bluuebunny/crossref_metadata_2025_split huggingface dataset:
The nuclear envelopathies and human diseases
Authors: Chi Ya-Hui , Chen Zi-Jie , Jeang Kuan-Teh 
Published: October 2009

Abstract
The nuclear envelope (NE) consists of two membrane layers that segregate the nuclear from the cytoplasmic contents. Recent progress in our understanding of nuclear-lamina associated diseases has revealed intriguing connections between the envelope components and nuclear processes. Here, we review the functions of the nuclear envelope in chromosome organization, gene expression, DNA repair and cell cycle progression, and correlate deficiencies in envelope function with human pathologies.
Predicting for activity of second-line trastuzumab-based therapy in her2-positive advanced breast cancer
Authors: Bartsch Rupert , De Vries Catharina , Pluschnig Ursula , Dubsky Peter , Bago-Horvath Zsuzsanna , Gampenrieder Simon P , Rudas Margaretha , Mader Robert M , Rottenfusser Andrea , Wiltschke Christoph , Gnant Michael , Zielinski Christoph C , Steger Guenther G 
Published: October 2009

Abstract

Background
In Her2-positive advanced breast cancer, the upfront use of trastuzumab is well established. Upon progression on first-line therapy, patients may be switched to lapatinib. Others however remain candidates for continued antibody treatment (treatment beyond progression). Here, we aimed to identify factors predicting for activity of second-line trastuzumab-based therapy.

Methods
Ninety-seven patients treated with > 1 line of trastuzumab-containing therapy were available for this analysis. Her2-status was determined by immunohistochemistry and re-analyzed by FISH if a score of 2+ was gained. Time to progression (TTP) on second-line therapy was defined as primary study endpoint. TTP and overall survival (OS) were estimated using the Kaplan-Meier product limit method. Multivariate analyses (Cox proportional hazards model, multinomial logistic regression) were applied in order to identify factors associated with TTP, response, OS, and incidence of brain metastases. p values < 0.05 were considered to indicate statistical significance.

Results
Median TTP on second-line trastuzumab-based therapy was 7 months (95% CI 5.74-8.26), and 8 months (95% CI 6.25-9.74) on first-line, respectively (n.s.). In the multivariate models, none of the clinical or histopthological features could reliably predict for activity of second-line trastuzumab-based treatment. OS was 43 months suggesting improved survival in patients treated with trastuzumab in multiple-lines. A significant deterioration of cardiac function was observed in three patients; 40.2% developed brain metastases while on second-line trastuzumab or thereafter.

Conclusion
Trastuzumab beyond progression showed considerable activity. None of the variables investigated correlated with activity of second-line therapy. In order to predict for activity of second-line trastuzumab, it appears necessary to evaluate factors known to confer trastuzumab-resistance.
Measuring disease-specific quality of life in rare populations: a practical approach to cross-cultural translation
Authors: Price Victoria E , Klaassen Robert J , Bolton-Maggs Paula HB , Grainger John D , Curtis Christine , Wakefield Cindy , Dufort Gustavo , Riedlinger Arne , Soltner Christophe , Blanchette Victor S , Young Nancy L 
Published: October 2009

Abstract

Background
Disease-specific quality of life (QoL) measures have enhanced the capacity of outcome measures to evaluate subtle changes and differences between groups. However, when the specific disease is rare, the cohort of patients is small and international collaboration is often necessary to accomplish meaningful research. As many of the QoL measures have been developed in North American English, they require translation to ensure their usefulness in a multi-cultural and/or international society. Published guidelines provide formal methods to achieve cross-culturally comparable versions of a QoL tool. However, these guidelines describe a rigorous process that is not always feasible, particularly in rare disease groups. The objective of this manuscript is to describe the process that was developed to achieve accurate cross-cultural translations of a disease-specific QoL measure, to overcome the challenges of a small sample size, i.e. children with a rare disorder.

Procedure
A measurement study was conducted in the United Kingdom (UK), France, Germany and Uruguay, during which the validated measure was translated into the languages of the respective countries.

Results
This is a report of a modified, child-centric, cross-cultural translation and adaptation process in which culturally appropriate and methodologically valid translations of a disease-specific QoL measure, the Kids' ITP Tools (KIT), were performed in children with immune thrombocytopenic purpura (ITP). The KIT was translated from North American English into UK English, French, German, and Spanish.

