bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of Early Warming With Self-Warming Blankets on Postoperative Hypothermia in Total Hip and Knee Arthroplasty
Authors: Koc Baris B. , Schotanus Martijn G. M. , Kollenburg Jean-Paul A. P. A. C. , Janssen Maurice J. A. , Tijssen Fabian , Jansen Edwin J. P. 
Published: September 2017

BACKGROUND:
Hypothermia is an important complication in joint arthroplasty. Commonly, forced air warming (FAW) devices are used intraoperatively to maintain body temperature in patients undergoing surgery. However, it is believed that these convective warming systems could increase the risk of deep surgical site infections due to disruption of unidirectional downward laminar airflow. Conductive warming devices have no noticeable effect on ventilation airflow. Nevertheless, the effectiveness of the self-warming (SW) blanket, a novel conductive warming device, on postoperative hypothermia in elective joint arthroplasty is unknown.

PURPOSE:
The purpose of this study was to evaluate the effectiveness of early warming with SW blankets in the prevention of postoperative hypothermia in elective total hip (THA) and knee arthroplasty (TKA) compared with FAW devices.

METHODS:
Patients who underwent elective THA or TKA between May and June 2014 were assigned in the FAW or SW group. A total of 105 patients were enrolled into the study. In the FAW group, the FAW devices were applied after disinfection of the surgical site. In the SW group, the SW blankets were already applied in the orthopaedic department. The duration of warming with SW blankets before anesthetic induction was documented. The body temperature was measured preoperatively upon arrival in the orthopaedic department and postoperatively upon arrival in the postanesthesia care unit. The patient's body temperature was measured at the tympanic membrane, and hypothermia was defined as a body temperature of less than 35.5°C.

RESULTS:
The SW blankets were applied for a median of 86.8 minutes (78.8–94.8) before anesthetic induction. Postoperative hypothermia was observed in 15 (31.3%) and eight (14.0%) patients in the FAW group and the SW group, respectively (p = .029). The median postoperative body temperature was 35.59°C (35.44–35.74) and 35.95°C (35.83–36.06) in the FAW group and the SW group, respectively (p < .001).

CONCLUSION:
Early warming with SW blankets was more effective than FAW devices in the prevention of postoperative hypothermia in elective THA and TKA.
Variability in Usual Care Mechanical Ventilation for Pediatric Acute Respiratory Distress Syndrome: Time for a Decision Support Protocol?*
Authors: Newth Christopher J. L. , Sward Katherine A. , Khemani Robinder G. , Page Kent , Meert Kathleen L. , Carcillo Joseph A. , Shanley Thomas P. , Moler Frank W. , Pollack Murray M. , Dalton Heidi J. , Wessel David L. , Berger John T. , Berg Robert A. , Harrison Rick E. , Holubkov Richard , Doctor Allan , Dean J. Michael , Jenkins Tammara L. , Nicholson Carol E. 
Published: September 2017

Objectives:
Although pediatric intensivists philosophically embrace lung protective ventilation for acute lung injury and acute respiratory distress syndrome, we hypothesized that ventilator management varies. We assessed ventilator management by evaluating changes to ventilator settings in response to blood gases, pulse oximetry, or end-tidal Co
2. We also assessed the potential impact that a pediatric mechanical ventilation protocol adapted from National Heart Lung and Blood Institute acute respiratory distress syndrome network protocols could have on reducing variability by comparing actual changes in ventilator settings to those recommended by the protocol.

Design:
Prospective observational study.

Setting:
Eight tertiary care U.S. PICUs, October 2011 to April 2012.

Patients:
One hundred twenty patients (age range 17 d to 18 yr) with acute lung injury/acute respiratory distress syndrome.

Measurements and Main Results:
Two thousand hundred arterial and capillary blood gases, 3,964 oxygen saturation by pulse oximetry, and 2,757 end-tidal Co
2 values were associated with 3,983 ventilator settings. Ventilation mode at study onset was pressure control 60%, volume control 19%, pressure-regulated volume control 18%, and high-frequency oscillatory ventilation 3%. Clinicians changed Fio
2 by ±5 or ±10% increments every 8 hours. Positive end-expiratory pressure was limited at ~10 cm H2O as oxygenation worsened, lower than would have been recommended by the protocol. In the first 72 hours of mechanical ventilation, maximum tidal volume/kg using predicted versus actual body weight was 10.3 (8.5–12.9) (median [interquartile range]) versus 9.2 mL/kg (7.6–12.0) (p < 0.001). Intensivists made changes similar to protocol recommendations 29% of the time, opposite to the protocol’s recommendation 12% of the time and no changes 56% of the time.

