bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bias correction for selecting the minimal-error classifier from many machine learning models
Authors: Ding Ying , Tang Shaowu , Liao Serena G. , Jia Jia , Oesterreich Steffi , Lin Yan , Tseng George C. 
Published: August 2014

Abstract
Motivation: Supervised machine learning is commonly applied in genomic research to construct a classifier from the training data that is generalizable to predict independent testing data. When test datasets are not available, cross-validation is commonly used to estimate the error rate. Many machine learning methods are available, and it is well known that no universally best method exists in general. It has been a common practice to apply many machine learning methods and report the method that produces the smallest cross-validation error rate. Theoretically, such a procedure produces a selection bias. Consequently, many clinical studies with moderate sample sizes (e.g. n = 30–60) risk reporting a falsely small cross-validation error rate that could not be validated later in independent cohorts.
Results: In this article, we illustrated the probabilistic framework of the problem and explored the statistical and asymptotic properties. We proposed a new bias correction method based on learning curve fitting by inverse power law (IPL) and compared it with three existing methods: nested cross-validation, weighted mean correction and Tibshirani-Tibshirani procedure. All methods were compared in simulation datasets, five moderate size real datasets and two large breast cancer datasets. The result showed that IPL outperforms the other methods in bias correction with smaller variance, and it has an additional advantage to extrapolate error estimates for larger sample sizes, a practical feature to recommend whether more samples should be recruited to improve the classifier and accuracy. An R package ‘MLbias’ and all source files are publicly available.
Availability and implementation: tsenglab.biostat.pitt.edu/software.htm.
Contact: ctseng@pitt.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Tibetan Plateau climate dynamics: recent research progress and outlook
Authors: Wu Guoxiong , Duan Anmin , Liu Yimin , Mao Jiangyu , Ren Rongcai , Bao Qing , He Bian , Liu Boqi , Hu Wenting 
Published: August 2014

Abstract
This paper reviews progress in the study of Tibetan Plateau (TP) climate dynamics over the past decade. Several theoretical frameworks, including thermal adaptation and the TP sensible heat (SH) driving air-pump, have been developed to identify the mechanisms responsible for the circulation anomaly produced by thermal forcing of the TP. Numerical simulations demonstrate that the thermal effects of large-scale orography, including the Tibetan and Iranian Plateaus (TIP), are crucial for the formation of the East Asian and South Asian summer monsoons (SASM) because the surface SH of the TIP is the major driver of the water vapor transport required for the genesis of the north branch of the SASM. The large-scale orography of the TP affects the Asian climate through thermal forcing in spring and summer, and mechanical forcing in winter. The TP forcing can also influence the Asian summer monsoon (ASM) onset over the Bay of Bengal (BOB) by enhancing the BOB warm pool at the surface and by modulating the South Asian High (SAH) in the upper troposphere. On intra-seasonal timescales, the TP thermal forcing significantly modulates spring rainfall in southern China and generates the biweekly oscillation of the SAH in summer. Despite climate warming, the atmospheric heat source over the TP, particularly the spring SH, exhibits a clear weakening trend from the 1980s to 2000s. This weakening of the spring SH contributed to the anomalous ‘dry in the north’ and ‘wet in the south’ rainfall pattern observed over East China. Also discussed are challenges to further understanding the mechanism of TP forcing on the multi-scale variability of the ASM.
Sensitivity and Specificity of Procalcitonin in Predicting Bacterial Infections in Patients With Renal Impairment
Authors: El-sayed Dena , Grotts Jonathan , Golgert William A. , Sugar Alan M. 
Published: August 2014

