Representativeness of samples enrolled in Alzheimer's disease research centers.

Unlabelled: To generalize findings on the mechanisms and prognosis in Alzheimer's disease and related dementias (ADRD), it is critical for ADRD research to be representative of the population. Sociodemographic and health characteristics across ethnoracial groups included in the National Alzheimer's Coordinating Center sample (NACC) were compared to the nationally representative Health and Retirement Study (HRS). Baseline NACC data ( = 36,639) and the weighted 2010 HRS wave ( = 52,071,840) were included.

The major role of junctional diversity in the horse antibody repertoire.

The antibody repertoire (Rep-seq) sequencing revolutionized the diversity of antigen B cell receptor studies, allowing deep and quantitative analysis to decipher the role of adaptive immunity in health and disease. Particularly, horse (Equus caballus) polyclonal antibodies have been produced and used since the century XIX to treat and prophylaxis diphtheria, tuberculosis, tetanus, pneumonia, and, more recently, COVID-19. However, our knowledge about the horse B cell receptors repertories is minimal.

Impact of cardiovascular risk factors on the relationships of physical activity with mood and cognitive function in a diverse sample.

Physical activity has well-known benefits for older adults' mood and cognitive functioning; however, it is not clear whether risk factors for cardiovascular disease (CVD) affect the relationships of physical activity with these health outcomes among diverse older adults. This study investigated the impact of CVD risk burden on the relationships among self-reported physical activity, mood, and cognitive functioning in a diverse sample of 62 adults age 45 and older. We found that higher physical activity was associated with better attention and verbal working memory at lower CVD risk, but with worse attention and verbal working memory at higher CVD risk levels.

Subthreshold depressive symptoms relate to cuneus structure: Thickness asymmetry and sex differences.

Despite the prominence of frontolimbic regions in depression research, recent studies also implicate posterior brain regions, including the cuneus. The current study examined the relationship between depressive symptoms and asymmetry in cuneal cortical thickness in healthy adults between the ages of 18 and 81 with primarily subthreshold levels of depressive symptoms. An asymmetry index was calculated for cortical thickness in the cuneus [(left - right) × 100/(left + right)], and regression analyses were conducted with total scores on the Center for Epidemiologic Studies Depression Scale predicting this asymmetry index, controlling for age and sex.

Clinical Neuropsychological Evaluation in Older Adults With Major Depressive Disorder.

Purpose Of The Review: Older adults with major depressive disorder are particularly vulnerable to MDD-associated adverse cognitive effects including slowed processing speed, decreased attention, and executive dysfunction. The purpose of this review is to describe the approach to a clinical neuropsychological evaluation in older adults with MDD. Specifically, this review compares and contrasts neurocognitive screening and clinical neuropsychological evaluation procedures and details the multiple components of the clinical neuropsychological evaluation.

Be Fit, Be Sharp, Be Well: The Case for Exercise as a Treatment for Cognitive Impairment in Late-life Depression.

Objective: To lay out the argument that exercise impacts neurobiological targets common to both mood and cognitive functioning, and thus more research should be conducted on its use as an alternative or adjunctive treatment for cognitive impairment in late-life depression (LLD).

Method: This narrative review summarizes the literature on cognitive impairment in LLD, describes the structural and functional brain changes and neurochemical changes that are linked to both cognitive impairment and mood disruption, and explains how exercise targets these same neurobiological changes and can thus provide an alternative or adjunctive treatment for cognitive impairment in LLD.

Results: Cognitive impairment is common in LLD and predicts recurrence of depression, poor response to antidepressant treatment, and overall disability.

Orbitofrontal and Cingulate Thickness Asymmetry Associated with Depressive Symptom Dimensions.

Both clinical depression and subthreshold depressive symptoms have been associated with alterations in cortical thickness. Studies have yielded conflicting results regarding whether cortical thinning or cortical thickening best characterize the depressive state. Also unclear is whether cortical thickness differences are lateralized.

