bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico analysis of the two tandem somatomedin B domains of ENPP1 reveals hints on the homodimerization of the protein
Authors: Bellacchio Emanuele 
Published: January 2012

AbstractThe homodimerization of ENPP1 is mediated by the two somatomedin B (SMB) domains of the protein through a mechanism that is yet unknown at the atomistic level. The tandem arrangement of these domains without an intermediate spacer implies their possible packing into a functional assembly, which we explored by rigid docking. To exclude potential bias in the docking search we assessed the absence of flexible protein regions by evaluating the normalized B‐factors calculated from the Cα atom displacements derived from molecular dynamics simulations. After filtering the docking results exploiting the criterion that residues located at the inter‐domain interfaces are more conserved than non‐interface residues, the resulting best model of the tandem SMB domains revealed the presence of two large conserved surface patches not engaged in the inter‐domain contact. The largest patch is flat and contains all the invariant positively charged residues characterized by fully solvent‐exposed side chains within the tandem SMB domains, suggesting as a possible role its interaction with the negative phospholipids on the cell surface. We envisage that an ENPP1 monomer bound to the cell membrane via the transmembrane segment can also interact with the cell surface through the largest conserved patch favoring a specific geometry of the tandem SMB module on the cell that optimally exposes the second conserved patch for the symmetric interaction with another membrane‐bound ENPP1 monomer, finally promoting the homodimerization. Biological implications of this model and insights into the effects of the K173Q variant associated with insulin resistance and related abnormalities are presented. J. Cell. Physiol. 227: 3566–3574, 2012. © 2012 Wiley Periodicals, Inc.
Synthesis and bioanalytical evaluation of morphine‐3‐O‐sulfate and morphine‐6‐O‐sulfate in human urine and plasma using LC‐MS/MS
Authors: Andersson Maria , Janosik Tomasz , Shirani Hamid , Slätt Johnny , Fischer Andreas , Beck Olof 
Published: January 2012

AbstractThe aim of this work was to synthesize morphine‐3‐O‐sulfate and morphine‐6‐O‐sulfate for use as reference substances, and to determine the sulfate conjugates as possible heroin and morphine metabolites in plasma and urine by a validated LC‐MS/MS method. Morphine‐6‐O‐sulfate and morphine‐3‐O‐sulfate were prepared as dihydrates from morphine hydrochloride, in overall yields of 41 and 39% with product purities of >99.5% and >98%, respectively. For bioanalysis, the chromatographic system consisted of a reversed‐phase column and gradient elution. The tandem mass spectrometer was operated in the positive electrospray mode using selected reaction monitoring, of transition m/z 366.15 to 286.40. The measuring range was 5–500 ng/mL for morphine‐3‐O‐sulfate and 4.5–454 ng/mL for morphine‐6‐O‐sulfate in plasma. In urine, the measuring range was 50–5000 ng/mL for morphine‐3‐O‐sulfate and 45.4–4544 ng/mL for morphine‐6‐O‐sulfate. The intra‐assay and total imprecision (coefficient of variation) was below 11% for both analytes in urine and plasma. Quantifiable levels of morphine‐3‐O‐sulfate in authentic urine and plasma samples were found. Only one authentic urine sample contained a detectable level of morphine‐6‐O‐sulfate, while no detectable morphine‐6‐O‐sulfate was found in plasma samples.
The importance of supervision in retention of CNAs
Authors: Choi JiSun , Johantgen Meg 
Published: January 2012

