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Unconditional Cash Transfers For Reducing Poverty And Vulnerabilities: Effect On Use Of Health Services And Health Outcomes In Low-And Middle-Income Countries, Frank Pega, Sze Yan Liu, Stefan Walter, Roman Pabayo, Ruhi Saith, S L. Lhachimi

Sze Yan Liu

Background

Unconditional cash transfers (UCTs; provided without obligation) for reducing poverty and vulnerabilities (e.g. orphanhood, old age or HIV infection) are a type of social protection intervention that addresses a key social determinant of health (income) in low‐ and middle‐income countries (LMICs). The relative effectiveness of UCTs compared with conditional cash transfers (CCTs; provided so long as the recipient engages in prescribed behaviours such as using a health service or attending school) is unknown.

Objectives

To assess the effects of UCTs for improving health services use and health outcomes in vulnerable children and adults in LMICs. Secondary objectives are to …

Integrated Transcriptome Analysis Reveals Mirna-Mrna Crosstalk In Laryngeal Squamous Cell Carcinoma., Yang Zhang, Yong Chen, Jinhai Yu, Guiming Liu, Zhigang Huang

Yong Chen

Next generation sequencing (NGS) has proven to be a powerful tool in delineating myriads of molecular subtypes of cancer, as well as in revealing accumulation of genomic mutations throughout cancer progression. Whole genome microRNA (miRNA) and mRNA expression profiles were obtained from patients with laryngeal squamous cell carcinoma (LSCC) using deep sequencing technology, and were analyzed by utilizing integrative computational approaches. A large number of protein-coding and non-coding genes were detected to be differentially expressed, indicating a functional switch in LSCC cells. A total of 127 mutated genes were detected to be significantly associated with ectoderm and epidermis development. Eleven …

Uncover Disease Genes By Maximizing Information Flow In The Phenome-Interactome Network., Yong Chen, Tao Jiang, Rui Jiang

Yong Chen

MOTIVATION: Pinpointing genes that underlie human inherited diseases among candidate genes in susceptibility genetic regions is the primary step towards the understanding of pathogenesis of diseases. Although several probabilistic models have been proposed to prioritize candidate genes using phenotype similarities and protein-protein interactions, no combinatorial approaches have been proposed in the literature.

RESULTS: We propose the first combinatorial approach for prioritizing candidate genes. We first construct a phenome-interactome network by integrating the given phenotype similarity profile, protein-protein interaction network and associations between diseases and genes. Then, we introduce a computational method called MAXIF to maximize the information flow in this …

Integrating Human Omics Data To Prioritize Candidate Genes., Yong Chen, Xuebing Wu, Rui Jiang

Yong Chen

BACKGROUND: The identification of genes involved in human complex diseases remains a great challenge in computational systems biology. Although methods have been developed to use disease phenotypic similarities with a protein-protein interaction network for the prioritization of candidate genes, other valuable omics data sources have been largely overlooked in these methods.

METHODS: With this understanding, we proposed a method called BRIDGE to prioritize candidate genes by integrating disease phenotypic similarities with such omics data as protein-protein interactions, gene sequence similarities, gene expression patterns, gene ontology annotations, and gene pathway memberships. BRIDGE utilizes a multiple regression model with lasso penalty to …

Domainrbf: A Bayesian Regression Approach To The Prioritization Of Candidate Domains For Complex Diseases., Wangshu Zhang, Yong Chen, Fengzhu Sun, Rui Jiang

Yong Chen

BACKGROUND: Domains are basic units of proteins, and thus exploring associations between protein domains and human inherited diseases will greatly improve our understanding of the pathogenesis of human complex diseases and further benefit the medical prevention, diagnosis and treatment of these diseases. Within a given domain-domain interaction network, we make the assumption that similarities of disease phenotypes can be explained using proximities of domains associated with such diseases. Based on this assumption, we propose a Bayesian regression approach named "domainRBF" (domain Rank with Bayes Factor) to prioritize candidate domains for human complex diseases.

RESULTS: Using a compiled dataset containing 1,614 …

The Proteomics Of Lipid Droplets: Structure, Dynamics, And Functions Of The Organelle Conserved From Bacteria To Humans., Li Yang, Yunfeng Ding, Yong Chen, Shuyan Zhang, Chaoxing Huo, Yang Wang, Jinhai Yu, Peng Zhang, Huimin Na, Huina Zhang, Yanbin Ma, Pingsheng Liu

Yong Chen

Lipid droplets are cellular organelles that consists of a neutral lipid core covered by a monolayer of phospholipids and many proteins. They are thought to function in the storage, transport, and metabolism of lipids, in signaling, and as a specialized microenvironment for metabolism in most types of cells from prokaryotic to eukaryotic organisms. Lipid droplets have received a lot of attention in the last 10 years as they are linked to the progression of many metabolic diseases and hold great potential for the development of neutral lipid-derived products, such as biofuels, food supplements, hormones, and medicines. Proteomic analysis of lipid …

