bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic fusion to albumin improves the pharmacokinetic properties of factor IX
Authors: Weimer Thomas , Kronthaler Ulrich , Lang Wiegand , Schulte Stefan , Metzner Hubert J. 
Published: September 2009

SummaryHaemophilia B is a X-chromosome linked disease characterised by a deficiency of functionally active coagulation Factor IX (FIX). Patients with severe haemophilia B at risk of recurrent bleeding are treated approximately twice a week in a prophylactic setting by application of FIX concentrates.To increase convenience and compliance of the therapy it is desirable to reduce the dosing frequency by improving the pharmacokinetic properties of FIX. Here a concept of rFIX (recombinant factor IX) albumin fusion proteins (rIX-FPs) with cleavable linker peptides derived from the FIX activation sequence is presented. Constructs of the genetic fusion of FIX to albumin via cleavable linkers were expressed in mammalian cells and characterised after purification. In vitro activation studies with FXIa demonstrated that cleavage of the linker and the activation peptide proceeded comparably well. In a clotting assay the rIX-FPs with cleavable linker showed a 10- to 30-fold increase in the molar specific clotting activity compared to fusion proteins with non-cleavable linkers. Furthermore, in-vivo recovery, terminal half-life and the AUC of rIX-FPs in rats and rabbits as determined by FIX antigen measurements were significantly increased compared to rFIX (BeneFIX®). In FIX deficient (FIX−/−) mice the in-vivo recovery and the AUC were also significantly increased.The efficacy in reducing bleeding time was shown in FIX−/−mice by a tail tip bleeding model. The results suggest that rIX-FPs with a cleavable linker between FIX and albumin are a promising concept that may support the use of the albumin fusion technology to extend the half-life of FIX.
Association of fatigue and psychological distress with quality of life in patients with a previous venous thromboembolic event
Authors: Lukas Paul , Krummenacher René , Biasiutti Franziska , Begré Stefan , Znoj Hansjörg , von Känel Roland 
Published: September 2009

SummaryHealth-related quality of life (QoL) has been associated with several social and medical conditions in patients with deep vein thrombosis (DVT) and pulmonary embolism (PE).To the best of our knowledge,there is no study investigating the relationship of QoL with psychological variables in this patient population.We assumed as a hypothesis an association between heightened levels of fatigue and psychological distress, as well as decreased QoL in patients with an objectively diagnosed venous thromboembolic event. Study participants were 205 consecutively enrolled out-patients (47.4 years, 54.6% men) with DVT and/or PE. Approximately 10 days before blood collection for thrombophilia work-up, QoL, fatigue, and psychological distress were assessed using the Short Form Health Survey (SF-12), the Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) as well as the Hospitality Anxiety and Depression scale (HADS). After controlling for demographic and medical factors, fatigue (p<0.01) but not psychological distress (p>0.05) was negatively associated with physical QoL, explaining 11.0% of the variance. Fatigue (p<0.001) and psychological distress (p<0.001) were significant predictors of mental QoL,explaining an additional 36.2% and 3.6% of the variance. Further analyses revealed that all subscales of the HADS (e.g. anxiety and depression) and of the MFSI-SF (e.g. general fatigue, physical fatigue, emotional fatigue, mental fatigue and vigor) were significant predictors of mental QoL. MFSI-SF subscales also predicted physical QoL. The findings suggest that fatigue and psychological distress substantially predict QoL in patients with a previous venous thromboembolic event above and beyond demographic factors.
Risk factors for cerebral venous thrombosis and deep venous thrombosis in patients aged between 15 and 50 years
Authors: Uyttenboogaart Maarten , Vroomen Patrick C. A. J. , De Keyser Jacques , Luijckx Gert-Jan , Koopman Karen , van der Meer Jan 
Published: September 2009

