bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Doubly Blended Model for Multiscale Atmospheric Dynamics
Authors: Klein Rupert , Benacchio Tommaso 
Published: January 2016

Abstract
The compressible flow equations for a moist, multicomponent fluid constitute the most comprehensive description of atmospheric dynamics used in meteorological practice. Yet, compressibility effects are often considered weak and acoustic waves outright unimportant in the atmosphere, except possibly for Lamb waves on very large scales. This has led to the development of “soundproof” models, which suppress sound waves entirely and provide good approximations for small-scale to mesoscale motions. Most global flow models are based instead on the hydrostatic primitive equations that only suppress vertically propagating acoustic modes and are applicable to relatively large-scale motions. Generalized models have been proposed that combine the advantages of the hydrostatic primitive and the soundproof equation sets. In this note, the authors reveal close relationships between the compressible, pseudoincompressible (soundproof), hydrostatic primitive, and the Arakawa and Konor unified model equations by introducing a continuous two-parameter (i.e., “doubly blended”) family of models that defaults to either of these limiting cases for particular parameter constellations.
Data Assimilation for Bathymetry Estimation at a Tidal Inlet
Authors: Moghimi S. , Özkan-Haller H. T. , Wilson G. W. , Kurapov A. 
Published: January 2016

AbstractThis study involved developing and testing a data assimilation framework that accommodates different types of geophysical ocean data (i.e., surface velocity and wave information) and provides an estimation of the bathymetry of a mixed-energy tidal inlet. This framework was successfully applied to a highly variable tidal environment using synthetic data (twin test). The synthetic data consisted of surface velocity components associated with the tidal circulation and wavenumber–frequency pairs of incoming surface gravity waves that mimic data that could be derived from an airborne synthetic aperture radar system and a tower-mounted X-band radar system, respectively. The present ensemble-based assimilation framework has previously been applied in both wave-dominated coastal and current-dominated riverine environments. In contrast, the inlet environment is neither wave nor current dominated. The assimilation of wave and current data together was most useful to obtain a skillful estimate of the spatial map of bathymetry.
Closing up and moving on: a personal perspective of psychiatric practice closure
Authors: Neill Diane 
Published: January 2016

Objectives: This paper sets out a process for the elective closure of a clinical practice. The details are described for a particular example of a practice closure. The common elements to all practice closures are identified. A range of other factors which may be relevant to other practice closure circumstances are also listed and the literature is referenced. Conclusions: The closure of a clinical practice is a major stage in professional life and merits preparation, support and accessible resources.
What is going on between defibrotide and endothelial cells? Snapshots reveal the hot spots of their romance
Authors: Palomo Marta , Mir Enrique , Rovira Montse , Escolar Ginés , Carreras Enric , Diaz-Ricart Maribel 
Published: January 2016

Key PointsSpecific interaction of DF with EC membranes is followed by its internalization mainly through macropinocytic mechanisms. DF attachment to the cell membrane is sufficient to perform its antiinflammatory and antioxidant effects on the endothelium.
Combining location-and-scale batch effect adjustment with data cleaning by latent factor adjustment
Authors: Hornung Roman , Boulesteix Anne-Laure , Causeur David 
Published: January 2016

Abstract
Background
In the context of high-throughput molecular data analysis it is common that the observations included in a dataset form distinct groups; for example, measured at different times, under different conditions or even in different labs. These groups are generally denoted as batches. Systematic differences between these batches not attributable to the biological signal of interest are denoted as batch effects. If ignored when conducting analyses on the combined data, batch effects can lead to distortions in the results. In this paper we present FAbatch, a general, model-based method for correcting for such batch effects in the case of an analysis involving a binary target variable. It is a combination of two commonly used approaches: location-and-scale adjustment and data cleaning by adjustment for distortions due to latent factors. We compare FAbatch extensively to the most commonly applied competitors on the basis of several performance metrics. FAbatch can also be used in the context of prediction modelling to eliminate batch effects from new test data. This important application is illustrated using real and simulated data. We implemented FAbatch and various other functionalities in the R package available online from CRAN.

