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https://www.readbyqxmd.com/read/28330089/discovery-of-potential-alk-inhibitors-by-virtual-screening-approach
#1
Anish Kumar, V Shanthi, K Ramanathan
Crizotinib is an anticancer drug used for the treatment of non-small cell lung cancer. Evidences available suggest that there is a development of an acquired resistance against crizotinib action due to the emergence of several mutations in the ALK gene. It is therefore necessary to develop potent anti-cancer drugs for the treatment of crizotinib resistance non-small cell lung cancer types. In the present study, a novel class of lead molecule was identified using virtual screening, molecular docking and molecular dynamic approach...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28328144/diagnosing-and-preventing-iron-overload
#2
Ganesh Ramanathan, John K Olynyk, Paolo Ferrari
Absolute or functional iron (Fe) deficiency is an important determinant of anemia in hemodialysis patients and parenteral Fe is routinely used to treat this condition in conjunction with erythropoiesis stimulating agents. While restoration of hemoglobin toward the target range is a good outcome of Fe replacement, it is well known that Fe overload and toxicity may be adverse consequences of this therapy. Dialysis clinical practice guidelines recommend tailoring Fe therapy based on transferrin saturation and serum ferritin levels...
March 22, 2017: Hemodialysis International
https://www.readbyqxmd.com/read/28296636/discovering-sparse-transcription-factor-codes-for-cell-states-and-state-transitions-during-development
#3
Leon A Furchtgott, Samuel Melton, Vilas Menon, Sharad Ramanathan
Computational analysis of gene expression to determine both the sequence of lineage choices made by multipotent cells and to identify the genes influencing these decisions is challenging. Here we discover a pattern in the expression levels of a sparse subset of genes among cell types in B- and T-cell developmental lineages that correlates with developmental topologies. We develop a statistical framework using this pattern to simultaneously infer lineage transitions and the genes that determine these relationships...
March 15, 2017: ELife
https://www.readbyqxmd.com/read/28296635/dynamics-of-embryonic-stem-cell-differentiation-inferred-from-single-cell-transcriptomics-show-a-series-of-transitions-through-discrete-cell-states
#4
Sumin Jang, Sandeep Choubey, Leon Furchtgott, Ling-Nan Zou, Adele Doyle, Vilas Menon, Ethan B Loew, Anne-Rachel Krostag, Refugio A Martinez, Linda Madisen, Boaz P Levi, Sharad Ramanathan
The complexity of gene regulatory networks that lead multipotent cells to acquire different cell fates makes a quantitative understanding of differentiation challenging. Using a statistical framework to analyze single-cell transcriptomics data, we infer the gene expression dynamics of early mouse embryonic stem (mES) cell differentiation, uncovering discrete transitions across nine cell states. We validate the predicted transitions across discrete states using flow cytometry. Moreover, using live-cell microscopy, we show that individual cells undergo abrupt transitions from a naïve to primed pluripotent state...
March 15, 2017: ELife
https://www.readbyqxmd.com/read/28288952/outcomes-after-umbilical-cord-blood-transplantation-for-myelodysplastic-syndromes
#5
Aaron T Gerds, Kwang Woo Ahn, Zhen-Huan Hu, Hisham Abdel-Azim, Gorgun Akpek, Mahmoud Aljurf, Karen K Ballen, Amer Beitinjaneh, Ulrike Bacher, Jean-Yves Cahn, Saurabh Chhabra, Corey Cutler, Andrew Daly, Zachariah DeFilipp, Robert Peter Gale, Usama Gergis, Michael R Grunwald, Gregory A Hale, Betty Ky Hamilton, Madan Jagasia, Rammurti T Kamble, Tamila Kindwall-Keller, Taiga Nishihori, Richard F Olsson, Muthalagu Ramanathan, Ayman A Saad, Melhem Solh, Celalettin Ustun, David Valcárcel, Erica Warlick, Baldeep M Wirk, Matt Kalaycio, Edwin Alyea, Uday Popat, Ronald Sobecks, Wael Saber
For patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation, umbilical cord blood transplantation (UCBT) has become an acceptable alternative donor source in the absence of a matched sibling or unrelated donor. However, there have been few published series dedicated solely to describing the outcomes of adult patients with myelodysplastic syndrome (MDS) who have undergone UCBT. From 2004 to 2013, 176 adult MDS patients underwent UCBT as reported to the Center for International Blood and Marrow Transplant Research...
