperitoneally) following intermittent treatment in female (PND35) adolescent mice. Inflammatory molecules, myelin proteins, and apoptotic markers were assessed in the prefrontal cortex (PFC) and striatum/nucleus accumbens (STR/NAcc). The effect of NF on alcohol drinking preference was evaluated in both the wild‐type and TLR4 knockout (KO) adolescent mice. Using astroglial cells, the inhibitory potential of NT, NX, and NF on lipopolysaccharide (LPS), or the EtOH‐triggered TLR4 response, was compared.ResultsOur findings indicate that NF prevents the up‐regulation of cytokines (IL‐1β, IL‐17A, TNF‐α), chemokines (MCP‐1, MIP‐1, KC), and pro‐inflammatory mediators (iNOS, COX‐2), along with myelin damage and apoptotic events, in both PFC and STR/NAcc. NF also abolishes EtOH‐induced escalation of alcohol preference/consumption, but has no effect when administered to TLR4‐KO mice. In vitro experiments indicate that NX and NF inhibit TLR4 activation upon LPS or EtOH stimulation. Immunofluorescence studies and lipid rafts isolation show that NF is able to prevent TLR4 translocation to lipid rafts/caveolae in astrocytes.ConclusionsThese results suggest that NF prevents neuroinflammation and brain damage by blocking the TLR4 response and also support the role of central pro‐inflammatory immune signaling in the modulation of alcohol consumption/addiction.
Neuropsychological functioning in college students who misuse prescription stimulants
Authors: Wilens Timothy E. , Carrellas Nicholas W. , Martelon MaryKate , Yule Amy M. , Fried Ronna , Anselmo Rayce , McCabe Sean Esteban 
Published: May 2017

Background and ObjectivesRelatively little is known about the neuropsychological profiles of college students who misuse prescription stimulant medications.MethodsData presented are from college students aged 18–28 years who misused prescription stimulants prescribed for attention‐deficit/hyperactivity disorder and controls (no prescription stimulant misuse). Students were assessed neuropsychologically using the self‐report Behavioral Rating Inventory of Executive Functioning (BRIEF‐A), the Cambridge Automated Neuropsychological Test and Battery (CANTAB), and other tests of cognitive functioning. The analyses included 198 controls (age 20.7 ± 2.6 years) and 100 prescription stimulant misusers (age 20.7 ± 1.7 years).ResultsOn the BRIEF‐A, misusers were more likely than controls to endorse greater dysfunction on 8 of 12 measures including Inhibition, Self Monitor, Initiation, Working Memory, and Plan/Organize, when adjusting for race and sex (all p's < .05). Similarly, when dichotomizing the BRIEF‐A as abnormal (T score ≥ 65), misusers had more abnormalities on five of nine subscales, as well as all major indices (p's < .05). Misusers also performed worse on several subtests of the CANTAB and standardized cognitive battery (p's < .05). A proxy of prescription stimulant misuse frequency was positively correlated with greater executive dysfunction on the BRIEF‐A.Discussion and ConclusionsThese data demonstrate elevated risk for neuropsychological dysfunction among students who misuse prescription stimulants compared to non‐misusing peers. The presence of ADHD contributed significantly to these cognitive findings. Students who misuse prescription stimulants should be screened for neuropsychological dysfunction.Scientific SignificanceThese data may better elucidate the neuropsychological profile of college‐aged prescription stimulant misusers. (Am J Addict 2017;26:379–387)
Adverse effects of obesity on cognitive functions in individuals at ultra high risk for bipolar disorder: Results from the global mood and brain science initiative
Authors: McIntyre Roger S. , Mansur Rodrigo B. , Lee Yena , Japiassú Letícia , Chen Kun , Lu Rui , Lu Weicong , Chen Xiaodong , Li Ting , Xu Guiyun , Lin Kangguang 
Published: May 2017

BackgroundThe burden of illness associated with bipolar disorder (BD) warrants early pre‐emption/prevention. Prediction models limited to psychiatric phenomenology have insufficient predictive power. Herein, we aimed to evaluate whether the presence of overweight/obesity is associated with greater cognitive decline in individuals at high risk (HR) or ultra high risk (UHR) for BD.MethodsWe conducted a retrospective analysis to investigate the moderational role of body mass index (BMI) on measures of cognitive function. Subjects between the ages of 8 and 28 years with a positive family history of BD were compared to age‐matched controls with a negative family history of BD. Subjects with at least one biological parent with bipolar I/II disorder were further stratified into UHR or HR status by the presence or absence, respectively, of subthreshold hypomanic, major depressive, attenuated psychotic, and/or attention‐deficit/hyperactivity disorder symptoms.ResultsA total of 36 individuals at HR for BD, 33 individuals at UHR for BD, and 48 age‐matched controls were included in the analysis. Higher BMI was significantly associated with lower performance on measures of processing speed (i.e. Brief Assessment of Cognition in Schizophrenia−symbol coding: r=−.186, P=.047) and attention/vigilance (i.e. Continuous Performance Test−Identical Pairs: r=−.257, P=.006). There were trends for negative correlations between BMI and measures of working memory (i.e. Wechsler Memory Scale‐III Spatial Span: r=−0.177, P=.059) and overall cognitive function (i.e. Measurement and Treatment Research to Improve Cognition in Schizophrenia composite score: r=−.157, P=.097). Negative associations between BMI and cognitive performance were significantly stronger in the UHR group than in the HR group, when compared to controls.ConclusionsIndividuals at varying degrees of risk for BD exhibit greater cognitive impairment as a function of co‐existing overweight/obesity. Prediction models for BD may be substantively informed by including information related to overweight/obesity and, perhaps, other general medical conditions that share pathology with BD. Our findings herein, as well as the salutary effects of bariatric surgery on measures of cognitive function in obese populations, provide the rationale for hypothesizing that mitigating excess weight in individuals at elevated risk for BD may forestall or prevent declaration of illness.