Results
FAbatch is seen to be competitive in many cases and above average in others. In our analyses, the only cases where it failed to adequately preserve the biological signal were when there were extremely outlying batches and when the batch effects were very weak compared to the biological signal.

Conclusions
As seen in this paper batch effect structures found in real datasets are diverse. Current batch effect adjustment methods are often either too simplistic or make restrictive assumptions, which can be violated in real datasets. Due to the generality of its underlying model and its ability to perform well FAbatch represents a reliable tool for batch effect adjustment for most situations found in practice.
Biological impact of xeno-free chemically defined cryopreservation medium on amniotic epithelial cells
Authors: Miki Toshio , Wong Wisia , Zhou Elton , Gonzalez Anthony , Garcia Irving , Grubbs Brendan H. 
Published: January 2016

Abstract
Background
Amnion-derived stem cells have been proposed for cell replacement therapy and tissue regeneration. An easily accessible cell source, the placenta, allows us to potentially establish a bio-bank of cells for immunotype matched clinical applications. Several xeno-free (XF) cryopreservation media are currently available for pluripotent stem cells, however, these media have not yet been evaluated for the cryopreservation of amnion-derived stem cells.

Methods
Human amniotic epithelial cells were collected using standard protocols, and stored at −160 °C in one of five commercially available media. Cells frozen in standard media containing fetal bovine serum served as controls. Cells were then thawed, and evaluated for viability, mitochondrial membrane stability, and senescence status. Quantitative real time PCR was utilized to assess for expression of stem cell genes, and flow cytometry was used to identify the stem cell surface markers.

Results
Cell recovery and repopulation assays indicated no significant difference between XF media versus standard cryopreservation medium. In addition, no impact was observed on the senescence status, the cytostructural or mitochondrial morphology between the tested cryopreservation media. Differences were observed on the expression of stem cell marker genes (OCT4, SOX2, and NANOG) and a cell surface marker (TRA1-60) following cryopreservation in different chemically defined XF media, however, these were not statistically significant.

Conclusions
Xeno-free cryopreservation of human amnion-derived stem cells is feasible and can be standardized to establish a bio-bank with human amnion-derived stem cells for future clinical application. Optimization of this media may allow for improved preservation of stem cell-like characteristics.
Atezolizumab, an Anti–Programmed Death-Ligand 1 Antibody, in Metastatic Renal Cell Carcinoma: Long-Term Safety, Clinical Activity, and Immune Correlates From a Phase Ia Study
Authors: McDermott David F. , Sosman Jeffrey A. , Sznol Mario , Massard Christophe , Gordon Michael S. , Hamid Omid , Powderly John D. , Infante Jeffrey R. , Fassò Marcella , Wang Yan V. , Zou Wei , Hegde Priti S. , Fine Gregg D. , Powles Thomas 
Published: January 2016

