A Corpus of Potentially Contradictory Research Claims from Cardiovascular Research Abstracts

Background: Research literature in biomedicine and related fields contains a huge number of claims, such as the effectiveness of treatments. These claims are not always consistent and may even contradict each other. Being able to identify contradictory claims is important for those who rely on the biomedical literature. Automated methods to identify and resolve them are required to cope with the amount of information available. However, research in this area has been hampered by a lack of suitable resources. We describe a methodology to develop a corpus which addresses this gap by providing examples of potentially contradictory claims and demonstrate how it can be applied to identify these claims from Medline abstracts related to the topic of cardiovascular disease. Methods A set of systematic reviews concerned with four topics in cardiovascular disease were identified from Medline and analysed to determine whether the abstracts they reviewed contained contradictory research claims. For each review, annotators were asked to analyse these abstracts to identify claims within them that answered the question addressed in the review. The annotators were also asked to indicate how the claim related to that question and the type of the claim. Results: A total of 259 abstracts associated with 24 systematic reviews were used to form the corpus. Agreement between the annotators was high, suggesting that the information they provided is reliable. Conclusions: The paper describes a methodology for constructing a corpus containing contradictory research claims from the biomedical literature. The corpus is made available to enable further research into this area and support the development of automated approaches to contradiction identification

Cross-Serotype Immunity Induced by Immunization with a Conserved Rhinovirus Capsid Protein

Human rhinovirus (RV) infections are the principle cause of common colds and precipitate asthma and COPD exacerbations. There is currently no RV vaccine, largely due to the existence of ∼150 strains. We aimed to define highly conserved areas of the RV proteome and test their usefulness as candidate antigens for a broadly cross-reactive vaccine, using a mouse infection model. Regions of the VP0 (VP4+VP2) capsid protein were identified as having high homology across RVs. Immunization with a recombinant VP0 combined with a Th1 promoting adjuvant induced systemic, antigen specific, cross-serotype, cellular and humoral immune responses. Similar cross-reactive responses were observed in the lungs of immunized mice after infection with heterologous RV strains. Immunization enhanced the generation of heterosubtypic neutralizing antibodies and lung memory T cells, and caused more rapid virus clearance. Conserved domains of the RV capsid therefore induce cross-reactive immune responses and represent candidates for a subunit RV vaccine

Epilepsy and Psychiatric Comorbidities: Drug Selection.

Purpose of review The pharmacological treatment of patients with epilepsy and psychiatric comorbidities may sometimes represent a therapeutic challenge. This review is focused on the pharmacological management of patients with epilepsy and psychiatric problems in terms of rationalization of the antiepileptic drug (AED) treatment and the pharmacological management of the most clinically relevant psychiatric comorbidities, namely mood and anxiety disorders, psychoses, and attention deficit hyperactivity disorder (ADHD). Recent findings Up to 8% of patients with drug-resistant epilepsy develop treatment-emergent psychiatric adverse events of AED regardless of the mechanism of action of the drug and this is usually related to an underlying predisposition given by the previous psychiatric history and the involvement of mesolimbic structures. Careful history taking, periodic screening for mood and anxiety disorders, low starting doses, and slow titration schedules can reduce the possibility of AED-related problems. A pragmatic checklist for the pharmacological management of patients with epilepsy and psychiatric disorders is presented. Summary patients should be informed of potential behavioral effects of AEDs but no drugs should be excluded a priori. Any psychiatric comorbidity should be addressed in the appropriate setting and full remission and recovery should always represent the first goal of any therapeutic intervention. Neurologists should be aware of the side effects of major psychotropic drug classes in order to fully counsel their patients and other health professionals involved

Inherited epidermolysis bullosa

Inherited epidermolysis bullosa (EB) encompasses a number of disorders characterized by recurrent blister formation as the result of structural fragility within the skin and selected other tissues. All types and subtypes of EB are rare; the overall incidence and prevalence of the disease within the United States is approximately 19 per one million live births and 8 per one million population, respectively. Clinical manifestations range widely, from localized blistering of the hands and feet to generalized blistering of the skin and oral cavity, and injury to many internal organs. Each EB subtype is known to arise from mutations within the genes encoding for several different proteins, each of which is intimately involved in the maintenance of keratinocyte structural stability or adhesion of the keratinocyte to the underlying dermis. EB is best diagnosed and subclassified by the collective findings obtained via detailed personal and family history, in concert with the results of immunofluorescence antigenic mapping, transmission electron microscopy, and in some cases, by DNA analysis. Optimal patient management requires a multidisciplinary approach, and revolves around the protection of susceptible tissues against trauma, use of sophisticated wound care dressings, aggressive nutritional support, and early medical or surgical interventions to correct whenever possible the extracutaneous complications. Prognosis varies considerably and is based on both EB subtype and the overall health of the patient

Primate TNF Promoters Reveal Markers of Phylogeny and Evolution of Innate Immunity

Background. Tumor necrosis factor (TNF) is a critical cytokine in the immune response whose transcriptional activation is controlled by a proximal promoter region that is highly conserved in mammals and, in particular, primates. Specific single nucleotide polymorphisms (SNPs) upstream of the proximal human TNF promoter have been identified, which are markers of human ancestry. Methodology/Principal findings. Using a comparative genomics approach we show that certain fixed genetic differences in the TNF promoter serve as markers of primate speciation. We also demonstrate that distinct alleles of most human TNF promoter SNPs are identical to fixed nucleotides in primate TNF promoters. Furthermore, we identify fixed genetic differences within the proximal TNF promoters of Asian apes that do not occur in African ape or human TNF promoters. Strikingly, protein-DNA binding assays and gene reporter assays comparing these Asian ape TNF promoters to African ape and human TNF promoters demonstrate that, unlike the fixed differences that we define that are associated with primate phylogeny, these Asian ape-specific fixed differences impair transcription factor binding at an Sp1 site and decrease TNF transcription induced by bacterial stimulation of macrophages. Conclusions/significance. Here, we have presented the broadest interspecies comparison of a regulatory region of an innate immune response gene to date. We have characterized nucleotide positions in Asian ape TNF promoters that underlie functional changes in cell type- and stimulus-specific activation of the TNF gene. We have also identified ancestral TNF promoter nucleotide states in the primate lineage that correspond to human SNP alleles. These findings may reflect evolution of Asian and African apes under a distinct set of infectious disease pressures involving the innate immune response and TNF