Conclusion
This study was a successful international collaboration. The modified process through which culturally appropriate and methodologically valid translations of QoL measures may be achieved in a pediatric population with a relatively rare disorder is reported.
Characterizing multisegment foot kinematics during gait in diabetic foot patients
Authors: Sawacha Zimi , Cristoferi Giuseppe , Guarneri Gabriella , Corazza Stefano , Donà Giulia , Denti Paolo , Facchinetti Andrea , Avogaro Angelo , Cobelli Claudio 
Published: October 2009

Abstract

Background
The prevalence of diabetes mellitus has reached epidemic proportions, this condition may result in multiple and chronic invalidating long term complications. Among these, the diabetic foot, is determined by the simultaneous presence of both peripheral neuropathy and vasculopathy that alter the biomechanics of the foot with the formation of callosity and ulcerations. To diagnose and treat the diabetic foot is crucial to understand the foot complex kinematics. Most of gait analysis protocols represent the entire foot as a rigid body connected to the shank. Nevertheless the existing multisegment models cannot completely decipher the impairments associated with the diabetic foot.

Methods
A four segment foot and ankle model for assessing the kinematics of the diabetic foot was developed. Ten normal subjects and 10 diabetics gait patterns were collected and major sources of variability were tested. Repeatability analysis was performed both on a normal and on a diabetic subject. Direct skin marker placement was chosen in correspondence of 13 anatomical landmarks and an optoelectronic system was used to collect the data.

Results
Joint rotation normative bands (mean plus/minus one standard deviation) were generated using the data of the control group. Three representative strides per subject were selected. The repeatability analysis on normal and pathological subjects results have been compared with literature and found comparable. Normal and pathological gait have been compared and showed major statistically significant differences in the forefoot and midfoot dorsi-plantarflexion.

Conclusion
Even though various biomechanical models have been developed so far to study the properties and behaviour of the foot, the present study focuses on developing a methodology for the functional assessment of the foot-ankle complex and for the definition of a functional model of the diabetic neuropathic foot. It is, of course, important to evaluate the major sources of variation (true variation in the subject's gait and artefacts from the measurement procedure). The repeatability of the protocol was therefore examined, and results showed the suitability of this method both on normal and pathological subjects. Comparison between normal and pathological kinematics analysis confirmed the validity of a similar approach in order to assess neuropathics biomechanics impairment.
Regulation of pathogenic IL-17 responses in collagen-induced arthritis: roles of endogenous interferon-gamma and IL-4
Authors: Sarkar Sujata , Cooney Laura A , White Peter , Dunlop Deborah B , Endres Judith , Jorns Julie M , Wasco Matthew J , Fox David A 
Published: October 2009

Abstract
Introduction
Interleukin (IL)-17 plays an important role in the pathogenesis of rheumatoid arthritis and the mouse model collagen-induced arthritis (CIA). Interferon(IFN)-γ and IL-4 have been shown to suppress Th17 development in vitro, but their potential immunoregulatory roles in vivo are uncertain. The goals of this study were to determine the relationship between Th17 responses and disease severity in CIA and to assess regulation of IL-17 by endogenous IFN-γ and IL-4.

Methods
DBA1/LacJ mice were immunized with type II collagen in complete Freund's adjuvant (CFA) to induce arthritis, and treated with neutralizing antibody to IFN-γ and/or IL-4. Systemic IL-17, IFN-γ, and IL-4 were measured in serum. At the peak of disease, cytokine production was measured by ELISA of supernatants from spleen, lymph node and paw cultures. Paws were also scored for histologic severity of arthritis.

Results
Joint inflammation was associated with a higher ratio of systemic IL-17/IFN-γ. Neutralization of IFN-γ accelerated the course of CIA and was associated with increased IL-17 levels in the serum and joints. The IFN-γ/IL-4/IL-17 responses in the lymphoid organ were distinct from such responses in the joints. Neutralization of IL-4 led to increased arthritis only in the absence of IFN-γ and was associated with increased bone and cartilage damage without an increase in the levels of IL-17.

