Joshua Anderson - Academia.edu (original) (raw)

Papers by Joshua Anderson

Landscape History of Hadramawt

Journal of Clinical Oncology

Journal of ovarian research, Jan 5, 2018

The ST6Gal-I sialyltransferase is upregulated in numerous cancers, and high expression of this en... more The ST6Gal-I sialyltransferase is upregulated in numerous cancers, and high expression of this enzyme correlates with poor patient prognosis in various malignancies, including ovarian cancer. Through its sialylation of a select cohort of cell surface receptors, ST6Gal-I modulates cell signaling to promote tumor cell survival. The goal of the present study was to investigate the influence of ST6Gal-I on another important receptor that controls cancer cell behavior, EGFR. Additionally, the effect of ST6Gal-I on cancer cells treated with the common EGFR inhibitor, gefitinib, was evaluated. Using the OV4 ovarian cancer cell line, which lacks endogenous ST6Gal-I expression, a kinomics assay revealed that cells with forced overexpression of ST6Gal-I exhibited increased global tyrosine kinase activity, a finding confirmed by immunoblotting whole cell lysates with an anti-phosphotyrosine antibody. Interestingly, the kinomics assay suggested that one of the most highly activated tyrosine kin...

SPINE

Retrospective cohort. Determine the impact of preoperative opioid use in workers&amp;amp;... more Retrospective cohort. Determine the impact of preoperative opioid use in workers&amp;amp;amp;amp;amp;#39; compensation (WC) patients undergoing lumbar diskectomy (LD). The prevalence of back pain among opioid users approached 60%. Long term opioid dependence in spine surgery patients is roughly 20%. Despite pervasive use, there is no evidence to support long-term opioid analgesic use for back pain. 10,592 patients received compensation from the Ohio Bureau of Workers&amp;amp;amp;amp;amp;#39; Compensation for a lumbar disc herniation between 2005-2012. Patients with spine comorbidities, smoking history, or multilevel surgery were excluded. Preoperatively, 566 patients had no opioid use, 126 had short term opioid use (STO), 315 had moderate opioid use (MTO), and 279 had long term opioid use (LTO). The primary outcome was whether subjects returned to work (RTW). 712 (55.4%) of patients met our RTW criteria. There was a significant difference in RTW rates among the no opioid (64.1%), MTO (52.7%), and LTO (36.9%) populations. Multivariate logistic regression analysis found several covariates to be independent negative predictors of RTW status: preoperative opioid use (P &amp;amp;amp;amp;amp;lt; 0.01;OR = 0.54), time to surgery (P &amp;amp;amp;amp;amp;lt; 0.01;OR = 0.98 per month), legal representation (P &amp;amp;amp;amp;amp;lt; 0.01;OR = 0.57), psychiatric comorbidity (P = 0.02;OR = 0.36). Patients in the LTO group had higher medical costs (P &amp;amp;amp;amp;amp;lt; 0.01), rates of psychiatric comorbidity (P &amp;amp;amp;amp;amp;lt; 0.01), incidence of failed back surgery syndrome (FBSS) (P &amp;amp;amp;amp;amp;lt; 0.01), and postoperative opioid use (P &amp;amp;amp;amp;amp;lt; 0.01) compared to the STO and no opioid groups. Preoperative opioid use was determined to be a negative predictor of RTW rates after LD in WC patients. Additionally, long-term preoperative opioid use was associated with higher medical costs, psychiatric illness, FBSS, and postoperative opioid use. Even a short, or moderate course of preoperative opioids was associated with worse outcomes compared to no use. For WC patients undergoing LD, judicious use of preoperative opioid analgesics may improve clinical outcomes and reduce the opioid burden. 3.