AbstractCertified nursing assistants (CNAs) provide the majority of direct care in nursing homes, yet recruiting and retaining CNAs has been difficult. Retaining CNAs is important because it has been linked to the better quality of resident care in nursing homes. In this study, the investigators examined the relationships of work‐related and personal factors to CNA job satisfaction and intent to leave. Linked data from the 2004 National Nursing Home Survey and the 2004 National Nursing Assistant Survey were analyzed using multilevel logistic regression. Personal factors such as age, education, and job history, were related to intent to leave but not to job satisfaction. Supportive supervision was a significant predictor of both job satisfaction and intent to leave. © 2012 Wiley Periodicals, Inc. Res Nurs Health 35:187–199, 2012
PAI‐1 promotes the accumulation of exudate macrophages and worsens pulmonary fibrosis following type II alveolar epithelial cell injury
Authors: Osterholzer John J , Christensen Paul J , Lama Vibha , Horowitz Jeffrey C , Hattori Noboru , Subbotina Natalya , Cunningham Andrew , Lin Yujing , Murdock Benjamin J , Morey Roger E , Olszewski Michal A , Lawrence Daniel A , Simon Richard H , Sisson Thomas H 
Published: January 2012

AbstractFibrotic disorders of the lung are associated with perturbations in the plasminogen activation system. Specifically, plasminogen activator inhibitor‐1 (PAI‐1) expression is increased relative to the plasminogen activators. A direct role for this imbalance in modulating the severity of lung scarring following injury has been substantiated in the bleomycin model of pulmonary fibrosis. However, it remains unclear whether derangements in the plasminogen activation system contribute more generally to the pathogenesis of lung fibrosis beyond bleomycin injury. To answer this question, we employed an alternative model of lung scarring, in which type II alveolar epithelial cells (AECs) are specifically injured by administering diphtheria toxin (DT) to mice genetically engineered to express the human DT receptor (DTR) off the surfactant protein C promoter. This targeted AEC injury results in the diffuse accumulation of interstitial collagen. In the present study, we found that this targeted type II cell insult also increases PAI‐1 expression in the alveolar compartment. We identified AECs and lung macrophages to be sources of PAI‐1 production. To determine whether this elevated PAI‐1 concentration was directly related to the severity of fibrosis, DTR+ mice were crossed into a PAI‐1‐deficient background (DTR+: PAI‐1−/−). DT administration to DTR+: PAI‐1−/− animals caused significantly less fibrosis than was measured in DTR+ mice with intact PAI‐1 production. PAI‐1 deficiency also abrogated the accumulation of CD11b+ exudate macrophages that were found to express PAI‐1 and type‐1 collagen. These observations substantiate the critical function of PAI‐1 in pulmonary fibrosis pathogenesis and provide new insight into a potential mechanism by which this pro‐fibrotic molecule influences collagen accumulation. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The organizational structure and governing principles of the Food and Drug Administration's Mini‐Sentinel pilot program
Authors: Forrow Susan , Campion Daniel M. , Herrinton Lisa J. , Nair Vinit P. , Robb Melissa A. , Wilson Marcus , Platt Richard 
Published: January 2012

ABSTRACTThe US Food and Drug Administration's Mini‐Sentinel pilot program is developing an organizational structure as well as principles and policies to govern its operations. These will inform the structure and function of the eventual Sentinel System. Mini‐Sentinel is a collaboration that includes 25 participating institutions. We describe the program's current organizational structure and its major principles and policies. The organization includes a coordinating center with program leadership provided by a principal investigator; a planning board and subcommittees; an operations center; and data, methods, and protocol cores. Ad hoc workgroups are created as needed. A privacy panel advises about protection of individual health information. Principles and policies are intended to ensure that Mini‐Sentinel conforms to the principles of fair information practices, protects the privacy of individual health information, maintains the security and integrity of data, assures the confidentiality of proprietary information, provides accurate and timely communications, prevents or manages conflicts of interest, and preserves respect for intellectual property rights. Copyright © 2012 John Wiley & Sons, Ltd.
A systematic review of validated methods for identifying heart failure using administrative data
Authors: Saczynski Jane S. , Andrade Susan E. , Harrold Leslie R. , Tjia Jennifer , Cutrona Sarah L. , Dodd Katherine S. , Goldberg Robert J. , Gurwitz Jerry H. 
Published: January 2012

