bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n‐3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure
Authors: Tavazzi Luigi , Tognoni Gianni , Franzosi Maria Grazia , Latini Roberto , Maggioni Aldo Pietro , Marchioli Roberto , Nicolosi Gian Luigi , Porcu Maurizio ,   on behalf of the GISSI‐HF investigators
Published: June 2004

AbstractBackground:The GISSI Heart Failure project is a large‐scale, randomized, double‐blind study designed to investigate the effects of n‐3 polyunsaturated fatty acids and rosuvastatin on mortality and morbidity in patients with symptomatic heart failure.Methods and results:Patients with New York Heart Association classes II to IV heart failure, already receiving optimized recommended therapy, will be recruited in a nation‐wide network of more than 300 cardiology and internal medicine services to be randomly allocated to treatment with n‐3 polyunsaturated fatty acids (1 g daily) or the corresponding placebo. Patients with no clear indication or contraindication to cholesterol‐lowering therapy will be further randomized to receive low‐dose rosuvastatin (10 mg daily) or placebo. According to data available in heart failure registries, it is expected that 70% of the patients will be suitable to enter both components of the trial, which assume the same co‐primary endpoints: (a) 15% reduction of all‐cause mortality and (b) 20% reduction of all‐cause mortality or cardiovascular hospitalizations. The trial is event‐driven and will continue either until at least 1252 deaths have been recorded or a reduction of all‐cause mortality will satisfy the significance boundaries, which have been established to stop the study. The recruitment of the planned sample size of approximately 7000 patients randomized in the n‐3 PUFA trial is expected to be completed within 18 months from the trial start. As of February 29, 2004, 4624 heart failure patients have been included in the trial.Conclusion:The GISSI‐HF project, with its protocol articulated into two independent randomization schemes, has the aim and the power to verify the hypothesis that n‐3 polyunsaturated fatty acids and rosuvastatin can favorably modify the prognosis of patients with symptomatic heart failure.
Neurotoxic effects of MDMA (“ecstasy”) administration to neonatal rats
Authors: Meyer Jerrold S. , Grande Mark , Johnson Kenneth , Ali Syed F. 
Published: June 2004

Abstract3,4‐Methylenedioxymethamphetamine damages fine serotonergic fibers and nerve terminals in adult organisms. Developing animals seem to be less susceptible to this effect, possibly due to a lack of drug‐induced hyperthermia. We tested this hypothesis by producing hyperthermia in neonatal rats for 2 h after each of twice‐daily MDMA (10 mg/kg s.c.) or saline injections administered from postnatal days 1–4. Other drug‐treated and control litters were maintained at normothermic temperatures following injection. Changes in forebrain serotonergic innervation were assessed at postnatal day 25 (serotonin transporter binding and serotonin levels), postnatal day 60 (serotonin transporter binding), and 9 months of age (serotonin transporter immunohistochemistry). We also determined the influence of MDMA treatment on apoptotic activity by means of immunohistochemistry for cleaved caspase‐3 at postnatal day 5. The hippocampus showed significant MDMA‐related reductions in serotonergic markers at postnatal day 25 and postnatal day 60. At 9 months, there was no effect of prior MDMA exposure on serotonin transporter‐immunoreactive fiber density in the hippocampus; however, significant reductions in fiber density were observed in two neocortical areas and a hyperinnervation was found in the caudate‐putamen and nucleus accumbens shell. MDMA treatment also produced a two‐fold increase in the number of cleaved caspase‐3‐immunoreactive cells in the rostral forebrain and hippocampus. All of these effects were completely independent of pup body temperature. These findings demonstrate that neonatal MDMA administration exposure stimulates apoptotic cell death in various forebrain areas and also leads to a long‐term reorganization of the forebrain serotonergic innervation. Consequently, offspring of MDMA‐using women may be at heightened risk for abnormal neural and behavioral development.
Retrotransposon‐derived elements in the mammalian genome: A potential source of disease
Authors: Druker R. , Whitelaw E. 
Published: June 2004

