Hybrid continuous reassessment method with overdose control for safer dose escalation.

Phase 1 oncology studies focus on safety of novel treatments and identifying a dose associated with acceptable toxicity level. Various model-based designs have been proposed for guiding dose escalation and estimating maximum tolerated dose in dose-finding studies. However, these methods are either excessively conservative or imprudent by allowing overly toxic doses.

Systematic Review and Meta-Analysis of Correlation of Progression-Free Survival-2 and Overall Survival in Solid Tumors.

Using progression-free survival (PFS)2, time from randomization to 2nd disease progression or death, is proposed as a surrogate for overall survival (OS) in oncology clinical trials. We used published data from solid tumor trials to assess whether PFS2 and OS are correlated. A literature search identified studies that reported PFS, PFS2, and OS.

Step-Growth Polymerization Method for Ultrahigh Molecular Weight Polymers.

The preparation of polymers with an ultrahigh molecular weight (>10 g/mol; UHMW) is always a challenge for homogeneous step-growth polymerization. Herein, a unique homogeneous step-growth polymerization method was developed to prepare various UHMW polymers. In this approach, a double-strain-promoted azide-alkyne click reaction (DSPAAC) with a reactive intermediate was used as the polymerization reaction, and -dibenzo-1,5-cyclooctadiene-3,7-diyne (DIBOD) and bis-azide compounds with 2,6-diisopropylphenyl azide terminals were used as the monomer pairs.

ATD: a comprehensive bioinformatics resource for deciphering the association of autophagy and diseases.

Autophagy is the natural, regulated, destructive mechanism of the eukaryotes cell that disassembles unnecessary or dysfunctional components. In recent years, the association between autophagy and diseases has attracted more and more attention, but our understanding of the molecular mechanism about the association in the system perspective is limited and ambiguous. Hence, we developed the comprehensive bioinformatics resource Autophagy To Disease (ATD, http://auto2disease.

A UV-Cleavable Bottlebrush Polymer with o-Nitrobenzyl-Linked Side Chains.

An ultraviolet (UV)-cleavable bottlebrush polymer is synthesized using the "grafting-onto" strategy by combining living radical polymerization and copper-catalyzed azide-alkyne cycloaddition (CuAAC). In this approach, reversible addition-fragmentation chain transfer polymerization is used to prepare a poly(methylacrylate) backbone with azide side groups, while atom transfer radical polymerization is employed to prepare polystyrene (PS) side chains end-functionalized with o-nitrobenzyl (UV-cleavable) propargyl groups. CuAAC is then used to graft PS side chains onto the polymer backbone, producing the corresponding bottlebrush polymers with UV-cleavable PS side chains.

A practical Bayesian design to identify the maximum tolerated dose contour for drug combination trials.

Drug combination therapy has become the mainstream approach to cancer treatment. One fundamental feature that makes combination trials different from single-agent trials is the existence of the maximum tolerated dose (MTD) contour, that is, multiple MTDs. As a result, unlike single-agent phase I trials, which aim to find a single MTD, it is often of interest to find the MTD contour for combination trials.

Dynamic and modular gene regulatory networks drive the development of gametogenesis.

Gametogenesis is a complex process, which includes mitosis and meiosis and results in the production of ovum and sperm. The development of gametogenesis is dynamic and needs many different genes to work synergistically, but it is lack of global perspective research about this process. In this study, we detected the dynamic process of gametogenesis from the perspective of systems biology based on protein-protein interaction networks (PPINs) and functional analysis.

Identification of recurrent focal copy number variations and their putative targeted driver genes in ovarian cancer.

Background: Genomic regions with recurrent DNA copy number variations (CNVs) are generally believed to encode oncogenes and tumor suppressor genes (TSGs) that drive cancer growth. However, it remains a challenge to delineate the key cancer driver genes from the regions encoding a large number of genes.

Results: In this study, we developed a new approach to CNV analysis based on spectral decomposition of CNV profiles into focal CNVs and broad CNVs.

PICALM rs3851179 Variant Confers Susceptibility to Alzheimer's Disease in Chinese Population.

The association between PICALM rs3851179 variant and Alzheimer's disease (AD) has been well established by previous genome-wide association studies (GWAS) and candidate gene studies in European population. Recent studies investigated the association between PICALM rs3851179 and AD susceptibility in Chinese population. However, these studies reported consistent and inconsistent results.

Association of single nucleotide polymorphism rs6983267 with the risk of prostate cancer.

Many studies have investigated the association between single nucleotide polymorphism (SNP) rs6983267 and the risk of prostate cancer. However, results of these studies are inconsistent. Therefore, we summarised available data and performed a meta-analysis to determine this association.

Genome-wide targets identification of "core" pluripotency transcription factors with integrated features in human embryonic stem cells.

Embryonic stem cells (ESCs) play an important role in developmental biology which is still lacking clear molecular mechanisms. The "core" transcription factors (TFs) including OCT4, SOX2 and NANOG are essential for maintaining the stemness of ESCs. But the downstream targets of these "core" TFs are still ambiguous.

Alzheimer's Disease Variants with the Genome-Wide Significance are Significantly Enriched in Immune Pathways and Active in Immune Cells.

The existing large-scale genome-wide association studies (GWAS) datasets provide strong support for investigating the mechanisms of Alzheimer's disease (AD) by applying multiple methods of pathway analysis. Previous studies using selected single nucleotide polymorphisms (SNPs) with several thresholds of nominal significance for pathway analysis determined that the threshold chosen for SNPs can reflect the disease model. Presumably, then, pathway analysis with a stringent threshold to define "associated" SNPs would test the hypothesis that highly associated SNPs are enriched in one or more particular pathways.

