bluuebunny/crossref_metadata_2025_split huggingface dataset:
HCAHPS Survey Results: Impact of Severity of Illness on Hospitals' Performance on HCAHPS Survey Results
Authors: Merlino James I. , Kestranek Carmen , Bokar Daniel , Sun Zhiyuan , Nissen Steven E. , Longworth David L. 
Published: March 2016

Background The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey is used by the Centers of Medicare and Medicaid (CMS) to assess inpatient satisfaction. HCAHPS survey results are publicly reported, and performance began to affect CMS reimbursement to hospitals as of FY2013. However, the impact of severity of illness on patients' self-reported inpatient satisfaction as measured by HCAHPS survey scores remains unknown. Objective To determine the impact of severity of illness on patients' self-reported inpatient satisfaction. Design The All Patient-Refined, Diagnosis Related Group (APR-DRG) classifies every patient into one of four levels of severity of illness. We evaluated the impact of APR-DRG severity of illness on five HCAHPS domains, two reputation and two environmental questions, using linear regression analysis. Setting Adult inpatients discharged from a large, academic, tertiary care hospital Patients 37,223 patients' HCAHPS survey data were combined with their APR-DRG severity of illness rating over a 39-month period between April 2008 and June 2011. Measurements HCAHPS scores Results Higher severity of illness was consistently and inversely associated with lower patients' self-reported perception of inpatient hospital satisfaction as measured by HCAHPS scores. For each one-unit increase in severity of illness, the average HCHAPS scores across all five domains were approximately 3 percent lower. Conclusions Hospitals treating patients with a higher severity of illness will have lower HCAHPS scores, potentially leading these hospitals to receive lower reimbursement from CMS. Conversely, hospitals with lower severity of illness will receive greater reimbursement. Failure to adequately adjust for severity of illness is a serious flaw in the current HCAHPS reporting system that should be corrected.
Financial versus Non-Financial Incentives for Improving Patient Experience
Authors: Lee Thomas H. 
Published: March 2016

Delivering compassionate and coordinated care is a goal for all health care providers. Humans are not always consistent, though, both individually and collectively, and this is why everyone needs incentives to be at their best and to try to always be improving. The endlessly interesting question in patient experience is, what should those incentives look like? Should they be financial or nonfinancial? Dr. Thomas H. Lee explores what is most effective in regard to engaging and motivating physicians. While different approaches will work in different organizational cultures, financial incentives have their role in performance improvement. Compassionate coordinated care should be a social norm and be pursued by all health care organizations.
p21-activated kinase 2 regulates HSPC cytoskeleton, migration, and homing via CDC42 activation and interaction with β-Pix
Authors: Reddy Pavankumar N. G. , Radu Maria , Xu Ke , Wood Jenna , Harris Chad E. , Chernoff Jonathan , Williams David A. 
Published: March 2016

Key PointsPak2 kinase activity and β-Pix interaction regulate HSPC directional migration, actin remodeling, homing, and engraftment. Pak2 regulates homing of HSPCs to the bone marrow via CDC42 activation.
MaGuS: a tool for quality assessment and scaffolding of genome assemblies with Whole Genome Profiling™ Data
Authors: Madoui Mohammed-Amin , Dossat Carole , d’Agata Léo , van Oeveren Jan , van der Vossen Edwin , Aury Jean-Marc 
Published: March 2016

Abstract
Background
Scaffolding is an essential step in the genome assembly process. Current methods based on large fragment paired-end reads or long reads allow an increase in contiguity but often lack consistency in repetitive regions, resulting in fragmented assemblies. Here, we describe a novel tool to link assemblies to a genome map to aid complex genome reconstruction by detecting assembly errors and allowing scaffold ordering and anchoring.

Results
We present MaGuS (map-guided scaffolding), a modular tool that uses a draft genome assembly, a Whole Genome Profiling™ (WGP) map, and high-throughput paired-end sequencing data to estimate the quality and to enhance the contiguity of an assembly. We generated several assemblies of the Arabidopsis genome using different scaffolding programs and applied MaGuS to select the best assembly using quality metrics. Then, we used MaGuS to perform map-guided scaffolding to increase contiguity by creating new scaffold links in low-covered and highly repetitive regions where other commonly used scaffolding methods lack consistency.