SummaryCerebral venous thrombosis (CVT) and deep vein thrombosis or pulmonary embolism (DVT/PE) are associated with many risk factors. It is unclear why CVT occurs less often than DVT/PE. Age dependent risk factors may play a role. The aim of our study was to compare risk factors in a uniform age group of CVT and DVT/PE patients aged between 15 and 50 years. Thrombophilic markers and clinical risk factors of 79 CVT patients and 173 DVT/PE patients aged 15–50 years were compared. Multivariable logistic regression analysis was performed to investigate if risk factors were independently associated with CVT or DVT/ PE. Cerebral venous thrombosis patients were younger (median age 30 years vs. 42 years; p<0.001) and more often female (82% vs. 52%; p<0.001). There were no differences in thrombophilic markers. Cerebral venous thrombosis was less often associated with trauma, immobilisation or surgery than DVT/PE (6% vs. 21%; adjusted OR 0.29; 95%CI 0.10–0.82). In women, CVT was more frequently associated with oral contraceptive use, pregnancy or puerperium (82% vs. 53%; adjusted OR 2.34; 95%CI 1.03–5.32).This study demonstrated no differences in thrombophilic markers between CVT patients and DVT/PE patients aged between 15 and 50 years, while the frequency of some transient risk factors was different. Cerebral venous thrombosis was relatively more common in women and hormonal factors may predispose to CVT compared to DVT/PE, while trauma, immobilisation and surgery may be less important in the pathophysiology of CVT.
The Humdrum Use of Ultimate Authority: Defining and Analysing Chapter VII Resolutions
Authors: Johansson Patrik 
Published: September 2009

AbstractUnder Chapter VII of the Charter of the United Nations, the Security Council has the unique authority to make decisions that are binding on member states. However, the lack of a standard definition of what makes a Security Council resolution "a Chapter VII resolution" has caused disagreement regarding the status of several resolutions. This is unfortunate as the international community should never have to doubt whether a Security Council resolution is in fact adopted under Chapter VII or not. It is also unnecessary. This article addresses this problem by proposing a definition of Chapter VII resolutions, based on two criteria referred to as "Article 39 determinations" and "Chapter VII decisions". On the basis of the proposed definition, the article describes and analyses a dramatic increase in the use of Chapter VII during the post-Cold War era. It concludes that as Chapter VII has come to constitute the majority of Security Council resolutions in recent years, the resort to Chapter VII no longer signifies exceptional determination and resolve, which it did during the Cold War; instead Chapter VII today implies business as usual. An appendix lists all Chapter VII resolutions from 1946–2008.
The Contribution of the International Court of Justice to the Law on the Use of Force: Missed Opportunities or Unrealistic Expectations?
Authors: McKeever David 
Published: September 2009

AbstractIn recent years, the International Court of Justice has been presented with opportunities to pronounce on important dimensions of the law on the use of force. An assessment of the court's handling of these issues must consider first the role attributed to the Court within the international legal regime for preventing and mitigating the use of force, and thus what exactly would amount to 'success' for the Court in such cases. Notwithstanding the inherent limitations on the Court's capacity in this area, this article argues that the Court has largely failed to provide clear guidance on pressing legal questions. An unwarranted caution in utilising the judicial tools at its disposal is one important factor in this regard. Finally, this article highlights some potential consequences of the Court's recent work for the development of international law on the use of force.
Hill-Sachs Defects and Repair Using Osteoarticular Allograft Transplantation
Authors: Sekiya Jon K. , Wickwire Alexis C. , Stehle Jens H. , Debski Richard E. 
Published: September 2009

