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https://www.readbyqxmd.com/read/28817588/phylogeography-of-the-reticulated-python-malayopython-reticulatus-ssp-conservation-implications-for-the-worlds-most-traded-snake-species
#1
Gillian Murray-Dickson, Muhammad Ghazali, Rob Ogden, Rafe Brown, Mark Auliya
As an important economic natural resource in Southeast Asia, reticulated pythons (Malayopython reticulatus ssp.) are primarily harvested from the wild for their skins-which are prized in the luxury leather goods industry. Trade dynamics of this CITES Appendix II listed species are complex and management approaches on the country or regional level appear obscure. Little is known about the actual geographic point-of-harvest of snakes, how genetic diversity is partitioned across the species range, how current harvest levels may affect the genetic viability of populations, and whether genetic structure could (or should) be accounted for when managing harvest quotas...
2017: PloS One
https://www.readbyqxmd.com/read/28816861/en-face-versus-12-line-radial-optical-coherence-tomography-scan-patterns-for-detection-of-macular-fluid-in-neovascular-age-related-macular-degeneration
#2
Murtaza K Adam, Abtin Shahlaee, Wasim A Samara, Joseph I Maguire, Allen C Ho, Jason Hsu
PURPOSE: To compare fluid detection of autosegmented en face to 12-line radial spectral domain optical coherence tomography scan patterns in neovascular age-related macular degeneration. METHODS: Retrospective observational case series. Sixty-seven patients (94 eyes) with neovascular age-related macular degeneration underwent autosegmented en face optical coherence tomography (with associated 304-line raster scan) and 12-line radial scan patterns. Sensitivity and specificity of fluid detection for en face scan and 12-line radial scans were determined by combining radial and 304-line raster scans as a gold standard...
August 14, 2017: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/28816016/the-discovery-of-new-and-more-potent-chloropyramine-c4-analogues-for-the-potential-treatment-of-invasive-breast-cancer
#3
Sahar Kandil, Filippo Prencipe, Samuel Jones, Stephen Hiscox, Andrew D Westwell
Breast cancer (BC) is the second most common cancer worldwide, accounting for 25% of all female cancers. Although the survival rate has increased significantly in the past few decades, patients who develop secondary site metastasis as well as those diagnosed with triple negative breast cancer (TNBC) still represent a real unmet medical challenge. Previous studies have shown that chloropyramine (C4) inhibits FAK-VEGFR3 signaling. More recently, C4 is reported to have SASH1 inducing properties. However, C4 exerts its antitumour and antiangiogenic effects at high micromolar concentrations (>100 μM) that would not be compatible with further drug development against invasive breast cancer driven by FAK signaling...
August 16, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28815490/generating-genetically-modified-mice-a-decision-guide
#4
Ivo J Huijbers
The generation of a new genetically modified mouse strain is a big hurdle to take for many researchers. It is often unclear which steps and decisions have to be made prior to obtaining the desired mouse model. This review aims to help researchers by providing a decision guide that answers the essential questions that need to be asked before generating the most suitable genetically modified mouse line in the most optimal timeframe. The review includes the latest technologies in both the stem cell culture and gene editing tools, particularly CRISPR/Cas9, and provides compatibility guidelines for selecting among the different types of genetic modifications that can be introduced in the mouse genome and the various routes for introducing these modifications into the mouse germline...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28814275/randomized-study-comparing-full-dose-monotherapy-s-1-followed-by-irinotecan-and-reduced-dose-combination-therapy-s-1-oxaliplatin-followed-by-s-1-irinotecan-as-initial-therapy-for-older-patients-with-metastatic-colorectal-cancer-nordic-9
#5
Stine Braendegaard Winther, Pia Österlund, Åke Berglund, Bengt Glimelius, Camilla Qvortrup, Halfdan Sorbye, Per Pfeiffer
BACKGROUND: Metastatic colorectal cancer (mCRC) is a disease of older age, but there is a relative lack of knowledge about effects of chemotherapy in older patients as they are under-represented in clinical trials. Little data can guide whether the strategy in older mCRC patients should be a sequential full-dose monotherapy chemotherapy approach or a dose-reduced combination chemotherapy approach. The oral 5FU prodrug S-1 seems to have less side effects than capecitabine and should be an optimal drug for older patients, but few data are available...
