Expression of TCF3 target genes defines a subclass of diffuse large B-cell lymphoma characterized by up-regulation of MYC target genes and poor clinical outcome following R-CHOP therapy.

TCF3 is a lymphopoietic transcription factor that acquires somatic driver mutations in diffuse large B-cell lymphoma (DLBCL). Hypothesizing that expression patterns of TCF3-regulated genes can inform clinical management, we found that unsupervised clustering analysis with 15 TCF3-regulated genes and eight additional ones resolved local DLBCL cases into two main clusters, denoted Groups A and B, of which Group A manifested inferior overall survival (OS,  = 0.0005).

Evidence-based review of genomic aberrations in diffuse large B cell lymphoma, not otherwise specified (DLBCL, NOS): Report from the cancer genomics consortium lymphoma working group.

Diffuse large B cell lymphoma, not otherwise specified (DLBCL, NOS) is the most common type of non-Hodgkin lymphoma (NHL). The 2016 World Health Organization (WHO) classification defined DLBCL, NOS and its subtypes based on clinical findings, morphology, immunophenotype, and genetics. However, even within the WHO subtypes, it is clear that additional clinical and genetic heterogeneity exists.

Validation, Implementation, and Clinical Impact of the Oncomine Myeloid Targeted-Amplicon DNA and RNA Ion Semiconductor Sequencing Assay.

The identification of clinically significant genes recurrently mutated in myeloid malignancies necessitates expanding diagnostic testing with higher throughput, such as targeted next-generation sequencing. We present validation of the Thermo Fisher Oncomine Myeloid Next-Generation Sequencing Panel (OMP), targeting 40 genes and 29 fusion drivers recurrently mutated in myeloid malignancies. The study includes data from a sample exchange between two Canadian hospitals demonstrating high concordance for detection of DNA and RNA aberrations.

Objective quantification of BCL2 protein by multiplex immunofluorescence in routine biopsy samples of diffuse large B-cell lymphoma demonstrates associations with survival and gene alterations.

Up-regulation of in cases of diffuse large B-cell lymphoma (DLBCL) can confer treatment resistance. Quantitative immunofluorescence (QIF) histology allows objective quantification of protein-based biomarkers. We investigated the utility of QIF for evaluating BCL2 as a biomarker in DLBCL by quantifying BCL2 selectively in CD20-expressing lymphoma cells in biopsy samples from 116 cases of DLBCL in two cohorts one of which consisted of relapsed/refractory cases from a clinical trial.

Simultaneous detection of lung fusions using a multiplex RT-PCR next generation sequencing-based approach: a multi-institutional research study.

Background: Gene fusion events resulting from chromosomal rearrangements play an important role in initiation of lung adenocarcinoma. The recent association of four oncogenic driver genes, ALK, ROS1, RET, and NTRK1, as lung tumor predictive biomarkers has increased the need for development of up-to-date technologies for detection of these biomarkers in limited amounts of material.

Methods: We describe here a multi-institutional study using the Ion AmpliSeq™ RNA Fusion Lung Cancer Research Panel to interrogate previously characterized lung tumor samples.

High-grade B-cell lymphoma with MYC and BCL2 rearrangements arising in a composite lymphoma.

Background: We report the first case of composite lymphoma consisting of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL) and high-grade B-cell lymphoma with MYC and BCL2 rearrangements within the same needle biopsy in which a clonal relationship between the FL and high-grade B-cell lymphoma components was demonstrated by molecular cytogenetics.

Case Presentation: An 85-year-old man presented with masses in his neck and right groin. Cutting needle biopsy of the inguinal mass revealed the three lymphoma types which were morphologically, immunophenotypically and topographically distinct.

Noninvasive Prenatal Detection of Trisomy 21 by Targeted Semiconductor Sequencing: A Technical Feasibility Study.

Objective: To develop an alternate noninvasive prenatal testing method for the assessment of trisomy 21 (T21) using a targeted semiconductor sequencing approach.

Methods: A customized AmpliSeq panel was designed with 1,067 primer pairs targeting specific regions on chromosomes 21, 18, 13, and others. A total of 235 samples, including 30 affected with T21, were sequenced with an Ion Torrent Proton sequencer, and a method was developed for assessing the probability of fetal aneuploidy via derivation of a risk score.

The CDK inhibitor AT7519M in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and mantle cell lymphoma. A Phase II study of the Canadian Cancer Trials Group.

AT7519M is a small molecule inhibitor of cyclin-dependent kinases 1, 2, 4, 5, and 9 with in vitro activity against lymphoid malignancies. In two concurrent Phase II trials, we evaluated AT7519M in relapsed or refractory chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) using the recommended Phase II dosing of 27 mg/m twice weekly for 2 of every 3 weeks. Primary objective was objective response rate (ORR).

X-linked deafness-2 (DFNX2) phenotype associated with a paracentric inversion upstream of POU3F4.