The genomic landscape of teenage and young adult T-cell acute lymphoblastic leukemia.

Background: Treatment on risk adapted intensive pediatric protocols has improved outcome for teenagers and young adults (TYA) with T-cell acute lymphoblastic leukemia (T-ALL). Understanding the biology of disease in this age group and the genetic basis of relapse is a key goal as patients with relapsed/refractory disease have poor outcomes with conventional chemotherapy and novel molecular targets are required. This study examines the question of whether TYA T-ALL has a specific biological-molecular profile distinct from pediatric or adult T-ALL.

A multi-camera dataset for depth estimation in an indoor scenario.

Time-of-Flight (ToF) sensors and stereo vision systems are two of the most diffused depth acquisition devices for commercial and industrial applications. They share complementary strengths and weaknesses. For this reason, the combination of data acquired from these devices can improve the final depth estimation accuracy.

A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia.

Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints.

Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukemia.

Somatic genetic abnormalities are initiators and drivers of disease and have proven clinical utility at initial diagnosis. However, the genetic landscape and its clinical utility at relapse are less well understood and have not been studied comprehensively. We analyzed cytogenetic data from 427 children with relapsed B-cell precursor ALL treated on the international trial, ALLR3.

The role of the RAS pathway in iAMP21-ALL.

Intrachromosomal amplification of chromosome 21 (iAMP21) identifies a high-risk subtype of acute lymphoblastic leukaemia (ALL), requiring intensive treatment to reduce their relapse risk. Improved understanding of the genomic landscape of iAMP21-ALL will ascertain whether these patients may benefit from targeted therapy. We performed whole-exome sequencing of eight iAMP21-ALL samples.

Quantitative proteomic analysis reveals maturation as a mechanism underlying glucocorticoid resistance in B lineage ALL and re-sensitization by JNK inhibition.

Glucocorticoid (GC) resistance is a continuing clinical problem in childhood acute lymphoblastic leukaemia (ALL) but the underlying mechanisms remain unclear. A proteomic approach was used to compare profiles of the B-lineage ALL GC-sensitive cell line, PreB 697, and its GC-resistant sub-line, R3F9, pre- and post-dexamethasone exposure. PAX5, a transcription factor critical to B-cell development was differentially regulated in the PreB 697 compared to the R3F9 cell line in response to GC.

Ras pathway mutations are prevalent in relapsed childhood acute lymphoblastic leukemia and confer sensitivity to MEK inhibition.

For most children who relapse with acute lymphoblastic leukemia (ALL), the prognosis is poor, and there is a need for novel therapies to improve outcome. We screened samples from children with B-lineage ALL entered into the ALL-REZ BFM 2002 clinical trial (www.clinicaltrials.

Casitas B lymphoma mutations in childhood acute lymphoblastic leukemia.

Casitas B-lineage lymphoma (CBL) proteins are RING finger ubiquitin E3 ligases that attenuate the signaling of receptor tyrosine kinases and are mutated in a number of myeloid disorders. In this study, mutational screening of the linker-RING domains of CBL and CBLB was performed by denaturing high performance liquid chromatography in a cohort of diagnostic (n = 180) or relapse (n = 46) samples from children with acute lymphoblastic leukemia. Somatic mutations were identified in three children, giving an overall incidence of 1.

Genomic characterization implicates iAMP21 as a likely primary genetic event in childhood B-cell precursor acute lymphoblastic leukemia.

Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct subgroup of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) that has a dismal outcome when treated with standard therapy. For improved diagnosis and risk stratification, the initiating genetic events need to be elucidated. To investigate the genetic basis of BCP-ALL, genomes of 94 iAMP21 patients were interrogated by arrays, FISH, and multiplex ligation-dependent probe amplification.

Mismatch repair and the downstream target genes, PAX5 and Ikaros, in childhood acute lymphoblastic leukemia.

