bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prolonged in-vivo half-life of factor VIIa by fusion to albumin
Authors: Weimer Thomas , Wormsbächer Wilfried , Kronthaler Ulrich , Lang Wiegand , Liebing Uwe , Schulte Stefan 
Published: March 2008

SummaryFor the treatment of haemophilia patients with inhibitors, recombinant factor VIIa (rFVIIa) is available as a therapeutic option to control bleeding episodes with a good balance of safety and efficacy. However, the short in-vivo half-life of approximately 2.5 hours makes multiple injections necessary, which is inconvenient for both physicians and patients. Here we describe the generation of a recombinant FVIIa molecule with an extended half-life based on genetic fusion to human albumin. The recombinant FVII albumin fusion protein (rVII-FP) was expressed in mammalian cells and upon activation displayed a FVII activity close to that of wild type FVIIa. Pharmacokinetic studies in rats demonstrated that the half-life of the activated recombinant FVII albumin fusion protein (rVIIa-FP) was extended six- to sevenfold compared with wild type rFVIIa. The in-vitro and in-vivo efficacy was evaluated and was found to be comparable to a commercially available rFVIIa (NovoSeven®). The results of this study demonstrate that it is feasible to develop a half-life extended FVIIa molecule with haemostatic properties very similar to the wild-type factor.
Inherited thrombophilic abnormalities and risk of portal vein thrombosis
Authors: Galli Matteo , Gianni Monica , Ageno Walter , Dentali Francesco 
Published: March 2008

SummaryInherited thrombophilic abnormalities may have a role in the development of portal vein thrombosis (PVT).However, the prevalence of these factors in patients with PVT has been evaluated only in small studies with non-conclusive results. It was the purpose of this study to assess the risk of PVT associated with factorV Leiden (FVL) and G20210A prothrombin mutation (PTM). The MEDLINE, EMBASE, Cochrane Library databases, reference lists of retrieved articles and contact with content experts were used. Studies carried out in Western Europe comparing the prevalence of prothrombotic abnormalities in patients with PVT and in controls without a history of thromboembolic disease were included. Two reviewers independently selected studies and extracted study characteristics, quality and outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each trial and pooled using a fixed and random-effects model. Statistical heterogeneity was evaluated using the I2 statistic. Sensitivity analyses were performed examining separately studies according to the etiology of PVT and to control population. Twelve studies involving more than 3,000 patients were included. The pooled OR for PVT was 1.90 (95%CI: 1.25, 2.90) in patients with FVL and 4.48 (95%CI: 3.10, 6.48) in patients with PTM. In conclusion, PVT is associated with the presence of FVL and PTM in Western Europe.
Death due to recurrent thromboembolism among younger healthier individuals hospitalized for idiopathic pulmonary embolism
Authors: Zhou Hong , Murin Susan , White Richard 
Published: March 2008

SummaryThe incidence of death due to recurrent pulmonary embolism (PE) after a first-time idiopathic PE is not well defined. We conducted a retrospective study of patients age 18 to 56 years who had idiopathic PE between 1994–2001.The incidence and cause of death within five years was determined using linked discharge records and a master death registry. A total of 3,456 patients had a first-time idiopathic PE. The rate of recurrent VTE 0–6 months after the index event was 13.1%/year, and 2.9%/year 6–60 months after the event. During the mean follow-up of 3.2 years 118 (3.4%, 95% confidence interval [CI]=2.8–4.1%) patients died. Fifty-two (44%) deaths occurred <29 days after the index PE (case-fatality rate =1.5%,95%CI=1.1–2.0%). Among the 66 cases (1.9%) that died after 28 days, 18 (0.52%) were due to recurrent PE or its sequelae: eight had recurrent PE alone, five had recurrent PE and a serious co-morbid illness, and five had thromboembolic pulmonary hypertension with or without acute PE. The person-time rate of death (deaths per 100 patientyears) attributed to any recurrent thromboembolism 6–60 months after the event was 0.16% (95%CI=0.1–0.26%). Ten of the 18 (56%) late thromboembolic deaths reflected a first-time recurrent PE. The 28-day case-fatality rate for recurrentVTE was 2.8% (95%CI= 1.5–4.9%).In this cohort of younger patients with idiopathic PE, the rate of death due to recurrentVTE, particularly to first-time recurrent PE, was low. Among the patients who died of thromboembolism >28 days after the index PE, 28% had developed pulmonary hypertension.
Allosteric regulation of αIIbβ3 by β3 95–105
Authors: Haas Thomas 
Published: March 2008