March 10, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28286568/immunotherapy-in-pancreatic-cancer-treatment-a-new-frontier
#6
REVIEW
Komal Thind, Leslie J Padrnos, Ramesh K Ramanathan, Mitesh J Borad
Pancreatic cancer is a highly aggressive and lethal cancer characterized by high invasiveness, local and extensive dissemination at time of diagnosis and resistance to treatment. Few therapies have shown efficacy in the past and even standard of care therapies yield only modest improvements in the mortality of patients with advanced or metastatic disease. Efforts have been undertaken to study the pancreatic tumor microenvironment and have established its complex and immunosuppressive nature which could explain the high resistance to chemotherapy...
January 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28280620/potential-actionable-targets-in-appendiceal-cancer-detected-by-immunohistochemistry-fluorescent-in-situ-hybridization-and-mutational-analysis
#7
Erkut Borazanci, Sherri Z Millis, Jeffery Kimbrough, Nancy Doll, Daniel Von Hoff, Ramesh K Ramanathan
BACKGROUND: Appendiceal cancers are rare and consist of carcinoid, mucocele, pseudomyxoma peritonei (PMP), goblet cell carcinoma, lymphoma, and adenocarcinoma histologies. Current treatment involves surgical resection or debulking, but no standard exists for adjuvant chemotherapy or treatment for metastatic disease. METHODS: Samples were identified from approximately 60,000 global tumors analyzed at a referral molecular profiling CLIA-certified laboratory. A total of 588 samples with appendix primary tumor sites were identified (male/female ratio of 2:3; mean age =55)...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28279351/single-cell-profiling-of-an-in%C3%A2-vitro-model-of-human-interneuron-development-reveals-temporal-dynamics-of-cell-type-production-and-maturation
#8
Jennie L Close, Zizhen Yao, Boaz P Levi, Jeremy A Miller, Trygve E Bakken, Vilas Menon, Jonathan T Ting, Abigail Wall, Anne-Rachel Krostag, Elliot R Thomsen, Angel M Nelson, John K Mich, Rebecca D Hodge, Soraya I Shehata, Ian A Glass, Susan Bort, Nadiya V Shapovalova, N Kiet Ngo, Joshua S Grimley, John W Phillips, Carol L Thompson, Sharad Ramanathan, Ed Lein
GABAergic interneurons are essential for neural circuit function, and their loss or dysfunction is implicated in human neuropsychiatric disease. In vitro methods for interneuron generation hold promise for studying human cellular and functional properties and, ultimately, for therapeutic cell replacement. Here we describe a protocol for generating cortical interneurons from hESCs and analyze the properties and maturation time course of cell types using single-cell RNA-seq. We find that the cell types produced mimic in vivo temporal patterns of neuron and glial production, with immature progenitors and neurons observed early and mature cortical neurons and glial cell types produced late...
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28268494/gaussian-mixture-model-for-the-identification-of-psychogenic-non-epileptic-seizures-using-a-wearable-accelerometer-sensor
#9
Shitanshu Kusmakar, Ramanathan Muthuganapathy, Bernard Yan, Terence J O'Brien, Marimuthu Palaniswami
Any abnormal hypersynchronus activity of neurons can be characterized as an epileptic seizure (ES). A broad class of non-epileptic seizures is comprised of Psychogenic non-epileptic seizures (PNES). PNES are paroxysmal events, which mimics epileptic seizures and pose a diagnostic challenge with epileptic seizures due to their clinical similarities. The diagnosis of PNES is done using video-electroencephalography (VEM) monitoring. VEM being a resource intensive process calls for alternative methods for detection of PNES...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28256392/endometrial-cancer-associated-biomarkers-in-bariatric-surgery-candidates-exploration-of-racial-differences
#10
Faina Linkov, Sharon L Goughnour, Robert P Edwards, Anna Lokshin, Ramesh C Ramanathan, Giselle G Hamad, Carol McCloskey, Dana H Bovbjerg
BACKGROUND: Obesity is the main risk factor for endometrial cancer (EC), the most common gynecologic malignancy in the United States. A number of potential risk biomarkers have been associated with EC development, including altered proinflammatory cytokines, chemokines, and adipokines. OBJECTIVES: The overarching aim of this research is to investigate racial differences in the expression of EC-associated biomarkers among bariatric surgery candidates. SETTING: Tertiary academic medical center METHODS: Blood samples were collected from 175 women aged 18 to 72 (mean age: 42...
