bluuebunny/crossref_metadata_2025_split huggingface dataset:
Considerations for the design of vaccine efficacy trials during public health emergencies
Authors: Dean Natalie E. , Gsell Pierre-Stéphane , Brookmeyer Ron , De Gruttola Victor , Donnelly Christl A. , Halloran M. Elizabeth , Jasseh Momodou , Nason Martha , Riveros Ximena , Watson Conall , Henao-Restrepo Ana Maria , Longini Ira M. 
Published: February 2018

AbstractPublic Health Emergencies (PHEs) provide a complex and challenging environment for vaccine evaluation. Under the R&D Blueprint Plan of Action, the World Health Organization (WHO) has convened a group of experts to agree on standard procedures to rapidly evaluate experimental vaccines during PHEs while maintaining the highest scientific and ethical standards. The Blueprint priority diseases, selected for their likelihood to cause PHEs and the lack of adequate medical countermeasures, were used to frame our methodological discussions. Here, we outline major vaccine study designs to be used in PHEs and summarize high-level recommendations for their use in this setting. We recognize that the epidemiology and transmission dynamics of the Blueprint priority diseases may be highly uncertain and that the unique characteristics of the vaccines and outbreak settings may affect our study design. To address these challenges, our group underscores the need for novel, flexible, and responsive trial designs. We conclude that assignment to study groups using randomization is a key principle underlying rigorous study design and should be utilized except in exceptional circumstances. Advance planning for vaccine trial designs is critical for rapid and effective response to a PHE and to advance knowledge to address and mitigate future PHEs.One Sentence SummaryAs part of the WHO research and development Blueprint for action to prevent epidemics, we describe key considerations for the design and analysis of trials and studies to evaluate experimental vaccines during public health emergencies.
Two levels of host-specificity in a fig-associatedCaenorhabditis
Authors: Woodruff Gavin C. , Phillips Patrick C. 
Published: February 2018

AbstractBackgroundBiotic interactions are ubiquitous and require information from ecology, evolutionary biology, and functional genetics in order to be completely understood. However, study systems that are amenable to investigations across such disparate fields are rare. Figs and fig wasps are a classic system for ecology and evolutionary biology with poor functional genetics;C. elegansis a classic system for functional genetics with poor ecology. In order to help bridge these disciplines, here we describe the natural history of a close relative ofC. elegans,C.sp. 34, that is associated with the figFicus septicaand its pollinatingCeratosolenwasps.ResultsTo understand the natural context of fig-associatedCaenorhabditis, freshF. septicafigs from four Okinawan islands were sampled, dissected, and observed under microscopy.C.sp. 34 was found in all islands whereF. septicafigs were found.C.sp. 34 was routinely found in the fig interior and almost never observed on the outside surface.Caenorhabditiswas only found in pollinated figs, andC.sp. 34 was more likely to be observed in figs with more foundress pollinating wasps. Actively reproducingC.sp. 34 dominated younger figs, whereas older figs with emerging wasp progeny harboredC.sp. 34 dispersal larvae. Additionally,C. sp. 34was observed dismounting from platedCeratosolenpollinating wasps.C.sp. 34 was never found on non-pollinating, parasiticPhilotrypesiswasps. Finally,C.sp. 34 was only observed inF. septicafigs among five OkinawanFicusspecies sampled.ConclusionThese observations suggest a natural history whereC.sp. 34 proliferates in youngF. septicafigs and disperses from old figs onCeratosolenpollinating fig wasps. The fig and wasp host specificity of thisCaenorhabditisis highly divergent from its close relatives and frames hypotheses for future investigations. This natural co-occurrence of the fig/fig wasp andCaenorhabditisstudy systems sets the stage for an integrated research program that can help to explain the evolution of interspecific interactions.
Cardiovascular Disease Risk Factor Responses to a Type 2 Diabetes Care Model Including Nutritional Ketosis at One Year: An Open Label, Non-Randomized, Controlled Study
Authors: Bhanpuri Nasir H. , Hallberg Sarah J. , Williams Paul T. , McKenzie Amy L. , Ballard Kevin D. , Campbell Wayne W. , McCarter James P. , Phinney Stephen D. , Volek Jeff S. 
Published: February 2018