Conclusions
MaGuS is a powerful reference-free evaluator of assembly quality and a WGP map-guided scaffolder that is freely available at https://github.com/institut-de-genomique/MaGuS. Its use can be extended to other high-throughput sequencing data (e.g., long-read data) and also to other map data (e.g., genetic maps) to improve the quality and the contiguity of large and complex genome assemblies.
PGE2-treated macrophages inhibit development of allergic lung inflammation in mice
Authors: Draijer Christina , Boorsma Carian E , Reker-Smit Catharina , Post Eduard , Poelstra Klaas , Melgert Barbro N 
Published: March 2016

Abstract
In healthy lungs, many macrophages are characterized by IL-10 production, and few are characterized by expression of IFN regulatory factor 5 (formerly M1) or YM1 and/or CD206 (formerly M2), whereas in asthma, this balance shifts toward few producing IL-10 and many expressing IFN regulatory factor 5 or YM1/CD206. In this study, we tested whether redressing the balance by reinstating IL-10 production could prevent house dust mite-induced allergic lung inflammation. PGE2 was found to be the best inducer of IL-10 in macrophages in vitro. Mice were then sensitized and challenged to house dust mites during a 2 wk protocol while treated with PGE2 in different ways. Lung inflammation was assessed 3 d after the last house dust mite challenge. House dust mite-exposed mice treated with free PGE2 had fewer infiltrating eosinophils in lungs and lower YM1 serum levels than vehicle-treated mice. Macrophage-specific delivery of PGE2 did not affect lung inflammation. Adoptive transfer of PGE2-treated macrophages led to fewer infiltrating eosinophils, macrophages, (activated) CD4+, and regulatory T lymphocytes in lungs. Our study shows that the redirection of macrophage polarization by using PGE2 inhibits development of allergic lung inflammation. This beneficial effect of macrophage repolarization is a novel avenue to explore for therapeutic purposes.
Linked in: immunologic membrane nanotube networks
Authors: Zaccard C R , Rinaldo C R , Mailliard R B 
Published: March 2016

Abstract
Membrane nanotubes, also termed tunneling nanotubes, are F-actin-based structures that can form direct cytoplasmic connections and support rapid communication between distant cells. These nanoscale conduits have been observed in diverse cell types, including immune, neuronal, stromal, cancer, and stem cells. Until recently, little was known about the mechanisms involved in membrane nanotube development in myeloid origin APCs or how membrane nanotube networks support their ability to bridge innate and adaptive immunity. New research has provided insight into the modes of induction and regulation of the immune process of “reticulation” or the development of multicellular membrane nanotube networks in dendritic cells. Preprogramming by acute type 1 inflammatory mediators at their immature stage licenses mature type 1-polarized dendritic cells to reticulate upon subsequent interaction with CD40 ligand-expressing CD4+ Th cells. Dendritic cell reticulation can support direct antigen transfer for amplification of specific T cell responses and can be positively or negatively regulated by signals from distinct Th cell subsets. Membrane nanotubes not only enhance the ability of immature dendritic cells to sense pathogens and rapidly mobilize nearby antigen-presenting cells in the peripheral tissues but also likely support communication of pathogen-related information from mature migratory dendritic cells to resident dendritic cells in lymph nodes. Therefore, the reticulation process facilitates a coordinated multicellular response for the efficient initiation of cell-mediated adaptive immune responses. Herein, we discuss studies focused on the molecular mechanisms of membrane nanotube formation, structure, and function in the context of immunity and how pathogens, such as HIV-1, may use dendritic cell reticulation to circumvent host defenses.
Role of CXCR4-mediated bone marrow colonization in CNS infiltration by T cell acute lymphoblastic leukemia
Authors: Jost Tanja Rezzonico , Borga Chiara , Radaelli Enrico , Romagnani Andrea , Perruzza Lisa , Omodho Lorna , Cazzaniga Giovanni , Biondi Andrea , Indraccolo Stefano , Thelen Marcus , te Kronnie Geertruy , Grassi Fabio 
Published: March 2016