ABSTRACTPurposeTo identify and describe the validity of algorithms used to detect heart failure (HF) using administrative and claims data sources.MethodsA systematic review of PubMed and Iowa Drug Information Service searches of the English language was performed to identify studies published between 1990 and 2010 that evaluated the validity of algorithms for the identification of patients with HF using and claims data. Abstracts and articles were reviewed by two study investigators to determine their relevance on the basis of predetermined criteria.ResultsThe initial search strategy identified 887 abstracts. Of these, 499 full articles were reviewed and 35 studies included data to evaluate the validity of identifying patients with HF. Positive predictive values (PPVs) were in the acceptable to high range, with most being very high (>90%). Studies that included patients with a primary hospital discharge diagnosis of International Classification of Diseases, Ninth Revision, code 428.X had the highest PPV and specificity for HF. PPVs for this algorithm ranged from 84% to 100%. This algorithm, however, may compromise sensitivity because many HF patients are managed on an outpatient basis. The most common ‘gold standard’ for the validation of HF was the Framingham Heart Study criteria.ConclusionsThe algorithms and definitions used to identify HF using administrative and claims data perform well, particularly when using a primary hospital discharge diagnosis. Attention should be paid to whether patients who are managed on an outpatient basis are included in the study sample. Including outpatient codes in the described algorithms would increase the sensitivity for identifying new cases of HF. Copyright © 2012 John Wiley & Sons, Ltd.
Mini‐Sentinel's systematic reviews of validated methods for identifying health outcomes using administrative data: summary of findings and suggestions for future research
Authors: Carnahan Ryan M. 
Published: January 2012

ABSTRACTPurposeThe validity of findings from surveillance activities, which use administrative and claims data to link exposures to adverse events, depends in part on the validity of algorithms to identify health outcomes using these data. This review provides a high level overview of the findings of 19 systematic reviews of studies, which have examined the validity of algorithms to identify health outcomes using these data. The author categorized outcomes on the basis of the strength of evidence supporting valid algorithms to identify acute or incident events and suggested priorities for future validation studies.MethodsThe 19 reviews were evaluated, and key findings and suggestions for future research were summarized by a single reviewer. Outcomes with algorithms that consistently identified acute events or incident conditions with positive predictive values of greater than 70% across multiple studies and populations are described as low priority for future algorithm validation studies.ResultsAlgorithms to identify cerebrovascular accidents, transient ischemic attacks, congestive heart failure, deep vein thrombosis, pulmonary embolism, angioedema, and total hip arthroplasty revision performed well across multiple studies and are considered low priority for future validation studies. Other outcomes were generally thought to require additional validation studies or algorithm refinement to be confident in algorithms. Few studies examined the validity of International Classification of Diseases, 10th Revision, codes.ConclusionUsers of these reviews need to consider the generalizability of findings to their study populations. For some outcomes with poorly performing codes, it may always be necessary to validate cases. Copyright © 2012 John Wiley & Sons, Ltd.
A systematic review of validated methods for identifying transfusion‐related ABO incompatibility reactions using administrative and claims data
Authors: Carnahan Ryan M. , Kee Vicki R. 
Published: January 2012

