bluuebunny/crossref_metadata_2025_split huggingface dataset:
The anti-CD74 humanized monoclonal antibody, milatuzumab, which targets the invariant chain of MHC II complexes, alters B-cell proliferation, migration, and adhesion molecule expression
Authors: Frölich Daniela , Blaβfeld Daniela , Reiter Karin , Giesecke Claudia , Daridon Capucine , Mei Henrik E , Burmester Gerd R , Goldenberg David M , Salama Abdulagabar , Dörner Thomas 
Published: March 2012

Abstract
Introduction
Targeting CD74 as the invariant chain of major histocompatibility complexes (MHC) became possible by the availability of a specific humanized monoclonal antibody, milatuzumab, which is under investigation in patients with hematological neoplasms. CD74 has been reported to regulate chemo-attractant migration of macrophages and dendritic cells, while the role of CD74 on peripheral naïve and memory B cells also expressing CD74 remains unknown. Therefore, the current study addressed the influence of milatuzumab on B-cell proliferation, chemo-attractant migration, and adhesion molecule expression.

Methods
Surface expression of CD74 on CD27- naïve and CD27+ memory B cells as well as other peripheral blood mononuclear cells (PBMCs) obtained from normals, including the co-expression of CD44, CXCR4, and the adhesion molecules CD62L, β7-integrin, β1-integrin and CD9 were studied after binding of milatuzumab using multicolor flow cytometry. The influence of the antibody on B-cell proliferation and migration was analyzed in vitro in detail.

Results
In addition to monocytes, milatuzumab also specifically bound to human peripheral B cells, with a higher intensity on CD27+ memory versus CD27- naïve B cells. The antibody reduced B-cell proliferation significantly but moderately, induced enhanced spontaneous and CXCL12-dependent migration together with changes in the expression of adhesion molecules, CD44, β7-integrin and CD62L, mainly of CD27- naïve B cells. This was independent of macrophage migration-inhibitory factor as a ligand of CD74/CD44 complexes.

Conclusions
Milatuzumab leads to modestly reduced proliferation, alterations in migration, and adhesion molecule expression preferentially of CD27- naïve B cells. It thus may be a candidate antibody for the autoimmune disease therapy by modifying B cell functions.
Economic analyses of venous thromboembolism prevention strategies in hospitalized patients: a systematic review
Authors: Thirugnanam Subarna , Pinto Ruxandra , Cook Deborah J , Geerts William H , Fowler Robert A 
Published: March 2012

Abstract
Introduction
Despite evidence-based guidelines for venous thromboembolism prevention, substantial variability is found in practice. Many economic evaluations of new drugs for thromboembolism prevention do not occur prospectively with efficacy studies and are sponsored by the manufacturers, raising the possibility of bias. We performed a systematic review of economic analyses of venous thromboembolism prevention in hospitalized patients to inform clinicians and policy makers about cost-effectiveness and the potential influence of sponsorship.

Methods
We searched MEDLINE, EMBASE, Cochrane Databases, ACP Journal Club, and Database of Abstracts of Reviews of Effects, from 1946 to September 2011. We extracted data on study characteristics, quality, costs, and efficacy.

Results
From 5,180 identified studies, 39 met eligibility and quality criteria. Each addressed pharmacologic prevention: low-molecular-weight heparins versus placebo (five), unfractionated heparin (12), warfarin (eight), one or another agents (five); fondaparinux versus enoxaparin (11); and rivaroxaban and dabigatran versus enoxaparin (two). Low-molecular-weight heparins were most economically attractive among most medical and surgical patients, whereas fondaparinux was favored for orthopedic patients. Fondaparinux was associated with increased bleeding events. Newer agents rivaroxaban and dabigatran may offer additional value. Of all economic evaluations, 64% were supported by manufacturers of a "new" agent. The new agent had a favorable outcome in 38 (97.4%) of 39 evaluations [95% confidence interval [CI] (86.5 to 99.9)]. Among studies supported by a pharmaceutical company, the sponsored medication was economically attractive in 24 (96.0%) of 25 [95% CI, 80.0 to 99.9)]. We could not detect a consistent bias in outcome based on sponsorship; however, only a minority of studies were unsponsored.