AbstractSummary: The plethora of genomic information gathered by the sequencing of the human and mouse genomes has paved the way for a new era of genetics. While in the past we focused mainly on the small percentage of DNA that codes for proteins, we can now concentrate on the remainder, i.e. the noncoding sequences that interrupt and separate genes. This portion of the genome is made up, in most part, of repetitive DNA sequences including DNA transposons, long terminal repeat (LTR) retrotransposons, LINEs (long interspersed nuclear elements) and SINEs (short interspersed nuclear elements). Some of these elements are transcriptionally active and can transpose or retrotranspose around the genome, resulting in insertional mutagenesis that can cause disease. In these cases, insertions have occurred in the coding sequence. However, recent evidence suggests that the main effect of these elements is their ability to influence transcription of neighbouring genes. The elements themselves contain promoters that can initiate transcription of flanking genomic DNA. Furthermore, they are susceptible to epigenetic silencing, which is often stochastic and incomplete, resulting in complex patterns of transcription. This review discusses some diseases in both human and mouse that are caused by these repetitive elements.
Mitochondrial disorders: Prevalence, myths and advances
Authors: Thorburn D. R. 
Published: June 2004

AbstractSummary: Disorders of mitochondrial oxidative phosphorylation (OXPHOS) are renowned for their variability in clinical features and genetic causes. This makes it difficult to determine their true prevalence, but recent studies have documented a minimum birth prevalence of 13.1/100 000 or 1/7634 for oxidative phosphorylation disorders with onset at any age. This clearly remains an underestimate but it indicates that oxidative phosphorylation disorders can be regarded as the most common group of inborn errors of metabolism. Pathogenic mutations causing human oxidative phosphorylation disorders have now been identified in more than 30 of the 37 mitochondrial DNA genes and in more than 30 nuclear genes. Most of the nuclear gene defects cause autosomal recessive diseases, but autosomal dominant and X‐linked disorders also occur. It is likely that at least another 30, and perhaps over 100, nuclear‐encoded oxidative phosphorylation disorders await identification. Oxidative phosphorylation genetics are complex and there appear to be a number of common misconceptions about mitochondrial DNA mutations that may impede optimal investigation and management of patients. In our experience, mitochondrial DNA mutations are not a negligible cause of OXPHOS disorders in children but account for 20–25% of cases. Similarly, a family history suggesting maternal inheritance is the exception rather than the norm for children with mitochondrial DNA mutations, many of whom have de novo mutations. Only some mitochondrial DNA mutations disappear from cultured cells, so deficient enzyme activity in fibroblasts does not imply the presence of a nuclear defect. Finally, it is still widely thought that there are very few reproductive options that can be offered to women at risk of transmitting a mitochondrial DNA mutation. While a cautious approach is needed, there is now a consensus that prenatal diagnosis should be offered to some women, particularly those at lower recurrence risk. Preimplantation genetic diagnosis can also be an option.
Protein substitutes for PKU: What's new?
Authors: Macdonald A. , Daly A. , Davies P. , Asplin D. , Hall S. K. , Rylance G. , Chakrapani A. 
Published: June 2004

AbstractSummary: Protein substitutes are an essential component in the management of phenylketonuria. A series of studies at Birmingham Children's Hospital have investigated their optimal dosage, timing and practical administration as well as the efficacy and tolerance of novel protein substitutes. The key findings are as follows. (1) Lower dosages of protein substitute (1.2 g/kg per day of protein equivalent) adversely affect blood phenylalanine control in children aged 1–10 years. (2) There is wide variability in 24 h blood phenylalanine concentrations. (3) Adjusting protein substitute timing during daytime does not reduce blood phenylalanine variability. (4) Repeated 4 h administration of protein substitute throughout 24 h markedly reduces phenylalanine variability and leads to lower phenylalanine concentrations. (5) The new, concentrated, low‐volume protein substitutes and amino acid tablet preparations are efficacious and well tolerated by patients. (6) Administration of protein substitute as a gel or paste has reduced difficulties with administration of protein substitute in children. These findings are important in rationalizing treatment strategies, improving patient compliance and overall in improving blood phenylalanine control.
Multi-trophic level interactions in a cassava–maize mixed cropping system in the humid tropics of West Africa
Authors: Schulthess F. , Chabi-Olaye A. , Gounou S. 
Published: June 2004

