bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of Care and Preventive Screening Use in the CareFirst Patient-Centered Medical Home Program
Authors: Kicinger Iwona M. , Cuellar Alison , Helmchen Lorens A. , Gimm Gilbert , Want Jay , Kells Bradley J. , Nichols Len M. 
Published: January 2019

ABSTRACT
Despite their value, comprehensive diabetes care and screening for common cancers remain underutilized. We examined the association between participation in a patient-centered medical home (PCMH) program with strong financial incentives and receipt of preventive care in the first 5 years after program launch. Using multivariate regression analysis, we compared outcomes for adults under the care of participating primary care providers (PCPs) with adults under the care of nonparticipating PCPs. Outcomes were breast, cervical and colorectal cancer screenings, and elements of diabetes care. The analytic sample included 818,623 adults living in Maryland, Virginia, or the District of Columbia, and enrolled with CareFirst for at least 1 year during 2010–2015. By Year 5, enrollees in the intervention group were 7.9 (95% confidence interval [CI]: 2.8–13.0), 6.1 (95% CI: 1.4–10.7), 3.1 (95% CI: 2.1–4.0), and 7.6 (95% CI: 7.0–8.2) percentage points more likely to undergo HbA1c tests, nephropathy examinations, breast, and cervical cancer screenings, respectively. We found no significant change in the propensity to receive colorectal cancer screening or an eye examination. Our study shows that a PCMH program with strong financial incentives can raise the provision of preventive care but could require additional adjustment.
Alerting Wisely: Reducing Inappropriate Blood Chemistry Panel Orders Using a Clinical Decision Support Tool
Authors: Anderson Jonathan W. , Greenwood Mark R. , Borsato Gisele G. , Kuttler Kathryn G. 
Published: January 2019

ABSTRACT
The Choosing Wisely (CW) initiative provides recommendations for healthcare providers, aimed at reducing unnecessary or inappropriate tests and procedures. A clinical decision support (CDS) alert in the electronic health record was developed to reflect organizational CW guidelines regarding blood chemistry panel ordering in the primary care setting. An interrupted time series design was used to analyze the weekly proportion of inappropriate blood chemistry panel orders prior to and after implementation of the CDS alert in treatment and control groups. Implementation of the CDS alert significantly decreased the average weekly proportion of inappropriate blood chemistry panels from 28.64% to 15.69% in the treatment group (p < .001). Apart from other efforts implemented simultaneously to reduce inappropriate lab ordering, the CDS alert produced a significant reduction in inappropriate lab ordering. We conclude that CDS alerts can be an effective strategy for healthcare organizations seeking to more closely adhere to CW guidelines.
Triage of Mild Head-Injured Intoxicated Patients Could Be Aided by Use of an Electroencephalogram-Based Biomarker
Authors: Michelson Edward , Huff J. Stephen , Garrett John , Naunheim Rosanne 
Published: January 2019

ABSTRACT

Objective: Drug and alcohol (DA)–related emergency department (ED) visits represent an increasing fraction the head-injured population seen in the ED. Such patients present a challenge to the evaluation of head injury and determination of need for computed tomographic (CT) scan and further clinical path. This effort examined whether an electroencephalogram (EEG)-based biomarker could aid in reducing unnecessary CT scans in the intoxicated ED population. Method: This is a retrospective secondary study of an independent prospective US Food and Drug Administration validation trial that demonstrated the efficacy of (1) an automatic Structural Injury Classifier for the likelihood of injury visible on a CT (CT+) and (2) an EEG-based Brain Function Index to assess functional impairment in minimally impaired, head-injured adults presenting within 3 days of injury. Impact on the biomarker performance in patients who presented with or without DA was studied. Results: Structural Injury Classifier sensitivity was not significantly impacted by the presence of DA. Although specificity decreased, it remained several times higher than obtained using standard CT decision rules. Furthermore, the potential to reduce the number of unnecessary scans by approximately 30% was demonstrated when the Structural Injury Classifier was integrated into CT clinical triage. The Brain Function Index was demonstrated to be independent of the presence of DA. Conclusion: This EEG-based assessment technology used to identify the likelihood of structural or functional brain injury in mildly head-injured patients represents an objective way to aid in triage patients with DA on presentation, with the potential to decrease overscanning while not sacrificing sensitivity to injuries visible on CT.
Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome Is Associated With Dysregulation of IL-7/IL-7 Receptor Signaling Pathway in T Cells and Monocyte Activation
Authors: Akilimali Ngomu Akeem , Muema Daniel M. , Specht Charles , Chang Christina C. , Moosa Mahomed-Yunus S. , Levitz Stuart M. , Lewin Sharon R. , French Martyn A. , Ndung'u Thumbi 
Published: January 2019