Purpose The objective was to determine the safety and clinical activity of atezolizumab (MPDL3280A), a humanized programmed death-ligand 1 (PD-L1) antibody, in renal cell carcinoma (RCC). Exploratory biomarkers were analyzed and associated with outcomes. Patients and Methods Seventy patients with metastatic RCC, including clear cell (ccRCC; n = 63) and non–clear cell (ncc; n = 7) histologies, received atezolizumab intravenously every 3 weeks. PD-L1 expression was scored at four diagnostic levels (0/1/2/3) that were based on PD-L1 staining on tumor cells and tumor-infiltrating immune cells (IC) with the SP142 assay. Primary end points were safety and toxicity; secondary end points assessed clinical activity per Response Evaluation Criteria in Solid Tumors version 1.1 and immune-related response criteria. Plasma and tissue were analyzed for potential biomarkers of atezolizumab response. Results Grade 3 treatment-related and immune-mediated adverse events occurred in 17% and 4% of patients, respectively, and there were no grade 4 or 5 events. Sixty-three patients with ccRCC were evaluable for overall survival (median, 28.9 months; 95% CI, 20.0 months to not reached) and progression-free survival (median, 5.6 months; 95% CI, 3.9 to 8.2 months), and 62 patients were evaluable for objective response rate (ORR; 15%; 95% CI, 7% to 26%). ORR was evaluated on the basis of PD-L1 IC expression (IC1/2/3: n = 33; 18%; 95% CI, 7% to 35%; and IC0: n = 22; 9%; 95% CI, 1% to 29%). The ORR for patients with Fuhrman grade 4 and/or sarcomatoid histology was 22% (n = 18; 95% CI, 6% to 48%). Decreases in circulating plasma markers and acute-phase proteins and an increased baseline effector T-cell–to–regulatory T-cell gene expression ratio correlated with response to atezolizumab. Conclusion Atezolizumab demonstrated a manageable safety profile and promising antitumor activity in patients with metastatic RCC. Correlative studies identified potential predictive and pharmacodynamic biomarkers. These results have guided ongoing studies and combinations with atezolizumab in RCC.
Histologic and Molecular Profile of Pediatric Insulinomas: Evidence of a Paternal Parent-of-Origin Effect
Authors: Bhatti Tricia R. , Ganapathy Karthik , Huppmann Alison R. , Conlin Laura , Boodhansingh Kara E. , MacMullen Courtney , Becker Susan , Ernst Linda M. , Adzick N. Scott , Ruchelli Eduardo D. , Ganguly Arupa , Stanley Charles A. 
Published: January 2016

Abstract

Context:
Acquired insulinomas are rare causes of hyperinsulinemic hypoglycemia in children and are much less common than focal lesions of congenital hyperinsulinism. The latter are known to be associated with isodisomy for paternally transmitted ATP-sensitive potassium channel mutations on 11p15; however, the molecular basis for pediatric insulinomas is not well characterized.

Objective:
The purpose of this study was to characterize the histopathological and molecular defects in a large group of 12 pediatric insulinomas seen at The Children's Hospital of Philadelphia.

Results:
Twelve children with insulinomas were seen between 1971 and 2013, compared to 201 cases with focal congenital hyperinsulinism seen between 1997 and 2014. The age of insulinoma patients ranged from 4–16 years at the time of surgery. Features of MEN1 syndrome were present in five of the 12, including four cases with heterozygous mutations of MEN1 on 11q. Immunohistochemical analysis revealed nuclear loss of p57 staining consistent with loss of the maternal 11p15 allele in 11 of the 12 insulinomas, including all five MEN1-associated tumors. Imbalance of the paternal 11p allele was confirmed by single nucleotide polymorphism genotyping and methylation assays of the 11p imprinting control loci in four of five MEN1-associated tumors and six of seven sporadic insulinomas. In addition, single nucleotide polymorphism genotyping revealed extensive tumor aneuploidy beyond chromosome 11.

Conclusions:
These data indicate that MEN1 mutations are more common in insulinomas in children than in adults. Aneuploidy of chromosome 11 and other chromosomes is common in both MEN1 and non-MEN1 insulinomas. The novel observation of a paternal parent-of-origin effect in all MEN1 and most non-MEN1 tumors suggests a critical role for imprinted growth-regulatory genes in the 11p region in the genesis of β-cell endocrine tumors in children.
Insulin Enhances Endothelial Function Throughout the Arterial Tree in Healthy But Not Metabolic Syndrome Subjects
Authors: Jahn Linda A. , Hartline Lee , Rao Nagashree , Logan Brent , Kim Justin J. , Aylor Kevin , Gan Li-Ming , Westergren Helena U. , Barrett Eugene J. 
Published: January 2016

Abstract

Context:
Insulin reportedly impairs endothelial function in conduit arteries but improves it in resistance and microvascular arterioles in healthy humans. No studies have assessed endothelial function at three arterial levels in healthy or metabolic syndrome (METSYN) subjects.