Background Humeral head defects have been associated with failed anterior shoulder instability repairs. Quantitative data are required to determine (1) the critical defect size for consideration of surgical repair and (2) the ability of proposed repair techniques to restore normal joint function. Hypotheses Increasing defect size will decrease stability and anterior translation before dislocation. Stability will decrease in shoulder positions where the defect is oriented in line with the anterior glenoid. Osteoarticular repair will restore joint stability to intact shoulder level. Study design Controlled laboratory study. Methods A robotic/universal force-moment sensor testing system was used to apply joint compression (22 N) and an anterior load (40 N) to cadaveric shoulders (n = 9) with all soft tissues removed (intact) at joint orientations with 60° of glenohumeral abduction and 0° and 60° of external rotation. Four posterolateral osteoarticular defects were created (12.5%, 25.0%, 37.5%, and 50.0% defect) followed by an osteoarticular allograft transplantation (repair). The loading protocol was repeated in each shoulder state for both joint orientations. The anterior translation and stability ratio (anterior load/compressive load) were recorded before dislocation. Results All shoulders dislocated at 60° of external rotation with all sizes of defects. At 0° of external rotation, shoulders with the 12.5% to 37.5% defects did not dislocate, and only 2 shoulders with the 50.0% defect dislocated. At 60° of external rotation, the 25.0% defect and 37.5% defect had significantly less anterior translation before dislocation, as compared with the intact ( P < .05), both of which became similar to the intact after repair ( P > .05). The stability ratio at 60° of external rotation significantly decreased in the 25.0% and 37.5% defects, as compared with the intact ( P < .05), representing a 25% and 40% decrease in stability ratio. The stability ratio became similar to intact after repair ( P > .05). Conclusion The size and orientation of the defect has important contributions to glenohumeral joint function. Increasing defect size required less anterior translation before dislocation and decreased the stability ratio, thereby increasing the risk of recurrent instability. Clinical Relevance Defects as small as 12.5% of the humeral head have biomechanical consequences that may affect joint stability. In addition, shoulders with large osteoarticular defects (37.5% or 50.0%) may benefit from osteoarticular allograft transplantation to restore shoulder stability.
Sequential Alterations in Magnetic Resonance Imaging Findings After Autologous Osteochondral Mosaicplasty for Young Athletes With Osteochondritis Dissecans of the Humeral Capitellum
Authors: Iwasaki Norimasa , Kato Hiroyuki , Kamishima Tamotsu , Minami Akio 
Published: September 2009

Background The goal of osteochondral mosaicplasty (mosaicplasty) against osteochondritis dissecans of the humeral capitellum (capitellar OCD) is to allow patients to return to their sports activities without functional disturbance of the affected elbow. Consequently, the rehabilitation protocol and the interval before returning to sports activities must be established. Although surgeons need this type of data for establishing sequential alterations of grafts in the elbow, no such data have been published. Hypothesis The findings of magnetic resonance imaging (MRI) improve with increasing time after mosaicplasty for capitellar OCD. Study Design Case series; Level of evidence, 4. Methods Ten young male athletes with advanced lesions of capitellar OCD, treated with mosaicplasties, underwent MRI scans at 3, 6, and 12 months, postoperatively. The surgical technique involved obtaining small-sized cylindrical osteochondral grafts from the lateral periphery of the femoral condyle at the level of the patellofemoral joint and transplanting them to the capitellar lesion. The MRI findings were semiquantitatively assessed according to the scoring system of Henderson et al (4, normal; 16, no repair). Results At 12 months, all patients returned to their competitive level of sports without any disturbances of the operated elbow. Fluid surrounding the graft was found in all patients at 3 months and 4 patients at 6 months. The grafts were all well seated within the recipient sites, with no MRI evidence of graft loosening at 12 months. The overall MRI scores significantly improved from 3 to 12 months. Conclusion The MRI findings indicate that the graft incorporation to the surrounding tissues occurs around or after 6 months, postoperatively. This finding suggests that rehabilitation precautions be taken for up to 6 months after mosaicplasty for young athletes with capitellar OCD.
Tibiofemoral and Patellofemoral Kinematics After Reconstruction of an Isolated Posterior Cruciate Ligament Injury
Authors: Gill Thomas J. , Van de Velde Samuel K. , Wing David W. , Oh Luke S. , Hosseini Ali , Li Guoan 
Published: September 2009

