Biomedical research is drowning in data, yet starving for knowledge. Current challenges in biomedical research and clinical practice include information overload - the need to combine vast amounts of structured, semi-structured, weakly structured data and vast amounts of unstructured information - and the need to optimize workflows, processes and guidelines, to increase capacity while reducing costs and improving efficiencies. In this paper we provide a very short overview on interactive and integrative solutions for knowledge discovery and data mining. In particular, we emphasize the benefits of including the end user into the "interactive" knowledge discovery process. We describe some of the most important challenges, including the need to develop and apply novel methods, algorithms and tools for the integration, fusion, pre-processing, mapping, analysis and interpretation of complex biomedical data with the aim to identify testable hypotheses, and build realistic models. The HCI-KDD approach, which is a synergistic combination of methodologies and approaches of two areas, Human-Computer Interaction (HCI) and Knowledge Discovery & Data Mining (KDD), offer ideal conditions towards solving these challenges: with the goal of supporting human intelligence with machine intelligence. There is an urgent need for integrative and interactive machine learning solutions, because no medical doctor or biomedical researcher can keep pace today with the increasingly large and complex data sets - often called "Big Data".

关键词：知识发现；数据挖掘；机器学习；生物医学

查看摘要 索取原文[18页]

Nanocomposites based on the integration of conducting polymer, polypyrrole (PPy) with other nanostructured-materials viz. carbon nanotubes (CNT) and gold nanoparticles (GNP) to construct a suitable host matrix for the functionalization of enzymes hold a great promise for the development of biosensors for the measurement of oxidative stress. Themitochondrial respiratory chain is an important source for the production of cellular reactive oxygen species (ROS) and reactive nitrogen species (RNS), causing a poptosis by the release of cytochromec(cyt c) from mitochondria. Therefore, the quantification of various biomarkers of oxidative stress could be of great importance in the clinical diagnosis and therapeutic research. This chapter presents the bio-functionalization of nanocomposites with enzymes for electrochemical biosensing of oxidative stress biomarkers viz. superoxide, nitricoxide, nitrite, nitrate, cysteine, and cyt c. The synergistic effect of the nanocomposites enhanced the direct electron transfer and catalytic activity of enzymes by providing a well ordered, stable and large surface for the functionalization without affecting their biological activity.

关键词：导电性聚合物；聚吡咯；生物医学

查看摘要 索取原文[26页]

Magnetic nanoparticles (MNPs) are one of the materials of great interest for presenting a unique combination of relevant properties such as high surface area, magnetic behavior and low toxicity, which can find potential use in different processes and applications in areas as catalysis (Lu et al., 2007), data storage (Frey et al., 2009), water treatment (Meng et al., 2011), drug delivery system (Anirudhan et al., 2013b), DNA separation (Chiang et al., 2005), tissue engineering (Ito and Honda, 2007), sensors (Baby and Ramaprabhu, 2010), hyperthermia (Alphandery et al., 2012), ferrofluids (Hee Kim et al., 2005), and as contrast agents in nuclear magnetic resonance (NMR) imaging (Choi et al., 2004). Modification of the particle surface induces changes in some properties such as high magnetization values and stable water dispersion and recent advances in nanotechnology have improved the range of use of MNPs in diagnosis and therapy. Among the biological uses of MNPs, we can highlight the biomedical imaging and therapeutic applications. Chemical modifications of the MNPs surface might result in non-toxic and biocompatible nanoparticles for biomedical applications like the development of new targeted nanoparticles for drug delivery systems for specific tissues. As previously mentioned, MNPs are used as a targeted carrier to be available for drug delivery to the specific site under the influence of a guiding magnet for treatment of diseases. Furthermore, MNPs offer excellent prospects for chemical and biological sensing. In the case of bioanalytical applications, MNPs can be adopted as nanoparticle-modined transducers for use as sensors and biomolecule-nanoparticle conjugates as labels for biosensing and bioassays. In the present review we will discuss current uses of MNPs in biomedicine and nanomedicine.