Abstract
Background.  It is unclear whether procalcitonin is an accurate predictor of bacterial infections in patients with renal impairment, although it is used as a biomarker for early diagnosis of sepsis. We determined the sensitivity, specificity, positive and negative predictive values, accuracy and best predictive value of procalcitonin for predicting bacterial infection in adult patients with severe renal impairment.
Methods.  Retrospective study at a single-center community teaching hospital involving 473 patients, ages 18–65, with Modification of Diet in Renal Disease eGFR ≤30 ml/min per 1.73 m2, admitted between January 2009 and June 2012, with 660 independent hospital visits. A positive or negative culture (blood or ide.jpegiable focus of infection) was paired to the highest procalcitonin result performed 48 hours before or after collecting the culture.
Results.  The sensitivity and specificity to predict bacterial infection, using a procalcitonin level threshold of 0.5 ng/mL, was 0.80 and 0.35 respectively. When isolating for presence of bacteremia, the sensitivity and specificity were 0.89 and 0.35 respectively. An equation adjusting for optimum thresholds of procalcitonin levels for predicting bacterial infection at different levels of eGFR had a sensitivity and specificity of 0.55 and 0.80 respectively.
Conclusions.  Procalcitonin is not a reliably sensitive or specific predictor of bacterial infection in patients with renal impairment when using a single threshold. Perhaps two thresholds should be employed, where below the lower threshold (i.e. 0.5 ng/mL) bacterial infection is unlikely with a sensitivity of 0.80, and above the higher threshold (i.e. 3.2 ng/mL) bacterial infection is very likely with a specificity of 0.75.
Novel Fidaxomicin Treatment Regimens for Patients With Multiple Clostridium difficile Infection Recurrences That Are Refractory to Standard Therapies
Authors: Soriano Melinda M. , Danziger Larry H. , Gerding Dale N. , Johnson Stuart 
Published: August 2014

Abstract
Reports of fidaxomicin treatment for patients with multiple recurrent Clostridium difficile infections ([mrCDI] ie, more than 2 CDI episodes) indicate symptomatic response to this agent, but 50% have subsequent mrCDI episodes. In an effort to improve outcomes in patients with mrCDI we used novel regimens of fidaxomicin based on strategies used with vancomycin. Of 8 patients who received a 10-day chaser of fidaxomicin given twice daily after a course of vancomycin, 3 (38%) experienced a subsequent recurrence. Two (18%) of 11 patients who completed a 14- to 33-day course of fidaxomicin in a tapering dose experienced a recurrence, both of whom received additional antibiotics before that recurrence. The median symptom-free interval (SFI) after fidaxomicin taper was greater than the median SFI after the most effective prior regimen for those patients (257 days [interquartile range, 280] vs 25 days [interquartile range, 30], respectively; P = .003). A fidaxomicin chaser or taper regimen may be effective in patients with mrCDI, but the number of patients treated is small, and randomized comparative data are not available.
Staphylococcus aureus Infections After Elective Cardiothoracic Surgery: Observations From an International Randomized Placebo-Controlled Trial of an Investigational S aureus Vaccine
Authors: Allen Keith B. , Fowler Vance G. , Gammie James S. , Hartzel Jonathan S. , Onorato Matthew T. , DiNubile Mark J. , Sobanjo-ter Meulen Ajoke 
Published: August 2014

Abstract
Background.  An unmet need to prevent Staphylococcus aureus (SA) infections after cardiothoracic surgery persists despite current practices. Cost-effective implementation of preventive strategies requires contemporary knowledge about modifiable risk factors.
Methods.  From 2007 to 2011, an international, double-blind, randomized placebo-controlled trial of a novel SA vaccine (V710) was conducted in 7664 adults scheduled for median sternotomy at 164 sites. We analyzed SA infections developing up to 360 days postoperatively in 3832 placebo recipients.
Results.  Coronary artery bypass grafting was performed in 80.8% (3096 of 3832) of placebo recipients. The overall incidence of any postoperative SA infection was 3.1% (120 of 3832). Invasive SA infections (including bacteremia and deep sternal-wound infections) developed in 1.0%. Methicillin-resistant SA (MRSA) accounted for 19% (23 of 120) of SA infections, with 57% (13 of 23) of the MRSA infections occurring in diabetic patients. All-cause mortality was 4.1% (153 of 3712) in patients without SA infection, 7.2% (7 of 97) in methicillin-susceptible SA (MSSA) infections, and 17.3% (4 of 23) in MRSA infections (P &lt; .01). Staphylococcus aureus nasal carriage was detected preoperatively in 18.3% (701 of 3096) patients, including 1.6% colonized with MRSA. Postoperative SA infections occurred in 7.0% (49 of 701) of colonized patients versus 2.3% (71 of 3131) of patients without colonization (relative risk = 3.1 [95% confidence interval, 2.2–4.4]).
Conclusions.  In this large international cohort of patients undergoing cardiac surgery and observed prospectively, invasive postoperative SA infections occurred in 1% of adult patients despite modern perioperative management. The attributable mortality rates were 3% for MSSA and 13% for MRSA infections. Preoperative nasal colonization with SA increased the risk of postoperative infection threefold. The utility of strategies to reduce this incidence warrants continued investigation.
Fundamental phenomena of quantum mechanics explored with neutron interferometers
Authors: Klepp Jürgen , Sponar Stephan , Hasegawa Yuji 
Published: August 2014