Conclusion
Low-molecular-weight heparins and fondaparinux are the most economically attractive drugs for venous thromboembolism prevention in hospitalized patients. Approximately two thirds of evaluations were supported by the manufacturer of the new agent; such drugs were likely to be reported as economically favorable.
Distinguishing adolescents who think about self-harm from those who engage in self-harm
Authors: O'Connor Rory C. , Rasmussen Susan , Hawton Keith 
Published: March 2012

BackgroundAdolescent self-harm is a major public health concern, yet little is known about the factors that distinguish adolescents who think about self-harm but do not act on these thoughts from those who act on such thoughts.AimsWithin a new theoretical model, the integrated motivational–volitional model, we investigated factors associated with adolescents having thoughts of self-harm (ideators)v.those associated with self-harm enaction (enactors).MethodObservational study of school pupils employing an anonymous self-report survey to compare three groups of adolescents: self-harm enactors (n= 628)v.self-harm ideators (n= 675)v.those without any self-harm history (n= 4219).ResultsEnactors differed from ideators on all of the volitional factors. Relative to ideators, enactors were more likely to have a family member/close friend who had self-harmed, more likely to think that their peers engaged in self-harm and they were more impulsive than the ideators. Enactors also reported more life stress than ideators. Conversely, the two self-harm groups did not differ on any of the variables associated with the development of self-harm thoughts.ConclusionsAs more adolescents think about self-harm than engage in it, a better understanding of the factors that govern behavioural enaction is crucial in the effective assessment of the risk of self-harm.
Myocardial infarction and generalised anxiety disorder: 10-year follow-up
Authors: Roest Annelieke M. , Zuidersma Marij , de Jonge Peter 
Published: March 2012

BackgroundFew studies have addressed the relationship between generalised anxiety disorder and cardiovascular prognosis using a diagnostic interview.AimsTo assess the association between generalised anxiety disorder and adverse outcomes in patients with myocardial infarction.MethodPatients with acute myocardial infarction (n = 438) were recruited between 1997 and 2000 and were followed up until 2007. Current generalised anxiety disorder and post-myocardial infarction depression were assessed with the Composite International Diagnostic Interview. The end-point consisted of all-cause mortality and cardiovascular-related readmissions.ResultsDuring the follow-up period, 198 patients had an adverse event. Generalised anxiety disorder was associated with an increased rate of adverse events after adjustment for age and gender (hazard ratio: 1.94; 95% confidence interval: 1.14–3.30; P = 0.01). Additional adjustment for measures of cardiac disease severity and depression did not change the results.ConclusionsGeneralised anxiety disorder was associated with an almost twofold increased risk of adverse outcomes independent demographic and clinical variables and depression.
Pax6 Is Crucial for β-Cell Function, Insulin Biosynthesis, and Glucose-Induced Insulin Secretion
Authors: Gosmain Yvan , Katz Liora S. , Masson Mounia Heddad , Cheyssac Claire , Poisson Caroline , Philippe Jacques 
Published: March 2012

AbstractThe Pax6 transcription factor is crucial for endocrine cell differentiation and function. Indeed, mutations of Pax6 are associated with a diabetic phenotype and a drastic decrease of insulin-positive cell number. Our aim was to better define the β-cell Pax6 transcriptional network and thus provide further information concerning the role of Pax6 in β-cell function. We developed a Pax6-deficient model in rat primary β-cells with specific small interfering RNA leading to a 75% knockdown of Pax6 expression. Through candidate gene approach, we confirmed that Pax6 controls the mRNA levels of the insulin 1 and 2, Pdx1, MafA, GLUT2, and PC1/3 genes in β-cells. Importantly, we identified new Pax6 target genes coding for GK, Nkx6.1, cMaf, PC2, GLP-1R and GIPR which are all involved in β-cell function. Furthermore, we demonstrated that Pax6 directly binds and activates specific elements on the promoter region of these genes. We also demonstrated that Pax6 knockdown led to decreases in insulin cell content, in insulin processing, and a specific defect of glucose-induced insulin secretion as well as a significant reduction of GLP-1 action in primary β-cells. Our results strongly suggest that Pax6 is crucial for β-cells through transcriptional control of key genes coding for proteins that are involved in insulin biosynthesis and secretion as well as glucose and incretin actions on β-cells. We provide further evidence that Pax6 represents a key element of mature β-cell function.
Clinical outcomes after percutaneous biliary interventions in patients with malignant biliary obstruction caused by metastatic gastric cancer
Authors: Gwon Dong II , Ko Gi-Young , Sung Kyu-Bo , Yoon Hyun-Ki , Kim Kyung-Ah , Kim Young Jun , Kim Tae Hwan , Lee Woong Hee 
Published: March 2012