Conclusions:
Ventilator management varies substantially in children with acute respiratory distress syndrome. Opportunities exist to minimize variability and potentially injurious ventilator settings by using a pediatric mechanical ventilation protocol offering adequately explicit instructions for given clinical situations. An accepted protocol could also reduce confounding by mechanical ventilation management in a clinical trial.
Temporal Changes in Prescription of Neuropharmacologic Drugs and Utilization of Resources Related to Neurologic Morbidity in Mechanically Ventilated Children With Bronchiolitis*
Authors: Shein Steven L. , Slain Katherine , Wilson-Costello Deanne , McKee Bryan , Rotta Alexandre T. 
Published: September 2017

Objectives:
Critically ill children with bronchiolitis may require neuropharmacologic medications and support for neuro-functional sequelae, but current practices are not well described. We aimed to describe recent trends in neuropharmacology and utilization of neuro-rehabilitation resources in mechanically ventilated children with bronchiolitis.

Design:
Analysis of the multicenter Pediatric Health Information System database.

Setting:
Forty-seven U.S. children’s hospitals.

Patients:
PICU patients less than 2 years old with bronchiolitis undergoing mechanical ventilation between 2006 and 2015.

Interventions:
None. Annual rates of utilization of neuropharmacologic medications (sedatives, analgesics, etc) and of neuro-rehabilitation services (physical therapy, neurologic consultation, etc) over the 10-year study period were compared.

Measurements and Main Results:
Neuropharmacologic medications prescribed on greater than or equal to 2 days were extracted. Utilization of MRI of the brain, neurologic consultation, swallow evaluation, occupational therapy, and physical therapy was also extracted. Among 12,508 subjects, the median age was 2.8 months, ~50% had comorbid conditions, and the median duration of mechanical ventilation was 7 days. The percentage of children prescribed greater than or equal to five drugs/drug classes increased over the study period from 36.5% to 55.8% (p < 0.001). There were significant increases over time in utilization of 10 of the 15 individual drugs/drug classes analyzed. More than half of subjects (6,294 [50.3%]) received at least one service that evaluates/treats neurologic morbidity. There were significant increases in the use of greater than or equal to one service (36.3% in 2006 to 59.6% in 2015; p < 0.001) and in the use of greater than or equal to two services (20.8% to 34.8%; p < 0.001). Utilization of each of the five individual resources increased significantly during the study period, but use of vasoactive medications and mortality did not.

Conclusions:
Prescription of neuropharmacologic agents increased over time using metrics of both overall drug burden and specific drug usage. Concurrently, the utilization of services that evaluate and/or treat neurologic morbidity was common and also increased over time.
A Systematic Review and Meta-analysis of Efficacy and Safety of Novel Interleukin Inhibitors in the Management of Psoriatic Arthritis
Authors: Bilal Jawad , Riaz Irbaz Bin , Kamal Muhammad Umar , Elyan Mazen , Sudano Dominick , Khan Muhammad Asim 
Published: September 2017

Objective
The aim of this study was to systemically review the efficacy and safety of inhibitors of interleukin 6 (IL-6): clazakizumab, IL-12/23: ustekinumab, and IL-17A: secukinumab, brodalumab, and ixekizumab in psoriatic arthritis (PsA).

Methods
The literature search was conducted using MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science. We included randomized controlled trials that assessed the efficacy of IL inhibitors and reported American College of Rheumatology 20 response at 24 weeks. Meta-analysis was done using random-effects model utilizing the DerSimonian and Laird method. Quality assessment was done using RobotReviewer Cochrane Risk-of-Bias Assessment Tool. Heterogeneity was assessed with Q statistic and quantified with I
2. Publication bias was assessed with a funnel plot.