AbstractMulti-trophic level interactions in a mixed crop, involving cassava and maize, were studied in derived-savanna in Benin, West Africa. Two trials were planted, one during the short rainy season two months before onset of the dry season and one during the long rainy season in spring. Key pests under study on maize were the noctuidSesamia calamistisHampson and the pyralidsEldana saccharinaWalker andMussidia nigrivenellaRagonot, and on cassava, the exotic mealybug,Phenacoccus manihotiMatile-Ferrero and its encyrtid parasitoidApoanagyrus lopeziDe Santis. Both crops received insecticide treatments to assess the crop loss by a pest species. On maize, intercropping with cassava reduced egg and immature numbers ofS. calamistisby 67 and 83%, respectively, as a result of reduced host finding by the ovipositing adult moth and of higher egg parasitism byTelenomusspp. Both trials showed similar effects on maize yields: on insecticide-treated maize, intercropping with cassava reduced maize yields by 9–16%, while on untreated maize the net effect of reduced pest density and increased plant competition resulted in zero yield differences; yield losses were lower in inter- compared to monocropped maize. For cassava, cropping system had no effect on parasitism byA. lopezi. Yield differences between mono- and intercropped cassava depended on time of harvest: they were large at the beginning and zero at final harvest. Land equivalent ratios were mostly > 1.5 indicating that a maize/cassava mixed crop, protected or unprotected, considerably increased the productivity per unit area of land.
Biological and chemical assays of pyrethroids in cattle dung
Authors: Vale G.A. , Grant I.F. , Dewhurst C.F. , Aigreau D. 
Published: June 2004

AbstractBioassays were developed in Zimbabwe to measure pyrethroid in cattle dung. These and chemical assays then estimated concentrations in dung from treated oxen and elucidated risks to dung fauna. Laboratory bioassays with adult beetles (Histeridae and Scarabaeinae, including Copris, Digitonthophagus, Onitis and Sisyphus spp.) and muscoid larvae (Musca lusoria Wiedemann) indicated that the LC50 of pyrethroids, as ppm in the wet weight, averaged 0.04 for deltamethrin pour-on, 0.25 for deltamethrin dip, 0.22 for alphacypermthrin pour-on, 0.10 for cyfluthrin pour-on, 0.23 for cypermethrin dip and 0.63 for flumethrin dip. Field bioassays involved artificial dung pats of 800 g, deployed in woodland and inspected after 24 h to record insects dead and alive. Beetles were most abundant in the wet season. Muscoid larvae were less seasonal. The LC50 of insecticides in the field confirmed laboratory indications. Adult Diptera (muscoids and Sgifidae) were not repelled or killed until the deltamethrin concentration reached 10 ppm. Pat dispersal by dung fauna and termites (Microtermes spp.) was halved by deltamethrin at 0.1–1 ppm. Scavenging of dead beetles by ants was greatest with small beetles (< 15 mm long) uncontaminated with insecticide. Dips and pour-ons of deltamethrin on cattle gave residues of about 0.01–0.1 ppm in dung produced in the fortnight after application. About 1.6% of the deltamethrin applied was transferred to dung. Deltamethrin and alphacypermethrin in dung showed no detectable degradation in 64 days. Contamination levels threaten populations of slow-breeding beetles.
Visceral Leishmaniasis (Kala‐Azar) and Pregnancy
Authors: Figueiró-Filho Ernesto Antonio , Duarte Geraldo , El-Beitune Patrícia , Quintana Silvana Maria , Maia Tamara Lemos 
Published: June 2004

Objective: The aim of the present review was to close the gap in the approach to pregnant women with
visceral leishmaniasis (kala‐azar) by providing up‐to‐date information to obstetricians about physiopathology,
epidemiology, vertical transmission, drugs and treatment during pregnancy.Background: Infection with Leishmania chagasi during pregnancy is rare and deserves special attention since
little information is available regarding the occurrence of visceral leishmaniasis during gestational period and the
real possibility of vertical transmission of this disease. Because specific areas in the world are endemic for the
disease and considering the continuous growth of the population, cases of pregnant women with visceral
leishmaniasis are becoming more frequent. Unfortunately, textbooks on infectious diseases do not include this
specific group of patients, and studies in the literature on aspects related to pregnancy and visceral leishmaniasis
are scarce.Conclusions: Vertical transmission of leishmaniasis is possible and the institution of treatment is imperative in
cases of pregnant women with kala‐azar. Amphotericin B is strongly recommended as the first choice drug due
to its fewer maternal‐fetal adverse effects.
Hepatitis C Virus (HCV): Prevalence in a Gynecological UrgentCare Clinic Population
Authors: Adusumalli J. , Bonney E. A. , Odenat L. , Jamieson D. J. 
Published: June 2004