Oncotarget, 2017

The introduction of targeted therapies has caused a paradigm shift in the treatment of metastatic... more The introduction of targeted therapies has caused a paradigm shift in the treatment of metastatic clear cell (cc)-renal cell carcinoma (RCC). We hypothesized that determining differential kinase activity between primary and metastatic tumor sites may identify critical drivers of progression and relevant therapeutic targets in metastatic disease. Kinomic profiling was performed on primary tumor and metastatic tumor deposits utilizing a peptide substrate microarray to detect relative tyrosine phosphorylation activity. Pharmacologic and genetic loss of function experiments were used to assess the biologic significance of the top scoring kinase on in vitro and in vivo tumor phenotypes. Kinomics identified 7 peptides with increased tyrosine phosphorylation in metastases that were significantly altered (p<0.005). Based on these peptides, bioinformatics analyses identified several candidate kinases activated in metastases compared to primary tumors. The highest ranked upstream kinase was Focal Adhesion Kinase 1 (FAK1). RCC lines demonstrate evidence of elevated FAK1 activation relative to non-transformed renal epithelial cells. Pharmacologic inhibition of FAK1 with GSK2256098 suppresses in vitro tumor phenotypes. In turn, FAK1 knockdown in RCC cells suppresses both in vitro phenotypes and in vivo tumor growth. Collectively, these data demonstrate functional activation of FAK1 in metastases and provide preclinical rationale for targeting this kinase in the setting of advanced ccRCC.

Journal of Clinical Oncology, 2014

409 Background: Comprehensive high throughput functional kinase activity in localized cc-RCC tumo... more 409 Background: Comprehensive high throughput functional kinase activity in localized cc-RCC tumors may assist in devising a classification system and help identify potential therapeutic targets. Methods: Patients (pts) with localized tumors undergoing surgery with minimum follow-up of 18 months underwent kinomics of fresh frozen cc-RCC tumors and matched normal renal tissue using the PamStation12 high-content phospho-peptide substrate microarray system (PamGene). The protein tyrosine kinome (PTK) and serine/threonine kinome (STK) PamChips were used to measure global kinase activity. Advanced network modeling of altered phospho-peptides was performed using MetaCore while upstream kinase prediction scoring was based off of phosphonet (phosphonet.ca). Both unsupervised analyses and supervised analyses of kinomics were done guided by tumor recurrence. Kinomics of tumor and matched normal tissue were compared. Results: Of 41 evaluable pts, the median age was 61 and pathologic stage was ...

Journal of Proteomics & Bioinformatics, 2016

Kinases play a role in every cellular process involved in tumorigenesis ranging from proliferatio... more Kinases play a role in every cellular process involved in tumorigenesis ranging from proliferation, migration, and protein synthesis to DNA repair. While genetic sequencing has identified most kinases in the human genome, it does not describe the 'kinome' at the level of activity of kinases against their substrate targets. An attempt to address that limitation and give researchers a more direct view of cellular kinase activity is found in the PamGene PamChip® system, which records and compares the phosphorylation of 144 tyrosine or serine/threonine peptides as they are phosphorylated by cellular kinases. Accordingly, the kinetics of this time dependent kinomic signal needs to be well understood in order to transduce a parameter set into an accurate and meaningful mathematical model. Here we report the analysis and mathematical modeling of kinomic time series, which achieves a more accurate description of the accumulation of phosphorylated product than the current model, which assumes first order enzyme-substrate kinetics. Reproducibility of the proposed solution was of particular attention. Specifically, the non-linear parameterization procedure is delivered as a public open source web application where kinomic time series can be accurately decomposed into the model's two parameter values measuring phosphorylation rate and capacity. The ability to deliver model parameterization entirely as a client side web application is an important result on its own given increasing scientific preoccupation with reproducibility. There is also no need for a potentially transitory and opaque server-side component maintained by the authors, nor of exchanging potentially sensitive data as part of the model parameterization process since the code is transferred to the browser client where it can be inspected and executed.