The mismatch repair (MMR) pathway is a post-replicative DNA repair process and MMR deficiency is a common feature of ALL cell lines. In this study we have investigated MMR deficiency in a large cohort of primary relapsed ALL (n=40) and investigated coding microsatellites (MS) of the lymphoid transcription factors, PAX5 and IKZF1 as downstream target genes. Only one patient showed MMR deficiency, as evidenced by microsatellite instability, which was acquired at relapse and was associated with reduced expression of both MLH1 and MSH2.

Flow minimal residual disease monitoring of candidate leukemic stem cells defined by the immunophenotype, CD34+CD38lowCD19+ in B-lineage childhood acute lymphoblastic leukemia.

Flow cytometric minimal residual disease (MRD) monitoring could become more powerful if directed towards the disease-maintaining leukemic stem cell (LSC) compartment. Using a cohort of 48 children with B-lineage acute lymphoblastic leukemia (ALL), we sought the newly proposed candidate-LSC population, CD34(+)CD38(low)CD19(+), at presentation and in end of induction bone marrow samples. We identified the candidate LSC population in 60% of diagnostic samples and its presence correlated with expression of CD38, relative to that of normal B-cell progenitors.

Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia.

We report 2 novel, cryptic chromosomal abnormalities in precursor B-cell acute lymphoblastic leukemia (BCP-ALL): a translocation, either t(X;14)(p22;q32) or t(Y;14)(p11;q32), in 33 patients and an interstitial deletion, either del(X)(p22.33p22.33) or del(Y)(p11.

Establishment and validation of a standard protocol for the detection of minimal residual disease in B lineage childhood acute lymphoblastic leukemia by flow cytometry in a multi-center setting.

Minimal residual disease detection, used for clinical management of children with acute lymphoblastic leukemia, can be performed by molecular analysis of antigen-receptor gene rearrangements or by flow cytometric analysis of aberrant immunophenotypes. For flow minimal residual disease to be incorporated into larger national and international trials, a quality assured, standardized method is needed which can be performed in a multi-center setting. We report a four color, flow cytometric protocol established and validated by the UK acute lymphoblastic leukemia Flow minimal residual disease group.

Variable breakpoints target PAX5 in patients with dicentric chromosomes: a model for the basis of unbalanced translocations in cancer.

The search for target genes involved in unbalanced acquired chromosomal abnormalities has been largely unsuccessful, because the breakpoints of these rearrangements are too variable. Here, we use the example of dicentric chromosomes in B cell precursor acute lymphoblastic leukemia to show that, despite this heterogeneity, single genes are targeted through a variety of mechanisms. FISH showed that, although they were heterogeneous, breakpoints on 9p resulted in the partial or complete deletion of PAX5.

A comprehensive analysis of the CDKN2A gene in childhood acute lymphoblastic leukemia reveals genomic deletion, copy number neutral loss of heterozygosity, and association with specific cytogenetic subgroups.

Inactivation of the tumor suppressor gene, CDKN2A, can occur by deletion, methylation, or mutation. We assessed the principal mode of inactivation in childhood acute lymphoblastic leukemia (ALL) and frequency in biologically relevant subgroups. Mutation or methylation was rare, whereas genomic deletion occurred in 21% of B-cell precursor ALL and 50% of T-ALL patients.

Mutation of genes affecting the RAS pathway is common in childhood acute lymphoblastic leukemia.

Deregulation of the RAS-RAF-mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK signaling cascade is often caused by somatic mutations in genes encoding proteins which influence the activity of this pathway and include NRAS, KRAS2, FLT3, PTPN11, and BRAF. We report the first comprehensive mutational screen of key exons of these genes in a large cohort of unselected acute lymphoblastic leukemia (ALL) cases at diagnosis (n = 86) and in a more selected cohort at disease recurrence (n = 47) using the sensitive method of denaturing high-performance liquid chromatography. We show that somatic mutations that deregulate the pathway constitute one of the most common genetic aberrations in childhood ALL (cALL), being found in 35% of diagnostic and 25% of relapse samples.