bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highly sensitive proximity mediated immunoassay reveals HER2 status conversion in the circulating tumor cells of metastatic breast cancer patients
Authors: Kim Phillip , Liu Xinjun , Lee Tani , Liu Limin , Barham Robert , Kirkland Richard , Leesman Glen , Kuller Anne , Ybarrondo Belen , Ng Shi-Chung , Singh Sharat 
Published: December 2011

AbstractBackgroundThe clinical benefits associated with targeted oncology agents are generally limited to subsets of patients. Even with favorable biomarker profiles, many patients do not respond or acquire resistance. Existing technologies are ineffective for treatment monitoring as they provide only static and limited information and require substantial amounts of tissue. Therefore, there is an urgent need to develop methods that can profile potential therapeutic targets with limited clinical specimens during the course of treatment.MethodsWe have developed a novel proteomics-based assay,CollaborativeEnzymeEnhancedReactive-immunoassay (CEER) that can be used for analyzing clinical samples. CEER utilizes the formation of unique immuno-complex between capture-antibodies and two additional detector-Abs on a microarray surface. One of the detector-Abs is conjugated to glucose oxidase (GO), and the other is conjugated to Horse Radish Peroxidase (HRP). Target detection requires the presence of both detector-Abs because the enzyme channeling event between GO and HRP will not occur unless both Abs are in close proximity.ResultsCEER was able to detect single-cell level expression and phosphorylation of human epidermal growth factor receptor 2 (HER2) and human epidermal growth factor receptor 1 (HER1) in breast cancer (BCa) systems. The shift in phosphorylation profiles of receptor tyrosine kinases (RTKs) and other signal transduction proteins upon differential ligand stimulation further demonstrated extreme assay specificity in a multiplexed array format. HER2 analysis by CEER in 227 BCa tissues showed superior accuracy when compared to the outcome from immunohistochemistry (IHC) (83% vs. 96%). A significant incidence of HER2 status alteration with recurrent disease was observed via circulating tumor cell (CTC) analysis, suggesting an evolving and dynamic disease progression. HER2-positive CTCs were found in 41% (7/17) while CTCs with significant HER2-activation without apparent over-expression were found in 18% (3/17) of relapsed BCa patients with HER2-negative primary tumors. The apparent 'HER2 status conversion' observed in recurrent BCa may have significant implications on understanding breast cancer metastasis and associated therapeutic development.ConclusionCEER can be multiplexed to analyze pathway proteins in a comprehensive manner with extreme specificity and sensitivity. This format is ideal for analyzing clinical samples with limited availability.
The splenic Littoral cell angioma in China: a case report and review
Authors: Hu Zong-Qiang , A Yong-Jun , Sun Qiang-Ming , Li Wen , Li Li 
Published: December 2011

Abstract
Littoral cell angioma (LCA) is a rare splenic vascular neoplasm that arises from the cells lining the red pulp sinuses. It is deemed to be a benign and incidental lesion. The earliest literature report of littoral cell angioma has been described by Falk. The examination of samples after splenectomy reveals similar pathological change and its change rule is summarized. However, many recent reports have described it to be a malignant tumor with congenital and immunological associations. Generally speaking, the definitive diagnosis can only be made after histological and immunohistochemical profiles. In this case report, we presented the case of a 48-year-old woman with multiple splenic LCAs. Initially, the patient was characteristics of abdominal distension, weakness and fatigue. Multiple hemangiomas were observed in the spleen through abdominal ultrasonic diagnosis. Computed tomography (CT) scans revealed the splenomegaly with multiple round and hyperdense lesions. The patient subsequently underwent splenectomy. Postoperative histological and immunohistochemical studies confirmed the diagnosis of LCA. Based on the presentation of this case, clinical, radiographic and pathological results of LCA as well as recent advances in our understanding of this uncommon splenic lesion were reviewed. LCA is an uncommon splenic tumor diagnosed in patients with or without abdominal discomfort. Only a few case reports regarding this kind of tumor have been published as inconsistent results. In the present paper, we have reported a case of LCA and reviewed the literature.
Biomarker analysis of Morquio syndrome: identification of disease state and drug responsive markers
Authors: Martell Lisa , Lau Kelly , Mei Miranda , Burnett Vicki , Decker Celeste , Foehr Erik D 
Published: December 2011

Abstract

Background
This study was conducted to identify potential biomarkers that could be used to evaluate disease progression and monitor responses to enzyme replacement therapy (ERT) in patients with mucopolysaccharidosis (MPS) IVA.