AbstractBackgroundCardiovascular disease (CVD) is a leading cause of death among adults with type 2 diabetes mellitus (T2D). We recently reported that glycemic control in patients with T2D can be significantly improved through a continuous care intervention (CCI) including nutritional ketosis. The purpose of this study was to examine CVD risk factors in this cohort.MethodsWe investigated CVD risk factors in patients with T2D who participated in a one year open label, non-randomized, controlled study. The CCI group (n = 262) received treatment from a health coach and medical provider. A usual care (UC) group (n = 87) was independently recruited to track customary T2D progression. Circulating biomarkers of cholesterol metabolism and inflammation, blood pressure (BP), carotid intima media thickness (cIMT), multi-factorial risk scores and medication use were examined.ResultsThe CCI group consisted of 262 patients (baseline mean(SD): age 54(8) y, BMI 40.4(8.8) kg/m2). Intention-to-treat analysis (% change) revealed the following at 1-year with P values < 0.0019 indicating statistical significance after adjustment for multiple comparisons: total LDL-particles (LDL-P) (−4.9%, P=0.02), small LDL-P (−20.8%, P=1.2×10−12), LDL-P size (+1.1%, P=6.0×10−10), ApoB (−1.6%, P=0.37), ApoA1 (+9.8%, P<10−16), ApoB/ApoA1 ratio (−9.5%, P=1.9×10−7), triglyceride/HDL-C ratio (−29.1%, P<10−16), large VLDL-P (−38.9%, P=4.2×10−15), and LDL-C (+9.9%, P=4.9×10−5). Additional effects were reductions in blood pressure, high sensitivity C-reactive protein, and white blood cell count (all P<1×10−7) while cIMT was unchanged. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score decreased −11.9% (P=4.9×10−5). Antihypertensive medication use was discontinued in 11.4 % of CCI participants (P=5.3×10−5). The UC group of 87 patients (baseline mean(SD): age 52(10)y, BMI 36.7(7.2) kg/m2) showed no significant changes. After adjusting for baseline differences when comparing CCI and UC groups, significant improvements for the CCI group included small LDL-P, ApoA1, triglyceride/HDL-C ratio, HDL-C, hs-CRP, and ASCVD score. The CCI group showed a greater rise in LDL-C.ConclusionsA continuous care treatment including nutritional ketosis in patients with T2D improved most biomarkers of CVD risk after one year. The increase in LDL-cholesterol appeared limited to the large LDL subfraction. LDL particle size increased, total LDL-P and ApoB were unchanged, and inflammation and blood pressure decreased.Trial registrationClinicaltrials.gov:NCT02519309. Registered 10 August 2015
The Spectre of Too Many Species
Authors: Leaché Adam D. , Zhu Tianqi , Rannala Bruce , Yang Ziheng 
Published: February 2018

AbstractRecent simulation studies examining the performance of Bayesian species delimitation as implemented in the BPP program have suggested that BPP may detect population splits but not species divergences and that it tends to over-split when data of many loci are analyzed. Here we confirm several of these results and provide their mathematical justifications. We point out that the distinction between population and species splits made in the protracted speciation model has no influence on the generation of gene trees and sequence data, which explains why no method can use such data to distinguish between population splits and speciation. We suggest that the the protracted speciation model is unrealistic and its mechanism for assigning species status contradicts prevailing taxonomic practice. We confirm the suggestion, based on simulation, that in the case of speciation with gene flow, Bayesian model selection as implemented in BPP tends to detect population splits when the amount of data (the number of loci) increases so over-splitting is a legitimate concern. We discuss the use of a recently proposed empirical genealogical divergence index (gdi) for species delimitation and illustrate that parameter estimates produced by a full likelihood analysis as implemented in BPP provide much more reliable inference under thegdithan the approximate method PHRAPL. We suggest that the Bayesian model-selection approach is useful for identifying sympatric cryptic species while Bayesian parameter estimation under the multispecies coalescent can be used to implement empirical criteria for determining species status among allopatric populations.
Lower performance of Toxoplasma-infected, Rh-negative subjects in the weight holding and hand-grip tests
Authors: Flegr Jaroslav , Šebánková Blanka , Příplatová Lenka , Chvátalová Veronika , Kaňková Šárka 
Published: February 2018