Conclusions
IL-4 and IFN-γ both play protective roles in CIA, but through different mechanisms. Our data suggests that the absolute level of IL-17 is not the only determinant of joint inflammation. Instead, the balance of Th1, Th2 and Th17 cytokines control the immune events leading to joint inflammation.
Small Ubiquitin-Like Modifier-2 Modification of Retinoic Acid Receptor-α Regulates Its Subcellular Localization and Transcriptional Activity
Authors: Zhu Li , Santos Nadine C. , Kim Kwan Hee 
Published: October 2009

Abstract
The retinoic acid receptor-α (Rara) gene is critical for germ cell development in the testis, as demonstrated by infertile Rara knockout male mice. The encoded protein for Rara (RARA) is expressed in both Sertoli cells and germ cells, but it is not always in the nucleus. Previously, all-trans retinoic acid (ATRA) was shown to increase the nuclear localization and transcriptional activity of RARA in Sertoli cells. Here, we identified a small ubiquitin-like modifier-2 (SUMO-2) modification as a novel posttranslational regulatory mechanism controlling the ATRA-dependent RARA subcellular localization and transcription. ATRA increased the SUMO-2 modification of RARA. In the presence of ATRA, lysine 166 (K166) and K171 of RARA were modified at a physiological concentration of SUMO-2, whereas in the absence of ATRA, K399 was the only site that was modified, but at a higher SUMO-2 concentration. However, K399 was critical for ATRA-controlled nuclear trafficking of RARA. In the presence of ATRA, a K399 mutation to arginine resulted in the cytoplasmic localization of K399R mutant, indicating that K166 and K171 sumoylations were inhibitory to nuclear localization. This may be due to SUMO/sentrin-specific peptidase 6 (SENP6) not being able to bind K399R mutant to desumoylate K166 and K171 in Sertoli cells, whereas it can bind RARA with intact K399. On the other hand, functional K166 and K171 sites for sumoylation were required for a full transcriptional activity, when K399 was intact. These results together suggest that both K166 and K171 sumoylation and desumoylation are critical for optimal RARA function.
Revenue Management with Costly Price Adjustments
Authors: Çelik Sabri , Muharremoglu Alp , Savin Sergei 
Published: October 2009

We consider a novel variant of the perishable inventory profit management problem faced by a firm that sells a fixed inventory over a finite horizon in the presence of price-adjustment costs. In economics literature, such price-adjustment costs are widely studied and are typically assumed to include a fixed component (e.g., advertising costs), an inventory-dependent component (e.g., inventory relabeling costs), as well as a component that depends on the magnitude of the price adjustment (e.g., cognitive and coordination managerial costs). We formulate the firm's profit management problem as a finite-horizon dynamic program in which the state of the system is described by the inventory level as well as the current price level. We derive first-order properties of the optimal value function and give a complete characterization of optimal policies for the case of ample inventory. Through a set of examples we demonstrate the complex and counterintuitive nature of optimal price-adjustment policies. Consequently, we focus on developing easily computable and implementable heuristics with demonstrably good performance. To this end, we develop and solve a fluid model based on the original stochastic dynamics and propose three fluid-based heuristic policies. We derive expressions for the expected profit generated by each one of these heuristics when applied to the stochastic problem and derive sufficient conditions for the asymptotic optimality of the policies when the initial inventory levels and planning horizons are proportionally scaled up. We test the performance of the heuristics in a numerical study and demonstrate a robust, near-optimal performance of one of the heuristics (which we call the “Fluid Time” heuristic) for a wide range of problem parameters. Finally, we demonstrate the importance of proper accounting of price-adjustment costs in several alternative business settings.
Cerebrospinal Fluid Secretory Ca2+-Dependent Phospholipase A2 Activity Is Increased in Alzheimer Disease
Authors: Chalbot Sonia , Zetterberg Henrik , Blennow Kaj , Fladby Tormod , Grundke-Iqbal Inge , Iqbal Khalid 
Published: October 2009

AbstractBackground: The phospholipase A2 (PLA2) family comprises multiple isoenzymes that vary in their physicochemical properties, cellular localizations, calcium sensitivities, and substrate specificities. Despite these differences, PLA2s share the ability to catalyze the synthesis of the precursors of the proinflammatory mediators. To investigate the potential of PLA2 as a biomarker in screening neuroinflammatory disorders in both clinical and research settings, we developed a PLA2 assay and determined the predominant types of PLA2 activity in cerebrospinal fluid (CSF).Methods: We used liposomes composed of a fluorescent probe (bis-Bodipy® FL C11-PC [1,2-bis-(4,4- difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-undecanoyl)-sn-glycero-3-phosphocholine]) and 1,2-dioleoyl-l-α-phosphatidylcholine as a substrate to measure CSF PLA2 activity in a 96-well microtiter plate format. We established the type of CSF PLA2 activity using type-specific inhibitors of PLA2.Results: Using 5 μL CSF per assay, our PLA2 activity assay was reproducible with CVs &lt;15% in 2 CSF samples and for recombinant secretory Ca2+-dependent PLA2 (sPLA2) in concentrations ranging from 0.25 to 1 μmol/L. This PLA2 assay allowed identification of sPLA2 activity in lumbar CSF from healthy individuals 20–77 years old that did not depend on either sex or age. Additionally, CSF sPLA2 activity was found to be increased (P = 0.0008) in patients with Alzheimer disease.Conclusions: Adult human CSF has sPLA2 activity that can be measured reliably with the assay described. This enzyme activity in the CSF is independent of both sex and age and might serve as a valuable biomarker of neuroinflammation, as we demonstrated in Alzheimer disease.
Vergleich datenbasierter Lernverfahren für den Einsatz in der ZylinderdruckmodellierungComparative Analysis of Data Based Modeling Techniques for Cylinder Pressure Modeling
Authors: Weißenborn Erik , Bossmeyer Thomas , Bertram Torsten 
Published: October 2009