Background No report has appeared on the histologic characteristics as influencing factors associated with clinical outcomes and survival of patients who underwent percutaneous biliary interventions to treat malignant biliary obstruction caused by metastatic gastric cancer. Purpose To investigate the clinical outcomes after percutaneous biliary interventions in patients with malignant biliary obstruction caused by metastatic gastric cancer and to identify prognostic factors associated with clinical outcomes. Material and Methods We retrospectively assessed 117 patients who underwent percutaneous transhepatic biliary drainage (PTBD) between January 2005 and December 2009, for treatment of malignant biliary obstructions caused by metastatic gastric cancer. Of these 117 patients, 54 subsequently underwent metallic stent placement. Results The technical success rates of PTBD and metallic stent placement were 100% and 100%, respectively. Self-limiting hemobilia after PTBD occurred in eight (7%) patients, and self-limiting hemobilia ( n = 4) and acute pancreatitis ( n = 3) after stent placement occurred in seven (13%) patients. Successful drainage was achieved in 105 (90%) of the 117 patients who underwent PTBD and in 49 (91%) of 54 patients who underwent metallic stent placement. Multiple Cox's regression analysis showed that the histology of primary gastric cancer ( P = 0.011), serum bilirubin after PTBD ( P = 0.002) and stenting ( P = 0.017), and chemotherapy after PTBD ( P < 0.001) and stenting ( P = 0.033) were independent predictors of survival. Conclusion PTBD and subsequent metallic stent placement were safe and effective methods for palliative treatment in patients with malignant biliary obstruction caused by metastatic gastric cancer. Patients with a differentiated histology of primary gastric cancer and serum bilirubin level ≤2 mg/dl after PTBD are probably the best candidates for treatment with a combination of metallic stent placement and chemotherapy.
Naturwissenschaften und manifestes Weltbild. Über den Naturalismus
Authors: Beckermann Ansgar 
Published: March 2012

Abstract
It is argued that an attractive version of naturalism may be characterized by five theses: 1. There is no substantial evidence that there are supernatural entities or forces that have an effect on the world. 2. The core of the modern scientific world view – the theory of atoms that tells us that all things in the world are made up of atoms and molecules and that all properties of any object can be explained by reference to the atoms it consists of and their spatial arrangement – is a very well confirmed empirical theory. 3. There is no methodological a priori to the effect that science is limited to the investigation of natural facts and to explanations that only refer to natural phenomena. 4. The scientific image of the world is not in conflict with the manifest image, it is rather an enlargement and an improvement of this image. 5. In case of seeming conflict, it is not a good idea to assume that there are aspects of reality that are beyond the scope of science or that above the natural world which is accessible to science there is another world in which things are different from what science tells us. Whatever the manifest image of the world tells us about reality must be compatible with what science tells about it. It is further argued that there are very good reasons to accept all these five theses as true.
Moral und Glück. Hoffnung bei Kant und Adorno
Authors: Wesche Tilo 
Published: March 2012

Abstract
Kant and Adorno alike have assumed that hope plays a central role in the relation between ethics and happiness. After comparing some of their different interpretations of hope, this paper traces the phil¬osophical account of the concept of hope which Kant and Adorno, however, agree on. They both see hope as essential for bridging the gulf between normativity and realities. Hope, they argue, features a weaker doxastic state than belief but a stronger one than wishful thinking. For Kant, the question “what may I hope? ” is part of the interests of human reason. By modifying this conception of hope, Adorno advocates a notion of hope, which accounts for a critique of religion and metaphysics.
„Krokodile hoffen nicht. Menschen hoffen.“. Bedeutung und Wert des Hoffens in der menschlichen Lebensform
Authors: Schmitz Barbara 
Published: March 2012

