GoIFISH: a system for the quantification of single cell heterogeneity from IFISH images.

Molecular analysis has revealed extensive intra-tumor heterogeneity in human cancer samples, but cannot identify cell-to-cell variations within the tissue microenvironment. In contrast, in situ analysis can identify genetic aberrations in phenotypically defined cell subpopulations while preserving tissue-context specificity. GoIFISHGoIFISH is a widely applicable, user-friendly system tailored for the objective and semi-automated visualization, detection and quantification of genomic alterations and protein expression obtained from fluorescence in situ analysis. In a sample set of HER2-positive breast cancers GoIFISHGoIFISH is highly robust in visual analysis and its accuracy compares favorably to other leading image analysis methods. GoIFISHGoIFISH is freely available at www.sourceforge.net/projects/goifish/.This is the final published version. It is also available from Genome Biology at http://genomebiology.com/2014/15/8/442

Oral language skills and mental health in female prisoners: pragmatic skills are essential

IntroductionThere are strong indications of an elevated incidence of both language problems and problems with mental health among prisoners. We also know that women in prison are a particularly vulnerable group who often face conditions that foremost accommodate the needs of men. In order to adapt prison conditions to women’s needs and give better help, we need more information about their characteristics. In this study, we wanted to explore associations between oral language problems and mental health (depression and anxiety) in women in prison.MethodParticipants were 58 women, recruited from high and low security women’s and mixed prisons. They completed a questionnaire covering demographic variables and several self-report measures. In the present study, the language measures were a Language Composite score (comprising articulation, impressive and expressive language, and pragmatics) and the La Trobe Communication Questionnaire (LCQ), measuring pragmatic skills specifically. Hopkins Symptom Checklist-10 (HSCL) was used as a measure of psychological distress. First, we assessed correlations between the language measures and mental health. Second, we performed group comparisons with groups defined as over or under cut-off on the Language Composite, LCQ total, and HSCL total scores.ResultsResults supported a clear connection between overall language and overall mental health. Pragmatic skills were the main driver of this effect. There was no difference in mental health between those scoring above and below cut-off for general language problems but the group with possible pragmatic impairment showed poorer mental health than those without. Conversely, there was no difference in general language skills between the groups scoring within and outside the range of psychological distress, but the first group evaluated their pragmatic skills as significantly poorer than the latter.DiscussionWe conclude that pragmatics seem to be core to the association between oral language skills and mental health among female prisoners. This should have implications for language services in prisons, as attending to these issues could positively affect prognosis and outcome

On p-saturable groups

AbstractA pro-p group G is a PF-group if it has central series of closed subgroups {Ni}i∈N with trivial intersection satisfying N1=G and [Ni,G,…p−1,G]⩽Ni+1p. In this paper, we prove that a finitely generated pro-p group G is a p-saturable group, in the sense of Lazard, if and only if it is a torsion free PF-group. Using this characterization, we study certain families of subgroups of p-saturable groups. For example, we prove that any normal subgroup of a p-saturable group contained in the Frattini is again p-saturable

DNA methylation signature (SAM40) identifies subgroups of the Luminal A breast cancer samples with distinct survival

Breast cancer patients with Luminal A disease generally have a good prognosis, but among this patient group are patients with good prognosis that are currently overtreated with adjuvant chemotherapy, and also patients that have a bad prognosis and should be given more aggressive treatment. There is no available method for subclassification of this patient group. Here we present a DNA methylation signature (SAM40) that segregates Luminal A patients based on prognosis, and identify one good prognosis group and one bad prognosis group. The prognostic impact of SAM40 was validated in four independent patient cohorts. Being able to subdivide the Luminal A patients may give the two-sided benefit of identifying one subgroup that may benefit from a more aggressive treatment than what is given today, and importantly, identifying a subgroup that may benefit from less treatment.Peer reviewe

A federated learning system for precision oncology in Europe: DigiONE

DigiONE is a pilot European learning health system in precision oncology that aims to identify optimal cancer treatments by learning from every patient, not just those in trials, through privacy-preserving interrogation of their standardized routine electronic health record

Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism

Mice lacking ALK activity have previously been reported to exhibit subtle behavioral phenotypes. In this study of ALK of loss of function mice we present data supporting a role for ALK in hypogonadotropic hypogonadism in male mice. We observed lower level of serum testosterone at P40 in ALK knock-out males, accompanied by mild disorganization of seminiferous tubules exhibiting decreased numbers of GATA4 expressing cells. These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed. Oral administration of crizotinib resulted in a decrease of serum testosterone levels in adult wild type male mice, which reverted to normal levels after cessation of treatment. Analysis of GnRH expression in neurons of the hypothalamus revealed a significant decrease in the number of GnRH positive neurons in ALK knock-out mice at P40 when compared with control littermates. Thus, ALK appears to be involved in hypogonadotropic hypogonadism by regulating the timing of pubertal onset and testis function at the upper levels of the hypothalamic-pituitary gonadal axis

Flavonoids Isolated from Rumex aquaticus Exhibit Neuroprotective and Neurorestorative Properties by Enhancing Neurite Outgrowth and Synaptophysin

Mice lacking ALK activity have previously been reported to exhibit subtle behavioral phenotypes. In this study of ALK of loss of function mice we present data supporting a role for ALK in hypogonadotropic hypogonadism in male mice. We observed lower level of serum testosterone at P40 in ALK knock-out males, accompanied by mild disorganization of seminiferous tubules exhibiting decreased numbers of GATA4 expressing cells. These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed. Oral administration of crizotinib resulted in a decrease of serum testosterone levels in adult wild type male mice, which reverted to normal levels after cessation of treatment. Analysis of GnRH expression in neurons of the hypothalamus revealed a significant decrease in the number of GnRH positive neurons in ALK knock-out mice at P40 when compared with control littermates. Thus, ALK appears to be involved in hypogonadotropic hypogonadism by regulating the timing of pubertal onset and testis function at the upper levels of the hypothalamic-pituitary gonadal axis

Prognostic Significance of the Loss of Heterozygosity of KRAS in Early-Stage Lung Adenocarcinoma

Lung cancer is a common disease with a poor prognosis. Genomic alterations involving the KRAS gene are common in lung carcinomas, although much is unknown about how different mutations, deletions, and expressions influence the disease course. The first approval of a KRAS-directed inhibitor was recently approved by the FDA. Mutations in the KRAS gene have been associated with poor prognosis for lung adenocarcinomas, but implications of the loss of heterozygosity (LOH) of KRAS have not been investigated. In this study, we have assessed the LOH of KRAS in early-stage lung adenocarcinoma by analyzing DNA copy number profiles and have investigated the effect on patient outcome in association with mRNA expression and somatic hotspot mutations. KRAS mutation was present in 36% of cases and was associated with elevated mRNA expression. LOH in KRAS was associated with a favorable prognosis, more prominently in KRAS mutated than in wild-type patients. The presence of both LOH and mutation in KRAS conferred a better prognosis than KRAS mutation alone. For wild-type tumors, no difference in prognosis was observed between patients with and without LOH in KRAS. Our study indicates that LOH in KRAS is an independent prognostic factor that may refine the existing prognostic groups of lung adenocarcinomas