bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease association tests by inferring ancestral haplotypes using a hidden markov model
Authors: Su Shu-Yi , Balding David J. , Coin Lachlan J.M. 
Published: February 2008

Abstract
Motivation: Most genome-wide association studies rely on single nucleotide polymorphism (SNP) analyses to identify causal loci. The increased stringency required for genome-wide analyses (with per-SNP significance threshold typically ≈ 10−7) means that many real signals will be missed. Thus it is still highly relevant to develop methods with improved power at low type I error. Haplotype-based methods provide a promising approach; however, they suffer from statistical problems such as abundance of rare haplotypes and ambiguity in defining haplotype block boundaries.
Results: We have developed an ancestral haplotype clustering (AncesHC) association method which addresses many of these problems. It can be applied to biallelic or multiallelic markers typed in haploid, diploid or multiploid organisms, and also handles missing genotypes. Our model is free from the assumption of a rigid block structure but recognizes a block-like structure if it exists in the data. We employ a Hidden Markov Model (HMM) to cluster the haplotypes into groups of predicted common ancestral origin. We then test each cluster for association with disease by comparing the numbers of cases and controls with 0, 1 and 2 chromosomes in the cluster. We demonstrate the power of this approach by simulation of case-control status under a range of disease models for 1500 outcrossed mice originating from eight inbred lines. Our results suggest that AncesHC has substantially more power than single-SNP analyses to detect disease association, and is also more powerful than the cladistic haplotype clustering method CLADHC.
Availability: The software can be downloaded from http://www.imperial.ac.uk/medicine/people/l.coin
Contact: I.coin@imperial.ac.uk
Supplementary Information: Supplementary data are available at Bioinformatics online.
Design of a highly specific and noninvasive biosensor suitable for real‐time in vivo imaging of mercury (II) uptake
Authors: Chapleau Richard R. , Blomberg Rebecca , Ford Peter C. , Sagermann Martin 
Published: February 2008

AbstractMercury is a ubiquitous pollutant that when absorbed is extremely toxic to a wide variety of biochemical processes. Mercury (II) is a strong, “invisible” poison that is rapidly absorbed by tissues of the intestinal tract, kidneys, and liver upon ingestion. In this study, a novel fluorescence‐based biosensor is presented that allows for the direct monitoring of the uptake and distribution of the metal under noninvasive in vivo conditions. With the introduction of a cysteine residue at position 205, located in close proximity to the chromophore, the green fluorescent protein (GFP) from Aequorea victoria was converted into a highly specific biosensor for this metal ion. The mutant protein exhibits a dramatic absorbance and fluorescence change upon mercuration at neutral pH. Absorbance and fluorescence properties with respect to the metal concentration exhibit sigmoidal binding behavior with a detection limit in the low nanomolar range. Time‐resolved binding studies indicate rapid subsecond binding of the metal to the protein. The crystal structures obtained of mutant eGFP205C indicate a possible access route of the metal into the core of the protein. To our knowledge, this engineered protein is a first example of a biosensor that allows for noninvasive and real‐time imaging of mercury uptake in a living cell. A major advantage is that its expression can be genetically controlled in many organisms to enable unprecedented studies of tissue specific mercury uptake.
Direct visualization and quantification of the anticancer agent, cis‐diamminedichloro‐platinum(II), in human lung cancer cells using in‐air microparticle‐induced X‐ray emission analysis
Authors: Sakurai Hideyuki , Okamoto Masahiko , Hasegawa Masatoshi , Satoh Takahiro , Oikawa Masakazu , Kamiya Tomihiro , Arakawa Kazuo , Nakano Takashi 
Published: February 2008