Background The actual in vivo tibiofemoral and patellofemoral kinematics of the posterior cruciate ligament (PCL)-reconstructed knee joint are unknown. Hypothesis Current single-bundle PCL reconstruction is unable to correct the abnormal tibiofemoral and patellofemoral kinematics caused by rupture of the ligament. Study Design Controlled laboratory study/case series; Level of evidence, 4. Methods Seven patients with an isolated PCL injury in 1 knee and the contralateral side intact were included in the study. Magnetic resonance and dual fluoroscopic imaging techniques were used to compare the tibiofemoral and patellofemoral kinematics between the intact contralateral (control group), PCL-deficient, and PCL-reconstructed knee during physiologic loading with a single-legged lunge. Data were collected preoperatively and 2 years after single-bundle reconstruction. Results The PCL reconstruction reduced the abnormal posterior tibial translation in PCL-deficient knees to levels not significantly different from those of the intact knee. Posterior cruciate ligament deficiency resulted in an increased lateral tibial translation between 75° and 120° of flexion, and reconstruction was unable to restore these values to normal. No differences were detected among the groups in varus-valgus and internal-external rotation. The PCL reconstruction reduced the increased patellar flexion of PCL-deficient knees between 90° and 120° of knee flexion and the lateral shift at 120°. The abnormal patellar rotation and tilt seen in PCL deficiency at flexion angles of 75° and greater persisted after reconstruction. Conclusion Single-bundle PCL reconstruction was successful in restoring normal anteroposterior translation of the tibia, as well as the patellar flexion and shift. However, single-bundle PCL reconstruction was unable to achieve the same success in mediolateral translation of the tibia or in the patellar rotation and tilt. Clinical Relevance The persistent abnormal mediolateral translation of the tibia, as well as decreased patellar rotation and tilt, provide a possible explanation for the development of cartilage degeneration after reconstruction of an isolated PCL injury.
Testosterone and phosphodiesterase type-5 inhibitors: new strategy for preventing endothelial damage in internal and sexual medicine?
Authors: Aversa Antonio , Bruzziches Roberto , Francomano Davide , Natali Marco , Lenzi Andrea 
Published: September 2009

Normal vascular endothelium is essential for the synthesis and release of substances affecting vascular tone (e.g. nitric oxide; NO), cell adhesion (e.g. endothelins, interleukins), and the homeostasis of clotting and fibrinolysis (e.g. plasminogen inhibitors, von Willebrand factor). The degeneration of endothelial integrity promotes adverse events (AEs) leading to increased atherogenesis and to the development of vascular systemic and penile end-organ disease. Testosterone (T) is an important player in the regulation of vascular tone through non-genomic actions exerted via blockade of extracellular-calcium entry or activation of potassium channels; also, adequate T concentrations are paramount for the regulation of phosphodiesterase type-5 (PDE5) expression and finally, for the actions exerted by hydrogen sulphide, a gas involved in the alternative pathway controlling vasodilator responses in penile tissue. It is known that an age-related decline of serum T is reported in approximately 20 to 30% of men whereas T deficiency is reported in up to 50% of men with metabolic syndrome or diabetes. A number of laboratory and human studies have shown the combination of T and other treatments for erectile dysfunction (ED), such as PDE5 inhibitors, to be more beneficial in patients with ED and hypogonadism, who fail monotherapy for sexual disturbances.The aim of this review is to show evidence on the role of T and PDE5 inhibitors, alone or in combination, as potential boosters of endothelial function in internal medicine diseases associated with reduced T or NO bioavailability, i.e. metabolic syndrome, obesity, diabetes, coronary artery disease, hyperhomocysteinemia, that share common risk factors with ED. Furthermore, the possibility of such a strategy to prevent endothelial dysfunction in men at increased cardiovascular risk is discussed.
In vivo prostaglandin E2 treatment alters the bone marrow microenvironment and preferentially expands short-term hematopoietic stem cells
Authors: Frisch Benjamin J. , Porter Rebecca L. , Gigliotti Benjamin J. , Olm-Shipman Adam J. , Weber Jonathan M. , O'Keefe Regis J. , Jordan Craig T. , Calvi Laura M. 
Published: September 2009