AbstractOngoing fascination with quantum mechanics keeps driving the development of the wide field of quantum optics, including its neutron optics branch. Application of neutron-optical methods and, in particular, neutron interferometry and polarimetry has a long-standing tradition for experimental investigations of fundamental quantum phenomena. We give an overview of related experimental efforts made in recent years.
Brain Neuroplastic Changes Accompany Anxiety and Memory Deficits in a Model of Complex Regional Pain Syndrome
Authors: Tajerian Maral , Leu David , Zou Yani , Sahbaie Peyman , Li Wenwu , Khan Hamda , Hsu Vivian , Kingery Wade , Huang Ting Ting , Becerra Lino , Clark J. David 
Published: August 2014

Abstract

Background:
Complex regional pain syndrome (CRPS) is a painful condition with approximately 50,000 annual new cases in the United States. It is a major cause of work-related disability, chronic pain after limb fractures, and persistent pain after extremity surgery. Additionally, CRPS patients often experience cognitive changes, anxiety, and depression. The supraspinal mechanisms linked to these CRPS-related comorbidities remain poorly understood.

Methods:
The authors used a previously characterized mouse model of tibia fracture/cast immobilization showing the principal stigmata of CRPS (n = 8 to 20 per group) observed in humans. The central hypothesis was that fracture/cast mice manifest changes in measures of thigmotaxis (indicative of anxiety) and working memory reflected in neuroplastic changes in amygdala, perirhinal cortex, and hippocampus.

Results:
The authors demonstrate that nociceptive sensitization in these mice is accompanied by altered thigmotactic behaviors in the zero maze but not open field assay, and working memory dysfunction in novel object recognition and social memory but not in novel location recognition. Furthermore, the authors found evidence of structural changes and synaptic plasticity including changes in dendritic architecture and decreased levels of synaptophysin and brain-derived neurotrophic factor in specific brain regions.

Conclusions:
The study findings provide novel observations regarding behavioral changes and brain plasticity in a mouse model of CRPS. In addition to elucidating some of the supraspinal correlates of the syndrome, this work supports the potential use of therapeutic interventions that not only directly target sensory input and other peripheral mechanisms, but also attempt to ameliorate the broader pain experience by modifying its associated cognitive and emotional comorbidities.
Hsp90 promotes kinase evolution
Authors: Lachowiec Jennifer , Lemus Tzitziki , Borenstein Elhanan , Queitsch Christine 
Published: August 2014