Objective: To determine the prevalence of hepatitis C virus (HCV) among women seeking urgent gynecological
care.Methods: Women were asked to complete a short self‐assessment screening of HCV risk. Those answering yes
to any of the screening questions were offered HCV testing and were asked to complete a more detailed
questionnaire.Results: Among the 125 women who completed the screening questionnaire, 80% (100) answered yes to one
or more of the screening questions. Of the 99 women who underwent testing, six (6.1%) were HCV
seropositive; a history of injection drug use was the only finding associated with HCV seropositivity (R.R 9.7:
95% CI 1.90–49.40).Conclusions: Women seeking urgent outpatient gynecological care, particularly those who are injection drug
users, are at a substantial risk of HCV infection. A careful risk assessment should be completed in order to
identify women who should be offered HCV testing.
Transmembrane proteins in the Protein Data Bank: identification and classification
Authors: Tusnády Gábor E. , Dosztányi Zsuzsanna , Simon István 
Published: June 2004

Abstract
Motivation: Integral membrane proteins play important roles in living cells. Although these proteins are estimated to constitute 25% of proteins at a genomic scale, the Protein Data Bank (PDB) contains only a few hundred membrane proteins due to the difficulties with experimental techniques. The presence of transmembrane proteins in the structure data bank, however, is quite invisible, as the annotation of these entries is rather poor. Even if a protein is identified as a transmembrane one, the possible location of the lipid bilayer is not indicated in the PDB because these proteins are crystallized without their natural lipid bilayer, and currently no method is publicly available to detect the possible membrane plane using the atomic coordinates of membrane proteins.
Results: Here, we present a new geometrical approach to distinguish between transmembrane and globular proteins using structural information only and to locate the most likely position of the lipid bilayer. An automated algorithm (TMDET) is given to determine the membrane planes relative to the position of atomic coordinates, together with a discrimination function which is able to separate transmembrane and globular proteins even in cases of low resolution or incomplete structures such as fragments or parts of large multi chain complexes. This method can be used for the proper annotation of protein structures containing transmembrane segments and paves the way to an up-to-date database containing the structure of all known transmembrane proteins and fragments (PDB_TM) which can be automatically updated. The algorithm is equally important for the purpose of constructing databases purely of globular proteins.
Availability: The PDB_TM database is available for academic users on http://www.enzim.hu/PDB_TM.
Supplementary information: Data files used in this article can be found under the PDB_TM homepage (http://www.enzim.hu/PDB_TM/index.php?method=docs).
Supervised machine learning techniques for the classification of metabolic disorders in newborns
Authors: Baumgartner C. , Böhm C. , Baumgartner D. , Marini G. , Weinberger K. , Olgemöller B. , Liebl B. , Roscher A. A. 
Published: June 2004

Abstract
Motivation: During the Bavarian newborn screening programme all newborns have been tested for about 20 inherited metabolic disorders. Owing to the amount and complexity of the generated experimental data, machine learning techniques provide a promising approach to investigate novel patterns in high-dimensional metabolic data which form the source for constructing classification rules with high discriminatory power.
Results: Six machine learning techniques have been investigated for their classification accuracy focusing on two metabolic disorders, phenylketo nuria (PKU) and medium-chain acyl-CoA dehydrogenase deficiency (MCADD). Logistic regression analysis led to superior classification rules (sensitivity &gt;96.8%, specificity &gt;99.98%) compared to all investigated algorithms. Including novel constellations of metabolites into the models, the positive predictive value could be strongly increased (PKU 71.9% versus 16.2%, MCADD 88.4% versus 54.6% compared to the established diagnostic markers). Our results clearly prove that the mined data confirm the known and indicate some novel metabolic patterns which may contribute to a better understanding of newborn metabolism.
Availability: WEKA machine learning package: www.cs.waikato.ac.nz/~ml/weka and statistical software package ADE-4: http://pbil.univ-lyon1.fr/ADE-4
Comparative analysis of protein unfoldedness in human housekeeping and non-housekeeping proteins
Authors: Pandey Neeraj , Ganapathi Mythily , Kumar Kaushal , Dasgupta Dipayan , Das Sutar Sushanta Kumar , Dash Debasis 
Published: June 2004