Background:
Systemic levels of interleukin (IL)-7 at antiretroviral therapy (ART) initiation have previously been shown to be predictive of HIV-linked paradoxical cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS). We therefore explored IL-7/IL-7 receptor (IL-7/IL-7R) signaling pathway dysfunction, with related alterations in immune function, as a mechanism underlying C-IRIS.

Method:
HIV-infected patients with cryptococcal meningitis who experienced C-IRIS (n = 27) were compared with CD4+ T-cell count-matched counterparts without C-IRIS (n = 27), after antifungal therapy and pre-ART initiation. Flow cytometry was used to assess T-cell and monocyte phenotypes and functions.

Results:
Proportions of IL-7R+ CD4+ or CD8+ T cells correlated positively with CD4+ T-cell counts and proportions of central memory and naive CD4+ and CD8+ T-cell pre-ART (all r > 0.50 and P < 0.05); however, the former negatively correlated with CD4+ T-cell counts fold-increase on ART in non–C-IRIS but not C-IRIS patients. Higher frequencies of activated monocytes (CD14+CD86+ or CD14+HLA-DR+; P ≤ 0.038) were also observed in C-IRIS compared with non–C-IRIS patients, and those who failed to clear cryptococci from cerebrospinal fluid before ART had higher levels of activated monocytes (CD14+HLA-DR+, P = 0.017) compared with those who cleared. In multivariate regression, CD14+HLA-DR+ monocytes were independently associated with C-IRIS [hazard ratio = 1.055 (1.013–1.098); P = 0.009].

Conclusion:
In contrast to non–C-IRIS patients, C-IRIS patients displayed a lack of association between proportions of IL-7R+ T cells and several markers of T-cell homeostasis. They also exhibited higher monocyte activation linked to cerebrospinal fluid cryptococcal culture positivity before ART. These data suggest a role for IL-7/IL-7R signaling pathway dysregulation in the pathogenesis of C-IRIS, possibly linked to monocyte activation and residual pathogen burden before ART.
Validation of the American College of Surgeons National Surgical Quality Improvement Program Risk Model for Patients Undergoing Panniculectomy
Authors: Suresh Visakha , Levites Heather , Peskoe Sarah , Hein Rachel , Avashia Yash , Erdmann Detlev 
Published: January 2019

Purpose
Panniculectomy procedures have been reported to significantly improve quality of life, increase mobility, and improve hygiene in patients with a significant pannus formation. The primary aims of this study were to determine which preoperative risk factors may be used to differentiate postoperative complication rate among patient cohorts and to validate utilization of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) risk calculator in patients undergoing panniculectomies.

Methods
This retrospective study included all patients who underwent a panniculectomy procedure at our institution from 2005 to 2016. Baseline characteristics, preoperative risk factors, medical comorbidities, and postoperative complications were collected via retrospective chart review.

Results
Two hundred sixty-four patients who underwent a panniculectomy were identified. The odds ratios of any postoperative complication were 8.26, 7.76, and 16.6 for patients with classes 1, 2, and 3 obesity, respectively (P < 0.05). Statistical modeling was utilized to evaluate the predictive performance of the ACS-NSQIP Surgical Risk Calculator. We calculated the C-statistic for the ACS-NSQIP model to be only 0.61, indicating that although the model is associated with the risk of complication, it does not have a strong predictive value for this particular procedure.