January 13, 2017: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/28254336/nanofibrous-matrixes-with-biologically-active-hydroxybenzophenazine-pyrazolone-compound-for-cancer-theranostics
#11
Subramani Kandhasamy, Giriprasath Ramanathan, Thangavelu Muthukumar, SitaLakshmi Thyagarajan, Narayanan Umamaheshwari, V P Santhanakrishnan, Uma Tiruchirapalli Sivagnanam, Paramasivan Thirumalai Perumal
The nanomaterial with the novel biologically active compounds has been actively investigated for application in cancer research. Substantial use of nanofibrous scaffold for cancer research with potentially bioactive compounds through electrospinning has not been fully explored. Here, we describe the series of fabrication of nanofibrous scaffold loaded with novel potential biologically active hydroxybenzo[a]phenazine pyrazol-5(4H)-one derivatives were designed, synthesized by a simple one-pot, two step four component condensation based on Michael type addition reaction of lawsone, benzene-1,2-diamine, aromatic aldehydes and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one as the substrates...
May 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28252534/extracorporeal-membrane-oxygenation-for-adult-community-acquired-pneumonia-outcomes-and-predictors-of-mortality
#12
Kollengode Ramanathan, Chuen Seng Tan, Peter Rycus, Graeme Maclaren
OBJECTIVES: Extracorporeal membrane oxygenation is a rescue therapy used to support severe cardiorespiratory failure. Data on outcomes from severe community-acquired pneumonia in adults receiving rescue extracorporeal membrane oxygenation are mainly confined to single-center experiences or specific pathogens. We examined data from the Extracorporeal Life Support Organisation registry to identify risk factors for poor outcomes in adult patients with community-acquired pneumonia. DESIGN: Retrospective data analysis...
March 1, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28249483/thermal-management-and-prototype-testing-of-compton-scattering-x-ray-beam-position-monitor-for-the-advanced-photon-source-upgrade
#13
S H Lee, B X Yang, J T Collins, M Ramanathan
Accurate and stable x-ray beam position monitors (XBPMs) are key elements in obtaining the desired user beam stability in the Advanced Photon Source Upgrade. In the next-generation XBPMs for the canted-undulator front ends, where two undulator beams are separated by 1.0 mrad, the lower beam power (<10 kW) per undulator allows us to explore lower-cost solutions based on Compton scattering from a diamond placed edge-on to the x-ray beam. Because of the high peak power density of the x-ray beams, this diamond experiences high temperatures and has to be clamped to a water-cooled heat spreader using thermal interface materials (TIMs), which play a key role in reducing the temperature of the diamond...
February 2017: Review of Scientific Instruments
https://www.readbyqxmd.com/read/28246011/administrative-databases-can-yield-false-conclusions-an-example-of-obesity-in-total-joint-arthroplasty
#14
Jaiben George, Jared M Newman, Deepak Ramanathan, Alison K Klika, Carlos A Higuera, Wael K Barsoum
BACKGROUND: Research using large administrative databases has substantially increased in recent years. Accuracy with which comorbidities are represented in these databases has been questioned. The purpose of this study was to evaluate the extent of errors in obesity coding and its impact on arthroplasty research. METHODS: Eighteen thousand thirty primary total knee arthroplasties (TKAs) and 10,475 total hip arthroplasties (THAs) performed at a single healthcare system from 2004-2014 were included...
February 7, 2017: Journal of Arthroplasty
https://www.readbyqxmd.com/read/28245149/airborne-particulate-matter-induces-non-allergic-eosinophilic-sinonasal-inflammation-in-mice
#15
Murugappan Ramanathan, Nyall R London, Anuj Tharakan, Nitya Surya, Thomas E Sussan, Xiaoquan Rao, Sandra Y Lin, Elina Toskala, Sanjay Rajagopalan, Shyam Biswal
RATIONALE: Exposure to airborne particulate matter has been linked to aggravation of respiratory symptoms, increased risk of cardiovascular disease, and all-cause mortality. While the health effects of particulate matter on the lower pulmonary airway have been extensively studied, little is known regarding the impact of chronic particulate matter exposure on the upper sinonasal airway. OBJECTIVES: To test the impact of chronic airborne particulate matter exposure on the upper respiratory system in vivo...