Prioritizing Protein Complexes Implicated In Human Diseases By Network Optimization., Yong Chen, Thibault Jacquemin, Shuyan Zhang, Rui Jiang

Yong Chen

BACKGROUND: The detection of associations between protein complexes and human inherited diseases is of great importance in understanding mechanisms of diseases. Dysfunctions of a protein complex are usually defined by its member disturbance and consequently result in certain diseases. Although individual disease proteins have been widely predicted, computational methods are still absent for systematically investigating disease-related protein complexes.

RESULTS: We propose a method, MAXCOM, for the prioritization of candidate protein complexes. MAXCOM performs a maximum information flow algorithm to optimize relationships between a query disease and candidate protein complexes through a heterogeneous network that is constructed by combining protein-protein interactions …

Identifying Potential Cancer Driver Genes By Genomic Data Integration., Yong Chen, Jingjing Hao, Wei Jiang, Tong He, Xuegong Zhang, Tao Jiang, Rui Jiang

Yong Chen

Cancer is a genomic disease associated with a plethora of gene mutations resulting in a loss of control over vital cellular functions. Among these mutated genes, driver genes are defined as being causally linked to oncogenesis, while passenger genes are thought to be irrelevant for cancer development. With increasing numbers of large-scale genomic datasets available, integrating these genomic data to identify driver genes from aberration regions of cancer genomes becomes an important goal of cancer genome analysis and investigations into mechanisms responsible for cancer development. A computational method, MAXDRIVER, is proposed here to identify potential driver genes on the basis …

Fishermp: Fully Parallel Algorithm For Detecting Combinatorial Motifs From Large Chip-Seq Datasets., Shaoqiang Zhang, Ying Liang, Xiangyun Wang, Zhengchang Su, Yong Chen

Yong Chen

Detecting binding motifs of combinatorial transcription factors (TFs) from chromatin immunoprecipitation sequencing (ChIP-seq) experiments is an important and challenging computational problem for understanding gene regulations. Although a number of motif-finding algorithms have been presented, most are either time consuming or have sub-optimal accuracy for processing large-scale datasets. In this article, we present a fully parallelized algorithm for detecting combinatorial motifs from ChIP-seq datasets by using Fisher combined method and OpenMP parallel design. Large scale validations on both synthetic data and 350 ChIP-seq datasets from the ENCODE database showed that FisherMP has not only super speeds on large datasets, but also …

In Situ Capture Of Chromatin Interactions By Biotinylated Dcas9., Xin Liu, Yuannyu Zhang, Yong Chen, Mushan Li, Feng Zhou, Kailong Li, Hui Cao, Min Ni, Yuxuan Liu, Zhimin Gu, Kathryn E Dickerson, Shiqi Xie, Gary C Hon, Zhenyu Xuan, Michael Q Zhang, Zhen Shao, Jian Xu

Yong Chen

Cis-regulatory elements (CREs) are commonly recognized by correlative chromatin features, yet the molecular composition of the vast majority of CREs in chromatin remains unknown. Here, we describe a CRISPR affinity purification in situ of regulatory elements (CAPTURE) approach to unbiasedly identify locus-specific chromatin-regulating protein complexes and long-range DNA interactions. Using an in vivo biotinylated nuclease-deficient Cas9 protein and sequence-specific guide RNAs, we show high-resolution and selective isolation of chromatin interactions at a single-copy genomic locus. Purification of human telomeres using CAPTURE identifies known and new telomeric factors. In situ capture of individual constituents of the enhancer cluster controlling human β-globin …

Differential Activation Of Frontoparietal Attention Networks By Social And Symbolic Spatial Cues, Andrew D. Engell, Lauri Nummenmaa, Nikolaas N. Oosterhof, Richard N. Henson, James V. Haxby, Andrew J. Calder

Andrew D. Engell

Perception of both gaze-direction and symbolic directional cues (e.g. arrows) orient an observer’s attention toward the indicated location. It is unclear, however, whether these similar behavioral effects are examples of the same attentional phenomenon and, therefore, subserved by the same neural substrate. It has been proposed that gaze, given its evolutionary significance, constitutes a ‘special’ category of spatial cue. As such, it is predicted that the neural systems supporting spatial reorienting will be different for gaze than for non-biological symbols. We tested this prediction using functional magnetic resonance imaging to measure the brain’s response during target localization in which laterally …