关键词：磁性纳米粒子；生物分子；生物医药

查看摘要 索取原文[35页]

Hematopoietic stem cells (HSC) and their progeny reside in specialized niches of the microenvironment (ME) in the bone marrow. The ME niches control HSC self-renewal, differentiation, and maturation. The ME niche cells are derived from non-hematopoietic cells, including fibroblasts, osteoblastic and endothelial cells. Macrophages, which are hematopoietic in origin, are also a critical component of the ME niches, and can influence the function of the ME niche cells. I hypothesize that the macrophages can acquire defects that may compromise ME function and lead to bone marrow failure. To test this hypothesis, I proposed to develop a new in vivo model that allows the inducible depletion of the macrophages in dogs, followed by the documentation of marrow failure, and subsequent therapeutic interventions. At this period, I achieved 4 goals: (1) Optimize culture conditions for generating dog macrophages, (2) Optimize transduction efficiency of a macrophage-specific CD163 promoter construct in dog CD34+ HSC and test its macrophage-specific expression, (3) Establish a luciferase reporter assay to test the macrophage- specific promoter activity, and (4) Generate multiple lentiviral vectors containing the dog/human CD163 promoter, iCasp9, and p140MGMT constructs.

关键词：造血干细胞；骨髓；干细胞；造血干细胞

查看摘要 索取原文[18页]

In this chapter, a detailed discussion on the salient features of structures of biomolecules like proteins, carbohydrates and nucleic acids is presented. Intermolecular interactions leading to phase separation, coacervation and nano-particle formation is discussed herein. Biomolecular solutions exist as gels, coacervates, dispersions and melts with each of these phases having its signature physico-chemical properties, which is discussed in this chapter. The discussions are supported by robust experimental data obtained from an array of methods like turbidimetry, elecrophoresis, viscosity, light scattering etc. The inevitability of the phenomenon of self-organization in biopolymers results in the generation of a variety of soft matter phases which do not, however, make it predictable. For instance, the associative aggregation is a process which remains obscure, as every protein aggregates in a different manner under different conditions. One known feature to the aggregation of proteins is the strong dependence upon pH, salt concentration and temperature. Beyond the influence of these factors and their effects on aggregation, the process is not well understood. An increase in protein usage in biomedical and pharmaceutical studies implicates protein aggregation in Alzheimer's, Parkinson's and other diseases, and have placed a growing importance upon understanding this behaviour in general. Comparison of the system to other protein-polyelectrolyte systems suggests that the preferential binding of the two could be a result of complexation of the two molecules which often lead to coacervation. Such association can even occur at pH greater than the isoelectric points (pI), when the net charge of protein is of the same sign as that of polyelectrolyte. Such binding though prevalent in nature is not well understood. In summary, a comprehensive account of biomolecular phase states and their inherent attributes are presented in this review.

关键词：蛋白质；碳水化合物；生物分子；生物医学

查看摘要 索取原文[70页]

The beneficial effects of soy on established breast cancer is controversial. The goal of this research is to investigate the potential molecular mechanisms by which soy isoflavones affect established breast cancers.

关键词：乳腺癌；转移；大豆蛋白；解剖模型

查看摘要 索取原文[28页]

We performed untargeted serum metabolomic profiling of two large population-based prostate cancer populations. Molecular features have been derived and explored for association with prostate cancer status (6,138 features, 475 subjects) and prostate cancer survival (5,209 features, 534 subjects). Assessment of metabolite features revealed two features as studywide significantly associated with prostate cancer status; however, due to low observed abundance we were not able to identify the molecular identity of these features. Among features indicated in pairwise analysis molecular identification revealed Caprolactam, L-Phosphatidic acid, and Peptide (Tyr-Lys- Thr) as possibly associated with prostate cancer aetiology. Genomewide assessment of the four top associated metabolite features implicated four genes PDE7B, NRG3, ILI3RA1 and UGT3A1 of which the association between metabolite feature 174.1-53 and gene ILI3RA1 was genome-wide significant (P = 1.4 x 10-8). This finding is interesting since although IL13RA1 itself has not been associated with prostate cancer, the alpha 2 chain of the same receptor (IL13RA2) has been reported to be differentially expressed in a metastatic prostate cancer cell line, and suggested as a target for prostate cancer treatment. In summary, several metabolite features associated with prostate cancer were discovered that warrant further investigation to advance our understanding of the underlying biological processes.