The authors designed an elemental analysis system using an ion microbeam combined with a microparticle‐induced X‐ray emission (micro‐PIXE) method for the analysis of biomedical samples in air with a spatial resolution of 1 µm (in‐air micro‐PIXE system). This system was used to develop an imaging and quantification method for intracellular cis‐diamminedichloro‐platinum(II) (CDDP) in a human lung cancer cell line. A human lung adenocarcinoma cell line, A549, was cultured and nuclear labeling was carried out by incubating the cells with BrdU. The cells were then exposed to CDDP at concentrations ranging from 1 µmol to 1 mmol, for 30 min to 24 h. After drug treatment, samples were washed and frozen with liquid nitrogen, and freeze‐dried for 24 h. Standard samples were made using agar containing several concentrations of CDDP. Experiments using standard samples showed a linear correlation between CDDP concentration and platinum signal strength. No clear platinum signal was detected after exposure to CDDP for 24 h at doses between 1 and 100 µmol. However, significant platinum signals were observed at 1 mmol. When nucleus and cytoplasm visualization was sufficiently clear to efficiently use in‐air micro‐PIXE, the platinum image quality was considered satisfactory. The detected signals of CDDP were stronger in the nucleus than in the cytoplasm. A time‐course study showed increased CDDP uptake in cells after longer drug exposure periods. The present study demonstrates the application of element analysis using in‐air micro‐PIXE to biomedical samples. The use of this system enables the high‐resolution visualization of intracellular CDDP distribution and measurement of intracellular CDDP concentrations. (Cancer Sci 2008; 99: 901–904)
Co‐administration of carcinoembryonic antigen and HIV TAT fusion protein with CpG‐oligodeoxynucleotide induces potent antitumor immunity
Authors: Woo Sun‐Je , Kim Chang‐Hyun , Park Mi‐Young , Kim Hye‐Sung , Sohn Hyun‐Jung , Park Jung‐Sun , Kim Hyung‐Jin , Oh Seong‐Taek , Kim Tai‐Gyu 
Published: February 2008

Although dendritic cells (DC) have been well demonstrated as a strong cellular adjuvant for a tumor vaccine, there are several limitations for clinical application. A protein‐based vaccine using a potent adjuvant is an appealing approach for tumor antigen‐specific immunotherapy because of their simplicity, safety, efficacy and capacity for repeated administration. CpG‐oligodeoxynucleotides (ODN) have been used as adjuvants to stimulate innate and adaptive immune responses for cancer treatment. The authors evaluated the adjuvant effects of CpG‐ODN in a vaccine incorporating recombinant fusion protein of the HIV TAT PTD domain and carcinoembryonic antigen (TAT‐CEA). Mice vaccinated with TAT‐CEA and CpG‐ODN (TAT‐CEA + CpG) showed enhanced CEA‐specific immunity, including cytotoxic T‐lymphocytes (CTL) activity and interferon (IFN)‐γ secreting T cells compared with CEA and CpG‐ODN (CEA + CpG) or TAT‐CEA vaccination alone. Vaccination with TAT‐CEA + CpG elicited Th1‐based responses, as indicated by the higher ratio of immunoglobulin (Ig)G2a antibody/IgG1 antibodies specific for CEA. The survival rate was significantly increased after vaccination with TAT‐CEA + CpG in a tumor model using MC38/CEA2. Furthermore, the TAT‐CEA ± CpG vaccine groups showed similar antitumor immunity to the CEA peptide‐pulsed DC (CEA peptide/DC) vaccine groups. These data suggest that coadministration of TAT fusion protein with CpG‐ODN may serve as a potential formulation for enhancing antitumor activity. (Cancer Sci 2008; 99: 1034–1039)
Impact of CYP2D6*10 on recurrence‐free survival in breast cancer patients receiving adjuvant tamoxifen therapy
Authors: Kiyotani Kazuma , Mushiroda Taisei , Sasa Mitsunori , Bando Yoshimi , Sumitomo Ikuko , Hosono Naoya , Kubo Michiaki , Nakamura Yusuke , Zembutsu Hitoshi 
Published: February 2008

The clinical outcomes of breast cancer patients treated with tamoxifen may be influenced by the activity of cytochrome P450 2D6 (CYP2D6) enzyme because tamixifen is metabolized by CYP2D6 to its active forms of antiestrogenic metabolite, 4‐hydroxytamoxifen and endoxifen. We investigated the predictive value of the CYP2D6*10 allele, which decreased CYP2D6 activity, for clinical outcomes of patients that received adjuvant tamoxifen monotherapy after surgical operation on breast cancer. Among 67 patients examined, those homozygous for the CYP2D6*10 alleles revealed a significantly higher incidence of recurrence within 10 years after the operation (P = 0.0057; odds ratio, 16.63; 95% confidence interval, 1.75–158.12), compared with those homozygous for the wild‐type CYP2D6*1 alleles. The elevated risk of recurrence seemed to be dependent on the number of CYP2D6*10 alleles (P = 0.0031 for trend). Cox proportional hazard analysis demonstrated that the CYP2D6 genotype and tumor size were independent factors affecting recurrence‐free survival. Patients with the CYP2D6*10/*10 genotype showed a significantly shorter recurrence‐free survival period (P = 0.036; adjusted hazard ratio, 10.04; 95% confidence interval, 1.17–86.27) compared to patients with CYP2D6*1/*1 after adjustment of other prognosis factors. The present study suggests that the CYP2D6 genotype should be considered when selecting adjuvant hormonal therapy for breast cancer patients. (Cancer Sci 2008; 99: 995–999)
Does constrained oviposition influence offspring sex ratio in the solitary parasitoid wasp Venturia canescens?
Authors: METZGER MARIE , BERNSTEIN CARLOS , DESOUHANT EMMANUEL 
Published: March 2008