Abstract
Hope is a neglected topic in philosophy. This article tries to show that hope belongs to the human form of life. We start with Wittgenstein’s remark that human beings hope, while crocodiles cannot and explore the nature of hoping via three different routes: Firstly, we discuss the question whether hope is an emotion or a more or less rational attitude. Secondly, we put forward five characteristics of hope: the possibility of that which is hoped for, the temporality of the object of hope, the connection of hope and action, hope and passivity, and hope’s connection to language. Finally, we address the main counterarguments against the value of hope and argue that hope plays an important role in the ability to lead a human life, despite all the criticism it has received in philosophical thinking.
Entscheidend ist, was von unserem Willen abhängt
Authors: Beckermann Ansgar 
Published: March 2012

Zusammenfassung
Julius Schälike: Spielräume und Spuren des Willens. Eine Theorie der Freiheit und der moralischen Verantwortung. Mentis Verlag, Paderborn 2010, 296 S.
Efficacy and Tolerance of Urea Compared with Vaptans for Long-Term Treatment of Patients with SIADH
Authors: Soupart Alain , Coffernils Michel , Couturier Bruno , Gankam-Kengne Fabrice , Decaux Guy 
Published: March 2012

Summary

Background and objectives
Vaptans (vasopressin V2-receptor antagonists) are a new approach for the treatment of hyponatremia. However, their indications remain to be determined, and their benefit compared with that of the usual treatments for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) have not been evaluated. This prospective, long-term study compared the efficacy, tolerability, and safety of two oral vaptans with those of oral urea in patients with SIADH.

Design, setting, participants, & measurements
Patients with chronic SIADH of various origins were treated first with vaptans for 1 year. After an 8-day holiday period, they received oral urea for an additional 1-year follow-up. Serum sodium was measured every 2 months, and drug doses were adjusted accordingly.

Results
Thirteen participants were initially included in the study (serum sodium, 125±3 mEq/L); 12 completed the 2-year treatment period. Treatment with vaptans (satavaptan, 5–50 mg/d, n=10; tolvaptan, 30–60 mg/day, n=2) increased natremia (serum sodium, 135±3 mEq/L) during the 1-year vaptan period without escape. Hyponatremia recurred in the 12 participants when vaptans were stopped (holiday period). Urea improved the natremia with the same efficacy (serum sodium, 135±2 mEq/L) as vaptans during the 1-year urea treatment period. One participant treated with tolvaptan withdrew from the study early because of excessive thirst. Another patient receiving urea developed hypernatremia without complications.

Conclusions
Urea has efficacy similar to that of vaptans for treatment of chronic SIADH. Tolerance is generally good for both agents.
Modifiable Practices Associated with Sudden Death among Hemodialysis Patients in the Dialysis Outcomes and Practice Patterns Study
Authors: Jadoul Michel , Thumma Jyothi , Fuller Douglas S. , Tentori Francesca , Li Yun , Morgenstern Hal , Mendelssohn David , Tomo Tadashi , Ethier Jean , Port Friedrich , Robinson Bruce M. 
Published: March 2012

Summary

Background and objectives
Sudden death is common in hemodialysis patients, but whether modifiable practices affect the risk of sudden death remains unclear.

Design, setting, participants, & measurements
This study analyzed 37,765 participants in 12 countries in the Dialysis Outcomes and Practice Patterns Study to explore the association of the following practices with sudden death (due to cardiac arrhythmia, cardiac arrest, and/or hyperkalemia): treatment time [TT] <210 minutes, Kt/V <1.2, ultrafiltration volume >5.7% of postdialysis weight, low dialysate potassium [KD <3]), and prescription of Q wave/T wave interval–prolonging drugs. Cox regression was used to estimate effects on mortality, adjusting for potential confounders. An instrumental variable approach was used to further control for unmeasured patient-level confounding.

Results
There were 9046 deaths, 26% of which were sudden (crude mortality rate, 15.3/100 patient-years; median follow-up, 1.59 years). Associations with sudden death included hazard ratios of 1.13 for short TT, 1.15 for large ultrafiltration volume, and 1.10 for low Kt/V. Compared with KD ≥3 mEq/L, the sudden death rate was higher for KD ≤1.5 and KD=2–2.5 mEq/L. The instrumental variable approach yielded generally consistent findings. The sudden death rate was elevated for patients taking amiodarone, but not other Q wave/T wave interval–prolonging drugs.