ABSTRACTPurposeThis paper aimed to systematically review algorithms to identify transfusion‐related ABO incompatibility reactions in administrative data, with a focus on studies that have examined the validity of the algorithms.MethodsA literature search was conducted using PubMed, Iowa Drug Information Service database, and Embase. A Google Scholar search was also conducted because of the difficulty identifying relevant studies. Reviews were conducted by two investigators to identify studies using data sources from the USA or Canada because these data sources were most likely to reflect the coding practices of Mini‐Sentinel data sources.ResultsOne study was found that validated International Classification of Diseases (ICD‐9‐CM) codes representing transfusion reactions. None of these cases were ABO incompatibility reactions. Several studies consistently used ICD‐9‐CM code 999.6, which represents ABO incompatibility reactions, and a technical report identified the ICD‐10 code for these reactions. One study included the E‐code E8760 for mismatched blood in transfusion in the algorithm. Another study reported finding no ABO incompatibility reaction codes in the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database, which contains data of 2.23 million patients who received transfusions, raising questions about the sensitivity of administrative data for identifying such reactions. Two studies reported perfect specificity, with sensitivity ranging from 21% to 83%, for the code identifying allogeneic red blood cell transfusions in hospitalized patients.ConclusionsThere is no information to assess the validity of algorithms to identify transfusion‐related ABO incompatibility reactions. Further information on the validity of algorithms to identify transfusions would also be useful. Copyright © 2012 John Wiley & Sons, Ltd.
A systematic review of validated methods for identifying anaphylaxis, including anaphylactic shock and angioneurotic edema, using administrative and claims data
Authors: Schneider Gary , Kachroo Sumesh , Jones Natalie , Crean Sheila , Rotella Philip , Avetisyan Ruzan , Reynolds Matthew W. 
Published: January 2012

ABSTRACTPurposeThe Food and Drug Administration's Mini‐Sentinel pilot program initially aims to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest from administrative and claims data. This article summarizes the process and findings of the algorithm review of anaphylaxis.MethodsPubMed and Iowa Drug Information Service searches were conducted to identify citations applicable to the anaphylaxis health outcome of interest. Level 1 abstract reviews and Level 2 full‐text reviews were conducted to find articles using administrative and claims data to identify anaphylaxis and including validation estimates of the coding algorithms.ResultsOur search revealed limited literature focusing on anaphylaxis that provided administrative and claims data–based algorithms and validation estimates. Only four studies identified via literature searches provided validated algorithms; however, two additional studies were identified by Mini‐Sentinel collaborators and were incorporated. The International Classification of Diseases, Ninth Revision, codes varied, as did the positive predictive value, depending on the cohort characteristics and the specific codes used to identify anaphylaxis.ConclusionsResearch needs to be conducted on designing validation studies to test anaphylaxis algorithms and estimating their predictive power, sensitivity, and specificity. Copyright © 2012 John Wiley & Sons, Ltd.
A systematic review of validated methods for identifying erythema multiforme major/minor/not otherwise specified, Stevens–Johnson Syndrome, or toxic epidermal necrolysis using administrative and claims data
Authors: Schneider Gary , Kachroo Sumesh , Jones Natalie , Crean Sheila , Rotella Philip , Avetisyan Ruzan , Reynolds Matthew W. 
Published: January 2012

ABSTRACTPurposeThe Food and Drug Administration's (FDA) Mini‐Sentinel pilot program aims to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest (HOIs) from administrative and claims data. This paper summarizes the process and findings of the algorithm review of erythema multiforme and related conditions.MethodsPubMed and Iowa Drug Information Service searches were conducted to identify citations applicable to the erythema multiforme HOI. Level 1 abstract reviews and Level 2 full‐text reviews were conducted to find articles that used administrative and claims data to identify erythema multiforme, Stevens–Johnson syndrome, or toxic epidermal necrolysis and that included validation estimates of the coding algorithms.ResultsOur search revealed limited literature focusing on erythema multiforme and related conditions that provided administrative and claims data‐based algorithms and validation estimates. Only four studies provided validated algorithms and all studies used the same International Classification of Diseases code, 695.1. Approximately half of cases subjected to expert review were consistent with erythema multiforme and related conditions.ConclusionsUpdated research needs to be conducted on designing validation studies that test algorithms for erythema multiforme and related conditions and that take into account recent changes in the diagnostic coding of these diseases. Copyright © 2012 John Wiley & Sons, Ltd.
A systematic review of validated methods for identifying hypersensitivity reactions other than anaphylaxis (fever, rash, and lymphadenopathy), using administrative and claims data
Authors: Schneider Gary , Kachroo Sumesh , Jones Natalie , Crean Sheila , Rotella Philip , Avetisyan Ruzan , Reynolds Matthew W. 
Published: January 2012