Abstract
Infiltration of the central nervous system is a severe trait of T cell acute lymphoblastic leukemia. Inhibition of CXC chemokine receptor 4 significantly ameliorates T cell acute lymphoblastic leukemia in murine models of the disease; however, signaling by CXC chemokine receptor 4 is important in limiting the divagation of peripheral blood mononuclear cells out of the perivascular space into the central nervous system parenchyma. Therefore, Inhibition of CXC chemokine receptor 4 potentially may untangle T cell acute lymphoblastic leukemia cells from retention outside the brain. Here, we show that leukemic lymphoblasts massively infiltrate cranial bone marrow, with diffusion to the meninges without invasion of the brain parenchyma, in mice that underwent xenotransplantation with human T cell acute lymphoblastic leukemia cells or that developed leukemia from transformed hematopoietic progenitors. We tested the hypothesis that T cell acute lymphoblastic leukemia neuropathology results from meningeal infiltration through CXC chemokine receptor 4–mediated bone marrow colonization. Inhibition of leukemia engraftment in the bone marrow by pharmacologic CXC chemokine receptor 4 antagonism significantly ameliorated neuropathologic aspects of the disease. Genetic deletion of CXCR4 in murine hematopoietic progenitors abrogated leukemogenesis induced by constitutively active Notch1, whereas lack of CCR6 and CCR7, which have been shown to be involved in T cell and leukemia extravasation into the central nervous system, respectively, did not influence T cell acute lymphoblastic leukemia development. We hypothesize that lymphoblastic meningeal infiltration as a result of bone marrow colonization is responsible for the degenerative alterations of the neuroparenchyma as well as the alteration of cerebrospinal fluid drainage in T cell acute lymphoblastic leukemia xenografts. Therefore, CXC chemokine receptor 4 may constitute a pharmacologic target for T cell acute lymphoblastic leukemia neuropathology.
Tumor Autonomous Effects of Vitamin D Deficiency Promote Breast Cancer Metastasis
Authors: Williams Jasmaine D. , Aggarwal Abhishek , Swami Srilatha , Krishnan Aruna V. , Ji Lijuan , Albertelli Megan A. , Feldman Brian J. 
Published: March 2016

Abstract
Patients with breast cancer (BCa) frequently have preexisting vitamin D deficiency (low serum 25-hydroxyvitamin D) when their cancer develops. A number of epidemiological studies show an inverse association between BCa risk and vitamin D status in humans, although some studies have failed to find an association. In addition, several studies have reported that BCa patients with vitamin D deficiency have a more aggressive molecular phenotype and worse prognostic indicators. However, it is unknown whether this association is mechanistically causative and, if so, whether it results from systemic or tumor autonomous effects of vitamin D signaling. We found that ablation of vitamin D receptor expression within BCa cells accelerates primary tumor growth and enables the development of metastases, demonstrating a tumor autonomous effect of vitamin D signaling to suppress BCa metastases. We show that vitamin D signaling inhibits the expression of the tumor progression gene Id1, and this pathway is abrogated in vitamin D deficiency in vivo in 2 murine models of BCa. These findings are relevant to humans, because we discovered that the mechanism of VDR regulation of Inhibitor of differentiation 1 (ID1) is conserved in human BCa cells, and there is a negative correlation between serum 25-hydroxyvitamin D levels and the level of ID1 in primary tumors from patients with BCa.
The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline
Authors: Funder John W. , Carey Robert M. , Mantero Franco , Murad M. Hassan , Reincke Martin , Shibata Hirotaka , Stowasser Michael , Young William F. 
Published: March 2016

Abstract

Objective:
To develop clinical practice guidelines for the management of patients with primary aldosteronism.