AbstractHeat-shock protein 90 (Hsp90) promotes the maturation and stability of its client proteins, including many kinases. In doing so, Hsp90 may allow its clients to accumulate mutations as previously proposed by the capacitor hypothesis. If true, Hsp90 clients should show increased evolutionary rate compared to non-clients; however, other factors, such as gene expression and protein connectivity, may confound or obscure the chaperone’s putative contribution. Here, we compared the evolutionary rates of many Hsp90 clients and non-clients in the human protein kinase superfamily. We show that Hsp90 client status promotes evolutionary rate independently of, but in a small magnitude similar to that of gene expression and protein connectivity. Hsp90’s effect on kinase evolutionary rate was detected across mammals, specifically relaxing purifying selection. Hsp90 clients also showed increased nucleotide diversity and harbored more damaging variation than non-client kinases across humans. These results are consistent with the central argument of the capacitor hypothesis that interaction with the chaperone allows its clients to harbor genetic variation. Hsp90 client status is thought to be highly dynamic with as few as one amino acid change rendering a protein dependent on the chaperone. Contrary to this expectation, we found that across protein kinase phylogeny Hsp90 client status tends to be gained, maintained, and shared among closely related kinases. We also infer that the ancestral protein kinase was not an Hsp90 client. Taken together, our results suggest that Hsp90 played an important role in shaping the kinase superfamily.
The meta-epigenomic structure of purified human stem cell populations is defined atcis-regulatory sequences
Authors: Wijetunga N. Ari , Delahaye Fabien , Zhao Yong Mei , Golden Aaron , Mar Jessica C. , Einstein Francine H. , Greally John M. 
Published: August 2014

ABSTRACTThe mechanism and significance of epigenetic variability in the same cell type between healthy individuals are not clear. Here, we purify human CD34+ hematopoietic stem and progenitor cells (HSPCs) from different individuals and find that there is increased variability of DNA methylation at loci with properties of promoters and enhancers. The variability is especially enriched at candidate enhancers near genes transitioning between silent and expressed states, and encoding proteins with leukocyte differentiation properties. Our findings of increased variability at loci with intermediate DNA methylation values, at candidate “poised” enhancers, and at genes involved in HSPC lineage commitment suggest that CD34+ cell subtype heterogeneity between individuals is a major mechanism for the variability observed. Epigenomic studies performed on cell populations, even when purified, are testing collections of epigenomes, or meta-epigenomes. Our findings show that meta-epigenomic approaches to data analysis can provide insights into cell subpopulation structure.
A comparison of control samples for ChIP-seq of histone modifications
Authors: Flensburg Christoffer , Kinkel Sarah A , Keniry Andrew , Blewitt Marnie E , Oshlack Alicia 
Published: August 2014

AbstractThe advent of high-throughput sequencing has allowed genome wide profiling of histone modifications by Chromatin ImmunoPrecipitation (ChIP) followed by sequencing (ChIP-seq). In this assay the histone mark of interest is enriched through a chromatin pull-down assay using an antibody for the mark. Due to imperfect antibodies and other factors, many of the sequenced fragments do not originate from the histone mark of interest, and are referred to as background reads. Background reads are not uniformly distributed and therefore control samples are usually used to estimate the background distribution at any given genomic position. The Encyclopedia of DNA Elements (ENCODE) Consortium guidelines suggest sequencing a whole cell extract (WCE, or “input”) sample, or a mock ChIP reaction such as an IgG control, as a background sample. However, for a histone modification ChIP-seq investigation it is also possible to use a Histone H3 (H3) pull-down to map the underlying distribution of histones.In this paper we generated data from a hematopoietic stem and progenitor cell population isolated from mouse foetal liver to compare WCE and H3 ChIP-seq as control samples. The quality of the control samples is estimated by a comparison to pull-downs of histone modifications and to expression data. We find minor differences between WCE and H3 ChIP-seq, such as coverage in mitochondria and behaviour close to transcription start sites. Where the two controls differ, the H3 pull-down is generally more similar to the ChIP-seq of histone modifications. However, the differences between H3 and WCE have a negligible impact on the quality of a standard analysis.
The Impacts of Historical Barriers on Floristic Patterns of Plant Groups with Different Dispersal Abilities in the Ryukyu Archipelago, Japan
Authors: Nakamura Koh , Suwa Rempei , Denda Tetsuo , Yokota Masatsugu 
Published: August 2014