AbstractToxoplasma, a protozoan parasite of cats, infects many species of intermediate and paratenic hosts, including about one-third of humans worldwide. After a short phase of acute infection, the tissue cysts containing slowly dividing bradyzoites are formed in various organs and toxoplasmosis proceeds spontaneously in its latent form. In immunocompetent subjects, latent toxoplasmosis was considered asymptomatic. However, dozens of studies performed on animals and humans in the past twenty years have shown that it is accompanied by a broad spectrum of specific behavioural, physiological and even morphological changes. In human hosts, the changes often go in the opposite direction in men and women, and are mostly weaker or non-existent in Rh-positive subjects. Here, we searched for the indices of lower endurance of the infected subjects by examining the performance of nearly five hundred university students tested for toxoplasmosis and Rh phenotype in two tests, a weight holding test and a grip test. The results confirmed the existence of a negative association of latent toxoplasmosis with the performance of students, especially Rh-negative men, in these tests. Surprisingly, but in an accordance with some already published data, Toxoplasma-infected, Rh-positive subjects expressed a higher, rather than lower, performance in our endurance tests. Therefore, the results only partly support the hypothesis for the lower endurance of Toxoplasma infected subjects as the performance of Rh-positive subjects (representing majority of population) correlated positively with the Toxoplasma infection.
Plant quarantine alarm: as much as 20 new alien insect pest species includingDrosophila suzukiiappeared in the Caucasus in the last seven years
Authors: Bieńkowski Andrzej O. , Orlova-Bienkowskaja Marina J. , Karpun Natalia N 
Published: February 2018

AbstractIn 2011-2017 an unusually high number of invasive pests new to European Russia were detected for the first time in Sochi on the Black Sea coast of the Caucasus. We present the first reports of two pests new for the Caucasus and European Russia found in 2017:Drosophila suzukii(a pest of fruit, included to EPPO A2 list) andOtiorhynchus armadillo(a pest of agricultural and ornamental plants). Other recently established insects: a polyphagous pestHalyomorpha halys(first record in 2014); pests of palm trees included to EPPO A2 list:Paysandisia archon(2014) andRhynchophorus ferrugineus(2012); a pest of Solanaceae:Epitrix hirtipennis(2013); a pest of ornamental flowers:Luperomorpha xanthodera(2016); a pest of soybeans:Medythia nigrobilineata(2016); a pest of wine production:Harmonia axyridis(2012); a pest of strawberry:Stelidota geminata(2013); pests ofEucalyptus: Ophelimus maskelli(2011),Glycaspis bremblecomblei(2014),Leptocybe invasa(2014); a pest of Cupressaceae:Lamprodila festiva(2013); a pest ofGleditsia: Dasineura gleditchiae(2011), a pest ofBuxus: Cydalima perspectalis(2012); a pest ofAlbizia: Acizzia jamatonica(2014); a pest ofCercis: Cacopsylla pulchella(2014). Probably most of insects were introduced with imported planting material during the landscaping of the city of Sochi in preparation for the Olympic Games (held in 2014). Quarantine measures should be taken to prevent dispersal of these pests to other regions of the Caucasus and countries of the Black Sea region. Attention should be paid to a new pest for EuropeMedythia nigrobilineata.
FGF21, a liver hormone that inhibits alcohol intake in mice, increases in human circulation after acute alcohol ingestion and sustained binge drinking at Oktoberfest
Authors: Søberg Susanna , Andersen Emilie S. , Dalgaard Niels B. , Jarlhelt Ida , Hansen Nina L. , Hoffmann Nina , Vilsbøll Tina , Chenchar Anne , Jensen Michal , Grevengoed Trisha J. , Trammell Sam A.J. , Knop Filip K. , Gillum Matthew P. 
Published: February 2018

