bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clearance of Vancomycin-Resistant Enterococcus Concomitant With Administration of a Microbiota-Based Drug Targeted at Recurrent Clostridium difficile Infection
Authors: Dubberke Erik R. , Mullane Kathleen M. , Gerding Dale N. , Lee Christine H. , Louie Thomas J. , Guthertz Harriet , Jones Courtney 
Published: June 2016

Abstract
Background.  Vancomycin-resistant Enterococcus (VRE) is a major healthcare-associated pathogen and a well known complication among transplant and immunocompromised patients. We report on stool VRE clearance in a post hoc analysis of the Phase 2 PUNCH CD study assessing a microbiota-based drug for recurrent Clostridium difficile infection (CDI).
Methods.  A total of 34 patients enrolled in the PUNCH CD study received 1 or 2 doses of RBX2660 (microbiota suspension). Patients were requested to voluntarily submit stool samples at baseline and at 7, 30, and 60 days and 6 months after the last administration of RBX2660. Stool samples were tested for VRE using bile esculin azide agar with 6 µg/mL vancomycin and Gram staining. Vancomycin resistance was confirmed by Etest.
Results.  VRE status (at least 1 test result) was available for 30 patients. All stool samples for 19 patients (63.3%, mean age 61.7 years, 68% female) tested VRE negative. Eleven patients (36.7%, mean age 75.5 years, 64% female) were VRE positive at the first test (baseline or 7-day follow-up). Of these patients, 72.7%, n = 8 converted to negative as of the last available follow-up (30 or 60 days or 6 months). Of the other 3: 1 died (follow-up data not available); 1 patient remained positive at all follow-ups; 1 patient retested positive at 6 months with negative tests during the interim.
Conclusions.  Although based on a small sample size, this secondary analysis demonstrated the possibility of successfully converting a high percentage of VRE-positive patients to negative in a recurrent CDI population with RBX2660.
Host Biomarkers Are Associated With Response to Therapy and Long-Term Mortality in Pediatric Severe Malaria
Authors: Conroy Andrea L. , Hawkes Michael , McDonald Chloe R. , Kim Hani , Higgins Sarah J. , Barker Kevin R. , Namasopo Sophie , Opoka Robert O. , John Chandy C. , Liles W. Conrad , Kain Kevin C. 
Published: June 2016

AbstractBackground.  Host responses to infection are critical determinants of disease severity and clinical outcome. The development of tools to risk stratify children with malaria is needed to identify children most likely to benefit from targeted interventions.Methods.  This study investigated the kinetics of candidate biomarkers of mortality associated with endothelial activation and dysfunction (angiopoietin-2 [Ang-2], soluble FMS-like tyrosine kinase-1 [sFlt-1], and soluble intercellular adhesion molecule-1 [sICAM-1]) and inflammation (10 kDa interferon γ-induced protein [CXCL10/IP-10] and soluble triggering receptor expressed on myeloid cells-1 [sTREM-1]) in the context of a randomized, double-blind, placebo-controlled, parallel-arm trial evaluating inhaled nitric oxide versus placebo as adjunctive therapy to parenteral artesunate for severe malaria. One hundred eighty children aged 1–10 years were enrolled at Jinja Regional Referral Hospital in Uganda and followed for up to 6 months.Results.  There were no differences between the 2 study arms in the rate of biomarker recovery. Median levels of Ang-2, CXCL10, and sFlt-1 were higher at admission in children who died in-hospital (n = 15 of 180; P &lt; .001, P = .027, and P = .004, respectively). Elevated levels of Ang-2, sTREM-1, CXCL10, and sICAM-1 were associated with prolonged clinical recovery times in survivors. The Ang-2 levels were also associated with postdischarge mortality (P &lt; .0001). No biomarkers were associated with neurodisability.Conclusions.  Persistent endothelial activation and dysfunction predict survival in children admitted with severe malaria.
Expected constraints on models of the epoch of reionization with the variance and skewness in redshifted 21 cm-line fluctuations
Authors: Kubota Kenji , Yoshiura Shintaro , Shimabukuro Hayato , Takahashi Keitaro 
Published: June 2016