ABSTRACT We have designed and implemented massively parallel rigid body constraint algorithms in ... more ABSTRACT We have designed and implemented massively parallel rigid body constraint algorithms in HOOMD-Blue[1], an open-source general purpose molecular dynamics simulation package optimized for graphics processing units (GPUs). In the HOOMD-Blue code package, rigid constraints can be used seamlessly with non-rigid parts of the system (e.g., point particles, bonded particles and walls), and with an array of integration methods (e.g. NVE, NVT, NPT, and Brownian Dynamics). We have also incorporated the FIRE energy minimizer[2], reformulated to be applicable to mixed systems of rigid bodies and non-rigid particles. For our typical simulations, the GPU implementation running on a single NVIDIA® GTX 480 card is twice as fast as LAMMPS[3] running on 32 CPUs. References [1] HOOMD-Blue, http://codeblue.umich.edu/hoomd-blue/. [2] E. Bitzek, P. Koskinen, F. Gaehler, M. Moseler, P. Gumbsch, Structural relaxation made simple, Physical Review Letters 2006, 97 170201. [3] LAMMPS, http://lammps.sandia.gov/.

Aps Meeting Abstracts, Mar 1, 2009

Using molecular dynamics simulations we show that triblock copolymers, designed to have specific ... more Using molecular dynamics simulations we show that triblock copolymers, designed to have specific affinity for nanoparticles at the chain ends, can successfully mediate assembly of nanoparticle/copolymer composites. In this talk, we will present a detailed investigation of ...

Fuel and Energy Abstracts, 2010

his patience and understanding, this thesis would not be possible. I would like to thank all of t... more his patience and understanding, this thesis would not be possible. I would like to thank all of the members of the RASA team including Dr. Joy McCorriston, Mike Harrower, Catherine Heine, and others. My experience in Yemen would not have been so inspiring without our Yemeni colleagues from GOAMM including, Abdalazziz Bin' Aquil, and Abdal Bassat Noman. I thank Nexen Inc. for their support of the project in Yemen.

Journal of Spine Surgery, 2016

The objective of this study is to evaluate the factors influencing the outcome of back pain and d... more The objective of this study is to evaluate the factors influencing the outcome of back pain and disability in patients operated for lumbar stenosis without instability and deformity using two classical surgical techniques: decompression alone and decompression plus fusion. This is a retrospective cohort study of patients who underwent lumbar surgery with standard posterior decompression or standard posterior decompression plus pedicle screw fixation for degenerative lumbar stenosis without deformity, spondylolisthesis or instability at our department from June 2010 to January 2014. They were divided into two groups: decompression group (D) and decompression-fusion group (F). We analyzed the following factors: age, gender, levels of stenosis, pre-surgical &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;micro-instability&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, and post-surgical &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;micro-instability&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;. A total of 174 patients were enrolled in the study. Both Graphic Rating Scale (GRS) and Oswestry Disability Index (ODI) scores were significantly decreased after surgery (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). Female patients appeared to have lesser improvements from surgery, for both D and F groups. An analysis of variance using the decrease of pain (GRS pre-post) as dependent variable and type of surgery, age, gender and their interaction as factors showed that the main effects of type of surgery and gender were significant. The analysis of variance for the decrease of pain (GRS) and disability (ODI) according to the levels of stenosis showed a significant interaction for GRS scores. Female patients that underwent fixation surgery reported the least improvement in disability. A significant interaction was found on the one-way analysis of variance for the D group without pre-surgical micro-instability using post-surgical micro-instability as factor. Our study supports posterior decompression alone as the gold standard option as treatment for lumbar stenosis without instability and deformity. Additional fusion should be considered only to prevent post-surgical instability. The &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;micro-instability&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; is a radiological finding that has its clinical surrogate but is not able to guide the choice of the type of surgery. Moreover the significance of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;micro-instability&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; is still unclear. We suggest a prospective study following patients with asymptomatic micro-instability to definitively understand the clinical history.

Circulation, Oct 31, 2006