Neurological Improvement Of Perineural And Leptomeningeal Spread Of Squamous Cell Carcinoma Treated With Intrathecal Chemotherapy And Systemic Egfr Inhibition., Vincent Alexander Van Vugt, Marlon Garzo Saria, Andres Javier, Navin Kesari, Tiffany Turpin, Santosh Kesari

Marlon Garzo Saria, PhD, RN, AOCNS, FAAN

Squamous cell carcinoma (SCC) is a common cancer of the skin. Risk factors include fair skin, excessive sun and ultraviolet light exposure, and history of xeroderma pigmentosa. Perineural invasion (PNI), an uncommon manifestation of SCC, involves microscopic tumor cells invading various layers of the nerve sheath. It is associated with a poorer prognosis. Standard treatment for PNI includes radiation therapy. Here, we describe a case an older gentleman with a history of SCC with PNI successfully treated with erlotinib and intrathecal chemotherapy.

Creating A Library Holding Group: An Approach To Large System Integration., Isaac R Huffman, Heather J Martin, Barbara (Basia) Delawska-Elliott

Basia Delawska-Elliott, MLIS, AHIP

PURPOSE: Faced with resource constraints, many hospital libraries have considered joint operations. This case study describes how Providence Health & Services created a single group to provide library services.

METHODS: Using a holding group model, staff worked to unify more than 6,100 nonlibrary subscriptions and 14 internal library sites.

RESULTS: Our library services grew by unifying 2,138 nonlibrary subscriptions and 11 library sites and hiring more library staff. We expanded access to 26,018 more patrons.

CONCLUSIONS: A model with built-in flexibility allowed successful library expansion. Although challenges remain, this success points to a viable model of unified operations.

Combining Resources, Combining Forces: Regionalizing Hospital Library Services In A Large Statewide Health System., Heather J Martin, Basia Delawska-Elliott

Basia Delawska-Elliott, MLIS, AHIP

After a reduction in full-time equivalents, 2 libraries in large teaching hospitals and 2 libraries in small community hospitals in a western US statewide health system saw opportunity for expansion through a regional reorganization. Despite a loss of 2/3 of the professional staff and a budgetary decrease of 27% over the previous 3 years, the libraries were able to grow business, usage, awareness, and collections through organizational innovation and improved efficiency. This paper describes the experience--including process, challenges, and lessons learned--of an organizational shift to regionalized services, collections, and staffing. Insights from this process may help similar organizations going through …

Robotic-Assistance Does Not Enhance Standard Laparoscopic Technique For Right-Sided Donor Nephrectomy., Xiaolong S Liu, Hadley W Narins, Warren R Maley, Adam M Frank, Costas D. Lallas

Adam M. Franks, MD

OBJECTIVE: To examine donor and recipient outcomes after right-sided robotic-assisted laparoscopic donor nephrectomy (RALDN) compared with standard laparoscopic donor nephrectomy (LDN) and to determine whether robotic-assistance enhances LDN.

MATERIALS & METHODS: From December 2005 to January 2011, 25 patients underwent right-sided LDN or RALDN. An IRB-approved retrospective review was performed of both donor and recipient medical charts. Primary endpoints included both intraoperative and postoperative outcomes.

RESULTS: Twenty right-sided LDNs and 5 RALDNs were performed during the study period. Neither estimated blood loss (76.4 mL vs. 30 mL, P = .07) nor operative time (231 min vs. 218 min, P = …

The Adipose Tissue Production Of Adiponectin Is Increased In End-Stage Renal Disease., Maria P Martinez Cantarin, Scott A Waldman, Cataldo Doria, Adam M Frank, Warren R Maley, Carlo B Ramirez, Scott W Keith, Bonita Falkner

Adam M. Franks, MD

Adiponectin has antidiabetic properties, and patients with obesity, diabetes, and insulin resistance have low plasma adiponectin levels. However, although kidney disease is associated with insulin resistance, adiponectin is elevated in end-stage renal disease. Here we determine whether adipose tissue production of adiponectin is increased in renal disease in a case-control study of 36 patients with end-stage renal disease and 23 kidney donors. Blood and tissue samples were obtained at kidney transplantation and donation. The mean plasma adiponectin level was significantly increased to 15.6 mg/ml in cases compared with 8.4 mg/ml in controls. Plasma levels of the inflammatory adipokines tumor necrosis …

Completely Steroid-Free Immunosuppression In Liver Transplantation: A Randomized Study., Carlo B. Ramirez, Md, Cataldo Doria, Md, Phd, Adam M. Frank, Md, Stephen T. Armenti, Ignazio R. Marino, Md

Adam M. Franks, MD

INTRODUCTION: Corticosteroids (CS) have been standard immunosuppression to prevent and treat rejection. However, CS are associated with increased risk of infection, obesity, hypertension, hyperlipidemia, diabetes, and accelerated hepatitis C virus (HCV) recurrence post-orthotopic liver transplantation (OLT). This study assesses the safety and efficacy of CS-free immunosuppressive regimen in adult OLT.