Objective:
The objective of the study was to compare endothelial responsiveness of conduit arteries, resistance, and microvascular arterioles to insulin in healthy and METSYN subjects.

Design:
We assessed conduit, resistance, and microvascular arterial function in the postabsorptive and postprandial states and during euglycemic hyperinsulinemia (insulin clamp).

Setting:
The study was conducted at a clinical research unit.

Participants:
Age-matched healthy and METSYN subjects participated in the study.

Interventions:
We used brachial flow-mediated dilation, forearm postischemic flow velocity, and contrast-enhanced ultrasound to assess the conduit artery, resistance arteriole, and microvascular arteriolar endothelial function, respectively. We also assessed the conduit artery stiffness (pulse wave velocity and augmentation index) and measured the plasma concentrations of 92 cardiovascular disease biomarkers at baseline and after the clamp.

Results:
Postabsorptive and postprandial endothelial function was similar in controls and METSYN in all tested vessels. METSYN subjects were metabolically insulin resistant (P &lt; .005). In controls, but not METSYN subjects, during euglycemic hyperinsulinemia, endothelial function improved at each level of arterial vasculature (P &lt; .05 or less for each). Conduit vessel stiffness (pulse wave velocity) was increased in the METSYN group. Twelve of 92 biomarkers differed at baseline (P &lt; .001) and remained different at the end of the insulin clamp.

Conclusions:
We conclude that insulin enhances arterial endothelial function in health but not in METSYN, and this vascular insulin resistance may underlie its increased cardiovascular disease risk.
Bone Structure and Predictors of Fracture in Type 1 and Type 2 Diabetes
Authors: Starup-Linde Jakob , Lykkeboe Simon , Gregersen Søren , Hauge Ellen-Magrethe , Langdahl Bente Lomholt , Handberg Aase , Vestergaard Peter 
Published: January 2016

Abstract

Context:
Type 1 and type 2 diabetes mellitus are associated with an increased risk of fracture.

Objective:
The objective of the study was to compare the bone structure and density between type 1 and type 2 diabetes patients and to investigate fracture associations.

Design:
This was a cross-sectional study.

Setting and Patients:
Physician-diagnosed type 1 and type 2 diabetes patients were included from the outpatient clinics at two university hospitals participated in the study.

Main Outcome Measures:
Bone density and structure were assessed by dual-energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography. Blood samples were collected for bone turnover markers. Prevalent vertebral fractures were assessed by vertebral fracture assessment and x-ray, and incident fractures were collected from The Danish National Hospital Discharge Register.

Results:
Bone mineral density (BMD) was higher in type 2 than type 1 diabetes patients at the hip, femur, and spine; however, only the hip differed in multivariate-adjusted models. Bone tissue stiffness at the tibia was increased in type 2 diabetes patients also in adjusted models. Sclerostin levels were inversely associated with fracture in type 1 diabetes patients. The patients with the highest tertile of sclerostin had an 81% decreased risk of a fracture compared with the lowest tertile.

Conclusions:
Type 1 and type 2 diabetes patients differ in BMD of the hip and tissue stiffness at the tibia. Sclerostin may be a marker independent of BMD to predict fractures in type 1 diabetes patients and thus potentially of clinical importance. Studies with longer follow-up are needed.
Measuring Medicaid Physician Participation Rates and Implications for Policy
Authors: Sommers Benjamin D. , Kronick Richard 
Published: January 2016