ABSTRACTPurposeThe Food and Drug Administration's Mini‐Sentinel pilot program aims to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest from administrative and claims data. This article summarizes the process and findings of the algorithm review of hypersensitivity reactions.MethodsPubMed and Iowa Drug Information Service searches were conducted to identify citations applicable to the hypersensitivity reactions of health outcomes of interest. Level 1 abstract reviews and Level 2 full‐text reviews were conducted to find articles using administrative and claims data to identify hypersensitivity reactions and including validation estimates of the coding algorithms.ResultsWe identified five studies that provided validated hypersensitivity‐reaction algorithms. Algorithm positive predictive values (PPVs) for various definitions of hypersensitivity reactions ranged from 3% to 95%. PPVs were high (i.e. 90%–95%) when both exposures and diagnoses were very specific. PPV generally decreased when the definition of hypersensitivity was expanded, except in one study that used data mining methodology for algorithm development.ConclusionsThe ability of coding algorithms to identify hypersensitivity reactions varied, with decreasing performance occurring with expanded outcome definitions. This examination of hypersensitivity‐reaction coding algorithms provides an example of surveillance bias resulting from outcome definitions that include mild cases. Data mining may provide tools for algorithm development for hypersensitivity and other health outcomes. Research needs to be conducted on designing validation studies to test hypersensitivity‐reaction algorithms and estimating their predictive power, sensitivity, and specificity. Copyright © 2012 John Wiley & Sons, Ltd.
The U.S. Food and Drug Administration's Mini‐Sentinel program: status and direction
Authors: Platt Richard , Carnahan Ryan M. , Brown Jeffrey S. , Chrischilles Elizabeth , Curtis Lesley H. , Hennessy Sean , Nelson Jennifer C. , Racoosin Judith A. , Robb Melissa , Schneeweiss Sebastian , Toh Sengwee , Weiner Mark G. 
Published: January 2012

ABSTRACTThe Mini‐Sentinel is a pilot program that is developing methods, tools, resources, policies, and procedures to facilitate the use of routinely collected electronic healthcare data to perform active surveillance of the safety of marketed medical products, including drugs, biologics, and medical devices. The U.S. Food and Drug Administration (FDA) initiated the program in 2009 as part of its Sentinel Initiative, in response to a Congressional mandate in the FDA Amendments Act of 2007.After two years, Mini‐Sentinel includes 31 academic and private organizations. It has developed policies, procedures, and technical specifications for developing and operating a secure distributed data system comprised of separate data sets that conform to a common data model covering enrollment, demographics, encounters, diagnoses, procedures, and ambulatory dispensing of prescription drugs. The distributed data sets currently include administrative and claims data from 2000 to 2011 for over 300 million person‐years, 2.4 billion encounters, 38 million inpatient hospitalizations, and 2.9 billion dispensings. Selected laboratory results and vital signs data recorded after 2005 are also available. There is an active data quality assessment and characterization program, and eligibility for medical care and pharmacy benefits is known. Systematic reviews of the literature have assessed the ability of administrative data to identify health outcomes of interest, and procedures have been developed and tested to obtain, abstract, and adjudicate full‐text medical records to validate coded diagnoses. Mini‐Sentinel has also created a taxonomy of study designs and analytical approaches for many commonly occurring situations, and it is developing new statistical and epidemiologic methods to address certain gaps in analytic capabilities.Assessments are performed by distributing computer programs that are executed locally by each data partner. The system is in active use by FDA, with the majority of assessments performed using customizable, reusable queries (programs). Prospective and retrospective assessments that use customized protocols are conducted as well. To date, several hundred unique programs have been distributed and executed.Current activities include active surveillance of several drugs and vaccines, expansion of the population, enhancement of the common data model to include additional types of data from electronic health records and registries, development of new methodologic capabilities, and assessment of methods to identify and validate additional health outcomes of interest. Copyright © 2012 John Wiley & Sons, Ltd.