SummaryThe linear recognition sequences of an anti-β3 antibody that blocked platelet aggregation were identified using β3 tryptic peptides. Two of these recognition sequence-containing peptides were mapped to β3 92–105, and antibodies affinity purified using these peptides blocked platelet aggregation. Examining the structure of αIIbβ3 identified β3 95–105 as the solvent accessible sequence within β3 92–105. A peptide corresponding to β3 95–105 was synthesized and used to affinity purify the β3 antibody. Anti-β3 95–105 completely blocked platelet aggregation and agonist-induced fibrinogen binding to platelets, but had no effect on cyclic-RGD binding. Binding of anti-β3 95–105 to αIIbβ3 also did not alter the structure of the αIIb cap subdomain, as measured by anti-αIIb 201–217 binding. β3 95–105 and peptides spanning two adjacent sequences in the structure of β3 did not bind fibrinogen and were ineffectual in blocking agonist-induced platelet aggregation. Structure analysis revealed that β3 95–105 is adjacent to one of the two hinges in β3 that allows for the outward swing of the hybrid and PSI domains which is central to the conversion of αIIbβ3 from a low into a high affinity state.Thus, the binding of an antibody to β3 95–105 could serve as a fulcrum for allosteric regulation of αIIbβ3 by regulating the movement of the hybrid-PSI domain.
Phylogenetic position of the langur genera Semnopithecus and Trachypithecus among Asian colobines, and genus affiliations of their species groups
Authors: Osterholz Martin , Walter Lutz , Roos Christian 
Published: March 2008

Abstract

Background
The evolutionary history of the Asian colobines is less understood. Although monophyly of the odd-nosed monkeys was recently confirmed, the relationships among the langur genera Presbytis, Semnopithecus and Trachypithecus and their position among Asian colobines remained unclear. Moreover, in Trachypithecus various species groups are recognized, but their affiliations are still disputed. To address these issues, mitochondrial and Y chromosomal sequence data were phylogenetically related and combined with presence/absence analyses of retroposon integrations.

Results
The analysed 5 kb fragment of the mitochondrial genome allows no resolution of the phylogenetic relationships among langur genera, but five retroposon integrations were detected which link Trachypithecus and Semnopithecus. According to Y chromosomal data and a 573 bp fragment of the mitochondrial cytochrome b gene, a common origin of the species groups T. [cristatus], T. [obscurus] and T. [francoisi] and their reciprocal monophyly is supported, which is also underpinned by an orthologous retroposon insertion. T. [vetulus] clusters within Semnopithecus, which is confirmed by two retroposon integrations. Moreover, this species group is paraphyletic, with T. vetulus forming a clade with the Sri Lankan, and T. johnii with the South Indian form of S. entellus. Incongruence between gene trees was detected for T. [pileatus], in that Y chromosomal data link it with T. [cristatus], T. [obscurus] and T. [francoisi], whereas mitochondrial data affiliates it with the Semnopithecus clade.

Conclusion
Neither relationships among the three langur genera nor their position within Asian colobines can be settled with 5 kb mitochondrial sequence data, but retroposon integrations confirm at least a common origin of Semnopithecus and Trachypithecus. According to Y chromosomal and 573 bp mitochondrial sequence data, T. [cristatus], T. [obscurus] and T. [francoisi] represent true members of the genus Trachypithecus, whereas T. [vetulus] clusters within Semnopithecus. Due to paraphyly of T. [vetulus] and polyphyly of Semnopithecus, a split of the genus into three species groups (S. entellus - North India, S. entellus - South India + T. johnii, S. entellus - Sri Lanka + T. vetulus) seems to be appropriate. T. [pileatus] posses an intermediate position between both genera, indicating that the species group might be the result of ancestral hybridization.
The CoLaus study: a population-based study to investigate the epidemiology and genetic determinants of cardiovascular risk factors and metabolic syndrome
Authors: Firmann Mathieu , Mayor Vladimir , Vidal Pedro Marques , Bochud Murielle , Pécoud Alain , Hayoz Daniel , Paccaud Fred , Preisig Martin , Song Kijoung S , Yuan Xin , Danoff Theodore M , Stirnadel Heide A , Waterworth Dawn , Mooser Vincent , Waeber Gérard , Vollenweider Peter 
Published: March 2008

Abstract

Background
Cardiovascular diseases and their associated risk factors remain the main cause of mortality in western societies. In order to assess the prevalence of cardiovascular risk factors (CVRFs) in the Caucasian population of Lausanne, Switzerland, we conducted a population-based study (Colaus Study). A secondary aim of the CoLaus study will be to determine new genetic determinants associated with CVRFs.