Zusammenfassung
Dieser Beitrag beinhaltet eine vergleichende Analyse datenbasierter Lernverfahren im Hinblick auf die Anwendung in einem empirischen Verbrennungsdruckmodell für Dieselmotoren. Neben den im Schwerpunkt betrachteten Neuro-Fuzzy-Modellen werden ein Polynommodell, ein Multilayer-Perceptron-Netz sowie ein nichtparametrischer Ansatz in die Analyse einbezogen. Als Ausgangspunkt dient eine Einführung in die Struktur des Zylinderdruckmodells mit Definition der konkreten Modellierungsprobleme sowie die kompakte Darstellung der Berechnungsvorschriften. Anschließend werden die Ergebnisse gegenübergestellt und die Verfahren anhand ausgewählter Bewertungskriterien verglichen.
Flachheitsbasierte Steuerung und Beobachtung von Transportprozessen mit verteiltem EingriffFlatness-based Control and Observer Design for Transport Processes with Distributed Control
Authors: Winkler Franz J. , Lohmann Boris 
Published: October 2009

Zusammenfassung
In diesem Artikel wird eine Methode zum Entwurf einer flachheitsbasierten Profilsteuerung für eine Klasse von Transportprozessen mit verteiltem Stelleingriff, basierend auf der Methode der Charakteristiken, vorgestellt. Die Entwurfsmethode wird an einem Durchlaufofen zur Lösung unterschiedlicher Steuerungsaufgaben angewendet. Zudem wird ein Beobachterentwurf eingeführt, der sich auf eine Sensorik stützt, welche mit dem Fördergut durch den Prozess transportiert wird.
Insulin resistance in hyperthyroidism: the role of IL6 and TNFα
Authors: Mitrou Panayota , Boutati Eleni , Lambadiari Vaia , Tsegka Aikaterini , Raptis Athanasios E , Tountas Nikolaos , Economopoulos Theofanis , Raptis Sotirios A , Dimitriadis George 
Published: October 2009

ObjectiveAlthough insulin resistance is a common finding in hyperthyroidism, the implicated mechanisms are obscure. The aim of this study was to investigate whether interleukin 6 (IL6) and tumour necrosis factor α (TNFα) are related to the development of insulin resistance in hyperthyroidism of nonautoimmune origin.Design and methodsA meal was given to ten hyperthyroid (HR) and ten euthyroid (EU) women. Plasma samples were taken for 360 min from the radial artery for measurements of glucose, insulin, and nonesterified fatty acids (NEFA). IL6 and TNFα were measured preprandially from the superficial epigastric vein and from the radial artery.Resultsi) In HR versus EU: (a) arterial glucose was similar (AUC0–3602087±57 vs 2010±43 mM×min), but insulin was increased (AUC0–36017 267±2447 vs 10 331±666 μU/ml×min,P=0.01), (b) homeostasis model assessment (HOMA) was increased (2.3±0.4 vs 1±0.1 kg/m2,P=0.007), (c) arterial NEFA were increased (AUC0–360136±18 vs 89±7 mmol/l×min,P=0.03), (d) arterial IL6 (2±0.3 vs 0.9±0.1 pg/ml,P=0.0009) and TNFα (4.2±0.8 vs 1.5±0.2 pg/ml,P=0.003) were increased, and (e) IL6 production from the subcutaneous adipose tissue (AT) was increased (18±6 vs 5±1 pg/min per 100 ml tissue,P=0.04). ii) (a) Subcutaneous venous IL6 was positively associated with HOMA (β-coefficient=1.7±0.7,P=0.049) and (b) although TNFα was not produced by the subcutaneous AT, arterial TNFα was positively associated with NEFA (AUC0–360;β-coefficient=0.045±0.01,P=0.005).ConclusionsIn hyperthyroidism: i) glucose and lipid metabolism are resistant to insulin, ii) subcutaneous AT releases IL6, which could then act as an endocrine mediator of insulin resistance, iii) although there is no net secretion of TNFα by the subcutaneous AT, increased systemic TNFα levels may be related to the development of insulin resistance in lipolysis.
Colon- és csepleszmetastasis okozta ileus mint a ductalis emlőrák első klinikai jeler
Authors: Bognár Gábor , Barabás Lóránd , Diczházi Csaba , Ondrejka Pál 
Published: October 2009