Methods
Levels of 88 candidate biomarkers were compared in plasma samples from 50 healthy controls and 78 MPSIVA patients not receiving ERT to test for significant correlations to the presence of MPSIVA. MPSIVA samples were also tested for correlations between candidate biomarkers and age, endurance, or urinary keratin sulfate (KS) levels. Then, levels of the same 88 analytes were followed over 36 weeks in 20 MPSIVA patients receiving ERT to test for significant correlations related to ERT, age, or endurance.

Results
Nineteen candidate biomarkers were significantly different between MPSIVA and unaffected individuals. Of these, five also changed significantly in response to ERT: alpha-1-antitrypsin, eotaxin, lipoprotein(a), matrix metalloprotein (MMP)-2, and serum amyloid P. Three of these were significantly lower in MPSIVA individuals versus unaffected controls and were increased during ERT: alpha-1-antitrypsin, lipoprotein(a), and serum amyloid P.

Conclusions
Candidate biomarkers alpha-1-antitrypsin, lipoprotein(a), and serum amyloid P may be suitable markers, in addition to urinary KS, to follow the response to ERT in MPSIVA patients.
Batch effect correction for genome-wide methylation data with Illumina Infinium platform
Authors: Sun Zhifu , Chai High Seng , Wu Yanhong , White Wendy M , Donkena Krishna V , Klein Christopher J , Garovic Vesna D , Therneau Terry M , Kocher Jean-Pierre A 
Published: December 2011

Abstract

Background
Genome-wide methylation profiling has led to more comprehensive insights into gene regulation mechanisms and potential therapeutic targets. Illumina Human Methylation BeadChip is one of the most commonly used genome-wide methylation platforms. Similar to other microarray experiments, methylation data is susceptible to various technical artifacts, particularly batch effects. To date, little attention has been given to issues related to normalization and batch effect correction for this kind of data.

Methods
We evaluated three common normalization approaches and investigated their performance in batch effect removal using three datasets with different degrees of batch effects generated from HumanMethylation27 platform: quantile normalization at average β value (QNβ); two step quantile normalization at probe signals implemented in "lumi" package of R (lumi); and quantile normalization of A and B signal separately (ABnorm). Subsequent Empirical Bayes (EB) batch adjustment was also evaluated.

Results
Each normalization could remove a portion of batch effects and their effectiveness differed depending on the severity of batch effects in a dataset. For the dataset with minor batch effects (Dataset 1), normalization alone appeared adequate and "lumi" showed the best performance. However, all methods left substantial batch effects intact in the datasets with obvious batch effects and further correction was necessary. Without any correction, 50 and 66 percent of CpGs were associated with batch effects in Dataset 2 and 3, respectively. After QNβ, lumi or ABnorm, the number of CpGs associated with batch effects were reduced to 24, 32, and 26 percent for Dataset 2; and 37, 46, and 35 percent for Dataset 3, respectively. Additional EB correction effectively removed such remaining non-biological effects. More importantly, the two-step procedure almost tripled the numbers of CpGs associated with the outcome of interest for the two datasets.

Conclusion
Genome-wide methylation data from Infinium Methylation BeadChip can be susceptible to batch effects with profound impacts on downstream analyses and conclusions. Normalization can reduce part but not all batch effects. EB correction along with normalization is recommended for effective batch effect removal.
A SNP in Steroid Receptor Coactivator-1 Disrupts a GSK3β Phosphorylation Site and Is Associated with Altered Tamoxifen Response in Bone
Authors: Hartmaier R. J. , Richter A. S. , Gillihan R. M. , Sallit J. Z. , McGuire S. E. , Wang J. , Lee A. V. , Osborne C. K. , O'Malley B. W. , Brown P. H. , Xu J. , Skaar T. C. , Philips S. , Rae J. M. , Azzouz F. , Li L. , Hayden J. , Henry N. L. , Nguyen A. T. , Stearns V. , Hayes D. F. , Flockhart D. A. , Oesterreich S. 
Published: December 2011

