A shallow parser based on closed-class words to capture relations in biomedical text

Natural language processing for biomedical text currently focuses mostly on entity and relation extraction. These entities and relations are usually pre-specified entities, e.g., proteins, and pre-specified relations, e.g., inhibit relations. A shallow parser that captures the relations between noun phrases automatically from free text has been developed and evaluated. It uses heuristics and a noun phraser to capture entities of interest in the text. Cascaded finite state automata structure the relations between individual entities. The automata are based on closed-class English words and model generic relations not limited to specific words. The parser also recognizes coordinating conjunctions and captures negation in text, a feature usually ignored by others. Three cancer researchers evaluated 330 relations extracted from 26 abstracts of interest to them. There were 296 relations correctly extracted from the abstracts resulting in 90% precision of the relations and an average of 11 correct relations per abstract.     

Tumors with reduced expression of a cytotoxic T lymphocyte recognized antigen lack immunogenicity but retain sensitivity to lysis by cytotoxic T lymphocytes

A murine solid tumor was transfected to express various levels of an allogeneic major histocompatibility complex class I gene (K²¹⁶), in order to test the effect of the level of antigen expression on immunogenicity and sensitivity to lysis by cytotoxic T lymphocytes (CTL). The growth rates of clones of tumor cells expressing different levels of the transfected gene were similar in vitro and in nude mice. Although all tumor cells, including cells freshly isolated from growing tumors, were equally sensitive to lysis by specific CTL, only tumor cells expressing the highest level of the K²¹⁶ antigen stimulated CTL and were rejected by normal mice. In contrast, tumor cells expressing lower levels of antigen failed to immunize for CTL and grew progressively in normal mice, despite retaining expression of the transfected gene and remaining fully sensitive to CTL-mediated lysis; thus, the threshold of antigen needed to stimulate CTL responses was considerably higher than that needed to lyse tumor cells. Reduction of K²¹⁶ antigen expression from 100-fold to 40-fold above background, impaired significantly the ability of the tumor cells to induce a K²¹⁶-specific immune response, while tumor cells expressing K²¹⁶ at levels 2-fold above background were as susceptible to CTL-mediated lysis as tumor cells expressing 50-fold more antigen. The important implication of these findings is that some tumors occurring in nature may not be immunogenic but nevertheless express antigens which are potential targets for immune therapy.     

Large-scale screen highlights the importance of capsule for virulence in the zoonotic pathogen Streptococcus iniae

Zoonotic pathogens have the unique ability to cross the species barrier, causing disease in both humans and specific animal hosts. Streptococcus iniae is a zoonotic pathogen of both fish and humans, and the clinical presentations of S. iniae infections in fish and humans are very similar to those caused by various human-specific streptococcal pathogens. Virulence mechanisms required for infection by this pathogen of either host have yet to be determined. Using the previously reported zebrafish infectious disease model, we performed a large-scale screening to determine genes required for systemic infection. Screening 1,128 signature-tagged transposon mutants through the zebrafish model allowed identification of 41 potential mutants that were unable to survive within the host environment. Greater than 50% of the mutants that could be identified through homology searches were highly homologous to genes found in other human-specific streptococcal pathogens, while 32% were found to have no homology to any sequences found in the databases, suggesting as yet unknown gram-positive bacterial virulence factors. A large percentage of the insertions were found to be located in several putative capsule synthesis genes, an important virulence component for other systemic pathogens. Density gradient assays demonstrated that several of these putative capsule mutants have dissimilar buoyant densities, suggesting different levels of capsule synthesis. Putative capsule mutants were also less resistant to phagocytosis in whole-blood assays than wild-type S. iniae. Our initial large-scale characterization of S. iniae virulence highlights the importance of the capsule for successful infection.     

The family bereavement program: efficacy evaluation of a theory-based prevention program for parentally bereaved children and adolescents

This article presents an experimental evaluation of the Family Bereavement Program (FBP), a 2-component group intervention for parentally bereaved children ages 8-16. The program involved separate groups for caregivers, adolescents, and children, which were designed to change potentially modifiable risk and protective factors for bereaved children. The evaluation involved random assignment of 156 families (244 children and adolescents) to the FBP or a self-study condition. Families participated in assessments at pretest, posttest, and 11-month follow-up. Results indicated that the FBP led to improved parenting, coping, and caregiver mental health and to reductions in stressful events at posttest. At follow-up, the FBP led to reduced internalizing and externalizing problems, but only for girls and those who had higher problem scores at baseline.     