Abstract 1. In haplodiploid organisms, virgin or sperm‐depleted females can reproduce but are constrained to produce only male progeny. According to Godfray’s constrained model, when p, the proportion of females constrained to produce only male progeny, is not null in a panmictic population, unconstrained females should bias their sex allocation towards females to compensate for the excess of males. These unconstrained females should be able to adjust the sex ratio in response to local variation of p.2. In this paper an experimental approach is used to test the hypotheses of this model in the solitary endoparasitoid Venturia canescens under both field and laboratory conditions. Specifically, it is tested whether unconstrained females use their encounters with conspecifics (either male or female) to estimate p and then adjust their sex ratio accordingly.3. As assumed by Godfray’s model, constrained females actively search for host patches in the field and under laboratory conditions produce the same number of offspring during their lifetime as unconstrained females. As predicted by the model, unconstrained females produce a sex ratio biased towards females both in the laboratory and in the field.4. The results show that this bias is not a response to encounters with conspecifics previous to oviposition. The hypothesis that the bias is due to differential mortality between sexes during ontogeny is also rejected. The proportions of constrained ovipositions estimated in two natural populations explain only a small fraction of the sex ratio bias observed in V. canescens.
CAN MEASUREMENT OF B‐TYPE NATRIURETIC PEPTIDE LEVELS IMPROVE CARDIOVASCULAR DISEASE PREVENTION?
Authors: Campbell Duncan J 
Published: February 2008

SUMMARY

The measurement of plasma levels of B‐type natriuretic peptide (BNP) and amino‐terminal pro‐BNP (NT‐proBNP) provides useful diagnostic information in patients with suspected heart failure and valuable prognostic information in patients with heart failure, acute coronary syndrome, valvular heart disease and other cardiac pathologies.
BNP‐ and NT‐proBNP‐guided heart failure therapy improves patient outcomes.
An increasing number of studies shows plasma BNP and NT‐proBNP levels predict all‐cause mortality and cardiovascular events including heart failure, myocardial infarction, stroke, atrial fibrillation and cardiovascular death in stable patients with or without known cardiovascular disease and provide information about cardiovascular risk additional to that provided by traditional risk factors.
Antihypertensive therapy reduces elevated NT‐proBNP levels in individuals at increased cardiovascular risk, thereby suggesting that change in NT‐proBNP levels provides a measure of risk reduction.
Thus, monitoring of BNP and NT‐proBNP levels offers the possibilities of improved targeting of individuals with increased cardiovascular risk and optimization of strategies for primary and secondary prevention of cardiovascular disease.
There is need for an outcome study to determine whether BNP‐ or NT‐proBNP‐guided therapy improves cardiovascular disease prevention.
CONTROL OF SYMPATHETIC, RESPIRATORY AND SOMATOMOTOR OUTFLOW BY AN INTRASPINAL PATTERN GENERATOR
Authors: Goodchild Ann K , Van Deurzen Bart T M , Hildreth Cara M , Pilowsky Paul M 
Published: February 2008