Conclusions
This study identified modifiable dialysis practices associated with higher risk of sudden death, including short TT, large ultrafiltration volume, and low KD. Because KD <3 mEq/L is common and easy to change, KD tailoring may prevent some sudden deaths. This hypothesis merits testing in clinical trials.
PTH—A Particularly Tricky Hormone
Authors: Garrett Giorgia , Sardiwal Sunita , Lamb Edmund J. , Goldsmith David J.A. 
Published: March 2012

Summary
Plasma parathyroid hormone (PTH) concentrations are commonly measured in the context of CKD, as PTH concentration elevation is typical in this clinical context. Much has been inferred from this raised PTH concentration tendency, both about the state of skeletal integrity and health and also about the potential clinical outcomes for patients. However, we feel that reliance on PTH concentrations alone is a dangerous substitute for the search for, and use of, more precise and reliable biomarkers. In this article, we rehearse these arguments, bringing together patient-level and analytical considerations for the first time.
Attending Rounds
Authors: Glassock Richard J. 
Published: March 2012

Summary
Nephrotic syndrome in older adult patients is a common clinical conundrum. Membranous nephropathy (MN) is a lesion frequently found to underlie the nephrotic state in such patients. Determining with reasonable certainty whether the nephrotic syndrome and MN is primary (idiopathic) or due to an underlying disease such as neoplasia can be a daunting clinical challenge. By way of a presentation of an illustrative case and a focused review of the relevant literature, the approach to evaluation of such patients, with an emphasis on the putative causative role of neoplasia in MN, is analyzed and a potential contemporary pathway for acquiring the correct diagnosis is offered.
Finding a Common Language for Patient Safety in CKD
Authors: Fink Jeffrey C. , Joy Melanie S. , St. Peter Wendy L. , Wahba Ihab M. 
Published: March 2012

Summary
Improving patient safety has become a primary objective of health systems; however, the frequency of adverse safety events continues to be unacceptable despite the attention and dedicated efforts of many stakeholders. CKD that does not require dialysis increases the risk for adverse safety events, and adverse safety events can account for a substantial portion of the poor outcomes typical of CKD. Because much of CKD care occurs outside the typical health care setting, systems designed to detect and reduce adverse safety events are not necessarily effective in this population. Underrecognition (or underappreciation) of CKD and the associated impairment of renal function contribute to the high risk for adverse safety events. Medication errors are common in CKD and account for many lapses in patient safety, but a wide range of other potentially modifiable care processes in CKD also contribute to the high rate of observed adverse safety events. This review describes the spectrum of safety concerns specific to CKD and the need for a common set of standards to improve on current general constructs and to reduce adverse safety events in this chronic disease. An accepted set of disease-specific indicators is necessary to gauge the extent of the disease-specific patient safety problem and to design means to reduce adverse safety events and improve outcomes in CKD.
A Case Study on the Determination of Lost Profits for the Forensic Accountant
Authors: DiGabriele James A. 
Published: March 2012

ABSTRACT
This paper illustrates a teaching case study for use in a forensic accounting course. The case study requires students to prepare and/or present their findings for the valuation of lost profits in the framework of a business interruption. Readers obtain requisite financial and qualitative information to complete a valuation of lost profits due to a business interruption.
XBRL Tagging of Financial Statement Data Using XMLSpy:The Small Company Case
Authors: Elam Rick , Wenger Mitchell R. , Williams Kelly L. 
Published: March 2012

ABSTRACT
Publicly traded companies in the U.S. are required by the Securities and Exchange Commission (SEC) to file their financial statement data using XBRL tags. Other countries using international accounting standards have adopted similar XBRL filing requirements. This case provides a brief introduction to XBRL for business or accounting majors, and uses freely available software products (Altova XMLSpy) and training tools that help learners quickly progress through a basic introduction to XML (the foundation for XBRL), the XBRL taxonomy schema, and actual tagging of financial statement numbers. The basic skills learned in this case give accountants and other business professionals a working knowledge of how XBRL and other XML-based business documents are and can be used in practice. The case also raises awareness of the XBRL taxonomy development bodies, filing repositories, and development tools available in this domain for those interested in pursuing this technology in more detail.