Results
Eight studies including 2722 subjects demonstrate the efficacy of IL inhibitors clazakizumab, secukinumab, ixekizumab, brodalumab, and ustekinumab in the treatment of PsA. The American College of Rheumatology 20/50/70 risk ratios were 2.02 (95% confidence interval [CI], 1.65–2.47; P = 0.000), 2.95 (95% CI, 2.32–3.73; P = 0.00), and 5.14 (95% CI, 3.28–8.06; P = 0.00), respectively, in favor of treatment versus placebo. There was no evidence of significant heterogeneity between trials. Subgroup analysis showed efficacy in patients who were tumor necrosis factor naive, as well as tumor necrosis factor nonresponders or inadequate responders. The number of adverse events was higher in the treatment groups versus placebo, the majority were mild and did not require treatment adjustment (risk ratio, 1.17; 95% CI, 1.06–1.28; P = 0.001). There was no significant difference in drug withdrawals.

Conclusions
Our meta-analysis shows that the inhibitors of IL-6 (clazakizumab), IL-12/23 (ustekinumab), and IL-17A (secukinumab, brodalumab, ixekizumab) are efficacious and generally well tolerated when used to treat patients with PsA.
Role of Fat-Soluble Vitamins in Osteoarthritis Management
Authors: Zheng Xiao-yan , Liang Jun , Li Yu-sheng , Tu Min 
Published: September 2017

Abstract
Osteoarthritis (OA) is a chronic degenerative joint disease, in which metabolic imbalance in bone is observed. The pathological mechanism of metabolic imbalance is not clear yet, but the nutritional factors, particularly the vitamins, might be intrinsic to the development and progression of OA. In this review article, we have explored databases such as PubMed, Scopus, and Google Scholar articles until the beginning of 2017 and reviewed the role of fat-soluble vitamins in pathological and therapeutic aspects of OA. Vitamin D plays an important role in the development and maintenance of the skeleton, as well as bone and cartilage metabolism, and its deficiency is implicated in the pathological process of OA. Vitamin E enhances chondrocyte growth and exhibits an anti-inflammatory activity, as well as plays an important role in the prevention of cartilage degeneration. In human OA cartilage, vitamin K deficiency produces abnormal growth plate calcification and inappropriate mineralization of cartilage. Thus, these fat-soluble vitamins play a key role in the pathophysiology of OA, and supplementation of these vitamins may provide innovative approaches for OA management. However, vitamin A has a different role, which is a regulator of cartilage and skeletal formation. When metabolite levels of vitamin A are elevated in synovial fluid, they appear to drive OA development. The role of inhibitors of vitamin A here remains unclear. More investigations are needed to examine the effects of fat-soluble vitamins on the various molecular pathways of OA, as well as to assess the efficacy and safety of their usage clinically.
Two diseases, same person: moving towards a combined HIV and TB continuum of care
Authors: Granich Reuben , Gupta Somya 
Published: September 2017

SummarySettingThe Human Immunodeficiency Virus (HIV) andMycobacterium tuberculosissyndemic remains a global public health threat. Separate HIV and TB global targets have been set, however, success will depend on achieving combined disease control objectives and care continua.ObjectiveReview available policy, budgets and data to re-conceptualize TB and HIV disease control objectives by combining HIV and TB care continua.MethodsFor 22 WHO TB and TB/HIV priority countries, we used 2014 and 2015 data from the HIV90-90-90watch website, UNAIDS Aidsinfo, and WHO 2016 Global TB Report. Global resources available in TB and HIV/TB activities for 2003-2017 was collected from publically available sources.ResultsIn 22 high burden countries people living with HIV (PLHIV) on ART ranged from 9-70%; viral suppression was 38-63%. TB treatment success ranged from 34-94% with 13 (43% HIV/TB burden) countries above 80% TB treatment success. From 2003-2017, global international and domestic resources for HIV-associated TB and TB averaged $2.6 billion per year; the total for 2003-2017 was 39 billion dollars.ConclusionReviewingcombined HIV and TB targets demonstrate disease control progress and challenges. Using an integrated HIV and TB continuum supports HIV and TB disease control efforts focused on improving both individual and public health.FundingNone
Sociodemographic patterning in the oral microbiome of a diverse sample of New Yorkers
Authors: Renson Audrey , Jones Heidi E. , Beghini Francesco , Segata Nicola , Zolnik Christine P. , Usyk Mykhaylo , Moody Thomas U. , Thorpe Lorna , Burk Robert , Waldron Levi , Dowd Jennifer B. 
Published: September 2017