Abstract
The redshifted 21 cm-line signal from neutral hydrogen in the intergalactic medium (IGM) gives a direct probe of the epoch of reionization (EoR). In this paper, we investigate the potential of the variance and skewness of the probability distribution function of the 21 cm brightness temperature for constraining EoR models. These statistical quantities are simple, easy to calculate from the observed visibility, and thus suitable for the early exploration of the EoR with current telescopes such as the Murchison Widefield Array (MWA) and LOw Frequency ARray (LOFAR). We show, by performing Fisher analysis, that the variance and skewness at z = 7–9 are complementary to each other to constrain the EoR model parameters such as the minimum virial temperature of halos which host luminous objects, ionizing efficiency, and mean free path of ionizing photons in the IGM. Quantitatively, the constraining power highly depends on the quality of the foreground subtraction and calibration. We give a best case estimate of the constraints on the parameters, neglecting the systematics other than the thermal noise.
Bayesian phylogenetic estimation of fossil ages
Authors: Drummond Alexei J. , Stadler Tanja 
Published: June 2016

Recent advances have allowed for both morphological fossil evidence and molecular sequences to be integrated into a single combined inference of divergence dates under the rule of Bayesian probability. In particular, the fossilized birth–death tree prior and the Lewis-Mk model of discrete morphological evolution allow for the estimation of both divergence times and phylogenetic relationships between fossil and extant taxa. We exploit this statistical framework to investigate the internal consistency of these models by producing phylogenetic estimates of the age of each fossil in turn, within two rich and well-characterized datasets of fossil and extant species (penguins and canids). We find that the estimation accuracy of fossil ages is generally high with credible intervals seldom excluding the true age and median relative error in the two datasets of 5.7% and 13.2%, respectively. The median relative standard error (RSD) was 9.2% and 7.2%, respectively, suggesting good precision, although with some outliers. In fact, in the two datasets we analyse, the phylogenetic estimate of fossil age is on average less than 2 Myr from the mid-point age of the geological strata from which it was excavated. The high level of internal consistency found in our analyses suggests that the Bayesian statistical model employed is an adequate fit for both the geological and morphological data, and provides evidence from real data that the framework used can accurately model the evolution of discrete morphological traits coded from fossil and extant taxa. We anticipate that this approach will have diverse applications beyond divergence time dating, including dating fossils that are temporally unconstrained, testing of the ‘morphological clock', and for uncovering potential model misspecification and/or data errors when controversial phylogenetic hypotheses are obtained based on combined divergence dating analyses.
This article is part of the themed issue ‘Dating species divergences using rocks and clocks’.
A mixed relaxed clock model
Authors: Lartillot Nicolas , Phillips Matthew J. , Ronquist Fredrik 
Published: June 2016

Over recent years, several alternative relaxed clock models have been proposed in the context of Bayesian dating. These models fall in two distinct categories: uncorrelated and autocorrelated across branches. The choice between these two classes of relaxed clocks is still an open question. More fundamentally, the true process of rate variation may have both long-term trends and short-term fluctuations, suggesting that more sophisticated clock models unfolding over multiple time scales should ultimately be developed. Here, a mixed relaxed clock model is introduced, which can be mechanistically interpreted as a rate variation process undergoing short-term fluctuations on the top of Brownian long-term trends. Statistically, this mixed clock represents an alternative solution to the problem of choosing between autocorrelated and uncorrelated relaxed clocks, by proposing instead to combine their respective merits. Fitting this model on a dataset of 105 placental mammals, using both node-dating and tip-dating approaches, suggests that the two pure clocks, Brownian and white noise, are rejected in favour of a mixed model with approximately equal contributions for its uncorrelated and autocorrelated components. The tip-dating analysis is particularly sensitive to the choice of the relaxed clock model. In this context, the classical pure Brownian relaxed clock appears to be overly rigid, leading to biases in divergence time estimation. By contrast, the use of a mixed clock leads to more recent and more reasonable estimates for the crown ages of placental orders and superorders. Altogether, the mixed clock introduced here represents a first step towards empirically more adequate models of the patterns of rate variation across phylogenetic trees.This article is part of the themed issue ‘Dating species divergences using rocks and clocks’.
A molecular palaeobiological exploration of arthropod terrestrialization
Authors: Lozano-Fernandez Jesus , Carton Robert , Tanner Alastair R. , Puttick Mark N. , Blaxter Mark , Vinther Jakob , Olesen Jørgen , Giribet Gonzalo , Edgecombe Gregory D. , Pisani Davide 
Published: June 2016

