Tools for loading MEDLINE into a local relational database

BACKGROUND: Researchers who use MEDLINE for text mining, information extraction, or natural language processing may benefit from having a copy of MEDLINE that they can manage locally. The National Library of Medicine (NLM) distributes MEDLINE in eXtensible Markup Language (XML)-formatted text files, but it is difficult to query MEDLINE in that format. We have developed software tools to parse the MEDLINE data files and load their contents into a relational database. Although the task is conceptually straightforward, the size and scope of MEDLINE make the task nontrivial. Given the increasing importance of text analysis in biology and medicine, we believe a local installation of MEDLINE will provide helpful computing infrastructure for researchers. RESULTS: We developed three software packages that parse and load MEDLINE, and ran each package to install separate instances of the MEDLINE database. For each installation, we collected data on loading time and disk-space utilization to provide examples of the process in different settings. Settings differed in terms of commercial database-management system (IBM DB2 or Oracle 9i), processor (Intel or Sun), programming language of installation software (Java or Perl), and methods employed in different versions of the software. The loading times for the three installations were 76 hours, 196 hours, and 132 hours, and disk-space utilization was 46.3 GB, 37.7 GB, and 31.6 GB, respectively. Loading times varied due to a variety of differences among the systems. Loading time also depended on whether data were written to intermediate files or not, and on whether input files were processed in sequence or in parallel. Disk-space utilization depended on the number of MEDLINE files processed, amount of indexing, and whether abstracts were stored as character large objects or truncated. CONCLUSIONS: Relational database (RDBMS) technology supports indexing and querying of very large datasets, and can accommodate a locally stored version of MEDLINE. RDBMS systems support a wide range of queries and facilitate certain tasks that are not directly supported by the application programming interface to PubMed. Because there is variation in hardware, software, and network infrastructures across sites, we cannot predict the exact time required for a user to load MEDLINE, but our results suggest that performance of the software is reasonable. Our database schemas and conversion software are publicly available at

Family/Partnership-centered Conjoint Behavioral Consultation: The Reconceptualization of a Model

• The importance of working meaningfully and constructively with families in promoting a child’s learning and adjustment is unequivocal. Home-school partnerships have been shown to relate to many positive outcomes for children, families, teachers, and schools. • Conjoint Behavioral Consultation (CBC; Sheridan, Kratochwill, & Bergan, 1996) is a structured, indirect model of service delivery whereby parents and teachers are joined to collaboratively address needs and concerns of a child with the assistance of a consultant. Goals of CBC encompass those focused on addressing child needs, and developing home-school partnerships. • CBC is procedurally operationalized via conjoint interviews (Problem Identification, Problem Analysis, and Treatment Evaluation) aimed at prioritizing shared concerns across home and school settings, evaluating factors contributing to the identified concern, developing an agreeable plan, and evaluating the child’s progress toward goals. • Traditional approaches to CBC emphasize a problem-solving orientation, aimed largely at addressing problems experienced by individual children

Clinical and Experimental Applications of NIR-LED Photobiomodulation

This review presents current research on the use of far-red to near-infrared (NIR) light treatment in various in vitro and in vivo models. Low-intensity light therapy, commonly referred to as “photobiomodulation,” uses light in the far-red to near-infrared region of the spectrum (630–1000 nm) and modulates numerous cellular functions. Positive effects of NIR–light-emitting diode (LED) light treatment include acceleration of wound healing, improved recovery from ischemic injury of the heart, and attenuated degeneration of injured optic nerves by improving mitochondrial energy metabolism and production. Various in vitro and in vivo models of mitochondrial dysfunction were treated with a variety of wavelengths of NIR-LED light. These studies were performed to determine the effect of NIR-LED light treatment on physiologic and pathologic processes. NIRLED light treatment stimulates the photoacceptor cytochrome c oxidase, resulting in increased energy metabolism and production. NIR-LED light treatment accelerates wound healing in ischemic rat and murine diabetic wound healing models, attenuates the retinotoxic effects of methanol-derived formic acid in rat models, and attenuates the developmental toxicity of dioxin in chicken embryos. Furthermore, NIR-LED light treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients. The experimental results demonstrate that NIR-LED light treatment stimulates mitochondrial oxidative metabolism in vitro, and accelerates cell and tissue repair in vivo. NIR-LED light represents a novel, noninvasive, therapeutic intervention for the treatment of numerous diseases linked to mitochondrial dysfunction

Communication Services and Supports for Individuals With Severe Disabilities: Guidance for Assessment and Intervention

The National Joint Committee for the Communication Needs of People with Severe Disabilities (NJC) reviewed literature regarding practices for people with severe disabilities in order to update guidance provided in documents originally published in 1992. Changes in laws, definitions, and policies that affect communication attainments by persons with severe disabilities are presented, along with guidance regarding assessment and intervention practices. A revised version of the Communication Bill of Rights, a powerful document that describes the communication rights of all individuals, including those with severe disabilities is included in this article. The information contained within this article is intended to be used by professionals, family members, and individuals with severe disabilities to inform and advocate for effective communication services and opportunities