1Abstract1.1PurposeVariations in the oral microbiome are potentially implicated in social inequalities in oral disease, cancers, and metabolic disease. We describe sociodemographic variation of oral microbiomes in a diverse sample.1.2MethodsWe performed 16S rRNA sequencing on mouthwash specimens in a subsample (n=282) of the 2013-14 population-based New York City Health and Nutrition Examination Study (NYC-HANES). We examined differential abundance of 216 operational taxonomic units (OTUs), and alpha and beta diversity by age, sex, income, education, nativity, and race/ethnicity. For comparison, we also examined differential abundance by diet, smoking status, and oral health behaviors.1.3Results69 OTUs were differentially abundant by any sociodemographic variable (false discovery rate < 0.01), including 27 by race/ethnicity, 21 by family income, 19 by education, three by sex. We also found 49 differentially abundant by smoking status, 23 by diet, 12 by oral health behaviors. Genera differing for multiple sociodemographic characteristics includedLactobacillus,Prevotella,Porphyromonas,Fusobacterium.1.4ConclusionsWe identified oral microbiome variation consistent with health inequalities, with more taxa differing by race/ethnicity than diet, and more by SES variables than oral health behaviors. Investigation is warranted into possible mediating effects of the oral microbiome in social disparities in oral, metabolic and cancers.HighlightsMost microbiome studies to date have had minimal sociodemographic variability, limiting what is known about associations of social factors and the microbiome.We examined the oral microbiome in a population-based sample of New Yorkers with wide sociodemographic variation.Numerous taxa were differentially abundant by race/ethnicity, income, education, marital status, and nativity.Frequently differentially abundant taxa includePorphyromonas,Fusobacterium,Streptococcus, andPrevotella, which are associated with oral and systemic disease.Mediation of health disparities by microbial factors may represent an important intervention site to reduce health disparities, and should be explored in prospective studies.
Pervasive contingency and entrenchment in a billion years of Hsp90 evolution
Authors: Starr Tyler N. , Flynn Julia M. , Mishra Parul , Bolon Daniel N. A. , Thornton Joseph W. 
Published: September 2017

AbstractInteractions among mutations within a protein have the potential to make molecular evolution contingent and irreversible, but the extent to which epistasis actually shaped historical evolutionary trajectories is unclear. We addressed this question by identifying all amino acid substitutions that occurred during the billion-year evolutionary history of the heat shock protein 90 (Hsp90) ATPase domain beginning from a deep eukaryotic ancestor to modernSaccharomyces cerevisiaeand then precisely measuring their fitness effects when introduced into both extant and reconstructed ancestral Hsp90 proteins. We find a pervasive influence of epistasis: of 98 derived states that evolved during history, most were deleterious at times before they happened, and the vast majority also became subsequently entrenched, with the ancestral state becoming deleterious after its substitution. This epistasis was primarily caused by specific interactions among sites rather than a general permissive or restrictive effect on the protein’s tolerance to mutation. Our results show that epistasis continually opens and closes windows of mutational opportunity over evolutionary timescales, producing histories and biological states that reflect the transient internal constraints imposed by a protein’s fleeting sequence states.Significance statementWhen mutations within a protein change each other’s functional effects—a phenomenon called epistasis—the trajectories available to evolution at any moment in time depend on the specific set of changes that previously occurred in the protein. The extent to which epistasis has shaped historical evolutionary trajectories is unknown. Using a high-precision bulk fitness assay and ancestral protein reconstruction, we measured the fitness effects in ancestral and extant sequences of all historical substitutions that occurred during the billion-year trajectory of an essential protein. We found that most historical substitutions were contingent on prior epistatic substitutions and/or entrenched by subsequent changes. These results establish that epistasis caused widespread, consequential shifts in the site-specific fitness constraints that shaped the protein’s historical trajectory.
A closer look at cross-validation for assessing the accuracy of gene regulatory networks and models
Authors: Tabe-Bordbar Shayan , Emad Amin , Zhao Sihai Dave , Sinha Saurabh 
Published: September 2017