Methods
Single-center, cross-sectional study including a random sample of 6,188 extensively phenotyped Caucasian subjects (3,251 women and 2,937 men) aged 35 to 75 years living in Lausanne, and genotyped using the 500 K Affymetrix chip technology.

Results
Obesity (body mass index ≥ 30 kg/m2), smoking, hypertension (blood pressure ≥ 140/90 mmHg and/or treatment), dyslipidemia (high LDL-cholesterol and/or low HDL-cholesterol and/or high triglyceride levels) and diabetes (fasting plasma glucose ≥ 7 mmol/l and/or treatment) were present in 947 (15.7%), 1673 (27.0%), 2268 (36.7%), 2113 (34.2%) and 407 (6.6%) of the participants, respectively, and the prevalence was higher in men than in women. In both genders, the prevalence of obesity, hypertension and diabetes increased with age.

Conclusion
The prevalence of major CVRFs is high in the Lausanne population in particular in men. We anticipate that given its size, the depth of the phenotypic analysis and the availability of dense genome-wide genetic data, the CoLaus Study will be a unique resource to investigate not only the epidemiology of isolated, or aggregated CVRFs like the metabolic syndrome, but can also serve as a discovery set, as well as replication set, to identify novel genes associated with these conditions.
Individual case safety reports in children in commonly used drug groups – signal detection
Authors: Brunlöf Gertrud , Tukukino Carina , Wallerstedt Susanna M 
Published: March 2008

Abstract

Background
Due to few paediatric drug safety studies, knowledge on risks of drug treatment in children is limited. The knowledge needs to be increased to make proper risk-benefit analyses possible when treating paediatric patients with drugs. The aim of the present study was to investigate drug groups commonly used in children concerning type and frequency of individual case safety reports in children.

Methods
Number and type of individual case safety reports in the 30 groups of drugs (5th level ATC-code) most sold (number of defined daily doses) in outpatient treatment to children (<15 years old) during 2005 were obtained. Descriptive analyses of the adverse drug reactions reported in children were performed.

Results
The number of individual case safety reports per million defined daily doses in children varied in the groups of drug between 0 and 24. The largest number was found in the drug group R03DC, the leukotriene receptor antagonist montelukast; the majority of the children being <5 years old and experiencing psychiatric adverse drug reactions.

Conclusion
The number of individual case safety reports per million defined daily doses varies in different groups of drugs. A possible signal for montelukast and psychiatric adverse drug reactions was found, which should be further explored.
Increased systemic and brain cytokine production and neuroinflammation by endotoxin following ethanol treatment
Authors: Qin Liya , He Jun , Hanes Richard N , Pluzarev Olivera , Hong Jau-Shyong , Crews Fulton T 
Published: March 2008