Polymorphisms in the DNA repair gene XRCC1 and age-related disease

The recent hypothesis that common variants (single nucleotide polymorphisms or SNPs) in the population may contribute significantly to genetic risk for common diseases permits a conceptually straightforward approach to identifying age-related disease-causing mutations. Functional variants of DNA replication and repair genes might be expected to be highly significant to cancer and aging since replication must proceed with high fidelity in a cellular environment where an estimated 10000 nucleotides are damaged daily. Single-strand breaks (SSB) are one of the results of DNA damage either by methylation, oxidation, reduction or fragmentation of bases by ionizing radiation, and arise in cells directly by disintegration of damaged sugars or indirectly as intermediates of base excision repair. Studies have demonstrated a role for XRCC1 both in vitro and in vivo during the repair of SSB. A number of SNPs have been identified for the XRCC1 gene, and several have been associated with age-related diseases, especially cancer. This report provides resequencing data confirming the existence of commonly occurring SNPs, including Arg194Trp and Arg399Gln, and briefly summarizes epidemiological and functional relevance to cancer and other age-related diseases. XRCC1 SNPs will be useful probes for investigating age-associated pathobiology in epidemiological and mechanistic studies.     

Lack of gender difference in ventilatory chemoresponsiveness and post-hypoxic ventilatory decline

Altered chemoresponsiveness has been postulated to explain the gender difference in the incidence of sleep disordered breathing (SDB). The purpose of this investigation was to ascertain a gender difference in the effect of hypocapnic hypoxia on ventilation. Hypocapnic hypoxia was induced in stable NREM sleep for 3 min periods. In the first analysis, hypoxic ventilatory response in a steady state (SHVR) was defined as the amount of change in minute ventilation (VI) between mean room air (RA) and hypoxia divided by the change in Sa O2 between RA and hypoxia (DeltaVI/DeltaSa O2). The mean group SHVR values were 0.23+/-0.15 and 0.20+/-0.10 L/min per %SaO2, for men and women, respectively (P = ns). In the second analysis, we analyzed the decline in ventilatory parameters after the cessation of hypoxia. There was no difference in VI between the genders (men, 5.6+/-1.7 L/min vs. women, 4.9+/-1.9 L/min, P = ns). We conclude that the gender difference in SDB is not explained by a difference in the ventilatory response to hypocapnic hypoxia.     

The clinical significance of karyotype in acute myelogenous leukemia

To evaluate further the prognostic significance of karyotype at diagnosis of acute myelogenous leukemia (AML), we have made a follow-up study of 711 patients who were diagnosed between January 1, 1980, and March 31, 1982, and who were originally reported by the Fourth International Workshop on Chromosomes in Leukemia (4IWCL). Three different chromosomal classifications were evaluated, including presence of normal and abnormal metaphases (NN-AN-AA classification), a modification of the Chicago classification, and a complexity classification. All three chromosomal classifications were shown to correlate significantly with outcome in patients with de novo AML. Furthermore, the NN-AN-AA classification and the complexity classification had independent prognostic significance when age, sex, and FAB morphology were also considered in multivariate analyses of survival. These data provide further evidence that karyotype is an important factor in predicting the outcome of patients with AML.     

Chromosome abnormalities in leukemia and lymphoma

Nonrandom chromosome changes have been identified in a number of malignant human tumors. The leukemias are among the best studied malignant cells and they provide the largest body of relevant cytogenetic data. In chronic myeloid leukemia, a reasonably consistent translocation [t(9;22) (q34;q11)] is observed in 93 percent of all Ph1 positive patients. In the other patients, translocations are either two-way, involving No. 22 with some other chromosome or complex translocations involving Nos. 9 and 22 and another chromosome. In acute nonlymphocytic leukemia, two translocations are each specifically associated with leukemic cells arrested at two different stages of maturation. One of these, t(8;21)(q22;q22), is found mainly in patients with acute myeloblastic leukemia with maturation (AML-M2). The other, t(15;17)(q22?;q21?), is seen only in patients with acute promyelocytic leukemia (APL-M3). Various translocations have been observed in B-cell acute lymphoblastic leukemia or in Burkitt lymphoma. The most common is t(8;14)(q24;q32), but variants of this, namely t(2;8)(p13?;q24) and t(8;22)(q24;q11), have also been observed; in all of these, the consistent change involves 8q24. The various immunoglobulin loci are located on chromosomes 2, 14, and 22 in the same chromosome band affected by the translocations in B-cell leukemia. These translocations may occur randomly. If a specific translocation provides a particular cell type with a growth advantage, then selection could act to cause the proliferation of this aneuploid cell line vis-a-vis cells with a normal karyotype. In this view, the chromosome change could be the fundamental event leading to the leukemic transformation of an otherwise normal cell. The challenge for the future is to define the genes located at the sites of consistent translocations in myeloid leukemias and to determine the alterations in gene function that are associated with the translocation.     

Spinal intraoperative three-dimensional navigation: correlation between clinical and absolute engineering accuracy

Background Context

Spinal intraoperative computer-assisted navigation (CAN) may guide pedicle screw placement. Computer-assisted navigation techniques have been reported to reduce pedicle screw breach rates across all spinal levels. However, definitions of screw breach vary widely across studies, if reported at all. The absolute quantitative error of spinal navigation systems is theoretically a more precise and generalizable metric of navigation accuracy. It has also been computed variably and reported in less than a quarter of clinical studies of CAN-guided pedicle screw accuracy.