Synthetic biology to access and expand nature's chemical diversity

Bacterial genomes encode the biosynthetic potential to produce hundreds of thousands of complex molecules with diverse applications, from medicine to agriculture and materials. Accessing these natural products promises to reinvigorate drug discovery pipelines and provide novel routes to synthesize complex chemicals. The pathways leading to the production of these molecules often comprise dozens of genes spanning large areas of the genome and are controlled by complex regulatory networks with some of the most interesting molecules being produced by non-model organisms. In this Review, we discuss how advances in synthetic biology — including novel DNA construction technologies, the use of genetic parts for the precise control of expression and for synthetic regulatory circuits — and multiplexed genome engineering can be used to optimize the design and synthesis of pathways that produce natural products

Idiopathic isolated clitoromegaly: A report of two cases

BACKGROUND: Clitoromegaly is a frequent congenital malformation, but acquired clitoral enlargement is relatively rare. METHODS: Two acquired clitoromegaly cases treated in Atatürk Training Hospital, Izmir, Turkey are presented. RESULTS: History from both patients revealed clitoromegaly over the last three years. Neither gynecological nor systemic abnormalities were detected in either patient. Karyotype analyses and hormonal tests were normal. Abdominal and gynaecological ultrasound did not show any cystic lesion or other abnormal finding. Computerized tomography scan of the adrenal glands was normal. Clitoroplasty with preservation of neurovascular pedicles was performed for the treatment of clitoromegaly. CONCLUSION: The patients were diagnosed as "idiopathic isolated" clitoromegaly. To the best of our knowledge, there has been no detailed report about idiopathic clitoromegaly in the literature

Chiral Nonet Mixing in pi pi Scattering

Pion pion scattering is studied in a generalized linear sigma model which contains two scalar nonets (one of quark-antiquark type and the other of diquark-antidiquark type) and two corresponding pseudoscalar nonets. An interesting feature concerns the mixing of the four isosinglet scalar mesons which yield poles in the scattering amplitude. Some realism is introduced by enforcing exact unitarity via the K-matrix method. It is shown that a reasonable agreement with experimental data is obtained up to about 1 GeV. The poles in the unitarized scattering amplitude are studied in some detail. The lowest pole clearly represents the sigma meson (or f0(600)) with a mass and decay width around 500 MeV. The second pole invites comparison with the f0(980) which has a mass around 1 GeV and decay width around 100 MeV. The third and fourth poles, resemble some of the isosinglet state in the complicated 1-2 GeV region. Some comparison is made to the situation in the usual SU(3) linear sigma model with a single scalar nonet

Comparison of prognostic scores and surgical approaches to treat spinal metastatic tumors: A review of 57 cases

Surgical treatment of metastatic spinal cord compression with or without neural deficit is controversial. Karnofsky and Tokuhashi scores have been proposed for prognosis of spinal metastasis. Here, we conducted a retrospective analysis of Karnofsky and modified Tokuhashi scores in 57 consecutive patients undergoing surgery for secondary spinal metastases to evaluate the value of these scores in aiding decision making for surgery. Comparison of preoperative Karnofsky and modified Tokuhashi scores with the type of the surgical approach for each patient revealed that both scores not only reliably estimate life expectancy, but also objectively improved surgical decisions. When the general status of the patient is poor (i.e., Karnofsky score less than 40% or modified Tokuhashi score of 5 or greater), palliative treatments and radiotherapy, rather than surgery, should be considered

A Frameshift Mutation in Golden Retriever Dogs with Progressive Retinal Atrophy Endorses SLC4A3 as a Candidate Gene for Human Retinal Degenerations

Progressive retinal atrophy (PRA) in dogs, the canine equivalent of retinitis pigmentosa (RP) in humans, is characterised by vision loss due to degeneration of the photoreceptor cells in the retina, eventually leading to complete blindness. It affects more than 100 dog breeds, and is caused by numerous mutations. RP affects 1 in 4000 people in the Western world and 70% of causal mutations remain unknown. Canine diseases are natural models for the study of human diseases and are becoming increasingly useful for the development of therapies in humans. One variant, prcd-PRA, only accounts for a small proportion of PRA cases in the Golden Retriever (GR) breed. Using genome-wide association with 27 cases and 19 controls we identified a novel PRA locus on CFA37 (praw = 1.94×10−10, pgenome = 1.0×10−5), where a 644 kb region was homozygous within cases. A frameshift mutation was identified in a solute carrier anion exchanger gene (SLC4A3) located within this region. This variant was present in 56% of PRA cases and 87% of obligate carriers, and displayed a recessive mode of inheritance with full penetrance within those lineages in which it segregated. Allele frequencies are approximately 4% in the UK, 6% in Sweden and 2% in France, but the variant has not been found in GRs from the US. A large proportion of cases (approximately 44%) remain unexplained, indicating that PRA in this breed is genetically heterogeneous and caused by at least three mutations. SLC4A3 is important for retinal function and has not previously been associated with spontaneously occurring retinal degenerations in any other species, including humans