A prognostic risk model for glioma patients by systematic evaluation of genomic variations.

The overall survival rate of gliomas has not significantly improved despite new effective treatments, mainly due to tumor heterogeneity and drug delivery. Here, we perform an integrated clinic-genomic analysis of 1, 477 glioma patients from a Chinese cohort and a TCGA cohort and propose a potential prognostic model for gliomas. We identify that SBS11 and SBS23 mutational signatures are associated with glioma recurrence and indicate worse prognosis only in low-grade type of gliomas and IDH-Mut subtype.

Investigation of Plasma Metabolic and Lipidomic Characteristics of a Chinese Cohort and a Pilot Study of Renal Cell Carcinoma Biomarker.

Plasma metabolomics and lipidomics have been commonly used for biomarker discovery. Studies in white and Japanese populations suggested that gender and age can affect circulating plasma metabolite profiles; however, the metabolomics characteristics in Chinese population has not been surveyed. In our study, we applied liquid chromatography-mass spectrometry-based approach to analyze Chinese plasma metabolome and lipidome in a cohort of 534 healthy adults (aging from 15 to 79).

Evolution of multiple cell clones over a 29-year period of a CLL patient.

Chronic lymphocytic leukaemia (CLL) is a frequent B-cell malignancy, characterized by recurrent somatic chromosome alterations and a low level of point mutations. Here we present single-nucleotide polymorphism microarray analyses of a single CLL patient over 29 years of observation and treatment, and transcriptome and whole-genome sequencing at selected time points. We identify chromosome alterations 13q14-, 6q- and 12q+ in early cell clones, elimination of clonal populations following therapy, and subsequent appearance of a clone containing trisomy 12 and chromosome 10 copy-neutral loss of heterogeneity that marks a major population dominant at death.

Comparison of variations detection between whole-genome amplification methods used in single-cell resequencing.

Background: Single-cell resequencing (SCRS) provides many biomedical advances in variations detection at the single-cell level, but it currently relies on whole genome amplification (WGA). Three methods are commonly used for WGA: multiple displacement amplification (MDA), degenerate-oligonucleotide-primed PCR (DOP-PCR) and multiple annealing and looping-based amplification cycles (MALBAC). However, a comprehensive comparison of variations detection performance between these WGA methods has not yet been performed.

Concurrent alterations in TERT, KDM6A, and the BRCA pathway in bladder cancer.

Purpose: Genetic analysis of bladder cancer has revealed a number of frequently altered genes, including frequent alterations of the telomerase (TERT) gene promoter, although few altered genes have been functionally evaluated. Our objective is to characterize alterations observed by exome sequencing and sequencing of the TERT promoter, and to examine the functional relevance of histone lysine (K)-specific demethylase 6A (KDM6A/UTX), a frequently mutated histone demethylase, in bladder cancer.

Experimental Design: We analyzed bladder cancer samples from 54 U.

Identification of gene signatures used to recognize biological characteristics of gastric cancer upon gene expression data.

High-throughput gene expression microarrays can be examined by machine-learning algorithms to identify gene signatures that recognize the biological characteristics of specific human diseases, including cancer, with high sensitivity and specificity. A previous study compared 20 gastric cancer (GC) samples against 20 normal tissue (NT) samples and identified 1,519 differentially expressed genes (DEGs). In this study, Classification Information Index (CII), Information Gain Index (IGI), and RELIEF algorithms are used to mine the previously reported gene expression profiling data.

Technical challenges of sparing infrahyoid swallowing organs at risk in oropharynx squamous cell cancer treated with IMRT.

This study reports clinical performance in the sparing of infrahyoid swallowing organs at risk (SWOARs) in oropharynx cancer intensity-modulated radiation therapy (IMRT) plans. Rates of meeting dose-volume planning goals are reported and compared with geometry-based estimates of what is achievable. This study also develops 3 measures of target-SWOAR geometry and tests their usefulness in providing geometry-based dose-volume planning goals.

Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation.

Bladder cancer is one of the most common cancers worldwide, with transitional cell carcinoma (TCC) being the predominant form. Here we report a genomic analysis of TCC by both whole-genome and whole-exome sequencing of 99 individuals with TCC. Beyond confirming recurrent mutations in genes previously identified as being mutated in TCC, we identified additional altered genes and pathways that were implicated in TCC.