August 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28814247/fluid-and-medication-considerations-in-the-traumatized-patient
#6
Amita Misir
This article reviews fluid therapy and medications in pediatric trauma. For resuscitation in the setting of hemorrhagic shock, isotonic crystalloid solution is the first-line agent of choice. Colloid solutions offer no additional benefit, introduce possible increased risks and cost more than crystalloids. Blood products, starting with pRBCs, should be introduced after 20-40 ml/kg of crystalloid has been administered if there is ongoing need for volume replacement. The use of a massive transfusion protocol of 1:1:1 (if >30 kg) or 30:20:20 (if <30 kg) of pRBCs:FFP:platelets is suggested after an initial 30 ml/kg of pRBcs have been administered...
August 14, 2017: Current Pediatric Reviews
https://www.readbyqxmd.com/read/28813638/impact-of-70-gene-signature-use-on-adjuvant-chemotherapy-decisions-in-patients-with-estrogen-receptor-positive-early-breast-cancer-results-of-a-prospective-cohort-study
#7
Anne Kuijer, Marieke Straver, Bianca den Dekker, Annelotte C M van Bommel, Sjoerd G Elias, Carolien H Smorenburg, Jelle Wesseling, Sabine C Linn, Emiel J Th Rutgers, Sabine Siesling, Thijs van Dalen
Purpose Gene-expression profiles increasingly are used in addition to conventional prognostic factors to guide adjuvant chemotherapy (CT) decisions. The Dutch guideline suggests use of validated gene-expression profiles in patients with estrogen receptor (ER) -positive, early-stage breast cancer without overt lymph node metastases. We aimed to assess the impact of a 70-gene signature (70-GS) test on CT decisions in patients with ER-positive, early-stage breast cancer. Patients and Methods In a prospective, observational, multicenter study in patients younger than 70 years old who had undergone surgery for ER-positive, early-stage breast cancer, physicians were asked whether they intended to administer adjuvant CT before deployment of the 70-GS test and after the test result was available...
August 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28811131/assessment-of-translational-risk-in-drug-research-role-of-biomarker-classification-and-mechanism-based-pkpd-concepts
#8
Sandra A G Visser, Tjerk J H Bueters
In 2005, Danhof and coauthors proposed a new biomarker classification in the context of the application of mechanism-based PKPD modeling. They defined the term 'biomarker' as a measure that characterizes a drug-induced response, which is on the causal path between drug administration and clinical outcome. The biomarker classification identified seven categories that provide different insights into the kinetics of drug action, such as target site distribution, target engagement, or into the impact of the drug on physiology or disease...
August 12, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28810611/three-dimensional-spiral-ct-measurement-of-atlantal-pedicle-and-its-clinical-application
#9
Wengui Xie, Pengfei Gao, Lixin Ji
The study aimed to establish the safe placement area and corresponding entry angle of atlantal pedicle screw using axial computed tomography (CT) measurement of atlas, in order to guide the clinical operation. Spiral thin-slice CT scan of atlas and three-dimensional reconstruction of 38 patients were randomly selected. Screw placement space was defined as the distance between the tangent lines of entry channel on the atlantal cross section and inner edge of transverse foramen and outer edge of spinal canal...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808394/antiproliferative-activity-of-haematoxylum-brasiletto-h-karst
#10
J Bello-Martínez, M Jiménez-Estrada, J L Rosas-Acevedo, L P Avila-Caballero, M Vidal-Gutierrez, C Patiño-Morales, E Ortiz-Sánchez, R E Robles-Zepeda
BACKGROUND: Haematoxylum brasiletto is a tree that grows in Central America, commonly known as "Palo de Brasil," which is used in the traditional medicine for the treatment of cancer and gastric ulcers. OBJECTIVE: The aim of this study was to isolate the compounds responsible for antiproliferative activity of H. brasiletto. MATERIALS AND METHODS: A bioassay-guided fractionation of ethanol extract of H. brasiletto was performed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide cell proliferation assay to measure the antiproliferative activity on six human cancer cell lines (A549, LS180, HeLa, SiHa, MDA-MB-231, and NCI-H1299) and one human noncancer cell line (ARPE-19)...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28808002/optimized-strategy-for-in-vivo-cas9-activation-in-drosophila
#11
Ben Ewen-Campen, Donghui Yang-Zhou, Vitória R Fernandes, Delfina P González, Lu-Ping Liu, Rong Tao, Xingjie Ren, Jin Sun, Yanhui Hu, Jonathan Zirin, Stephanie E Mohr, Jian-Quan Ni, Norbert Perrimon