Purpose: The authors report on a 7-year-old male, designated FR, who has severe sensorineural hearing loss. Features include a round face, hypertelorism, epicanthal folds, and flat nasal root. Although there were early developmental concerns regarding FR, all but his speech delay resolved when he was placed in an educational program that accommodated his hearing loss.

A framework for assessing global change risks to forest carbon stocks in the United States.

Among terrestrial environments, forests are not only the largest long-term sink of atmospheric carbon (C), but are also susceptible to global change themselves, with potential consequences including alterations of C cycles and potential C emission. To inform global change risk assessment of forest C across large spatial/temporal scales, this study constructed and evaluated a basic risk framework which combined the magnitude of C stocks and their associated probability of stock change in the context of global change across the US. For the purposes of this analysis, forest C was divided into five pools, two live (aboveground and belowground biomass) and three dead (dead wood, soil organic matter, and forest floor) with a risk framework parameterized using the US's national greenhouse gas inventory and associated forest inventory data across current and projected future Köppen-Geiger climate zones (A1F1 scenario).

Nablus mask-like facial syndrome: deletion of chromosome 8q22.1 is necessary but not sufficient to cause the phenotype.

Nablus mask-like facial syndrome (NMLFS) has many distinctive phenotypic features, particularly tight glistening skin with reduced facial expression, blepharophimosis, telecanthus, bulky nasal tip, abnormal external ear architecture, upswept frontal hairline, and sparse eyebrows. Over the last few years, several individuals with NMLFS have been reported to have a microdeletion of 8q21.3q22.

HLA-DR(negative), CD34(negative) hypergranular acute myeloid leukemia with trisomy 6 and del(5)(q22q33): case report and review of the literature.

We report a unique pediatric case of hypergranular acute myeloid leukemia with myelodysplasia-related changes. The patient presented with moderate leukocytosis with neutrophilia with left-shift maturation and dysplasia, anemia, and multiple sclerotic bone lesions. The bone marrow was hypercellular with a predominance of myeloblast cells and/or abnormal promyelocytes with hypergranular cytoplasm.

Real food matters for health.

Human health, an enigma that has been a part of human existence from its origins, is founded on the intake of food. Holistic health is concerned with issues of the body, soul/mind, and spirit. Using concepts from ecology, this article explores the relationships between food, nutrients, whole food diets, and health.

Expert to novice: clinicians learning new roles as clinical nurse educators.

The nursing shortage presents a challenge for both nursing education programs and clinical agencies to identify creative options for increasing the supply of nurse educators, especially those who can teach vital clinical skills to future nurses. Some clinicians have voiced that they would enjoy having opportunities to share their clinical expertise through teaching, but they lack preparation for this new role. Through written narratives of nurses enrolled in a Clinical Nurse Educator Academy, this study explored the research question: How can narratives of clinicians participating in a Clinical Nurse Educator Academy enhance understanding of the unique perspectives of these individuals as they prepare for roles as clinical nurse educators? Data consisted of 135 reflective narratives from 45 participants and were analyzed using van Manen's approach to human science research.

Penetrating the dark silence.

This study articulates women's lifeworld experience of unexplained and unexpected fatigue. Interpretive phenomenology situated within the perspective of Maurice Merleau-Ponty provides the study framework. Using purposive sampling, the study investigated the unexplained fatigue of 12 women in a southeastern state.

Choosing to eat your way toward healthy aging.

As individuals age, they face many choices to promote healthy aging. One important consideration relates to nutritional choices. It is easy to become overwhelmed with the information in the media that suggests the superiority of some new diet or breakthrough dietary supplement.

A preliminary study looking at parental emotions following cochlear implantation.

This preliminary research investigated the emotions of parents with cochlear implanted children. The object for the research was first to compare four emotions engendered in parents of deaf children before and after cochlear implantation. Second, to monitor changes in these emotions during a period of up to four years after implantation.

DNA microarray analysis of striatal gene expression in symptomatic transgenic Huntington's mice (R6/2) reveals neuroinflammation and insulin associations.

Huntington's disease (HD) is an inherited, progressive neurodegenerative disorder caused by CAG repeat expansion in the gene that codes for the protein huntingtin. The underlying neuropathological events leading to the selectivity of striatal neuronal loss are unknown. However, the huntingtin mutation interferes at several levels of normal cell function.

Huntingtin phosphorylation on serine 421 is significantly reduced in the striatum and by polyglutamine expansion in vivo.

Huntington disease (HD) results from polyglutamine expansion in the huntingtin protein (htt). Despite the widespread tissue expression pattern of htt, neuronal loss is highly selective to medium spiny neurons of the striatum. Huntingtin is phosphorylated on serine-421 (S421) by the pro-survival signaling protein kinase Akt (PKB) and this has been previously shown to be protective against the toxicity of polyglutamine-expanded htt in cell culture.