Discussion
This study is one of the first to characterize postoperative complication rate based on extremum of body mass index for panniculectomy patients. Our results show that the utilization of the ACS-NSQIP Risk Calculator in this particular patient population underestimates the complication risk as a whole, which may necessitate the future development of a separate risk assessment model for this procedure.
Improving the Reliability of V-Wave Responses in the Soleus Muscle
Authors: Mendonca Goncalo V. , Teodósio Carolina , Mouro Miguel , Freitas Sandro , Mil-Homens Pedro , Pezarat-Correia Pedro , Vila-Chã Carolina 
Published: January 2019

Purpose:
The V wave is an electrophysiologic variant of the H reflex that is evoked with supramaximal stimulus intensity. In this study, we explored whether the between-day reliability of V-wave normalized amplitude varies as a function of the number of intrasession measurement trials. We also determined whether the reliability of the V wave improves after the exclusion of the initial testing trials.

Methods:
Eighteen healthy, young participants (10 men and 8 women) were included in this study. Test–retest reliability was assessed using intraclass correlation coefficients and the standard error of the measurement (1.96*SEM).

Results:
The intraclass correlation coefficient values of the V-wave normalized amplitude increased in a progressive fashion with the inclusion of more than two measurement trials (from 0.41 to 0.75). The 1.96*SEM scores also decreased from 12.47% to 7.60% after calculating the V-wave normalized amplitude from five versus two measurement trials. After excluding the first two trials from V-wave calculations, the intraclass correlation coefficient and the 1.96*SEM score attained values of 0.88 and 6.54%, respectively.

Conclusions:
Our findings indicate that the test–retest reliability of the V-wave response increases in a progressive fashion with more than two intrasession measurement trials (up to five trials). It also shows that to ensure maximal reliability, the first two measurement trials should be discarded from V-wave computations.
Enhancing breakpoint resolution with deep segmentation model: a general refinement method for read-depth based structural variant callers
Authors: Zhang Yao-zhong , Imoto Seiya , Miyano Satoru , Yamaguchi Rui 
Published: January 2019

AbstractMotivationFor short-read sequencing, read-depth based structural variant (SV) callers are difficult to find single-nucleotide-resolution breakpoints due to the bin-size limitation.ResultsIn this paper, we present RDBKE to enhance the breakpoint resolution of read-depth SV callers using deep segmentation model UNet. We show that UNet can be trained with a small amount of data and applied for breakpoint enhancement both in-sample and cross-sample. On both simulation and real data, RDBKE significantly increases the number of SVs with more precise breakpoints.Availabilitysource code of RDBKE is available athttps://github.com/yaozhong/deepIntraSVContactyaozhong@ims.u-tokyo.ac.jp
Calcium/calmodulin-dependent protein kinase II regulates mammalian axon growth by affecting F-actin length in growth cone
Authors: Xi Feng , Xu Ren-Jie , Xu Jin-Hui , Wang Wei-Hua , Ma Jin-Jin , Wang Feng , Ma Yan-Xia , Qi Shi-Bin , Zhang Jing-Cheng , Zhang Hao-Nan , Qin Xu-Zhen , Chen Jian-Quan , Li Bin , Liu Chang-Mei , Yang Hui-Lin , Meng Bin , Saijilafu  
Published: January 2019

AbstractWhile axon regeneration is a key determinant of functional recovery of the nervous system after injury, it is often poor in the mature nervous system. Influx of extracellular calcium (Ca2+) is one of the first phenomena that occur following axonal injury, and calcium/calmodulin-dependent protein kinase (CaMKII), a target protein for calcium ions, regulates the status of cytoskeletal proteins such as F-actin. Herein, we found that peripheral axotomy activates CaMKII in dorsal root ganglion (DRG) sensory neurons, and inhibition of CaMKII impairs axon growth in both the peripheral and central nervous systems (PNS and CNS, respectively). Most importantly, we also found that activation of CaMKII promotes PNS and CNS axon growth, and regulatory effects of CaMKII on axon growth occur via affecting the length of the F-actin. Thus, we believe our findings provide clear evidence that CaMKII is a critical modulator of mammalian axon regeneration.
PBMC Treatment Significantly Changes Gene Expression Regulation in Horses
Authors: Mason Victor C. , Leeb Tosso , Gerber Vinzenz 
Published: January 2019