While several large-scale resources are available for in vivo loss-of-function studies in Drosophila, an analogous resource for overexpressing genes from their endogenous loci does not exist. We describe a strategy for generating such a resource using Cas9 transcriptional activators (CRISPRa). First, we compare a panel of CRISPRa approaches and demonstrate that, for in vivo studies, dCas9-VPR is the most optimal activator. Next, we demonstrate that this approach is scalable and has a high success rate, as >75% of the lines tested activate their target gene...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28805822/intrinsic-bet-inhibitor-resistance-in-spop-mutated-prostate-cancer-is-mediated-by-bet-protein-stabilization-and-akt-mtorc1-activation
#12
Pingzhao Zhang, Dejie Wang, Yu Zhao, Shancheng Ren, Kun Gao, Zhenqing Ye, Shangqian Wang, Chun-Wu Pan, Yasheng Zhu, Yuqian Yan, Yinhui Yang, Di Wu, Yundong He, Jun Zhang, Daru Lu, Xiuping Liu, Long Yu, Shimin Zhao, Yao Li, Dong Lin, Yuzhuo Wang, Liguo Wang, Yu Chen, Yinghao Sun, Chenji Wang, Haojie Huang
Bromodomain and extraterminal domain (BET) protein inhibitors are emerging as promising anticancer therapies. The gene encoding the E3 ubiquitin ligase substrate-binding adaptor speckle-type POZ protein (SPOP) is the most frequently mutated in primary prostate cancer. Here we demonstrate that wild-type SPOP binds to and induces ubiquitination and proteasomal degradation of BET proteins (BRD2, BRD3 and BRD4) by recognizing a degron motif common among them. In contrast, prostate cancer-associated SPOP mutants show impaired binding to BET proteins, resulting in decreased proteasomal degradation and accumulation of these proteins in prostate cancer cell lines and patient specimens and causing resistance to BET inhibitors...
August 14, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28805711/a-dereplication-and-bioguided-discovery-approach-to-reveal-new-compounds-from-a-marine-derived-fungus-stilbella-fimetaria
#13
Sara Kildgaard, Karolina Subko, Emma Phillips, Violaine Goidts, Mercedes de la Cruz, Caridad Díaz, Charlotte H Gotfredsen, Birgitte Andersen, Jens C Frisvad, Kristian F Nielsen, Thomas O Larsen
A marine-derived Stilbella fimetaria fungal strain was screened for new bioactive compounds based on two different approaches: (i) bio-guided approach using cytotoxicity and antimicrobial bioassays; and (ii) dereplication based approach using liquid chromatography with both diode array detection and high resolution mass spectrometry. This led to the discovery of several bioactive compound families with different biosynthetic origins, including pimarane-type diterpenoids and hybrid polyketide-non ribosomal peptide derived compounds...
August 13, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28805566/botulinum-toxin-therapy-for-nonmotor-aspects-of-parkinson-s-disease
#14
Jarosław Sławek, Mariusz Madaliński
The medical treatment of Parkinson's disease (PD) is symptomatic both in terms of motor and nonmotor aspects. The nonmotor symptoms therapy should be taken into account as many of them negatively influence the quality of life and are treatable. Botulinum neurotoxin (BoNT) offers effective treatment for drooling and bladder dysfunctions and alternative treatment for constipation and pain related to parkinsonism. BoNT for drooling is probably the best-documented therapy for nonmotor symptoms by clinical trials...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28804660/large-granular-lymphocytic-leukemia-a-report-of-response-to-rituximab
#15
Uroosa Ibrahim, Sara Parylo, Shiksha Kedia, Shafinaz Hussein, Jean Paul Atallah
Large granular lymphocytic (LGL) leukemia is a rare form of low grade leukemia characterized by large cytotoxic T cells or natural killer cells on morphological examination. Immunosuppressive therapy is employed as first-line therapy. Treatment options in refractory cases include the anti-CD52 antibody alemtuzumab and purine analogues. We report a rare case that responded to the anti-CD20 monoclonal antibody rituximab. A 77-year-old female presented with complaints of fatigue, fever, and chills of 3 months' duration...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28803161/on-line-prognosis-of-fatigue-crack-propagation-based-on-gaussian-weight-mixture-proposal-particle-filter
#16
Jian Chen, Shenfang Yuan, Lei Qiu, Hui Wang, Weibo Yang
Accurate on-line prognosis of fatigue crack propagation is of great meaning for prognostics and health management (PHM) technologies to ensure structural integrity, which is a challenging task because of uncertainties which arise from sources such as intrinsic material properties, loading, and environmental factors. The particle filter algorithm has been proved to be a powerful tool to deal with prognostic problems those are affected by uncertainties. However, most studies adopted the basic particle filter algorithm, which uses the transition probability density function as the importance density and may suffer from serious particle degeneracy problem...