Absztrakt
Az emlőrák távoli áttétet jellemzően a csontokba, tüdőbe, májba és a központi idegrendszerbe ad. A csepleszbe és a gastrointestinalis traktusba (GI) adott áttétek ritkák. Jelen esetünkben egy 48 éves nőbeteg kapcsán ismertetjük a kórképet. A beteg ileus miatt került felvételre és műtétre, mely során a nagycseplesz és a colon daganatos elváltozásait észleltük és távolítottuk el. A szövettan invazív ductalis emlőrák (IDC) áttéteit igazolta. A beteg jobb emlőjében lévő a bőrt fogó, centrális IDC miatt ablatiót és axillaris lymphadenectomiát végeztünk. A ductalis emlőrák GI vagy hasüregi peritonealis áttéte ritka, az ileust okozó manifesztáció irodalmi ritkaság.
Serum Levels of the Adipokine Chemerin in Relation to Renal Function
Authors: Pfau Dörte , Bachmann Anette , Lössner Ulrike , Kratzsch Jürgen , Blüher Matthias , Stumvoll Michael , Fasshauer Mathias 
Published: October 2009

OBJECTIVE
To investigate serum levels of the adipokine chemerin in patients on chronic hemodialysis (CD) as compared with control patients with a glomerular filtration rate (GFR) &gt;50 ml/min.

RESEARCH DESIGN AND METHODS
Chemerin was quantified by ELISA in control patients (n = 60) and CD patients (n = 60) and correlated with clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation, in both groups.

RESULTS
Median serum chemerin levels were more than twofold higher in CD patients (542.2 μg/l) compared with subjects with a GFR &gt;50 ml/min (254.3 μg/l) (P &lt; 0.001). Furthermore, GFR, as assessed by the original Modification of Diet in Renal Disease formula, independently predicted circulating chemerin concentrations in multiple regression analyses in both control patients (P &lt; 0.05) and CD patients (P &lt; 0.01).

CONCLUSIONS
We demonstrate that markers of renal function are independently related to circulating chemerin levels.
There Is Inadequate Evidence to Determine the Effectiveness of Nonpharmacological and Nonsurgical Interventions for Hand Osteoarthritis: An Overview of High-Quality Systematic Reviews
Authors: Moe Rikke H. , Kjeken Ingvild , Uhlig Till , Hagen Kåre Birger 
Published: October 2009

Background
Patients with hand osteoarthritis are commonly treated by health care professionals (allied to medicine). Practice should be informed by updated evidence from systematic reviews of randomized controlled trials.

Purpose
The purpose of this overview is to summarize the evidence from systematic reviews of the effectiveness of nonpharmacological and nonsurgical interventions for patients with hand osteoarthritis.

Data Sources and Study Selection
Systematic reviews published between January 2000 and October 2008 were identified by a comprehensive literature search.

Data Extraction and Synthesis
Two reviewers independently selected reviews for inclusion, assessed their methodological quality, and extracted and synthesized data according to predefined criteria. Four systematic reviews finally were included. Based on single randomized controlled trials, there is some evidence of the effect of pain relief from topical capsaicin compared with placebo and for favorable functional outcomes for exercise and education compared with osteoarthritis information alone.

Limitations
In overviews, results are dependent on available systematic reviews. They are important tools to guide choice of interventions and locate areas where more research is needed, but they might not be useful for deciding specifically how interventions should be carried out.

Conclusions
There currently is insufficient high-quality evidence regarding nonpharmacological and nonsurgical interventions for hand osteoarthritis. Considering the limited research evidence and the prevalence and impact of the disease, there is an urgent need for more trials of nonpharmacological and nonsurgical interventions for hand osteoarthritis.