February 28, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28242752/phase-i-dose-escalation-2-part-trial-of-poly-adp-ribose-polymerase-inhibitor-talazoparib-in-patients-with-advanced-germline-brca1-2-mutations-and-selected-sporadic-cancers
#16
Johann de Bono, Ramesh K Ramanathan, Lida Mina, Rashmi Chugh, John Glaspy, Saeed Rafii, Stan Kaye, Jasgit Sachdev, John Heymach, David C Smith, Joshua W Henshaw, Ashleigh Herriott, Miranda Patterson, Nicola J Curtin, Lauren Averett Byers, Zev A Wainberg
Talazoparib inhibits poly(ADP-ribose) polymerase (PARP) catalytic activity, trapping PARP1 on damaged DNA and causing cell death in BRCA1/2-mutated cells. We evaluated talazoparib therapy in this 2-part, phase I, first-in-human trial. Antitumor activity, maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of once-daily talazoparib were determined in an open-label, multicenter, dose-escalation study (NCT01286987). The MTD was 1.0 mg/day, with an elimination half-life of 50 hours. Treatment-related adverse events included fatigue (26/71 patients; 37%) and anemia (25/71 patients; 35%)...
February 27, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28235401/expression-of-socs1-and-the-downstream-targets-of-its-putative-tumor-suppressor-functions-in-prostate-cancer
#17
Martin Chevrier, Diwakar Bobbala, Alberto Villalobos-Hernandez, Md Gulam Musawwir Khan, Sheela Ramanathan, Caroline Saucier, Gerardo Ferbeyre, Sameh Geha, Subburaj Ilangumaran
BACKGROUND: Suppressor of cytokine signaling 1 (SOCS1) is considered a tumor suppressor due to frequent epigenetic and micro-RNA-mediated repression of its gene expression in diverse cancers. In prostate cancer (PCa), elevated expression of miR-30d that targets SOCS1 mRNA is associated with increased risk of disease recurrence. SOCS1 can mediate its tumor suppressor functions by diverse mechanisms such as inhibiting the JAK-STAT signaling pathway, promoting the tumor suppressor functions of p53, attenuating MET receptor tyrosine kinase signaling and blocking the oncogenic potential of the cell cycle inhibitor p21(CIP1) (p21)...
February 24, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28226668/gaussian-mixture-model-for-the-identification-of-psychogenic-non-epileptic-seizures-using-a-wearable-accelerometer-sensor
#18
Shitanshu Kusmakar, Ramanathan Muthuganapathy, Bernard Yan, Terence J O'Brien, Marimuthu Palaniswami, Shitanshu Kusmakar, Ramanathan Muthuganapathy, Bernard Yan, Terence J O'Brien, Marimuthu Palaniswami, Terence J O'Brien, Shitanshu Kusmakar, Bernard Yan, Ramanathan Muthuganapathy, Marimuthu Palaniswami
Any abnormal hypersynchronus activity of neurons can be characterized as an epileptic seizure (ES). A broad class of non-epileptic seizures is comprised of Psychogenic non-epileptic seizures (PNES). PNES are paroxysmal events, which mimics epileptic seizures and pose a diagnostic challenge with epileptic seizures due to their clinical similarities. The diagnosis of PNES is done using video-electroencephalography (VEM) monitoring. VEM being a resource intensive process calls for alternative methods for detection of PNES...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28223986/gtpase-of-the-immune-associated-nucleotide-protein-5-regulates-the-lysosomal-calcium-compartment-in-t-lymphocytes
#19
Daniel Serrano, Farnaz Ghobadi, Guylain Boulay, Subburaj Ilangumaran, Christine Lavoie, Sheela Ramanathan
T lymphocytes from Gimap5(lyp/lyp) rats carrying a recessive mutation in the GTPase of immune-associated protein 5 (Gimap5) gene undergo spontaneous apoptosis. Molecular mechanisms underlying this survival defect are not yet clear. We have shown that Gimap5(lyp/lyp) T lymphocytes display reduced calcium influx following T cell antigen receptor (TCR) stimulation that was associated with impaired buffering of calcium by mitochondria. Here, we investigated the subcellular localization of GIMAP5 and its influence on Ca(2+) response in HEK293T cells and T lymphocytes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28222335/sensitive-simultaneous-quantitation-of-testosterone-and-estradiol-in-serum-by-lc-ms-ms-without-derivatization-and-comparison-with-the-cdc-host-program
#20
COMPARATIVE STUDY
Ryan C Schofield, Damodara R Mendu, Lakshmi V Ramanathan, Melissa S Pessin, Dean C Carlow
BACKGROUND: Very sensitive measurements of serum estrogens and testosterone are important in adult and pediatric endocrinology and immunoassays are known to lack the required performance at very low levels. Our aim was to develop a sensitive HPLC-MS/MS assay for both estradiol (E2) and testosterone (Te) in serum without the need for chemical derivatization and using commercially available calibrators. METHODS: Serum samples were prepared by the addition of internal standards followed by extraction using hexane:ethyl acetate...
March 24, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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