July 25, 2017: Ultrasonics
https://www.readbyqxmd.com/read/28802695/scarce-resource-allocation-during-disasters-a-mixed-method-community-engagement-study
#17
Elizabeth Lee Daugherty Biddison, Howard S Gwon, Monica Schoch-Spana, Alan C Regenberg, Chrissie Juliano, Ruth R Faden, Eric S Toner
BACKGROUND: During a catastrophe, health care providers may face difficult questions regarding who will receive limited life-saving resources. The ethical principles that should guide decision-making have been considered by expert panels but have not been well explored with the public or front line clinicians. The objective of this study was to characterize the public's values regarding how scarce mechanical ventilators should be allocated during an influenza pandemic, with the ultimate goal of informing a statewide scare resource allocation framework...
August 9, 2017: Chest
https://www.readbyqxmd.com/read/28801777/an-internally-validated-new-clinical-and-inflammation-based-prognostic-score-for-patients-with-advanced-hepatocellular-carcinoma-treated-with-sorafenib
#18
R Diaz-Beveridge, G Bruixola, D Lorente, J Caballero, E Rodrigo, Á Segura, D Akhoundova, A Giménez, J Aparicio
BACKGROUND: Sorafenib is a standard treatment for patients (pts) with advanced hepatocellular carcinoma (aHCC), although the clinical benefit is heterogeneous between different pts groups. Among novel prognostic factors, a low baseline neutrophil-to-lymphocyte ratio (bNLR) and early-onset diarrhoea have been linked with a better prognosis. PURPOSE: To identify prognostic factors in pts with aHCC treated with 1st-line sorafenib and to develop a new prognostic score to guide management...
August 11, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28800781/knowledge-guided-gene-prioritization-reveals-new-insights-into-the-mechanisms-of-chemoresistance
#19
Amin Emad, Junmei Cairns, Krishna R Kalari, Liewei Wang, Saurabh Sinha
BACKGROUND: Identification of genes whose basal mRNA expression predicts the sensitivity of tumor cells to cytotoxic treatments can play an important role in individualized cancer medicine. It enables detailed characterization of the mechanism of action of drugs. Furthermore, screening the expression of these genes in the tumor tissue may suggest the best course of chemotherapy or a combination of drugs to overcome drug resistance. RESULTS: We developed a computational method called ProGENI to identify genes most associated with the variation of drug response across different individuals, based on gene expression data...
August 11, 2017: Genome Biology
https://www.readbyqxmd.com/read/28800587/highly-efficient-gene-inactivation-by-adenoviral-crispr-cas9-in-human-primary-cells
#20
Olaf Voets, Frans Tielen, Edo Elstak, Julian Benschop, Max Grimbergen, Jan Stallen, Richard Janssen, Andre van Marle, Christian Essrich
Phenotypic assays using human primary cells are highly valuable tools for target discovery and validation in drug discovery. Expression knockdown (KD) of such targets in these assays allows the investigation of their role in models of disease processes. Therefore, efficient and fast modes of protein KD in phenotypic assays are required. The CRISPR/Cas9 system has been shown to be a versatile and efficient means of gene inactivation in immortalized cell lines. Here we describe the use of adenoviral (AdV) CRISPR/Cas9 vectors for efficient gene inactivation in two human primary cell types, normal human lung fibroblasts and human bronchial epithelial cells...
2017: PloS One
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