ABSTRACTObjectiveExcessive alcohol consumption is a leading cause of global morbidity and mortality. However, knowledge of the biological factors that influence adlibitumalcohol intake may be incomplete. Two large studies recently linked variants in theKLBlocus with levels of alcohol intake in humans.KLBencodes ß-klotho, co-receptor for the liver-derived hormone fibroblast growth factor 21 (FGF21). In mice, FGF21 reduces alcohol intake, and humanFgf21variants are enriched among heavy drinkers. Thus, the liver may limit alcohol consumption by secreting FGF21. However, whether full-length, active plasma FGF21 (FGF21 (1-181)) levels in humans increase acutely or sub-chronically in response to alcohol ingestion is uncertain.MethodsWe recruited 10 healthy, fasted male subjects to receive an oral water or alcohol bolus with concurrent blood sampling for FGF21 (1-181) measurement in plasma. In addition, we measured circulating FGF21 (1-181) levels, liver stiffness, triglyceride, and other metabolic parameters in three healthy Danish men before and after consuming an average of 22.6 beers/person/day (4.4 g/kg/day of ethanol) for three days during Oktoberfest 2017 in Munich, Germany. We further correlated fasting FGF21 (1-181) levels in 49 healthy, non-alcoholic subjects of mixed sex with self-reports of alcohol-related behaviors, emotional responses, and problems. Finally, we characterized the effect of recombinant human FGF21 injection on adlibitumalcohol intake in mice.ResultsWe show that alcohol ingestion (25.3 grams or ~2.5 standard drinks) acutely increases plasma levels of FGF21 (1-181) 3.4-fold in fasting humans. We also find that binge drinking for three days at Oktoberfest is associated with a 2.1-fold increase in baseline FGF21 (1-181) levels, in contrast to minor deteriorations in metabolic and hepatic biomarkers. However, basal FGF21 (1-181) levels were not correlated with differences in alcohol-related behaviors, emotional responses, or problems in our non-alcoholic subjects. Finally, we show that once-daily injection of recombinant human FGF21 reduces adlibitumalcohol intake by 21% in mice.ConclusionsFGF21 (1-181) is markedly increased in circulation by both acute and sub-chronic alcohol intake in humans, and reduces alcohol intake in mice. These observations are consistent with a role for FGF21 as an endocrine inhibitor of alcohol appetite in humans.
Targeted mutation detection in breast cancer using MammaSeq™
Authors: Smith Nicholas G. , Gyanchandani Rekha , Gurda Grzegorz , Lucas Peter C. , Hartmaier Ryan J. , Brufsky Adam M. , Puhalla Shannon , Bahreini Amir , Kota Karthik , Wald Abigail I. , Nikiforov Yuri E. , Nikiforova Marina N. , Oesterrich Steffi , Lee Adrian V. 
Published: February 2018

AbstractBackgroundBreast cancer is the most common invasive cancer among women worldwide. Next-generation sequencing (NGS) has revolutionized the study of cancer across research labs around the globe, however genomic testing in clinical settings remain limited. Advances in sequencing reliability, pipeline analysis, accumulation of relevant data, and the reduction of costs are rapidly increasing the feasibility of NGS-based clinical decision making.MethodsWe report the development of MammaSeq, a breast cancer specific NGS panel, targeting 79 genes and 1369 mutations, optimized for use in primary and metastatic breast cancer. To validate the panel, 46 solid tumor and 14 plasma circulating-free cfDNA samples were sequenced to a mean depth of 2311X and 1820 X respectively. Variants were called using Ion Torrent Suite 4.0 and annotated with cravat CHASM. CNVKit was used to call copy number variants in the solid tumor cohort. The oncoKB Precision Oncology Database was used to identify clinically actionable variants. ddPCR was used to validate select cfDNA mutations.ResultsIn cohorts of 46 solid tumors and 14 cfDNA samples from patients with advanced breast cancer we identified 592 and 43 protein coding mutations. Mutations per sample in the solid tumor cohort ranged from 1 to 128 (median 3) and the cfDNA cohort ranged from 0 to 26 (median 2.5). Copy number analysis in the solid tumor cohort identified 46 amplifications and 35 deletions. We identified 26 clinically actionable variants (levels 1-3) annotated by OncoKB, distributed across 20 out of 46 cases (40%), in the solid tumor cohort. Allele frequencies of ESR1 and FOXA1 mutations correlated with CA.27.29 levels in patient matched blood draws.ConclusionsIn solid tumors biopsies and cfDNA, MammaSeq detects clinicaly actionable mutations (oncoKB levels 1-3) in 22/46 (48%) solid tumors and in 4/14 (29%) of cfDNA samples. MammaSeq is a targeted panel suitable for clinically actionable mutation detection in breast cancer.
Developmental Mechanisms Linking Form and Function During Jaw Evolution
Authors: Woronowicz Katherine C. , Gline Stephanie E. , Herfat Safa T. , Fields Aaron J. , Schneider Richard A. 
Published: February 2018