Abstract
Summary: Absence of any regular structure is increasingly being observed in structural studies of proteins. These disordered regions or random coils, which have been observed under physiological conditions, are indicators of protein plasticity. The wide variety of interactions possible due to the flexibility of these ‘natively disordered’ regions confers functional advantage to the protein and the organism in general. This concept is underscored by the increasing proportion of intrinsically unstructured proteins seen with the ascension in the complexity of the organisms.
The ‘natively unfolded/disordered’ state of the protein can be predicted utilizing Uversky's or Dunker's algorithm. We utilized Uversky's prediction scheme and based on the unique position of a protein in the charge–hydrophobicity plot, a derived net score was used to predict the overall disorder of the human housekeeping and non-housekeeping proteins. Substantial numbers of proteins in both the classes were predicted to be unfolded. However, comparative genomic analysis of predicted unfolded Homo sapiens proteins with homologues in Caenorhabditis elegans, Drosophila melanogaster and Mus musculus revealed significant increase in unfoldedness in non-housekeeping proteins in comparison with housekeeping proteins. Our analysis in the evolutionary context suggests addition or substitution of amino acid residues which favour unfoldedness in non-housekeeping proteins compared to housekeeping proteins.
Supplementary information: http://www.igib.res.in/data/pda/proteindisorderanalysis.html
Visualizations for taxonomic and phylogenetic trees
Authors: Parr Cynthia Sims , Lee Bongshin , Campbell Dana , Bederson Benjamin B. 
Published: June 2004

Abstract
Motivation: Despite substantial efforts to develop and populate the back-ends of biological databases, front-ends to these systems often rely on taxonomic expertise. This research applies techniques from human–computer interaction research to the biodiversity domain.
Results: We developed an interactive node-link tool, TaxonTree, illustrating the value of a carefully designed interaction model, animation, and integrated searching and browsing towards retrieval of biological names and other information. Users tested the tool using a new, large integrated dataset of animal names with phylogenetic-based and classification-based tree structures. These techniques also translated well for a tool, DoubleTree, to allow comparison of trees using coupled interaction. Our approaches will be useful not only for biological data but as general portal interfaces.
Availability: Working versions of TaxonTree and DoubleTree and video demonstrations of DoubleTree are available at http://www.cs.umd.edu/hcil/biodiversity
Supplementary information: All datasets and folk tree illustration are available at http://www.cs.umd.edu/hcil/biodiversity
Picky: oligo microarray design for large genomes
Authors: Chou Hui-Hsien , Hsia An-Ping , Mooney Denise L. , Schnable Patrick S. 
Published: June 2004

Abstract
Motivation: Many large genomes are getting sequenced nowadays. Biologists are eager to start microarray analysis taking advantage of all known genes of a species, but existing microarray design tools were very inefficient for large genomes. Also, many existing tools operate in a batch mode that does not assure best designs.
Results: Picky is an efficient oligo microarray design tool for large genomes. Picky integrates novel computer science techniques and the best known nearest-neighbor parameters to quickly identify sequence similarities and estimate their hybridization properties. Oligos designed by Picky are computationally optimized to guarantee the best specificity, sensitivity and uniformity under the given design constrains. Picky can be used to design arrays for whole genomes, or for only a subset of genes. The latter can still be screened against a whole genome to attain the same quality as a whole genome array, thereby permitting low budget, pathway-specific experiments to be conducted with large genomes. Picky is the fastest oligo array design tool currently available to the public, requiring only a few hours to process large gene sets from rice, maize or human.
Availability: Picky is independent of any external software to execute, is designed for non-programmers to easily operate through a graphical user interface, and is made available for all major computing platforms (e.g. Mac, Windows and Linux) at http://www.complex.iastate.edu.
Supplementary information: A short paper detailing the probability analysis for Picky, a program that implements functions mentioned in the paper, and the output of the program are available online from the Publisher's website.