Participants:
The Task Force included a chair, selected by the Clinical Guidelines Subcommittee of the Endocrine Society, six additional experts, a methodologist, and a medical writer. The guideline was cosponsored by American Heart Association, American Association of Endocrine Surgeons, European Society of Endocrinology, European Society of Hypertension, International Association of Endocrine Surgeons, International Society of Endocrinology, International Society of Hypertension, Japan Endocrine Society, and The Japanese Society of Hypertension. The Task Force received no corporate funding or remuneration.

Evidence:
We searched for systematic reviews and primary studies to formulate the key treatment and prevention recommendations. We used the Grading of Recommendations, Assessment, Development, and Evaluation group criteria to describe both the quality of evidence and the strength of recommendations. We used “recommend” for strong recommendations and “suggest” for weak recommendations.

Consensus Process:
We achieved consensus by collecting the best available evidence and conducting one group meeting, several conference calls, and multiple e-mail communications. With the help of a medical writer, the Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and Council successfully reviewed the drafts prepared by the Task Force. We placed the version approved by the Clinical Guidelines Subcommittee and Clinical Affairs Core Committee on the Endocrine Society's website for comments by members. At each stage of review, the Task Force received written comments and incorporated necessary changes.

Conclusions:
For high-risk groups of hypertensive patients and those with hypokalemia, we recommend case detection of primary aldosteronism by determining the aldosterone-renin ratio under standard conditions and recommend that a commonly used confirmatory test should confirm/exclude the condition. We recommend that all patients with primary aldosteronism undergo adrenal computed tomography as the initial study in subtype testing and to exclude adrenocortical carcinoma. We recommend that an experienced radiologist should establish/exclude unilateral primary aldosteronism using bilateral adrenal venous sampling, and if confirmed, this should optimally be treated by laparoscopic adrenalectomy. We recommend that patients with bilateral adrenal hyperplasia or those unsuitable for surgery should be treated primarily with a mineralocorticoid receptor antagonist.
Mouse myofibers lacking the SMYD1 methyltransferase are susceptible to atrophy, internalization of nuclei and myofibrillar disarray
Authors: Stewart M. David , Lopez Suhujey , Nagandla Harika , Soibam Benjamin , Benham Ashley , Nguyen Jasmine , Valenzuela Nicolas , Wu Harry J. , Burns Alan R. , Rasmussen Tara L. , Tucker Haley O. , Schwartz Robert J. 
Published: March 2016

ABSTRACTThe Smyd1 gene encodes a lysine methyltransferase specifically expressed in striated muscle. Because Smyd1-null mouse embryos die from heart malformation prior to formation of skeletal muscle, we developed a Smyd1 conditional-knockout allele to determine the consequence of SMYD1 loss in mammalian skeletal muscle. Ablation of SMYD1 specifically in skeletal myocytes after myofiber differentiation using Myf6cre produced a non-degenerative myopathy. Mutant mice exhibited weakness, myofiber hypotrophy, prevalence of oxidative myofibers, reduction in triad numbers, regional myofibrillar disorganization/breakdown and a high percentage of myofibers with centralized nuclei. Notably, we found broad upregulation of muscle development genes in the absence of regenerating or degenerating myofibers. These data suggest that the afflicted fibers are in a continual state of repair in an attempt to restore damaged myofibrils. Disease severity was greater for males than females. Despite equivalent expression in all fiber types, loss of SMYD1 primarily affected fast-twitch muscle, illustrating fiber-type-specific functions for SMYD1. This work illustrates a crucial role for SMYD1 in skeletal muscle physiology and myofibril integrity.
The interplay between intestinal bacteria and host metabolism in health and disease: lessons fromDrosophila melanogaster
Authors: Wong Adam C. N. , Vanhove Audrey S. , Watnick Paula I. 
Published: March 2016