Comparison of the Prognostic Utility of the Diverse Molecular Data among lncRNA, DNA Methylation, microRNA, and mRNA across Five Human Cancers.

Introduction: Advances in high-throughput technologies have generated diverse informative molecular markers for cancer outcome prediction. Long non-coding RNA (lncRNA) and DNA methylation as new classes of promising markers are emerging as key molecules in human cancers; however, the prognostic utility of such diverse molecular data remains to be explored.

Materials And Methods: We proposed a computational pipeline (IDFO) to predict patient survival by identifying prognosis-related biomarkers using multi-type molecular data (mRNA, microRNA, DNA methylation, and lncRNA) from 3198 samples of five cancer types.

Convergent Genetic and Expression Datasets Highlight TREM2 in Parkinson's Disease Susceptibility.

A rare TREM2 missense mutation (rs75932628-T) was reported to confer a significant Alzheimer's disease (AD) risk. A recent study indicated no evidence of the involvement of this variant in Parkinson's disease (PD). Here, we used the genetic and expression data to reinvestigate the potential association between TREM2 and PD susceptibility.

Analyzing large-scale samples highlights significant association between rs10411210 polymorphism and colorectal cancer.

Colorectal cancer (CRC) is the third most common form of cancer and the second leading cause of cancer-related death in the Western countries. In order to detect common CRC genetic variants, genome-wide association studies (GWAS) have been performed and reported some novel CRC susceptibility variants. RHPN2 is located on 9q13.

CR1 rs3818361 Polymorphism Contributes to Alzheimer's Disease Susceptibility in Chinese Population.

Recent genome-wide association studies (GWAS) reported CR1 rs3818361 polymorphism to be an Alzheimer's disease (AD) susceptibility variant in European ancestry. Three independent studies investigated this association in Chinese population. However, these studies reported weak or no significant association.

Cell adhesion molecule pathway genes are regulated by cis-regulatory SNPs and show significantly altered expression in Alzheimer's disease brains.

We previously identified the cell adhesion molecule (CAM) pathway as a consistent signal in 2 Alzheimer's disease (AD) genome-wide association studies (GWAS). However, the genetic mechanisms of the CAM pathway in AD are unclear. Here, we conducted pathway analysis using (1) Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathways; (2) 4 brain expression GWAS datasets; and (3) 2 whole-genome AD case-control expression datasets.

CLU rs9331888 Polymorphism Contributes to Alzheimer's Disease Susceptibility in Caucasian But Not East Asian Populations.

Large-scale genome-wide association studies (GWAS) identified three single nucleotide polymorphisms rs11136000, rs2279590, and rs9331888 in CLU gene to be significantly associated with Alzheimer's disease (AD) in Caucasian ancestry. Both rs11136000 and rs2279590 variants were successfully replicated in Asian population. However, previous studies reported either a weak association or no association between rs9331888 polymorphism and AD in Asian population.

Analyzing large-scale samples confirms the association between rs16892766 polymorphism and colorectal cancer susceptibility.

Colorectal cancer (CRC) is a common complex disease caused by the combination of genetic variants and environmental factors. Genome-wide association studies (GWAS) have been performed and reported some novel CRC susceptibility variants. The rs16892766 (8q23.

Identifying the Association Between Alzheimer's Disease and Parkinson's Disease Using Genome-Wide Association Studies and Protein-Protein Interaction Network.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the first and second most common neurodegenerative diseases in the elderly. Shared clinical and pathological features have been reported. Recent large-scale genome-wide association studies (GWAS) have been conducted and reported a number of AD and PD variants.

Pathway analysis of genome-wide association study and transcriptome data highlights new biological pathways in colorectal cancer.

Colorectal cancer (CRC) is a common malignancy that meets the definition of a complex disease. Genome-wide association study (GWAS) has identified several loci of weak predictive value in CRC, however, these do not fully explain the occurrence risk. Recently, gene set analysis has allowed enhanced interpretation of GWAS data in CRC, identifying a number of metabolic pathways as important for disease pathogenesis.

System analysis of LWDH related genes based on text mining in biological networks.

Liuwei-dihuang (LWDH) is widely used in traditional Chinese medicine (TCM), but its molecular mechanism about gene interactions is unclear. LWDH genes were extracted from the existing literatures based on text mining technology. To simulate the complex molecular interactions that occur in the whole body, protein-protein interaction networks (PPINs) were constructed and the topological properties of LWDH genes were analyzed.

Integrating Genome-Wide Association Study and Brain Expression Data Highlights Cell Adhesion Molecules and Purine Metabolism in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease in the elderly. Recently, genome-wide association studies (GWAS) have been used to investigate AD pathogenesis. However, a large proportion of AD heritability has yet to be explained.

CD33 rs3865444 Polymorphism Contributes to Alzheimer's Disease Susceptibility in Chinese, European, and North American Populations.

The CD33 rs3865444 polymorphism was first identified to be associated with Alzheimer's disease (AD) in European population. However, the following studies reported weak or no significant association in Chinese, Japanese, Korean, American, and Canadian populations. We think that these negative results may have been caused by either relatively small sample sizes compared with those used for the previous GWAS in European ancestry or the genetic heterogeneity of the rs3865444 polymorphism in different populations.