Abstract
Microenvironmental signals can determine hematopoietic stem cell (HSC) fate choices both directly and through stimulation of niche cells. In the bone marrow, prostaglandin E2 (PGE2) is known to affect both osteoblasts and osteoclasts, whereas in vitro it expands HSCs and affects differentiation of hematopoietic progenitors. We hypothesized that in vivo PGE2 treatment could expand HSCs through effects on both HSCs and their microenvironment. PGE2-treated mice had significantly decreased number of bone trabeculae, suggesting disruption of their microarchitecture. In addition, in vivo PGE2 increased lineage− Sca-1+ c-kit+ bone marrow cells without inhibiting their differentiation. However, detailed immunophenotyping demonstrated a PGE2-dependent increase in short-term HSCs/multipotent progenitors (ST-HSCs/MPPs) only. Bone marrow cells transplanted from PGE2 versus vehicle-treated donors had superior lymphomyeloid reconstitution, which ceased by 16 weeks, also suggesting that ST-HSCs were preferentially expanded. This was confirmed by serial transplantation studies. Thus in vivo PGE2 treatment, probably through a combination of direct and microenvironmental actions, preferentially expands ST-HSCs in the absence of marrow injury, with no negative impact on hematopoietic progenitors or long-term HSCs. These novel effects of PGE2 could be exploited clinically to increase donor ST-HSCs, which are highly proliferative and could accelerate hematopoietic recovery after stem cell transplantation.
A new pet for myeloma
Authors: Dimopoulos Meletios-Athanassios , Moulopoulos Lia A. , Terpos Evangelos 
Published: September 2009

Abstract
In this issue of Blood, Bartel and colleagues report the independent predictive value of the PET/CT and of the FDG suppression before transplantation in newly diagnosed myeloma patients who were treated using the TT3 regimen.1
GEM-TREND: a web tool for gene expression data mining toward relevant network discovery
Authors: Feng Chunlai , Araki Michihiro , Kunimoto Ryo , Tamon Akiko , Makiguchi Hiroki , Niijima Satoshi , Tsujimoto Gozoh , Okuno Yasushi 
Published: September 2009

Abstract

Background
DNA microarray technology provides us with a first step toward the goal of uncovering gene functions on a genomic scale. In recent years, vast amounts of gene expression data have been collected, much of which are available in public databases, such as the Gene Expression Omnibus (GEO). To date, most researchers have been manually retrieving data from databases through web browsers using accession numbers (IDs) or keywords, but gene-expression patterns are not considered when retrieving such data. The Connectivity Map was recently introduced to compare gene expression data by introducing gene-expression signatures (represented by a set of genes with up- or down-regulated labels according to their biological states) and is available as a web tool for detecting similar gene-expression signatures from a limited data set (approximately 7,000 expression profiles representing 1,309 compounds). In order to support researchers to utilize the public gene expression data more effectively, we developed a web tool for finding similar gene expression data and generating its co-expression networks from a publicly available database.

Results
GEM-TREND, a web tool for searching gene expression data, allows users to search data from GEO using gene-expression signatures or gene expression ratio data as a query and retrieve gene expression data by comparing gene-expression pattern between the query and GEO gene expression data. The comparison methods are based on the nonparametric, rank-based pattern matching approach of Lamb et al. (Science 2006) with the additional calculation of statistical significance. The web tool was tested using gene expression ratio data randomly extracted from the GEO and with in-house microarray data, respectively. The results validated the ability of GEM-TREND to retrieve gene expression entries biologically related to a query from GEO. For further analysis, a network visualization interface is also provided, whereby genes and gene annotations are dynamically linked to external data repositories.

Conclusion
GEM-TREND was developed to retrieve gene expression data by comparing query gene-expression pattern with those of GEO gene expression data. It could be a very useful resource for finding similar gene expression profiles and constructing its gene co-expression networks from a publicly available database. GEM-TREND was designed to be user-friendly and is expected to support knowledge discovery. GEM-TREND is freely available at http://cgs.pharm.kyoto-u.ac.jp/services/network.