Abstract
The coregulator steroid receptor coactivator (SRC)-1 increases transcriptional activity of the estrogen receptor (ER) in a number of tissues including bone. Mice deficient in SRC-1 are osteopenic and display skeletal resistance to estrogen treatment. SRC-1 is also known to modulate effects of selective ER modulators like tamoxifen. We hypothesized that single nucleotide polymorphisms (SNP) in SRC-1 may impact estrogen and/or tamoxifen action. Because the only nonsynonymous SNP in SRC-1 (rs1804645; P1272S) is located in an activation domain, it was examined for effects on estrogen and tamoxifen action. SRC-1 P1272S showed a decreased ability to coactivate ER compared with wild-type SRC-1 in multiple cell lines. Paradoxically, SRC-1 P1272S had an increased protein half-life. The Pro to Ser change disrupts a putative glycogen synthase 3 (GSK3)β phosphorylation site that was confirmed by in vitro kinase assays. Finally, knockdown of GSK3β increased SRC-1 protein levels, mimicking the loss of phosphorylation at P1272S. These findings are similar to the GSK3β-mediated phospho-ubiquitin clock previously described for the related coregulator SRC-3. To assess the potential clinical significance of this SNP, we examined whether there was an association between SRC-1 P1272S and selective ER modulators response in bone. SRC-1 P1272S was associated with a decrease in hip and lumbar bone mineral density in women receiving tamoxifen treatment, supporting our in vitro findings for decreased ER coactivation. In summary, we have identified a functional genetic variant of SRC-1 with decreased activity, resulting, at least in part, from the loss of a GSK3β phosphorylation site, which was also associated with decreased bone mineral density in tamoxifen-treated women.
A "Democracy Building" Development Project Indicator for NGOs and International Organizations
Authors: Lempert David H. 
Published: December 2011

Abstract
The article offers an easy-to-use indicator for scholars and practitioners to measure whether non-governmental organizations (NGOs), international organizations, and government policies and projects meet the criteria for “democracy” that have been established by various international treaties and that are recognized by experts in the field. Use of this indicator on more than a dozen standard interventions funded today by international development banks, United Nations organizations, country donors, and NGOs reveals that most of the major actors in the field of development are actually failing to promote democracy and good governance and points to the specific areas where they need to improve in order to fulfill democracy, governance and rights criteria. This article also offers a sample test of the indicator using the United Nations High Commissioner for Human Rights (UNHCHR) as a case study.
Formants and Institutions: Intellectual Meeting Points between Rodolfo Sacco and Douglass North
Authors: Biglino Irene 
Published: December 2011

Abstract
In the present paper, I attempt to unearth what I believe to be an extremely valuable, implicit dialogue between legal and economic discourse through an analysis of the contributions by two leading figures in the fields of comparative law and institutional economics, respectively: Rodolfo Sacco and Douglass North. By closely comparing two apparently far removed intellectual trajectories, I will sketch the manner in which the two scholars come to terms with the concept of change in their respective disciplines. How is legal change, on the one hand, and economic change, on the other hand, explained? I will examine how North addresses the question “why do economies perform differently through space and time?” and review Sacco’s inquires upon convergence and divergence in legal systems with different institutional premises. Once the distinctive features of the two theses have been outlined against the backdrop of the latter questions, I will identify intellectual meeting points, common threads, and parallel tracks drawing the scholars together. In the spirit of methodological pluralism, I will conclude by suggesting that a combined reading of the theses under scrutiny may provide a practical template for thinking about questions of legal change, legal transplants, and the diffusion of legal consciousness.
Contesting Property Rights: Towards an Integrated Theory of Institutional and System Change
Authors: Pistor Katharina 
Published: December 2011

Abstract
It is widely recognized that institutions are embedded in social systems and that institutions as well as social systems change over time. Several implications follow: First, institutions cannot be described and analyzed without referring to the system in which they operate; conversely, a system cannot be described without reference to its core institutions. Second, systems foster institutional change and can breed new institutions. Third, institutional change can have systemic implications and may even engender the formation of new systems. In short, the relation between institutions and systems is characterized by complex interactions. A better understanding of the dynamics of institutional change therefore necessitates a synthesis of social system and institutional theories and a re-direction of attention from institutions or systems to interdependencies between them. This paper seeks to develop the building blocks for an integrated theory of social and institutional change. Thematically it focuses on contested property rights. The paper argues that the scope and limits of property rights are determined by the manner in which contests for control can be resolved within a broader system, which may, but does not have to, be that of a nation state. A comparative analysis of transnational property rights cases shall help shed light on the relation between property rights institutions and the system that determines if and how they are realized. These case studies serve as heuristics for generating insights about the dynamics of institutional and systemic change.
Reversibility of the Effects of Aliskiren in the Renal Versus Systemic Circulation
Authors: Schneider Markus P. , Janka Rolf , Ziegler Thomas , Raff Ulrike , Ritt Martin , Ott Christian , Veelken Roland , Uder Michael , Schmieder Roland E. 
Published: December 2011