Free surface electrospinning of fibers containing microparticles.

Many materials have been fabricated using electrospinning, including pharmaceutical formulations, superhydrophobic surfaces, catalysis supports, filters, and tissue engineering scaffolds. Often these materials can benefit from microparticles included within the electrospun fibers. In this work, we evaluate a high-throughput free surface electrospinning technique to prepare fibers containing microparticles.

Single-cell exome sequencing reveals single-nucleotide mutation characteristics of a kidney tumor.

Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and has very few mutations that are shared between different patients. To better understand the intratumoral genetics underlying mutations of ccRCC, we carried out single-cell exome sequencing on a ccRCC tumor and its adjacent kidney tissue. Our data indicate that this tumor was unlikely to have resulted from mutations in VHL and PBRM1.

Single-cell sequencing analysis characterizes common and cell-lineage-specific mutations in a muscle-invasive bladder cancer.

Background: Cancers arise through an evolutionary process in which cell populations are subjected to selection; however, to date, the process of bladder cancer, which is one of the most common cancers in the world, remains unknown at a single-cell level.

Results: We carried out single-cell exome sequencing of 66 individual tumor cells from a muscle-invasive bladder transitional cell carcinoma (TCC). Analyses of the somatic mutant allele frequency spectrum and clonal structure revealed that the tumor cells were derived from a single ancestral cell, but that subsequent evolution occurred, leading to two distinct tumor cell subpopulations.

Bone loss during menopausal transition among southern Chinese women.

Objectives: Estrogen deficiency during menopausal transition is associated with rapid bone loss. The purpose of this study was to examine the time of onset, the rate, and predictors of menopausal bone loss.

Study Design: Prospective data were analyzed from 160 Chinese women between the ages of 45 to 55 years who participated in the Hong Kong Osteoporotic Study.

Gene Expression Browser: large-scale and cross-experiment microarray data integration, management, search & visualization.

Background: In the last decade, a large amount of microarray gene expression data has been accumulated in public repositories. Integrating and analyzing high-throughput gene expression data have become key activities for exploring gene functions, gene networks and biological pathways. Effectively utilizing these invaluable microarray data remains challenging due to a lack of powerful tools to integrate large-scale gene-expression information across diverse experiments and to search and visualize a large number of gene-expression data points.

Differential involvement of hippocampal serotonin1A receptors and re-uptake sites in non-cognitive behaviors of Alzheimer's disease.

Rationale: Previous studies have shown extensive serotonergic deficits in the hippocampus of Alzheimer's disease (AD) patients. However, it is unclear whether such deficits play a role in non-cognitive, neuropsychiatric behaviors that occur frequently in AD and cause significant caregiver distress.

Objectives: In this study, we aimed to correlate serotonergic markers in the AD hippocampus with neuropsychiatric behaviors.

When size matters: a clinical review of pathological micropenis.

Micropenis is a significantly small penis with normal internal male genitalia. Micropenis is usually diagnosed shortly after birth, and the cause should be established; in addition, it should be differentiated from other associated syndromes. The role of the pediatric nurse practitioner is to diagnose the micropenis, guide the parents through the options of management, and support all involved through the selected treatment, whether hormonal or surgical.

Validation of the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-31) in Chinese.

QUALEFFO-31 is a recently developed disease-specific instrument derived from QUALEFFO-41 and intended to have improved efficacy and response rates. We aimed to validate QUALEFFO-31 in Chinese and examine the use of QUALEFFO-31 in clinical practice. This questionnaire was translated into Chinese and applied to 118 case-control pairs aged between 50 and 85 years with prevalent osteoporotic vertebral fractures to evaluate its validity, repeatability, and discriminatory ability.

A serotoninergic basis for hyperphagic eating changes in Alzheimer's disease.

Hyperphagia and associated eating changes occur frequently in Alzheimer's disease (AD) and lead to considerable morbidity. However, the neurochemical basis for these neuropsychiatric behaviours is at present unclear. In this study, we measured serotonin transporters, 5-HT(1A), 5-HT(2A), and 5-HT(4) receptors using radioligand binding assays in the postmortem temporal cortex of a cohort of controls and AD patients longitudinally assessed for hyperphagia.