AbstractCross-validation (CV) is a technique to assess the generalizability of a model to unseen data. This technique relies on assumptions that may not be satisfied when studying genomics datasets. For example, random CV (RCV) assumes that a randomly selected set of samples, the test set, well represents unseen data. This assumption does not hold true where samples are obtained from different experimental conditions, and the goal is to learn regulatory relationships among the genes that generalize beyond the observed conditions. In this study, we investigated how the CV procedure affects the assessment of methods used to learn gene regulatory networks. We compared the performance of a regression-based method for gene expression prediction, estimated using RCV with that estimated using a clustering-based CV (CCV) procedure. Our analysis illustrates that RCV can produce over-optimistic estimates of generalizability of the model compared to CCV. Next, we defined the ‘distinctness’ of a test set from a training set and showed that this measure is predictive of the performance of the regression method. Finally, we introduced a simulated annealing method to construct partitions with gradually increasing distinctness and showed that performance of different gene expression prediction methods can be better evaluated using this method.
Gene-level differential analysis at transcript-level resolution
Authors: Yi Lynn , Pimentel Harold , Bray Nicolas L. , Pachter Lior 
Published: September 2017

AbstractGene-level differential expression analysis based on RNA-Seq is more robust, powerful and biologically actionable than transcript-level differential analysis. However aggregation of transcript counts prior to analysis results can mask transcript-level dynamics. We demonstrate that aggregating the results of transcript-level analysis allow for gene-level analysis with transcript-level resolution. We also show thatp-value aggregation methods, typically used for meta-analyses, greatly increase the sensitivity of gene-level differential analyses. Furthermore, such aggregation can be applied directly to transcript compatibility counts obtained during pseudoalignment, thereby allowing for rapid and accurate model-free differential testing. The methods are general, allowing for testing not only of genes but also of any groups of transcripts, and we showcase an example where we apply them to perturbation analysis of gene ontologies.
METHimpute: Imputation-guided construction of complete methylomes from WGBS data
Authors: Taudt Aaron , Roquis David , Vidalis Amaryllis , Wardenaar René , Johannes Frank , Colomé-Tatché Maria 
Published: September 2017

AbstractWhole-genome Bisulfite sequencing (WGBS) has become the standard method for interrogating plant methylomes at base resolution. However, deep WGBS measurements remain cost prohibitive for large, complex genomes and for population-level studies. As a result, most published plant methylomes are sequenced far below saturation, with a large proportion of cytosines having either missing data or insufficient coverage. Here we present METHimpute, a Hidden Markov Model (HMM) based imputation algorithm for the analysis of WGBS data. Unlike existing methods, METHimpute enables the construction of complete methylomes by inferring the methylation status and level of all cytosines in the genome regardless of coverage. Application of METHimpute to maize, rice and Arabidopsis shows that the algorithm infers cytosine-resolution methylomes with high accuracy from data as low as 6X, compared to data with 60X, thus making it a cost-effective solution for large-scale studies. Although METHimpute has been extensively tested in plants, it should be broadly applicable to other species.
An extensive enhancer-promoter map generated by genome-scale analysis of enhancer and gene activity patterns
Authors: Hait Tom Aharon , Amar David , Shamir Ron , Elkon Ran 
Published: September 2017

AbstractMassive efforts have documented hundreds of thousands of putative enhancers in the human genome. A pressing genomic challenge is to identify which of these enhancers are functional and map them to the genes they regulate. We developed a novel method for inferring enhancer-promoter (E-P) links based on correlated activity patterns across many samples. Our method, calledFOCS, uses rigorous statistical validation tailored for zero-inflated data, identifying the most important E-P links in each gene model. We applied FOCS to the wide epigenomic and transcriptomic datasets recorded by theENCODE,Roadmap EpigenomicsandFANTOM5projects, together covering 2,630 samples of human primary cells, tissues and cell lines. In addition, building on expression of enhancer RNAs (eRNAs) as an exquisite mark of enhancer activity and on the robust detection of eRNAs by the GRO-seq technique, we compiled a compendium of eRNA and gene expression profiles based on public GRO-seq data from 245 samples and 23 human cell types. Applying FOCS to this compendium further expanded the coverage of our inferred E-P map. Benchmarking against gold standard E-P links from ChIA-PET and eQTL data, we demonstrate that FOCS prediction of E-P links outperforms extant methods. Collectively, we inferred >300,000 cross-validated E-P links spanning~16K known genes. Our study presents an improved method for inferring regulatory links between enhancers and promoters, and provides an extensive resource of E-P maps that could greatly assist the functional interpretation of the noncoding regulatory genome. FOCS and our predicted E-P map are publicly available athttp://acgt.cs.tau.ac.il/focs.