Characterization of 3D genomic interactions in fetal pig muscle

Genome sequence alone is not sufficient to explain the overall coordination of nuclear activity in a particular tissue. The nuclear organisation and genomic long-range intra- and inter-chromosomal interactions play an important role in the regulation of gene expression and the activation of tissue- specific gene networks. Here we present an overview of the pig genome architecture in muscle at two late developmental stages. The muscle maturation process occurs between the 90th day and the end of gestation (114 days), a key period for survival at birth. To characterise this period we profiled chromatin interactions genome-wide with in situ Hi-C (High Throughput Chromosome Conformation Capture) in muscle samples collected at 90 and 110 days of gestation, specific moments where a drastic change in gene expression has been reported. About 200 million read pairs per library were generated (3 replicates per condition). This allowed: (a) the design of an experimental Hi-C protocol optimized for frozen fetal tissues, (b) the first Hi-C contact heatmaps in fetal porcine muscle cells, and (c) to profile Topologically Associated Domains (TADs) defined as genomic domains with high levels of chromatin interactions. Using the new assembly version Sus scrofa v11, we could map 82% of the Hi-C reads on the reference genome. After filtering, 49% of valid read pairs were used to infer the genomic interactions in both developmental stages. In addition, ChIP-seq experiments were performed to map the binding of the structural protein CTCF, known to regulate genome structure by promoting interactions between genes and distal enhancers. The Hi-C and ChIP-seq data were analysed in combination with the results of a previous transcriptome analysis, focusing on the hun-dreds of genes that were reported as differentially expressed during muscle maturation. We will report the observed general differences between both developmental stages in terms of transcription and structure

Profiling the landscape of transcription, chromatin accessibility and chromosome conformation of cattle, pig, chicken and goat genomes [FAANG pilot project]

Functional annotation of livestock genomes is a critical and obvious next step to derive maximum benefit for agriculture, animal science, animal welfare and human health. The aim of the Fr-AgENCODE project is to generate multi-species functional genome annotations by applying high-throughput molecular assays on three target tissues/cells relevant to the study of immune and metabolic traits. An extensive collection of stored samples from other tissues is available for further use (FAANG Biosamples ‘FR-AGENCODE’). From each of two males and two females per species (pig, cattle, goat, chicken), strand-oriented RNA-seq and chromatin accessibility ATAC-seq assays were performed on liver tissue and on two T-cell types (CD3+CD4+&CD3+CD8+) sorted from blood (mammals) or spleen (chicken). Chromosome Conformation Capture (in situ Hi-C) was also carried out on liver. Sequencing reads from the 3 assays were processed using standard processing pipelines. While most (50–70%) RNA-seq reads mapped to annotated exons, thousands of novel transcripts and genes were found, including extensions of annotated protein-coding genes and new lncRNAs (see abstract #69857). Consistency of ATAC-seq results was confirmed by the significant proportion of called peaks in promoter regions (36–66%) and by the specific accumulation pattern of peaks around gene starts (TSS) v. gene ends (TTS). Principal Component Analyses for RNA-seq (based on quantified gene expression) and ATAC-seq (based on quantified chromatin accessibility) highlighted clusters characterised by cell type and sex in all species. From Hi-C data, we generated 40kb-resolution interaction maps, profiled a genome-wide Directionality Index and identified from 4,100 (chicken) to 12,100 (pig) topologically-associating do- mains (TADs). Correlations were reported between RNA-seq and ATAC-seq results (see abstract #71581). In summary, we present here an overview of the first multi-species and -tissue annotations of chromatin accessibility and genome architecture related to gene expression for farm animals

Genetic and phenotypic spectrum associated with IFIH1 gain-of-function

IFIH1 gain-of-function has been reported as a cause of a type I interferonopathy encompassing a spectrum of autoinflammatory phenotypes including Aicardi–Goutières syndrome and Singleton Merten syndrome. Ascertaining patients through a European and North American collaboration, we set out to describe the molecular, clinical and interferon status of a cohort of individuals with pathogenic heterozygous mutations in IFIH1. We identified 74 individuals from 51 families segregating a total of 27 likely pathogenic mutations in IFIH1. Ten adult individuals, 13.5% of all mutation carriers, were clinically asymptomatic (with seven of these aged over 50 years). All mutations were associated with enhanced type I interferon signaling, including six variants (22%) which were predicted as benign according to multiple in silico pathogenicity programs. The identified mutations cluster close to the ATP binding region of the protein. These data confirm variable expression and nonpenetrance as important characteristics of the IFIH1 genotype, a consistent association with enhanced type I interferon signaling, and a common mutational mechanism involving increased RNA binding affinity or decreased efficiency of ATP hydrolysis and filament disassembly rate

Correction: Pathogenic LRRK2 Mutations Do Not Alter Gene Expression in Cell Model Systems or Human Brain Tissue.

Point mutations in LRRK2 cause autosomal dominant Parkinson's disease. Despite extensive efforts to determine the mechanism of cell death in patients with LRRK2 mutations, the aetiology of LRRK2 PD is not well understood. To examine possible alterations in gene expression linked to the presence of LRRK2 mutations, we carried out a case versus control analysis of global gene expression in three systems: fibroblasts isolated from LRRK2 mutation carriers and healthy, non-mutation carrying controls; brain tissue from G2019S mutation carriers and controls; and HEK293 inducible LRRK2 wild type and mutant cell lines. No significant alteration in gene expression was found in these systems following correction for multiple testing. These data suggest that any alterations in basal gene expression in fibroblasts or cell lines containing mutations in LRRK2 are likely to be quantitatively small. This work suggests that LRRK2 is unlikely to play a direct role in modulation of gene expression, although it remains possible that this protein can influence mRNA expression under pathogenic cicumstances