AbstractBackgroundCytokines and alcohol share a common modulation of inflammation and hormones as well as being implicated in multiple diseases, but the mechanisms are poorly understood. The purpose of this study was to investigate the interaction of liver, serum and brain cytokines as well as whether ethanol would potentiate endotoxin (Lipopolysaccharide, LPS) responses once ethanol had cleared.MethodsMale C57BL/6J mice were treated intragastrically with water (control) or ethanol (5 g/kg, i.g., 25% ethanol, w/v), with volumes matched, for 1 day or daily for 10 days. Mice were then injected intraperitoneally with saline (control) or LPS (3 mg/kg, i.p.) in saline 24 hrs after the last dose of ethanol. Gene expression and protein synthesis of proinflammatory cytokines and anti-inflammatory cytokine, oxidative enzymes, microglial activation and inhibition of neurogenesis were examined using real-time PCR, ELISA, and immunohistochemistry.ResultsLPS increased proinflammatory cytokines (TNFα, MCP-1, IL-1β) several fold in liver, brain and serum at 1 hr. Ethanol is known to increase liver cytokines and alter the risk of multiple chronic diseases. Ten daily doses of ethanol increased brain and liver TNFα, and pretreatment with ethanol potentiated LPS-induced increases in TNFα, MCP-1, IL-1βin liver, serum and brain. Proinflammatory cytokine levels in liver and serum returned to basal levels within a day, whereas brain proinflammatory cytokines remained elevated for long periods. IL-10, an anti-inflammatory cytokine, is reduced in brain by ethanol and LPS, while brain proinflammatory cytokines remain increased, whereas liver IL-10 is increased when proinflammatory cytokines have returned to control levels. Activation of brain microglia indicated by morphological changes, reduced neurogenesis and increased brain expression of COX-2 and gp91phoxNADPH oxidase subunit mRNA were found in the 10 daily doses of ethanol-pretreated LPS group.ConclusionAcute increases in serum cytokines induce long lasting increases in brain proinflammatory cytokines. Ten daily doses of ethanol exposure results in persistent alterations of cytokines and significantly increases the magnitude and duration of central and peripheral proinflammatory cytokines and microglial activation. Ethanol induced differential anti-inflammatory cytokine IL-10 responses in liver and brain could cause long lasting disruption of cytokine cascades that could contribute to protection or increased risk of multiple chronic diseases.
Complications post renal transplantation: literature focus on BK virus nephropathy and diagnostic tools actually available
Authors: Mischitelli Monica , Bellizzi Anna , Anzivino Elena , Fioriti Daniela , Boldorini Renzo , Miglio Umberto , Chiarini Fernanda , Di Monaco Franco , Pietropaolo Valeria 
Published: March 2008

Abstract
Clinical diagnosis of kidney transplants related illnesses is not a simple task. Several studies were conducted to define diseases and complications after renal transplantation, but there are no comprehensive guidelines about diagnostic tools for their prevention and detection.
The Authors of this review looked for the medical literature and pertinent publications in particular to understand the role of Human Polyomavirus BK (BKV) in renal failure and to recognize analytical techniques for BK virus associated nephropathy (BKVAN) detection.
Managerial and environmental determinants of clinical mastitis in Danish dairy herds
Authors: Sato Kenji , Bartlett Paul C , Alban Lis , Agger Jens F , Houe Hans 
Published: March 2008

Abstract

Background
Several management and environmental factors are known as contributory causes of clinical mastitis in dairy herd. The study objectives were to describe the structure of herd-specific mastitis management and environmental factors and to assess the relevance of these herd-specific indicators to mastitis incidence rate.

Methods
Disease reports from the Danish Cattle Data Base and a management questionnaire from 2,146 herds in three Danish regions were analyzed to identify and characterize risk factors of clinical mastitis. A total of 94 (18 continuous and 76 discrete) management and production variables were screened in separate bivariate regression models. Variables associated with mastitis incidence rate at a p-value < 0.10 were examined with a factor analysis to assess the construct of data. Separately, a multivariable regression model was used to estimate the association of management variables with herd mastitis rate.

Results
Three latent factors (quality of labor, region of Denmark and claw trimming, and quality of outdoor holding area) were identified from 14 variables. Daily milk production per cow, claw disease, quality of labor and region of Denmark were found to be significantly associated with mastitis incidence rate. A common multiple regression analysis with backward and forward selection procedures indicated there were 9 herd-specific risk factors.

Conclusion
Though risk factors ascertained by farmer-completed surveys explained a small percentage of the among-herd variability in crude herd-specific mastitis rates, the study suggested that farmer attitudes toward mastitis and lameness treatment were important determinants for mastitis incidence rate. Our factor analysis identified one significant latent factor, which was related to labor quality on the farm.
Molecular Characteristics of Bronchioloalveolar Carcinoma and Adenocarcinoma, Bronchioloalveolar Carcinoma Subtype, Predict Response to Erlotinib
Authors: Miller Vincent A. , Riely Gregory J. , Zakowski Maureen F. , Li Allan R. , Patel Jyoti D. , Heelan Robert T. , Kris Mark G. , Sandler Alan B. , Carbone David P. , Tsao Anne , Herbst Roy S. , Heller Glenn , Ladanyi Marc , Pao William , Johnson David H. 
Published: March 2008