SUMMARY

Sympathetic and somatic motor outflow results from the summation of excitatory and inhibitory inputs arising from intra‐ and supra‐spinal origins. Here we determined the contribution of intra‐ and supra‐spinal GABAergic inputs, utilizing GABA‐A receptors, in producing sympathetic and somatic motor outflow.
Spinal GABA‐A receptor blockade, with bicuculline or picrotoxin injected intrathecally at T9, increased the level and lability of arterial pressure, sympathetic (splanchnic and cervical sympathetic) and motor (phrenic) nerve activity. Bursts of activity occurring irregularly, at low frequency were seen in all nerves.
C1 spinal transection abolished phrenic nerve activity and reduced sympathetic nerve activities and arterial pressure. Intrathecal bicuculline‐induced bursting in sympathetic and motor (phrenic, sciatic and brachial) nerves was similar to that seen prior to C1 transection. Thus supraspinal control of sympathetic and somatomotor outflow is not dependent on GABA‐A receptors.
Bicuculline‐induced effects on phrenic nerve activity were eliminated after C8 spinal cord transection and regular phrenic rhythm resumed indicating that bicuculline was not acting directly on phrenic motoneurons.
Bicuculline evoked similar bursting characteristics in both sympathetic and motor nerves attributable to increased excitability of spinal cord neurons. The bursting patterns evoked were often coincident in sympathetic and motor nerves suggesting a common site of origin.
These data suggest there is intraspinal coupling between multiple sympathetic and motor outflows in the adult rat spinal cord in vivo. Cervicothoracic spinal cord generator/s perhaps in the form of interneuronal networks, utilizing GABA‐A and glutamate receptors, can simultaneously drive functionally independent nerves.
Implementation of the scientific evidence into daily practice – example from fast‐track colonic cancer surgery
Authors: Hammer J. , Harling H. , Wille‐Jørgensen P. 
Published: March 2008

AbstractObjective  To report the implementation and results of fast‐track surgery for colonic cancer in the daily routine.Method  A total of 131 consecutive patients scheduled for elective colonic cancer resections entered a fast‐track perioperative course after thorough information. The regimen contained: no preoperative bowel cleansing, transverse and small abdominal incisions, no dains nor tubes, mobilization and normal meal the evening on the day of surgery, epidural analgesia, oral laxatives, and a planned discharge on postoperative day 3.Results  Median number of days postoperative in hospital were 4 days (range 1–46). Eighty‐nine per cent experienced an uncomplicated course, 3% were readmitted within 30 days, and the 30‐day mortality was 3.8%.Conclusion  Fast‐track surgery is feasible in an unselected patient population scheduled for elective colon cancer resections without compromising quality.
Transformations of Cadastral Descriptions with Incomplete Information into Maps
Authors: Mueller Marina 
Published: March 2008

AbstractBrazil is one of the countries of the world where the ownership cadastre is still based on textual descriptions. Until 2001 (and for the urban cadastre still until today), no standards existed concerning obligatory elements or the necessary degree of precision for cadastral deeds. This resulted in documents similar to metes‐and‐bounds descriptions that often include vague expressions or relative references e.g. to neighbouring real estate. In order to facilitate error‐ and inconsistency‐checks as well as planning and decision‐making, the demand arises to visualise the textual information in maps. Existing programs for a transformation of metes‐and‐bounds descriptions already use additional logic to handle inconsistencies or missing information but are still rather limited in their abilities if too much uncertainty is incorporated in the text, i.e. corresponding maps to such texts are (if at all) only partially generated. Therefore, this article analysed whether or not all (even uncertain) of the spatial information in the descriptions can be transformed into a suitable map representation. This requires among other things a quantification of the qualitative expressions for lengths and directions that are used in the texts.
‘EVEN IF YOU'RE POSITIVE, YOU STILL HAVE RIGHTS BECAUSE YOU ARE A PERSON’: HUMAN RIGHTS AND THE REPRODUCTIVE CHOICE OF HIV‐POSITIVE PERSONS
Authors: LONDON LESLIE , ORNER PHYLLIS J. , MYER LANDON 
Published: March 2008

ABSTRACTGlobal debates in approaches to HIV/AIDS control have recently moved away from a uniformly strong human rights‐based focus. Public health utilitarianism has become increasingly important in shaping national and international policies. However, potentially contradictory imperatives may require reconciliation of individual reproductive and other human rights with public health objectives. Current reproductive health guidelines remain largely nonprescriptive on the advisability of pregnancy amongst HIV‐positive couples, mainly relying on effective counselling to enable autonomous decision‐making by clients. Yet, health care provider values and attitudes may substantially impact on the effectiveness of nonprescriptive guidelines, particularly where social norms and stereotypes regarding childbearing are powerful, and where providers are subjected to dual loyalty pressures, with potentially adverse impacts on rights of service users. Data from a study of user experiences and perceptions of reproductive and HIV/AIDS services are used to illustrate a rights analysis of how reproductive health policy should integrate a rights perspective into the way services engage with HIV‐positive persons and their reproductive choices. The analysis draws on recognised tools developed to evaluate health policies for their human rights impacts and on a model developed for health equity research in South Africa to argue for greater recognition of agency on the part of persons affected by HIV/AIDS in the development and content of policies on reproductive choices. We conclude by proposing strategies that are based upon a synergy between human rights and public health approaches to policy on reproductive health choices for persons with HIV/AIDS.
Safety and Feasibility of Transcatheter Closure of Large Patent Ductus Arteriosus Measuring ≥4 mm in Patients Weighing ≤6 kg
Authors: SIVAKUMAR KOTHANDAM , FRANCIS EDWIN , KRISHNAN PRASAD 
Published: February 2008

