Hermeneutic single case efficacy design: A systematic review of published research and current standards

open4siThis article systematically reviews the methodological characteristics of Hermeneutic Single Case Efficacy Design (HSCED) studies published in peer-reviewed journals. HSCED provides researchers with a flexible and viable alternative to both between-groups and within-subject experimental designs. This article includes a description of the evolution of the methodology distinctive to HSCED; a discussion of results of HSCED studies considered within a framework of contemporary standards and guidelines for systematic case study research; a presentation of recommendations for key characteristics (e.g., diagnosis, hermeneutic analysis, adjudication procedure). Overall, the aim is provide researchers and reviewers with a resource for conducting and evaluating HSCED research. The results of a systematic review of 13 studies suggests that published HSCED research meets contemporary criteria for systematic case study research. Hermeneutic analysis and adjudication emerged as areas of HSCED practice characterized by a diversity of procedures. Although consensus exists along key dimensions of HSCED, there remains a need for further evaluation of adjudication procedures and reporting standards.openBenelli, Enrico; De Carlo, Alessandro; Biffi, Diana; Mcleod, JohnBenelli, Enrico; De Carlo, Alessandro; Biffi, Diana; Mcleod, Joh

Integrated CGH/WES Analyses Advance Understanding of Aggressive Neuroblastoma Evolution: A Case Study

Neuroblastoma (NB) is the most common extra-cranial malignancy in preschool children. To portray the genetic landscape of an overly aggressive NB leading to a rapid clinical progression of the disease, tumor DNA collected pre- and post-treatment has been analyzed. Array comparative genomic hybridization (aCGH), whole-exome sequencing (WES), and pharmacogenetics approaches, respectively, have identified relevant copy number alterations (CNAs), single nucleotide variants (SNVs), and polymorphisms (SNPs) that were then combined into an integrated analysis. Spontaneously formed 3D tumoroids obtained from the recurrent mass have also been characterized. The results prove the power of combining CNAs, SNVs, and SNPs analyses to assess clonal evolution during the disease progression by evidencing multiple clones at disease onset and dynamic genomic alterations during therapy administration. The proposed molecular and cytogenetic integrated analysis empowers the disease follow-up and the prediction of tumor recurrence

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10)

The molecular basis of tumor metastasis and current approaches to decode targeted migration-promoting events in pediatric neuroblastoma

Cell motility is a crucial biological process that plays a critical role in the development of multicellular organisms and is essential for tissue formation and regeneration. However, uncontrolled cell motility can lead to the development of various diseases, including neoplasms. In this review, we discuss recent advances in the discovery of regulatory mechanisms underlying the metastatic spread of neuroblastoma, a solid pediatric tumor that originates in the embryonic migratory cells of the neural crest. The highly motile phenotype of metastatic neuroblastoma cells requires targeting of intracellular and extracellular processes, that, if affected, would be helpful for the treatment of high-risk patients with neuroblastoma, for whom current therapies remain inadequate. Development of new potentially migration-inhibiting compounds and standardized preclinical approaches for the selection of anti-metastatic drugs in neuroblastoma will also be discussed

CARACTERIZACIÓN GENÉTICA DE EJEMPLARES DE PAICHE Arapaima gigas (Cuvier, 1829) UTILIZADOS EN EL REPOBLAMIENTO DEL LAG0 IMIRIA (CUENCA DEL RÍO UCAYALI)

El paiche Arapaima gigas, es una de las especies de peces amazónicos con fuerte presión de pesca y subsecuente disminución de sus poblaciones naturales, por lo que es nominado como especie vulnerable en el apéndice II de CITES. En ese sentido el presente estudio tuvo como objetivo contribuir al manejo y conservación de esta especie a través de la caracterización genética de 400 ejemplares de paiche utilizados en el programa de repoblamiento del lago Imiría. Los resultados de la caracterización de las seis regiones microsatélites muestran un total de 68 genotipos, con una distribución desproporcional de los mismos entre los ejemplares estudiados: dos genotipos son compartidos entre solamente 153 individuos (82 AW y 71 AX respectivamente), mostrando una gran homogeneidad genética; mientras que 36 genotipos fueron genotipos únicos, es decir cada genotipo estuvo presente en un solo individuo. Una análisis factorial de correspondencia (AFC) muestra dos principales agrupaciones entre los ejemplares estudiados, la primera conformada por 61 perfiles genéticos que reúnen 393 ejemplares (98.25%), y la segunda por seis genotipos con solo siete ejemplares (1.75%). Los valores de heterocigosidad esperada (He) variaron de 0 en el locus Agi13 a 0.925 en el locus Agi12. En tanto que los valores de heterocigosidad observada (Ho) variaron de 0.002 en el locus Agi4 a 0.634 en el locus Agi10. Este elevado nivel de homogeneidad encontrado entre los ejemplares de paiche es probablemente un indicativo del alto nivel de parentesco entre estos individuos, es decir que probablemente descienden de un grupo reducido de reproductores provenientes de la piscicultura. Por lo que se recomienda que las futuras introducciones de especimenes de paiche en el lago Imiria consideren antes el genotipado de los ejemplares a utilizar en los programas de repoblamiento para asegurar la introducción de nuevos genotipos que permitan aumentar la diversidad genética del paiche en esta área