ABSTRACTThe effects of historical barriers in biogeographical patterns are expected to persist differently depending on dispersal abilities of organisms. We tested two hypotheses that plant groups with different dispersal abilities display different floristic patterns, and that historical barriers can explain floristic differentiation patterns in plants with low dispersal ability but not in plants with higher dispersal ability, in the seed plant flora of the Ryukyu Archipelago. This area is biogeographically interesting because several similar floristic differentiation patterns have been proposed, all of which are primarily explained by two historical barriers, the Tokara Tectonic Strait (Tokara Gap) and the Kerama Gap, which arose during the formation of the islands. We calculated floristic dissimilarity distance among 26 islands based on data sets for three dispersal-ability classes. Clustering analyses based on the floristic dissimilarity distance generated similar floristic patterns regardless of dispersal-ability class. We propose that because the landscape resistance is so strong that migration of plants is severely restricted regardless of their dispersal abilities, the similar floristic differentiation patterns are generated. Multivariate regression analyses using Mantel’s randomization test indicated that floristic differentiations among islands were explained by the both effects of the historical barriers and geographic distance in all dispersal-ability classes. Significance of the historical barriers is not determined by the plant dispersal abilities but presumably by the spatial distribution of the islands, stochastic dispersals, and time since the formation of the barriers.
Faster sequence alignment through GPU-accelerated restriction of the seed-and-extend search space
Authors: Wilton Richard , Budavari Tamas , Langmead Ben , Wheelan Sarah , Salzberg Steven L. , Szalay Alex 
Published: August 2014

ABSTRACTMotivationIn computing pairwise alignments of biological sequences, software implementations employ a variety of heuristics that decrease the computational effort involved in computing potential alignments. A key element in achieving high processing throughput is to identify and prioritize potential alignments where high-scoring mappings can be expected. These tasks involve listprocessing operations that can be efficiently performed on GPU hardware.ResultsWe implemented a read aligner called A21 that exploits GPU-based parallel sort and reduction techniques to restrict the number of locations where potential alignments may be found. When compared with other high-throughput aligners, this approach finds more high-scoring mappings without sacrificing speed or accuracy. A21 running on a single GPU is about 10 times faster than comparable CPU-based tools; it is also faster and more sensitive in comparison with other recent GPU-based aligners.AvailabilityThe A21 software is open source and available athttps://github.com/RWilton/A21.Contactrwilton@pha.jhu.eduSupplementary informationSupplementary results are available at <<<TBD>>>
Winter food limits timing of pre‐alternate moult in a short‐distance migratory bird
Authors: Danner Raymond M. , Greenberg Russell S. , Danner Julie E. , Walters Jeffrey R. 
Published: August 2014

Summary

Moult is critical for fitness for many organisms for several reasons: it allows growth and maintains the function of the integument for protection, thermoregulation and communication.

Feather moult in birds is costly and therefore typically does not overlap with migration or reproduction. In spring, the rapid succession of pre‐alternate moult, migration (if a migrant) and breeding suggests that timing of moult could constrain the initiation of breeding. A trade‐off between time spent moulting and breeding might also limit moult quality.

The proximate basis for the timing of pre‐alternate moult initiation is not well known, although it typically occurs during a resource poor time of year. Food limitation combined with fitness consequences of moulting earlier suggests that plasticity in timing of pre‐alternate moult in response to food abundance should be advantageous.

We experimentally tested, for the first time, if food abundance influences the timing of moult in the wild. We conducted a controlled food supplementation experiment on free‐living swamp sparrows (Melospiza georgiana) preceding and during the time of natural pre‐alternate moult (January–March 2009, 2010).

Supplemented birds began moulting the body, face and crown earlier than control birds (11, 14, and 8 days earlier, respectively), indicating that food abundance limits the initiation of moult. Along with interannual variation, these results indicate that photoperiod is not the sole cue for initiation of moult.

Both control and supplemented birds moulted in sequence, starting with the body, followed by the crown 9 days later, and the face 11 days after the body. The presence of a sequence further suggests energetic limitation of moult or possibly a strategy to moult‐specific regions first to ensure completion or growth at an optimal time.

This study provides novel experimental evidence that food abundance can: (i) limit pre‐alternate moult timing and (ii) limit moult timing in the wild. Food limitation of moult timing could allow earlier breeding or production of higher quality feathers and thus cascade through other life‐history stages and affect reproductive success. These results indicate that food availability is a cue for moult initiation, possibly acting secondarily to photostimulation.