AbstractHow does form arise during development and change during evolution? How does form relate to function, and what enables embryonic structures to presage their later use in adults? To address these questions, we leverage the distinct functional morphology of the jaw in duck, chick, and quail. In connection with their specialized mode of feeding, duck develop a secondary cartilage at the tendon insertion of their jaw adductor muscle on the mandible. An equivalent cartilage is absent in chick and quail. We hypothesize that species-specific jaw architecture and mechanical forces promote secondary cartilage in duck through the differential regulation of FGF and TGFβ signaling. First, we perform transplants between chick and duck embryos and demonstrate that the ability of neural crest mesenchyme (NCM) to direct the species-specific insertion of muscle and the formation of secondary cartilage depends upon the amount and spatial distribution of NCM-derived connective tissues. Second, we quantify motility and build finite element models of the jaw complex in duck and quail, which reveals a link between species-specific jaw architecture and the predicted mechanical force environment. Third, we investigate the extent to which mechanical load mediates FGF and TGFβ signaling in the duck jaw adductor insertion, and discover that both pathways are mechano-responsive and required for secondary cartilage formation. Additionally, we find that FGF and TGFβ signaling can also induce secondary cartilage in the absence of mechanical force or in the adductor insertion of quail embryos. Thus, our results provide novel insights on molecular, cellular, and biomechanical mechanisms that couple musculoskeletal form and function during development and evolution.
Generalizing clusters of similar species as a signature of coexistence under competition
Authors: D’Andrea Rafael , Riolo Maria , Ostling Annette 
Published: February 2018

AbstractPatterns of trait distribution among competing species can potentially reveal the processes that allow them to coexist. It has been recently proposed that competition may drive the spontaneous emergence of niches comprising clusters of similar species, in contrast with the dominant paradigm of greater-than-chance species differences. However, current clustering theory relies largely on heuristic rather than mechanistic models. Furthermore, studies of models incorporating demographic stochasticity and immigration, two key players in community assembly, did not observe clusters. Here we demonstrate clustering under partitioning of resources, partitioning of environmental gradients, and a competition-colonization tradeoff. We show that clusters are robust to demographic stochasticity, and can persist under immigration. While immigration may sustain clusters that are otherwise transient, too much dilutes the pattern. In order to detect and quantify clusters in nature, we introduce and validate metrics which have no free parameters nor require arbitrary trait binning, and weigh species by their abundances rather than relying on a presence-absence count. By generalizing beyond the circumstances where clusters have been observed, our study contributes to establishing them as an update to classical trait patterning theory.Author SummarySpecies traits determine how they compete with each other. As such, patterns in the distributions of traits in a community of competing species may reveal the processes responsible for coexistence. One central idea in theoretical ecology is that the strength of competition relates to similarity in species needs and strategies, and therefore if competition plays out at short timescales, coexisting species should be more different than expected by chance. However, recent theory suggests that competition may lead species to temporarily self-organize into groups with similar traits. Here we show that this clustering is a generic feature of competitive dynamics, which is robust to demographic stochasticity and can be indefinitely maintained by immigration. We show that clustering arises whether species coexist by partitioning resources, environmental preferences, or through tradeoffs in life-history strategies. We introduce and validate metrics that, given species traits and abundances, determine whether they are clustered, and if so, how many clusters occur. By showing the generality of self-organized species clusters and providing a tools for their detection, our study contributes to updating classical ideas about how competition shapes communities, and motivates searches for them in nature.
Determining Allele-Specific Protein Expression (ASPE) Using a QconCAT-Based Proteomics Method: a Novel Approach to Identify Cis-acting Genetic Variants
Authors: Shi Jian , Wang Xinwen , Zhu Huaijun , Jiang Hui , Wang Danxin , Nesvizhskii Alexey , Zhu Hao-Jie 
Published: February 2018

AbstractMeasuring allele-specific expression (ASE) is a powerful approach for identifying cis-regulatory genetic variants. Here we developed a novel targeted proteomics method for quantification of allele-specific protein expression (ASPE) based on scheduled high resolution multiple reaction monitoring (sMRM-HR) with a heavy stable isotope-labeled quantitative concatamer (QconCAT) internal protein standard. This strategy was applied to the determination of the ASPE of UGT2B15 in human livers using the common UGT2B15 nonsynonymous variant rs1902023 (i.e. Y85D) as the marker to differentiate expressions from the two alleles. The QconCAT standard contains both the wild type tryptic peptide and the Y85D mutant peptide at a ratio of 1:1 to ensure accurate measurement of the ASPE of UGT2B15. The results from 18 UGT2B15 Y85D heterozygotes revealed that the ratios between wild type Y allele and mutant D allele varied from 0.60 to 1.46, indicating the presence of cis-regulatory variants. In addition, we observed no significant correlations between the ASPE and mRNA ASE of UGT2B15, suggesting the involvement of different cis-acting variants in regulating the transcription and translation processes of the gene. This novel ASPE approach provides a powerful tool for capturing cis-genetic variants involved in post-transcription processes, an important yet understudied area of research.