AbstractExpression quantitative trait loci (eQTLs) are context dependent, and therefore change between tissues, cell types, and after cell treatment. In addition, SNP positions and RNAseq counts must be updated after assembly of new reference genome sequences. Therefore, we remapped eQTLs with Matrix eQTL using the previously generated and publicly available data from four contexts of peripheral blood mononuclear cells (PBMCs) from European Warmblood horses to the EquCab3.0 reference genome, and used a linear mixed model in R to identify eQTLs with significantly different gene expression regulation in treated PBMCs when compared to no treatment (baseline). We found no evidence that SNPs associated with significant changes in gene expression between MCK and a treatment in PBMCs caused strong opposing regulatory effects. We identified canonical pathways with a significant number of genes in PBMCs with altered gene expression regulation when treated with lipopolysaccharides (LPS) and hay-dust extract (HDE). Significant pathways included RhoA signaling in LPS, as well as histamine degradation, cholesterol biosynthesis, FcγRIIB signaling, and others in HDE. Our results support previous research indicating that pathways altered between baseline and treatment of PBMCs in horses with LPS or HDE affect inflammatory responses through RhoA, B-cell signaling, IL-4 and IFN-γ, and histamine.
Local adaptation and hybrid failure share a common genetic basis
Authors: Walter Greg M. , Aguirre J. David , Wilkinson Melanie J , Richards Thomas J. , Blows Mark W. , Ortiz-Barrientos Daniel 
Published: January 2019

AbstractTesting whether local adaptation and intrinsic reproductive isolation share a genetic basis can reveal important connections between adaptation and speciation. Local adaptation arises as advantageous alleles spread through a population, but whether these same advantageous alleles fail on the genetic backgrounds of other populations remains largely unknown. We used a quantitative genetic breeding design to produce a late generation (F4) recombinant hybrid population by equally mating amongst four contrasting ecotypes of a native Australian daisy for four generations. We tracked fitness across generations and measured morphological traits in the glasshouse, and used a reciprocal transplant to quantify fitness in all four parental habitats. In the glasshouse, plants in the second generation showed a reduction in fitness as a loss of fertility, but this was fully recovered in the following generation. The F4 hybrid lacked extreme phenotypes present in the parental ecotypes, suggesting that genes reducing hybrid fitness were linked to traits specific to each ecotype. In the natural habitats, additive genetic variance for fitness was greatest for habitats that showed stronger native-ecotype advantage, suggesting that a loss of genetic variation present in the parental ecotypes were adaptive in the natural habitats. Reductions in genetic variance for fitness were associated with a loss of ecological trade-offs previously described in the parental ecotypes. Furthermore, natural selection on morphological traits differed amongst the parental habitats, but was not predicted to occur towards the morphology of the parental ecotypes. Together, these results suggest that intrinsic reproductive isolation removed adaptive genetic variation present in the parental ecotypes. The evolution of these distinct ecotypes was likely governed by genetic variation that resulted in both ecological trade-offs and intrinsic reproductive isolation among populations adapted to contrasting environments.
YAMB: metagenome binning using nonlinear dimensionality reduction and density-based clustering
Authors: Korzhenkov Aleksei 
Published: January 2019

AbstractSummaryYAMB is a novel metagenome binning tool, which uses tetranucletotide composition and average contig coverage and performs t-SNE dimensionality reduction and sequential DBSCAN data clusterization. YAMB provided with metagenomics assembly and reads may be used for straightforward metagenome binning on a recent personal computer running Linux OS.Availability and ImplementationSource code of YAMB is freely available on GitHub (https://github.com/laxeye/YAMB), implemented in R, Perl and Bash and supported on Linux.ContactKorzhenkov_AA@nrcki.ru
Shedding light on biogas: a transparent reactor triggers the development of a biofilm dominated by Rhodopseudomonas faecalis that holds potential for improved biogas production
Authors: Abendroth Christian , Latorre- Pérez Adriel , Porcar Manuel , Simeonov Claudia , Luschnig Olaf , Vilanova Cristina , Pascual Javier 
Published: January 2019