Cyclooxygenase-2 polymorphisms, aspirin treatment, and risk for colorectal adenoma recurrence--data from a randomized clinical trial.

Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in the production of prostaglandins, potent mediators of inflammation. Chronic inflammation plays an important role in the development and progression of colorectal cancer. Aspirin inhibits COX-2 activity and lowers the risk for colorectal adenomas and cancer.

Protective effect of Cox-2 allelic variants on risk of colorectal adenoma development in African Americans.

Background: Recent evidence indicates that single nucleotide polymorphisms (SNPs) in the Cox-2 gene may modulate the risk of colorectal adenoma development.

Patients And Methods: We explored possible associations between Cox-2 polymorphisms and risk of adenoma development in an African American case-control study comprising 72 cases of advanced adenomas and 146 polyp-free controls. An exhaustive approach of genotyping 13 haplotype-tagging SNPs (ht SNPs) distributed over the entire COX-2 gene was used.

Candidate genes and cerebral palsy: a population-based study.

Objective: The objective of this study was to examine whether selected genetic polymorphisms in the infant are associated with later-diagnosed cerebral palsy.

Methods: A population-based case-control study was conducted of 28 single-nucleotide polymorphisms measured in newborn screening blood spots. A total of 413 children with later-diagnosed cerebral palsy were born to white women in South Australia in 1986-1999, and there were 856 control children.

MTHFR genotype and colorectal adenoma recurrence: data from a double-blind placebo-controlled clinical trial.

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. We assessed the association between two common MTHFR variants, 677C>T and 1298A>C, and adenoma recurrence in the context of a randomized double- blind clinical trial of aspirin use and folate supplementation. We used generalized linear regression to estimate risk ratios and 95% confidence intervals (95% CI) for recurrence, adjusting for age, sex, clinical center, follow-up time, and treatment status.

Vitamins B2, B6, and B12 and risk of new colorectal adenomas in a randomized trial of aspirin use and folic acid supplementation.

Background: Folate, other vitamin B cofactors, and genes involved in folate-mediated one-carbon metabolism all may play important roles in colorectal neoplasia. In this study, we examined the associations between dietary and circulating plasma levels of vitamins B(2), B(6), and B(12) and risk colorectal adenomas.

Methods: The Aspirin/Folate Polyp Prevention Study is a randomized clinical trial of folic acid supplementation and incidence of new colorectal adenomas in individuals with a history of adenomas (n = 1,084).

Involvement of an altered 5-HT -{6} receptor function in behavioral symptoms of Alzheimer's disease.

We studied the hypothesis that disturbances in 5-HT_{6} receptor function in the temporal cortex may contribute to clinical symptoms of Alzheimer's disease (AD). 5-HT_{6} density and 5-HT levels were significantly decreased in a cohort of AD patients prospectively assessed for cognitive/behavioral symptoms. cAMP formation after stimulation with the selective 5-HT_{6} receptor agonist E-6801 was significantly lower (p<0.

MC1R variants increase risk of melanomas harboring BRAF mutations.

Melanocortin-1 receptor (MC1R) variants have been associated with BRAF (v-raf murine sarcoma viral oncogene homolog B1) mutations in non-CSD (chronic solar-damaged) melanomas in an Italian and an American population. We studied an independent Italian population of 330 subjects (165 melanoma patients and 165 controls) to verify and estimate the magnitude of this association and to explore possible effect modifiers. We sequenced MC1R in all subjects and exon 15 of BRAF in 92/165 melanoma patients.

Real-time PCR analysis of candidate imprinted genes on mouse chromosome 11 shows balanced expression from the maternal and paternal chromosomes and strain-specific variation in expression levels.

Imprinted genes are monoallelically expressed from either the maternal or paternal genome. Because cancer develops through genetic and epigenetic alterations, imprinted genes affect tumorigenesis depending on which parental allele undergoes alteration. We have shown previously in a mouse model of neurofibromatosis type 1 (NF1) that inheriting mutant alleles of Nf1 and Trp53 on chromosome 11 from the mother or father dramatically changes the tumor spectrum of mutant progeny, likely due to alteration in an imprinted gene(s) linked to Nf1 and Trp53.