ABSTRACTAll higher organisms negotiate a truce with their commensal microbes and battle pathogenic microbes on a daily basis. Much attention has been given to the role of the innate immune system in controlling intestinal microbes and to the strategies used by intestinal microbes to overcome the host immune response. However, it is becoming increasingly clear that the metabolisms of intestinal microbes and their hosts are linked and that this interaction is equally important for host health and well-being. For instance, an individual's array of commensal microbes can influence their predisposition to chronic metabolic diseases such as diabetes and obesity. A better understanding of host–microbe metabolic interactions is important in defining the molecular bases of these disorders and could potentially lead to new therapeutic avenues. Key advances in this area have been made using Drosophila melanogaster. Here, we review studies that have explored the impact of both commensal and pathogenic intestinal microbes on Drosophila carbohydrate and lipid metabolism. These studies have helped to elucidate the metabolites produced by intestinal microbes, the intestinal receptors that sense these metabolites, and the signaling pathways through which these metabolites manipulate host metabolism. Furthermore, they suggest that targeting microbial metabolism could represent an effective therapeutic strategy for human metabolic diseases and intestinal infection.
Modeling congenital disease and inborn errors of development inDrosophila melanogaster
Authors: Moulton Matthew J. , Letsou Anthea 
Published: March 2016

ABSTRACTFly models that faithfully recapitulate various aspects of human disease and human health-related biology are being used for research into disease diagnosis and prevention. Established and new genetic strategies in Drosophila have yielded numerous substantial successes in modeling congenital disorders or inborn errors of human development, as well as neurodegenerative disease and cancer. Moreover, although our ability to generate sequence datasets continues to outpace our ability to analyze these datasets, the development of high-throughput analysis platforms in Drosophila has provided access through the bottleneck in the identification of disease gene candidates. In this Review, we describe both the traditional and newer methods that are facilitating the incorporation of Drosophila into the human disease discovery process, with a focus on the models that have enhanced our understanding of human developmental disorders and congenital disease. Enviable features of the Drosophila experimental system, which make it particularly useful in facilitating the much anticipated move from genotype to phenotype (understanding and predicting phenotypes directly from the primary DNA sequence), include its genetic tractability, the low cost for high-throughput discovery, and a genome and underlying biology that are highly evolutionarily conserved. In embracing the fly in the human disease-gene discovery process, we can expect to speed up and reduce the cost of this process, allowing experimental scales that are not feasible and/or would be too costly in higher eukaryotes.
Drosophilatools and assays for the study of human diseases
Authors: Ugur Berrak , Chen Kuchuan , Bellen Hugo J. 
Published: March 2016

ABSTRACTMany of the internal organ systems of Drosophila melanogaster are functionally analogous to those in vertebrates, including humans. Although humans and flies differ greatly in terms of their gross morphological and cellular features, many of the molecular mechanisms that govern development and drive cellular and physiological processes are conserved between both organisms. The morphological differences are deceiving and have led researchers to undervalue the study of invertebrate organs in unraveling pathogenic mechanisms of diseases. In this review and accompanying poster, we highlight the physiological and molecular parallels between fly and human organs that validate the use of Drosophila to study the molecular pathogenesis underlying human diseases. We discuss assays that have been developed in flies to study the function of specific genes in the central nervous system, heart, liver and kidney, and provide examples of the use of these assays to address questions related to human diseases. These assays provide us with simple yet powerful tools to study the pathogenic mechanisms associated with human disease-causing genes.
Fruit flies on the front line: the translational impact of Drosophila
Authors: Perrimon Norbert , Bonini Nancy M. , Dhillon Paraminder 
Published: March 2016

ABSTRACT
Drosophila melanogaster has been adopted as one of the most-used model systems since it was first introduced by Thomas Morgan for the study of heredity in the early 20th century. Its experimental tractability and similarity of its biological pathways to those of humans have placed the model at the forefront of research into human development and disease. With the ongoing accumulation of genetic tools and assays, the fly community has at its fingertips the resources to generate diverse Drosophila disease models for the study of genes and pathways involved in a wide range of disorders. In recent years, the fly has also been used successfully for drug screening. In this Editorial, we introduce a Special Collection of reviews, interviews and original research articles that highlight some of the many ways that Drosophila has made, and continues to make, an impact on basic biological insights and translational science.