Understanding animal terrestrialization, the process through which animals colonized the land, is crucial to clarify extant biodiversity and biological adaptation. Arthropoda (insects, spiders, centipedes and their allies) represent the largest majority of terrestrial biodiversity. Here we implemented a molecular palaeobiological approach, merging molecular and fossil evidence, to elucidate the deepest history of the terrestrial arthropods. We focused on the three independent, Palaeozoic arthropod terrestrialization events (those of Myriapoda, Hexapoda and Arachnida) and showed that a marine route to the colonization of land is the most likely scenario. Molecular clock analyses confirmed an origin for the three terrestrial lineages bracketed between the Cambrian and the Silurian. While molecular divergence times for Arachnida are consistent with the fossil record, Myriapoda are inferred to have colonized land earlier, substantially predating trace or body fossil evidence. An estimated origin of myriapods by the Early Cambrian precedes the appearance of embryophytes and perhaps even terrestrial fungi, raising the possibility that terrestrialization had independent origins in crown-group myriapod lineages, consistent with morphological arguments for convergence in tracheal systems.This article is part of the themed issue ‘Dating species divergences using rocks and clocks’.
Mutation rates and the evolution of germline structure
Authors: Scally Aylwyn 
Published: June 2016

Genome sequencing studies of de novo mutations in humans have revealed surprising incongruities in our understanding of human germline mutation. In particular, the mutation rate observed in modern humans is substantially lower than that estimated from calibration against the fossil record, and the paternal age effect in mutations transmitted to offspring is much weaker than expected from our long-standing model of spermatogenesis. I consider possible explanations for these discrepancies, including evolutionary changes in life-history parameters such as generation time and the age of puberty, a possible contribution from undetected post-zygotic mutations early in embryo development, and changes in cellular mutation processes at different stages of the germline. I suggest a revised model of stem-cell state transitions during spermatogenesis, in which ‘dark’ gonial stem cells play a more active role than hitherto envisaged, with a long cycle time undetected in experimental observations. More generally, I argue that the mutation rate and its evolution depend intimately on the structure of the germline in humans and other primates.
This article is part of the themed issue ‘Dating species divergences using rocks and clocks'.
Inferring species divergence times using pairwise sequential Markovian coalescent modelling and low-coverage genomic data
Authors: Cahill James A. , Soares André E. R. , Green Richard E. , Shapiro Beth 
Published: June 2016

Understanding when species diverged aids in identifying the drivers of speciation, but the end of gene flow between populations can be difficult to ascertain from genetic data. We explore the use of pairwise sequential Markovian coalescent (PSMC) modelling to infer the timing of divergence between species and populations. PSMC plots generated using artificial hybrid genomes show rapid increases in effective population size at the time when the two parent lineages diverge, and this approach has been used previously to infer divergence between human lineages. We show that, even without high coverage or phased input data, PSMC can detect the end of significant gene flow between populations by comparing the PSMC output from artificial hybrids to the output of simulations with known demographic histories. We then apply PSMC to detect divergence times among lineages within two real datasets: great apes and bears within the genusUrsus. Our results confirm most previously proposed divergence times for these lineages, and suggest that gene flow between recently diverged lineages may have been common among bears and great apes, including up to one million years of continued gene flow between chimpanzees and bonobos after the formation of the Congo River.This article is part of the themed issue ‘Dating species divergences using rocks and clocks'.
Mammal madness: is the mammal tree of life not yet resolved?
Authors: Foley Nicole M. , Springer Mark S. , Teeling Emma C. 
Published: June 2016