Purpose We conducted this phase II trial to determine the efficacy of erlotinib in patients with bronchioloalveolar carcinoma (BAC) and adenocarcinoma, BAC subtype, and to determine molecular characteristics associated with response. Patients and Methods Patients (n = 101) with BAC (n = 12) or adenocarcinoma, BAC subtype (n = 89), were enrolled. All patients received erlotinib 150 mg daily. Epidermal growth factor receptor (EGFR) mutation, EGFR copy number, EGFR immunohistochemistry (IHC), and KRAS mutation status were analyzed in available tumors. The primary end point was response rate (RR). Results Overall RR was 22% (95% CI, 14% to 31%). In patients with pure BAC, the RR and median survival were 20% and 4 months, as compared with 23% and 19 months in those with adenocarcinoma, BAC subtype. No patient (zero of 18; 95% CI, 0% to 19%) whose tumor harbored a KRAS mutation responded to erlotinib. Patients with EGFR mutations had an 83% RR (15 of 18; 95% CI, 65% to 94%) and 23-month median OS. On univariate analysis, EGFR mutation and copy number were associated with RR and PFS. EGFR IHC was not associated with RR or progression-free survival (PFS). After multivariate analysis, only EGFR mutation was associated with RR and PFS. No molecular factors were associated with overall survival. Conclusion Erlotinib is active in BAC and adenocarcinoma, mixed subtype, BAC. Testing for EGFR and KRAS mutations can predict RR and PFS after treatment with erlotinib in this histologically enriched subset of patients with non–small-cell lung cancer (NSCLC). These data suggest that histologic subtype and molecular characteristics should be reported in clinical trials in NSCLC using EGFR-directed therapy.
Randomization Reveals Unexpected Acute Leukemias in Southwest Oncology Group Prostate Cancer Trial
Authors: Flaig Thomas W. , Tangen Catherine M. , Hussain Maha H.A. , Stadler Walter M. , Raghavan Derek , Crawford E. David , Glodé L. Michael 
Published: March 2008

Purpose Southwest Oncology Group (SWOG) study 9921 is a randomized, phase III, intergroup study to define the role of adjuvant chemotherapy in patients with high-risk prostate cancer. Patients and Methods We allocated 983 patients with prostate cancer with high-risk features to receive 2 years of androgen-deprivation therapy (ADT) with or without six cycles of mitoxantrone (12 mg/m2) after prostatectomy. Results In January 2007, SWOG 9921 was closed to further accrual after three cases of acute myelogenous leukemia (AML) were reported of a total of 487 patients in the mitoxantrone treatment arm. The key cytogenetic features of these cases included inv(16) in the first case, t(15;17) in the second, and del(5) in the third case. Time from the start of mitoxantrone to the detection of AML was 13, 48, and 72 months, respectively. Before SWOG 9921, there were no cases of mitoxantrone-induced AML reported in patients treated for prostate cancer. Conclusion The emergence of this possible pattern of secondary malignancy emphasizes the importance of randomized controlled trials in defining safety and efficacy of new approaches for patients in the adjuvant setting.
Prognostic Value of Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography Imaging in Patients With Advanced-Stage Non–Small-Cell Lung Carcinoma
Authors: Hoang Jenny K. , Hoagland Luke F. , Coleman R. Edward , Coan April D. , Herndon James E. , Patz Edward F. 
Published: March 2008

PurposeTo determine whether the amount of fluorine-18 fluorodeoxyglucose (FDG) uptake in the primary lung cancer on positron emission tomography (PET) imaging at the time of presentation has prognostic significance in patients with advanced-stage non–small-cell lung cancer (NSCLC).Patients and MethodsA retrospective review identified 214 patients with advanced-stage NSCLC (stage IIIA, IIIB, and IV) who underwent FDG PET study at the time of diagnosis. Extensive clinical data, including tumor histologic cell type, pathologic stage at presentation, and treatment, were recorded. The maximum standardized uptake value (SUVmax) in the primary tumor on FDG PET on survival was examined using Cox proportional hazards regression.ResultsOne hundred fifty-eight (74%) of the 214 patients died and 56 patients were reported alive at 27 months (range, 3 to 140 months) after the diagnosis of NSCLC. Using the median SUVmaxof 11.1, the patient population was subdivided. The median survival of the 106 patients with the primary tumor having an SUVmaxless than 11.1 was 16 months (95% CI, 12 to 21 months), whereas the median survival of the 108 patients with the primary tumor having an SUVmax≥ 11.1 was 12 months (95% CI, 10 to 15 months). Univariate and multivariate analysis did not provide evidence that survival for patient subgroups defined by the median SUVmaxwere significantly different (univariate P = .11; multivariate P = .45).ConclusionFDG uptake of the primary lesions in patients with a new diagnosis of advanced-stage NSCLC does not have a significant relationship with survival.