Summary

Background and objectives
Renal hemodynamic effects of inhibitors of the renin-angiotensin system can increase the risk of acute kidney injury under certain conditions. The BP-lowering effects of the renin inhibitor aliskiren are sustained 3–4 weeks after withdrawal. In this study, the reversibility of the renal hemodynamic effects of aliskiren was tested.

Design, setting, participants, & measurements
In this open-label study, renal perfusion was measured by 1.5-T magnetic resonance imaging–arterial spin labeling in 34 subjects with arterial hypertension before aliskiren (pre-aliskiren), after 4 weeks of aliskiren treatment (300 mg), and 4–5 days (∼2.5–3.0× plasma half-life) after withdrawal (post-aliskiren).

Results
Aliskiren reduced systolic BP from 152 ± 14 to 139 ± 16 mmHg (P<0.0001), which was sustained post-aliskiren (136 ± 13 mmHg, P=1.00 versus aliskiren). Aliskiren significantly altered renal perfusion (P=0.005), increasing from 272 ± 25 pre-aliskiren to 287 ± 29 ml/min per 100 g during aliskiren (P=0.03). This increase in renal perfusion was completely reversed post-aliskiren (272 ± 26 ml/min per 100 g, P=0.03 versus aliskiren, P=0.63 versus pre-aliskiren). No changes were noted in urinary angiotensinogen levels. Plasma renin activity was reduced by aliskiren, which was sustained post-aliskiren. Angiotensin II and aldosterone were reduced by aliskiren but recovered post-aliskiren to pre-aliskiren levels.

Conclusions
After withdrawal of aliskiren, the effects on BP were sustained, whereas increase in renal perfusion was reversed, which was associated with recovery of angiotensin II and aldosterone to pretreatment levels. Renal hemodynamic effects are more readily reversible than systemic effects of aliskiren.
A Perspective on the Joint IASB/FASB Exposure Draft on Accounting for Leases
Authors: Biondi Yuri , Bloomfield Robert J. , Glover Jonathan C. , Jamal Karim , Ohlson James A. , Penman Stephen H. , Tsujiyama Eiko , Wilks T. Jeffrey 
Published: December 2011

SYNOPSIS
The International Accounting Standards Board (IASB) and the Financial Accounting Standards Board (FASB) recently issued a joint exposure draft on accounting for leases. This exposure draft seeks to shift lease accounting from an “ownership” model to a “right-of-use” model. Under the current ownership model, leases can be reported on balance sheet (finance leases) if certain tests are met, or off balance sheet (operating leases) if those tests are not met. The new model seeks to report all leases on the balance sheet based on the present value of lease obligations without any bright line tests, and no sharp on or off the balance sheet classifications.
We are sympathetic to the standard setters' concern that the current lease standard is being manipulated improperly by managers, resulting in large amounts of debt being reported off balance sheet. We provide a discussion of current lease accounting and the proposed exposure draft. We also comment on five key issues covered by the exposure draft: the definition of a lease, the initial measurement and eventual reassessment at fair values, the accounting for lessors, the impact of lease accounting on recognition and income measurement, and classification of lease accounting elements and their impact on accounting ratios.
JEL Classifications: M40.
A larger GL
2 large sieve in the level aspect
Authors: Djanković Goran 
Published: December 2011

Abstract
In this paper we study the orthogonality of Fourier coefficients of holomorphic cusp forms in the sense of large sieve inequality. We investigate the family of GL
2 cusp forms modular with respect to the congruence subgroups Γ1(q), with additional averaging over the levels q ∼ Q. We obtain the orthogonality in the range N ≪ Q
2−δ
for any δ > 0, where N is the length of linear forms in the large sieve.
Treatment of patients with traumatic subdural effusion and concomitant hydrocephalus
Authors: Tsuang Fon-Yih , Huang Abel Po-Hao , Tsai Yi-Hsin , Chen Jo-Yu , Lee Jing-Er , Tu Yong-Kwang , Wang Kuo-Chuan 
Published: December 2011