Most molecular phylogenetic studies place all placental mammals into four superordinal groups, Laurasiatheria (e.g. dogs, bats, whales), Euarchontoglires (e.g. humans, rodents, colugos), Xenarthra (e.g. armadillos, anteaters) and Afrotheria (e.g. elephants, sea cows, tenrecs), and estimate that these clades last shared a common ancestor 90–110 million years ago. This phylogeny has provided a framework for numerous functional and comparative studies. Despite the high level of congruence among most molecular studies, questions still remain regarding the position and divergence time of the root of placental mammals, and certain ‘hard nodes’ such as the Laurasiatheria polytomy and Paenungulata that seem impossible to resolve. Here, we explore recent consensus and conflict among mammalian phylogenetic studies and explore the reasons for the remaining conflicts. The question of whether the mammal tree of life is or can be ever resolved is also addressed.This article is part of the themed issue ‘Dating species divergences using rocks and clocks’.
Grouping substitution types into different relaxed molecular clocks
Authors: Lee Hui-Jie , Kishino Hirohisa , Rodrigue Nicolas , Thorne Jeffrey L. 
Published: June 2016

Different types of nucleotide substitutions experience different patterns of rate change over time. We propose clustering context-dependent (or context-independent) nucleotide substitution types according to how their rates change and then using the grouping for divergence time estimation. With our models, relative rates among types that are in the same group are fixed, whereas absolute rates of the types within a group change over time according to a shared relaxed molecular clock. We illustrate our procedure by analysing a 0.15 Mb intergenic region to infer divergence times relating eight primates. The different groupings of substitution types that we explore have little effect on the posterior means of divergence times, but the widths of the credibility intervals decrease as the number of groups increases.This article is part of the themed issue ‘Dating species divergences using rocks and clocks’.
The evolution of methods for establishing evolutionary timescales
Authors: Donoghue Philip C. J. , Yang Ziheng 
Published: June 2016

The fossil record is well known to be incomplete. Read literally, it provides a distorted view of the history of species divergence and extinction, because different species have different propensities to fossilize, the amount of rock fluctuates over geological timescales, as does the nature of the environments that it preserves. Even so, patterns in the fossil evidence allow us to assess the incompleteness of the fossil record. While the molecular clock can be used to extend the time estimates from fossil species to lineages not represented in the fossil record, fossils are the only source of information concerning absolute (geological) times in molecular dating analysis. We review different ways of incorporating fossil evidence in modern clock dating analyses, including node-calibrations where lineage divergence times are constrained using probability densities and tip-calibrations where fossil species at the tips of the tree are assigned dates from dated rock strata. While node-calibrations are often constructed by a crude assessment of the fossil evidence and thus involves arbitrariness, tip-calibrations may be too sensitive to the prior on divergence times or the branching process and influenced unduly affected by well-known problems of morphological character evolution, such as environmental influence on morphological phenotypes, correlation among traits, and convergent evolution in disparate species. We discuss the utility of time information from fossils in phylogeny estimation and the search for ancestors in the fossil record.This article is part of the themed issue ‘Dating species divergences using rocks and clocks’.
Latent infection of human bocavirus accompanied by flare of chronic cough, fatigue and episodes of viral replication in an immunocompetent adult patient, Cologne, Germany
Authors: Windisch Wolfram , Pieper Monika , Ziemele Inga , Rockstroh Jürgen , Brockmann Michael , Schildgen Oliver , Schildgen Verena 
Published: June 2016

Introduction:
The human bocavirus (HBoV) is a parvovirus and is associated with mild to life-threatening acute or persisting respiratory infections, frequently accompanied by further pathogens. So far, there is limited knowledge on the mechanisms of persistence, and no reports on chronic infections or latency have been published so far.