Objectives:

The study aims to find safety of transcatheter closure of large patent ductus arteriosus (PDA) ≥4 mm in patients weighing ≤6 kg.
Background:

Large PDA ≥4 mm in patients ≤6 kg challenge the interventionist due to need for large delivery sheath, kink of delivery sheath, and encroachment of aorta or pulmonary artery (PA) by the device. Many institutions refer them for surgery.
Methods:

Preterm neonates and ducts with coarctation were excluded. All other patients were taken for catheter closure. Ducts with roomy ampulla were closed with multiple coils aided by bioptome, and others with Amplatzer duct occluders.
Results:

Twenty‐eight patients aged 2–18 months (median 5.5 months) and weighing 3.8–6 kg (median 4.7 kg) had large PDA (mean diameter 6.3 ± 2 mm) with hyperkinetic pulmonary hypertension. Four patients had bioptome‐aided coil closure. Twenty‐two other ducts were closed with devices. Two procedures failed due to sheath kink in one patient and device pulling through a duct in the other patient. Four infants needed blood transfusions. The mean procedural time was 42 ± 20 minutes. On a mean follow‐up of 25.5 ± 14.8 months, there were no residual flows and no gradients across aorta or pulmonary artery.
Conclusions:

Transcatheter closure of large ducts ≥4 mm might be considered safe and effective in infants weighing ≤6 kg also. Decision on coils versus devices depends on ductal morphology. On midterm follow‐up with somatic growth, there was no occurrence of aortic or PA gradients.
Factor VIIa: Use in Patients With Hemophilia
Authors: Ingerslev Jøsrgen , Poulsen Lone Hvitfeldt , Søsrensen Benny 
Published: February 2008

SUMMARYIn 1988, researchers described the successful outcome of an elective knee‐joint surgical procedure during which hemostasis was secured in a hemophilia A patient with inhibitors by means of a new drug, recombinant activated factor VII (rFVIIa). Over the next 15 years, numerous published reports on the clinical management of hemophilia patients with inhibitors using rFVIIa have appeared. In this review, the authors summarize some of the major published works on rFVIIa and present surgical experiences from a single hemophilia treatment center.
The Use of Recombinant Factor VIIa in Gastrointestinal Bleeding
Authors: Parameswaran Rekha , Shapiro Amy D. 
Published: February 2008

SUMMARYRecombinant factor VIIa (rFVIIa) is licensed for use in hemophilic patients with inhibitors. Non‐hemophilic patients with uncontrolled hemorrhage, who have not responded to all available standard therapies, have been reported to respond to treatment with rFVIIa. These clinical observations have therefore led to the use of rFVIIa in a variety of other conditions with potentially impaired thrombin generation, with a resulting growing body of literature most often in the form of case reports and series. The response to rFVIIa in these patients may potentially be explained by the cell based mechanisms of action of rFVIIa. The use of rFVIIa in gastrointestinal (GI) bleeding refractory to conventional therapeutic interventions is reviewed in this report which includes diverse clinical situations representing liver disease, hematologic malignancies, bone marrow transplantation, platelet function disorders, Crohn's disease, peptic ulcer disease, and dengue hemorrhagic fever. In many cases patients were refractory to multiple therapeutic measures including standard hematologic and pharmacologic support, endoscopic and surgical interventions with administration of rFVIIa representing the only remaining option. Reported responses in these intractable situations have varied from temporary cessation of bleeding to complete response. Many patients were treated with multiple hemostatic agents concurrently with rFVIIa. There were no reported instances of disseminated intravascular coagulation or thrombotic events in the reviewed literature. Given the efficacy of rFVIIa noted in refractory settings, rFVIIa may prove to be a valuable hemostatic agent in standard first line therapy of GI bleeding, prior to development of hemostatic derangements. The efficacy and safety of rFVIIa as a single hemostatic agent in the setting of refractory GI hemorrhage and as part of standard first line therapy for GI hemorrhage are best evaluated in prospective randomized clinical trials. Several trials are currently in progress and are discussed here.