METHODS: A two-yr, prospective, randomized study of CS with delayed withdrawal (CS) or CS-free regimen with basiliximab, tacrolimus, and enteric-coated mycophenolate sodium (EC-MPS) was performed in 39 patients (CS=20; CS-free=19). CS group received intra-operative methylprednisolone weaned by six months. HCV patients had HCV PCR pre-OLT and 0.5, one, three, and …

Myxobacteria Versus Sponge-Derived Alkaloids: The Bengamide Family Identified As Potent Immune Modulating Agents By Scrutiny Of Lc-Ms/Elsd Libraries., Tyler A. Johnson, Johann Sohn, Yvette M Vaske, Kimberly N White, Tanya L Cohen, Helene C Vervoort, Karen Tenney, Frederick A Valeriote, Leonard F Bjeldanes, Phillip Crews

Tyler Johnson

A nuclear factor-κB (NF-κB) luciferase assay has been employed to identify the bengamides, previously known for their anti-tumor activity, as a new class of immune modulators. A unique element of this study was that the bengamide analogs were isolated from two disparate sources, Myxococcus virescens (bacterium) and Jaspis coriacea (sponge). Comparative LC-MS/ELSD and NMR analysis facilitated the isolation of M. viriscens derived samples of bengamide E (8) and two congeners, bengamide E' (13) and F' (14) each isolated as an insperable mixture of diastereomers. Additional compounds drawn from the UC, Santa Cruz repository allowed expansion of the structure activity relationship …

The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B Jekabsons, Tyler A. Johnson, Koneni V Sashidhara, Phillip Crews, Dale G Nagle, Yu-Dong Zhou

Tyler Johnson

A natural product chemistry-based approach was applied to discover small-molecule inhibitors of hypoxia-inducible factor-1 (HIF-1). A Petrosaspongia mycofijiensis marine sponge extract yielded mycothiazole (1), a solid tumor selective compound with no known mechanism for its cell line-dependent cytotoxic activity. Compound 1 inhibited hypoxic HIF-1 signaling in tumor cells (IC(50) 1nM) that correlated with the suppression of hypoxia-stimulated tumor angiogenesis in vitro. However, 1 exhibited pronounced neurotoxicity in vitro. Mechanistic studies revealed that 1 selectively suppresses mitochondrial respiration at complex I (NADH-ubiquinone oxidoreductase). Unlike rotenone, MPP(+), annonaceous acetogenins, piericidin A, and other complex I inhibitors, mycothiazole is a mixed polyketide/peptide-derived compound …

Chemically Diverse Microtubule Stabilizing Agents Initiate Distinct Mitotic Defects And Dysregulated Expression Of Key Mitotic Kinases., Cristina C Rohena, Jiangnan Peng, Tyler A. Johnson, Phillip Crews, Susan L Mooberry

Tyler Johnson

Microtubule stabilizers are some of the most successful drugs used in the treatment of adult solid tumors and yet the molecular events responsible for their antimitotic actions are not well defined. The mitotic events initiated by three structurally and biologically diverse microtubule stabilizers; taccalonolide AJ, laulimalide/fijianolide B and paclitaxel were studied. These microtubule stabilizers cause the formation of aberrant, but structurally distinct mitotic spindles leading to the hypothesis that they differentially affect mitotic signaling. Each microtubule stabilizer initiated different patterns of expression of key mitotic signaling proteins. Taccalonolide AJ causes centrosome separation and disjunction failure to a much greater extent …

Discovery Of Platelet-Type 12-Human Lipoxygenase Selective Inhibitors By High-Throughput Screening Of Structurally Diverse Libraries., Joshua D. Deschamps, Jeffrey T. Gautschi, Stephanie Whitman, Tyler A. Johnson, Nadine C. Gassner, Phillip Crews, Theodore R. Holman

Tyler Johnson

Human lipoxygenases (hLO) have been implicated in a variety of diseases and cancers and each hLO isozyme appears to have distinct roles in cellular biology. This fact emphasizes the need for discovering selective hLO inhibitors for both understanding the role of specific lipoxygenases in the cell and developing pharmaceutical therapeutics. To this end, we have modified a known lipoxygenase assay for high-throughput (HTP) screening of both the National Cancer Institute (NCI) and the UC Santa Cruz marine extract library (UCSC-MEL) in search of platelet-type 12-hLO (12-hLO) selective inhibitors. The HTP screen led to the characterization of five novel 12-hLO inhibitors …