Case presentation:
An immunocompetent male patient suffers from a chronic HBoV1 infection, i.e. viral DNA was detected in both serum and bronchoalveolar lavage (BAL) for >5 months without co-infections and with respiratory symptoms resolved spontaneously while receiving symptomatic treatment with montelukast and corticosteroids. Following the symptomatic medication of a chronic infection with HBoV1 viraemia indicating active viral replication lasting over 5 months, the patient cleared the viraemia and no further viral DNA was detectable in the BAL. However, by fluorescence in situ hybridization analyses of mucosal biopsies, it was shown that the virus genome still persisted in the absence of viral shedding but in a more compact manner possibly representing a supercoiled episomal form of this otherwise linear single-stranded DNA genome. This indicated the entry into a latency phase. Moreover, the cytokine profile and the IP-10/TARC ratio, a marker for fibrotization, seem to have been altered by HBoV1 replication. Although specific IgG antibodies were detectable during the whole observation period, they showed an apparently insufficient neutralising activity.

Conclusion:
On the one hand, these findings suggest that the symptomatic medication may have led to clearance of the virus from blood and airways and, moreover, that the viral DNA persists in the tissue as an altered episomal form favoured by lacking neutralising antibodies. This appears to be important in order to reduce possible long-term effects such as lung fibrosis.
Notes on the Nominal System of Bashkardi
Authors: Korn Agnes 
Published: June 2016

AbstractThis article studies the nominal system and noun phrase of Bashkardi, a language of the Iranian family spoken in Southern Iran in the region of Bashakerd. Bashkardi is a very little studied language, and is in particular need of being documented because it is a minority language endangered by heavy influence from Persian. The article is based on recordings made by Ilya Gershevitch in 1956. In discussing the Bashkardi nominal system, I compare it to that of geographically or historically neighbouring languages such as Balochi, spoken nearby in the province (and also in the form of the Koroshi dialect spoken in Fars province to the west). From a historical perspective, Middle Persian and Parthian, the only two Western Iranian languages attested from Middle Iranian times, are adduced to elucidate the development of the Bashkardi nominal system. I argue that the nominal system of Bashkardi agrees with Persian and other Western Ir. languages in having lost the distinction between direct and oblique case (preserved in Kurmanji, Balochi, etc.), but that a trace of the oblique case might be present in the possessive marker‐ī. Like Middle Persian, Bashkardi employs adpositions to mark syntactic relations, but none of these is used in a systematic way as of yet.
Hospital Quality Reporting in the United States: Does Report Card Design and Incorporation of Patient Narrative Comments Affect Hospital Choice?
Authors: Emmert Martin , Schlesinger Mark 
Published: June 2016

ObjectiveTo explore the impact of hospital report card design and incorporation of patient narrative comments on consumers' choices of hospitals.Data SourcesPrimary data collected from an online survey with 1,350 respondents in February, 2015.Study DesignA randomized 2 (narrative comments: yes, no) × 3 (design: representation of clinical performance in textual, star, numerical formats) between‐subject online‐based cross‐sectional experiment.Principal FindingsIn 51 percent of all cases, respondents selected the hospital with the best clinical results. Report cards with a numerical design induced choices more focused on clinical ratings (56.0 percent chose the highest rated hospital) than those with textual information (48.1 percent) or star ratings (47.3 percent) (p < .001). Report cards without narrative comments (49.7 percent) and with narratives (51.4 percent) were not associated with significant difference in selecting top‐rated clinical hospitals (p = .376). But there were significant interactions affecting choice of hospitals among exposure to narratives, formatting of clinical performance, and respondents' education.ConclusionsConsumers have a difficult time synthesizing quality data in various formats. Hospital report cards continue to pose challenging choices, especially for those with limited education. Narrative comments in their earliest emerging forms do not seem to be altering hospital choice as much as the literature has suggested for other providers, but they may have consequential impact on the choices of certain subsets of consumers.