Abstract
Policy makers continue to debate Medicaid expansion under the Affordable Care Act, and concerns remain about low provider participation in the program. However, there has been little research on how various measures of physician participation may reflect different elements of capacity for care within the Medicaid program and how these distinct measures correlate with one another across states. Our objectives were to describe several alternative measures of provider participation in Medicaid using recently publicly available data, to compare state rankings across these different metrics, and to discuss potential advantages and disadvantages of each measure for research and policy purposes. Overall, we find that Medicaid participation as measured by raw percentages of physicians taking new Medicaid patients is only weakly correlated with population-based measures that account for both participation rates and the numbers of physicians per capita or physicians per Medicaid beneficiary. Participation rates for all physicians versus primary care physicians also offer different information about state-level provider capacity. Policy makers should consider multiple dimensions of provider access in assessing policy options in Medicaid, and further research is needed to evaluate the linkages between these provider-based measures and beneficiaries' perceptions of access to care in the program.
Medicaid Contradictions: Adding, Subtracting, and Redeterminations in Illinois
Authors: Koetting Michael 
Published: January 2016

Abstract
States are required to conduct annual Medicaid redeterminations. How these redeterminations are undertaken is crucial to determining the nature of Medicaid coverage. There can be wide variations in the proportion of clients disenrolled, with potentially large numbers of people disenrolled each year. This case study of Illinois Medicaid shows how, as the Affordable Care Act added people, redeterminations were taking people off the rolls—about 25 percent of all Medicaid clients were disenrolled in one year. Many of these people were no longer eligible, but it appears that a larger number were in fact eligible but simply failed to comply with administrative requirements in a timely way. Balancing between the two imperatives of program integrity and continuity of care is a difficult act for Medicaid programs. The Illinois experience also illustrates impacts on information technology and outsourcing of eligibility functions, not to mention budget considerations.
Business Associations, Conservative Networks, and the Ongoing Republican War Over Medicaid Expansion
Authors: Hertel-Fernandez Alexander , Skocpol Theda , Lynch Daniel 
Published: January 2016

Abstract
A major component of the Affordable Care Act involves the expansion of state Medicaid programs to cover the uninsured poor. In the wake of the 2012 Supreme Court decision upholding and modifying reform legislation, states can decide whether to expand Medicaid—and twenty states are still not proceeding as of August 2015. What explains state choices about participation in expansion, including governors' decisions to endorse expansion or not as well as final state decisions? We tackle this puzzle, focusing closely on outcomes and battles in predominantly Republican-led states. Like earlier scholars, we find that partisan differences between Democrats and Republicans are central, but we go beyond earlier analyses to measure added effects from two dueling factions within the Republican coalition: statewide business associations and cross-state networks of ideologically conservative organizations. Using both statistical modeling and case studies, we show that GOP-leaning or GOP-dominated states have been most likely to embrace the expansion when organized business support outweighs pressures from conservative networks. Our findings help make sense of ongoing state-level debates over a core part of health reform and shed new light on mounting policy tensions within the Republican Party.
Antibody performance in ChIP-sequencing assays: From quality scores of public data sets to quantitative certification
Authors: Mendoza-Parra Marco-Antonio , Saravaki Vincent , Cholley Pierre-Etienne , Blum Matthias , Billoré Benjamin , Gronemeyer Hinrich 
Published: January 2016

We have established a certification system for antibodies to be used in chromatin immunoprecipitation assays coupled to massive parallel sequencing (ChIP-seq). This certification comprises a standardized ChIP procedure and the attribution of a numerical quality control indicator (QCi) to biological replicate experiments. The QCi computation is based on a universally applicable quality assessment that quantitates the global deviation of randomly sampled subsets of ChIP-seq dataset with the original genome-aligned sequence reads. Comparison with a QCi database for >28,000 ChIP-seq assays were used to attribute quality grades (ranging from ‘AAA’ to ‘DDD’) to a given dataset. In the present report we used the numerical QC system to assess the factors influencing the quality of ChIP-seq assays, including the nature of the target, the sequencing depth and the commercial source of the antibody. We have used this approach specifically to certify mono and polyclonal antibodies obtained from Active Motif directed against the histone modification marks H3K4me3, H3K27ac and H3K9ac for ChIP-seq. The antibodies received the grades AAA to BBC (www.ngs-qc.org). We propose to attribute such quantitative grading of all antibodies attributed with the label “ChIP-seq grade”.