关键词：代谢产物；前列腺癌；血清

查看摘要 索取原文[34页]

Brain tissue is highly heterogeneous with different functions localized in specific areas. Our results suggest that there is increased oxidative damage (as evidenced by increased lipid peroxidation, protein and DNA oxidation) coupled with reduced glutathione antioxidant capacity in the selective regions of the brain in the subjects with autism. These changes in autism were specific to the frontal cortex, temporal cortex and cerebellum, while parietal and occipital cortices were not affected. Free radicals and energy (ATP) are generated by the mitochondria in the cell with the help of mitochondrial electron transport chain (ETC) complexes. We have also reported brain region-specific deficit in mitochondrial ETC complexes in children with autism. Autism spectrum disorders (ASDs) are complex neurodevelopmental disorders. The complexity of ASDs is further increased because some affected individuals fall in the sub-group of regressive autism. We have reported that individuals with regressive autism have decreased activities of protein kinases, i.e. protein kinase A (PKA) and protein kinase C (PKC) in the frontal cortex of the brain. Such changes were not observed in individuals with non-regressive autism. These results suggest that abnormal cellular signaling in the frontal lobe of the brain may be associated with regression in autism.

关键词：生物化学；脑；磷转移；畸形细胞（生物学）

查看摘要 索取原文[68页]

The VA Office of Inspector General (OIG) Office of Healthcare Inspections conducted an inspection to evaluate how the Veterans Health Administration (VHA) followed up on the inappropriate use of insulin pens at the VA Western New York Healthcare System, Buffalo, NY (the Buffalo facility), and to determine what controls VHA has in place to minimize the risk of other incidents involving insulin pens and similar devices. We conducted the inspection at the request of the Ranking Member, Senate Committee on Veterans Affairs to look at issues related to VHAs management of patient safety alerts, new medical products and devices, and infection prevention activities. We prepared a separate report on the specific circumstances of the misuse at the Buffalo facility. VHAs internal assessments following the Buffalo incident did not include clear, standard guidance to facilities on how to perform and document their audits of insulin pen use, and we found no documentation to support their internal reviews and significant variation in how facilities conducted their reviews. However, our onsite work at 4 facilities, including interviews with over 150 nurses, found no evidence of widespread, systemic reuse of insulin pens on multiple patients. The majority of nurses we spoke to understood that insulin pens were intended for single-patient use. Furthermore, on January 17, 2013, VHA generally prohibited the use of multi-dose insulin pens on inpatient units, effective February 4, 2013.

关键词：财务管理；卫生保健设施；医疗设备

查看摘要 索取原文[29页]

Polyhydroxyalkanoates (PHAs) have been extensively investigated as biomaterials due to their good biocompatibility. However, the intrinsic hydrophobicity of PHAs, their hydrolytic stability under physiological conditions and lack of chemical functionalities restrict their biomedical applications. In order to widen the applications of PHAs, it is important to improve its properties such as mechanical, crystallinity, surface features, amphiphilicity and degradation rate. A useful strategy to improve the properties of PHAs is chemical modification, where functional groups are introduced to PHAs which cannot be normally achieved by bioconversion processes. In this chapter, well-established chemical modification methods of PHAs are summarized and discussed. Firstly, the preparation of PHAs functionalized by chemical processes of hydroxylation, carboxylation, epoxidation, chlorination, and thermal degradation at different temperatures are reviewed. Next, PHAs functionalization by graft copolymerization is described with respect to three important synthesis approaches: "graft onto", "graft from" and "graft through". Finally, the modification of PHAs by block copolymerization, with recent advances in literature, will be described through ester formation, urethane formation, and other formations prepared by atom transfer radical polymerization (ATRP) and "click" chemistry reactions. The biomedical significance of the functionalized PHAs in different areas will also be discussed.

关键词：聚羟基烷酸酯；PHA；微生物聚酯

查看摘要 索取原文[37页]