Object
Traumatic subdural effusion (TSE) is a common sequela of traumatic brain injury. Surgical intervention is suggested only when TSE exerts mass effect. The authors have found that many patients with TSE exerting mass effect have concomitant hydrocephalus. Patient experiencing this occurrence were studied, and the pathogenesis of this phenomenon was discussed in the context of recent advances in the understanding of CSF circulation.

Methods
During a 2-year period, the authors' institution treated 14 patients with TSE who developed hydrocephalus, after 1 of the patients suffered subdural drainage and other 13 received subdural peritoneal shunt (SPSs). Thirteen of those who had SPSs received programmable ventriculoperitoneal shunts (VPSs) for the hydrocephalus. The clinical characteristics as well as the imaging and operative findings of these patients were reviewed.

Results
All patients with symptomatic TSE exerting mass effect received SPSs. All of these patients had a modified Frontal Horn Index of more than 0.33 at presentation, and high opening pressure on durotomy. Following a brief period (4–7 days) of clinical improvement, the condition of all patients deteriorated due to hydrocephalus. Programmable VPSs were inserted with the initial pressure set at approximately 8–10 cm H2O according to opening pressure at ventriculostomy. Shunt valve pressure was gradually decreased to 5–7 cm H2O, according to clinical and radiological follow-up.

Conclusions
Elevated modified Frontal Horn Index in patients with TSE is suggestive of concomitant hydrocephalus. The authors propose that tearing of the dura-arachnoid plane following trauma contributes to TSE and may also impede CSF circulation, causing hydrocephalus. Shunt pressure was adjusted to relative low pressure, indicating the old age of the patients and poor reexpansion of brain parenchyma after the mass effect. Subdural peritoneal shunts and VPSs are indicated in those patients with TSE exerting mass effect with concomitant hydrocephalus.
Prognosis of 2009 A(H1N1) Influenza in Hospitalized Pregnant Women in a Context of Early Diagnosis and Antiviral Therapy
Authors: Paño-Pardo José Ramón , Rodríguez-Baño Jesús , Martínez-Sánchez Nuria , Viasus Diego , Fariñas M Carmen , Leyes María , López-Medrano Francisco , Pachón Jerónimo , Torre-Cisneros Julián , Oteo José Antonio , Pumarola Tomás , García-Gasalla Mercedes , Ortega Lucía , Segura Ferrán , Carratalá Jordi ,   the Novel Influenza A(H1N1) Study Group of the Spanish Network for Research in Infectious Diseases (REIPI)
Published: December 2011

Background Initial reports suggested that novel A(H1N1) influenza virus (2009 A[H1N1]v) infection was significantly more severe in pregnant than in non-pregnant women. In Spain, antiviral therapy was recommended for pregnant women from the beginning of the 2009 pandemic. Methods The prospective cohort study included consecutive pregnant and non-pregnant women of reproductive age with a proven diagnosis of 2009 A(H1N1)v admitted to any of the 13 participating Spanish hospitals between 12 June and 10 November 2009. Results In total, 98 pregnant and 112 non-pregnant women with proven 2009 A(H1N1)v hospitalized during the study period were included. Influenza was more severe among non-pregnant patients than pregnant patients with respect to outcomes of both intensive care unit admission (18% versus 2%; P<0.001) and death (5 versus 0; P=0.06). Pregnant women had fewer associated comorbid conditions other than pregnancy (18% versus 44%; P<0.001); they were also admitted earlier than non-pregnant women (median days since onset of symptoms: 2 versus 3; P<0.001) and a higher percentage received early antiviral therapy (41% versus 28%; P=0.03). Neither a multivariate nor a matched cohort analysis found pregnancy to be associated with greater severity than that associated with hospitalized, seriously ill non-pregnant women. Conclusions 2009 A(H1N1)v influenza was not associated with worse outcomes in hospitalized pregnant women compared with non-pregnant ones of reproductive age in a context of early diagnosis and antiviral therapy.