The Crest Phenotype in Chicken Is Associated with Ectopic Expression of HOXC8 in Cranial Skin

The Crest phenotype is characterised by a tuft of elongated feathers atop the head. A similar phenotype is also seen in several wild bird species. Crest shows an autosomal incompletely dominant mode of inheritance and is associated with cerebral hernia. Here we show, using linkage analysis and genome-wide association, that Crest is located on the E22C19W28 linkage group and that it shows complete association to the HOXC-cluster on this chromosome. Expression analysis of tissues from Crested and non-crested chickens, representing 26 different breeds, revealed that HOXC8, but not HOXC12 or HOXC13, showed ectopic expression in cranial skin during embryonic development. We propose that Crest is caused by a cis-acting regulatory mutation underlying the ectopic expression of HOXC8. However, the identification of the causative mutation(s) has to await until a method becomes available for assembling this chromosomal region. Crest is unfortunately located in a genomic region that has so far defied all attempts to establish a contiguous sequence

Recent advances in gastrointestinal oncology - updates and insights from the 2009 annual meeting of the American Society of Clinical Oncology

We have reviewed the pivotal presentations related to gastrointestinal malignancies from 2009 annual meeting of the American Society of Clinical Oncology with the theme of "personalizing cancer care". We have discussed the scientific findings and the impact on practice guidelines and ongoing clinical trials. Adding trastuzumab to chemotherapy improved the survival of patients with advanced gastric cancer overexpressing human epidermal growth factor receptor 2. Gemcitabine plus cisplatin has become a new standard for first-line treatment of advanced biliary cancer. Octreotide LAR significantly lengthened median time to tumor progression compared with placebo in patients with metastatic neuroendocrine tumors of the midgut. Addition of oxaliplatin to fluoropyrimidines for preoperative chemoradiotherapy in patients with stage II or III rectal cancer did not improve local tumor response but increased toxicities. Bevacizumab did not provide additional benefit to chemotherapy in adjuvant chemotherapy for stage II or III colon cancer. In patients with resected stage II colon cancer, recurrence score estimated by multigene RT-PCR assay has been shown to provide additional risk stratification. In stage IV colorectal cancer, data have supported the routine use of prophylactic skin treatment in patients receiving antibody against epidermal growth factor receptor, and the use of upfront chemotherapy as initial management in patients with synchronous metastasis without obstruction or bleeding from the primary site

Biomedical Discovery Acceleration, with Applications to Craniofacial Development

The profusion of high-throughput instruments and the explosion of new results in the scientific literature, particularly in molecular biomedicine, is both a blessing and a curse to the bench researcher. Even knowledgeable and experienced scientists can benefit from computational tools that help navigate this vast and rapidly evolving terrain. In this paper, we describe a novel computational approach to this challenge, a knowledge-based system that combines reading, reasoning, and reporting methods to facilitate analysis of experimental data. Reading methods extract information from external resources, either by parsing structured data or using biomedical language processing to extract information from unstructured data, and track knowledge provenance. Reasoning methods enrich the knowledge that results from reading by, for example, noting two genes that are annotated to the same ontology term or database entry. Reasoning is also used to combine all sources into a knowledge network that represents the integration of all sorts of relationships between a pair of genes, and to calculate a combined reliability score. Reporting methods combine the knowledge network with a congruent network constructed from experimental data and visualize the combined network in a tool that facilitates the knowledge-based analysis of that data. An implementation of this approach, called the Hanalyzer, is demonstrated on a large-scale gene expression array dataset relevant to craniofacial development. The use of the tool was critical in the creation of hypotheses regarding the roles of four genes never previously characterized as involved in craniofacial development; each of these hypotheses was validated by further experimental work

Systematic Review on Kinematic Assessments of Upper Limb Movements After Stroke

Background and Purpose- Assessing upper limb movements poststroke is crucial to monitor and understand sensorimotor recovery. Kinematic assessments are expected to enable a sensitive quantification of movement quality and distinguish between restitution and compensation. The nature and practice of these assessments are highly variable and used without knowledge of their clinimetric properties. This presents a challenge when interpreting and comparing results. The purpose of this review was to summarize the state of the art regarding kinematic upper limb assessments poststroke with respect to the assessment task, measurement system, and performance metrics with their clinimetric properties. Subsequently, we aimed to provide evidence-based recommendations for future applications of upper limb kinematics in stroke recovery research. Methods- A systematic search was conducted in PubMed, Embase, CINAHL, and IEEE Xplore. Studies investigating clinimetric properties of applied metrics were assessed for risk of bias using the Consensus-Based Standards for the Selection of Health Measurement Instruments checklist. The quality of evidence for metrics was determined according to the Grading of Recommendations Assessment, Development, and Evaluation approach. Results- A total of 225 studies (N=6197) using 151 different kinematic metrics were identified and allocated to 5 task and 3 measurement system groups. Thirty studies investigated clinimetrics of 62 metrics: reliability (n=8), measurement error (n=5), convergent validity (n=22), and responsiveness (n=2). The metrics task/movement time, number of movement onsets, number of movement ends, path length ratio, peak velocity, number of velocity peaks, trunk displacement, and shoulder flexion/extension received a sufficient evaluation for one clinimetric property. Conclusions- Studies on kinematic assessments of upper limb sensorimotor function are poorly standardized and rarely investigate clinimetrics in an unbiased manner. Based on the available evidence, recommendations on the assessment task, measurement system, and performance metrics were made with the goal to increase standardization. Further high-quality studies evaluating clinimetric properties are needed to validate kinematic assessments, with the long-term goal to elucidate upper limb sensorimotor recovery poststroke. Clinical Trial Registration- URL: https://www.crd.york.ac.uk/prospero/ . Unique identifier: CRD42017064279