AbstractConventional anaerobic digesters intended for the production of biogas usually operate in complete darkness. Therefore, little is known about the effect of light on microbial communities operating in anaerobic digesters. In the present work, we have studied through 16S rRNA gene amplicon Nanopore sequencing and shotgun metagenomic sequencing the taxonomic and functional structure of the microbial community forming a biofilm on the inner wall of a lab-scale transparent anaerobic biodigester illuminated with natural sunlight. The biofilm was composed of microorganisms involved in the four metabolic processes needed for biogas production. The biofilm proved surprisingly rich in Rhodopseudomonas faecalis, a versatile bacterium able to carry out a photoautotroph metabolism when grown under anaerobic conditions. Our results suggest that this bacterium, able to fix carbon dioxide, could be considered for its use in transparent biogas fermenters in order to contribute to the production of optimized biogas with a higher CH4:CO2 ratio than the biogas produced in regular, opaque digesters. To the best of our knowledge, this is the first study supporting illuminated bioreactors as a new bioprocess for the obtention of biogas enriched in methane.
scruff: An R/Bioconductor package for preprocessing single-cell RNA-sequencing data
Authors: Wang Zhe , Hu Junming , Johnson Evan W. , Campbell Joshua D. 
Published: January 2019

AbstractBackgroundSingle-cell RNA sequencing (scRNA-seq) enables the high-throughput quantification of transcriptional profiles in single cells. In contrast to bulk RNA-seq, additional preprocessing steps such as cell barcode identification or unique molecular identifier (UMI) deconvolution are necessary for preprocessing of data from single cell protocols. R packages that can easily preprocess data and rapidly visualize quality metrics and read alignments for individual cells across multiple samples or runs are still lacking.ResultsHere we present scruff, an R/Bioconductor package that preprocesses data generated from the CEL-Seq or CEL-Seq2 protocols and reports comprehensive data quality metrics and visualizations. scruff demultiplexes, aligns, and counts the reads mapped to genome features with deduplication of unique molecular identifier (UMI) tags. scruff also provides novel and extensive functions to visualize both pre- and post-alignment data quality metrics for cells from multiple experiments. Detailed read alignments with corresponding UMI information can be visualized at specific genome coordinates to display differences in isoform usage. The package also supports the visualization of quality metrics for sequence alignment files for multiple experiments generated by Cell Ranger from 10X Genomics. scruff is available as a free and open-source R/Bioconductor package.Conclusionsscruff streamlines the preprocessing of scRNA-seq data in a few simple R commands. It performs data demultiplexing, alignment, counting, quality report and visualization systematically and comprehensively, ensuring reproducible and reliable analysis of scRNA-seq data.
Parallel signaling through IRE1α and PERK regulates pancreatic neuroendocrine tumor growth and survival
Authors: Moore Paul C. , Qi Jenny Y. , Thamsen Maike , Ghosh Rajarshi , Peng Justin , Gliedt Micah J. , Meza-Acevedo Rosa , Warren Rachel E. , Hiniker Annie , Kim Grace E. , Maly Dustin J. , Backes Bradley J. , Papa Feroz R. , Oakes Scott A. 
Published: January 2019

AbstractMaster regulators of the unfolded protein response (UPR)—IRE1α and PERK— promote adaptation or apoptosis depending on levels of endoplasmic reticulum (ER) stress. While the UPR is activated in many cancers, its effects on tumor growth remain unclear. Derived from endocrine cells, pancreatic neuroendocrine tumors (PanNETs) universally hypersecrete one or more peptide hormones, likely sensitizing these cells to high ER protein-folding stress. For the nearly 1,500 Americans diagnosed with PanNETs annually, surgery is the only potentially curative treatment; however the five-year survival is extremely low for those who develop metastatic disease. To assess whether targeting the UPR is a viable therapeutic strategy, we analyzed human PanNET samples and found evidence of elevated ER stress and UPR activation. We then used genetic and pharmacologic approaches to modulate IRE1α and PERK in cultured cells and xenograft and spontaneous genetic (RIP-Tag2) mouse models of PanNETs. We found that UPR signaling is optimized for adaptation and that inhibiting either IRE1α or PERK leads to hyperactivation and apoptotic signaling through the reciprocal arm, thereby halting tumor growth and survival. Our results provide a strong rationale for therapeutically targeting the UPR in PanNETs and other cancers experiencing elevated ER stress.SignificanceThe unfolded protein response (UPR) is upregulated in human pancreatic neuroendocrine tumors and its genetic or pharmacological inhibition significantly reduces tumor growth in preclinical models, providing strong rationale for targeting the UPR in neoplasms with elevated ER stress.