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https://www.readbyqxmd.com/read/29778085/braf-and-mek-inhibitor-therapy-eliminates-nestin-expressing-melanoma-cells-in-human-tumors
#1
Deon B Doxie, Allison R Greenplate, Jocelyn S Gandelman, Kirsten E Diggins, Caroline E Roe, Kimberly B Dahlman, Jeffrey A Sosman, Mark C Kelley, Jonathan M Irish
Little is known about the in vivo impacts of targeted therapy on melanoma cell abundance and protein expression. Here, 21 antibodies were added to an established melanoma mass cytometry panel to measure 32 cellular features, distinguish malignant cells, and characterize dabrafenib and trametinib responses in BRAFV 600mut melanoma. Tumor cells were biopsied before neoadjuvant therapy and compared to cells surgically resected from the same site after 4 weeks of therapy. Approximately 50,000 cells per tumor were characterized by mass cytometry and computational tools t-SNE/viSNE, FlowSOM, and MEM...
May 19, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29778008/plasma-metabolic-changes-in-chinese-hiv-infected-patients-receiving-lopinavir-ritonavir-based-treatment-implications-for-hiv-precision-therapy
#2
Xiaolin Li, Tong Wu, Yongjun Jiang, Zining Zhang, Xiaoxu Han, Wenqing Geng, Haibo Ding, Jing Kang, Qi Wang, Hong Shang
OBJECTIVES: The goal of this study is to profile the metabolic changes in the plasma of HIV patients receiving lopinavir/ritonavir (LPV/r)-based highly active antiretroviral therapy (HAART) relative to their treatment-naïve phase, aimed to identify precision therapy for HIV for improving prognosis and predicting dyslipidemia caused by LPV/r. METHODS: 38 longitudinal plasma samples were collected from 19 HIV-infected patients both before and after antiretroviral therapy, and 18 samples from healthy individuals were used as controls...
May 16, 2018: Cytokine
https://www.readbyqxmd.com/read/29778006/environmentally-relevant-concentrations-of-tramadol-and-citalopram-alter-behaviour-of-an-aquatic-invertebrate
#3
M Buřič, K Grabicová, J Kubec, A Kouba, I Kuklina, P Kozák, R Grabic, T Randák
Environmental pollution by pharmaceutically active compounds, used in quantities similar to those of pesticides and other organic micropollutants, is increasingly recognized as a major threat to the aquatic environment. These compounds are only partly removed from wastewaters and, despite their low concentrations, directly and indirectly affect behaviour of freshwater organisms in natural habitats. The aim of this study was to behaviourally assess the effects of an opioid painkiller (tramadol) and antidepressant drug (citalopram) on behaviour patterns of a clonal model species, marbled crayfish...
May 14, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29777975/geriatric-analysis-from-prodige-20-randomized-phase-ii-trial-evaluating-bevacizumab-chemotherapy-versus-chemotherapy-alone-in-older-patients-with-untreated-metastatic-colorectal-cancer
#4
T Aparicio, O Bouché, E Francois, F Retornaz, E Barbier, J Taieb, S Kirscher, P-L Etienne, R Faroux, F Khemissa Akouz, F El Hajbi, C Locher, Y Rinaldi, T Lecomte, S Lavau-Denes, M Baconnier, A Oden-Gangloff, D Genet, L Bedenne, E Paillaud
BACKGROUND: Older patients have frailty characteristics that impair the transposition of treatment results found in younger patients. Predictive factors are needed to help with treatment choices for older patients. The PRODIGE 20 study is a randomized phase II study that evaluated chemotherapy associated with bevacizumab (BEV) or not (CT) in patients aged 75 years or older. PATIENTS AND METHODS: Patients underwent a geriatric assessment at randomization and at each evaluation...
May 16, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29777823/updated-efficacy-analysis-including-secondary-population-results-for-oak-a-randomized-phase-iii-study-of-atezolizumab-vs-docetaxel-in-patients-with-previously-treated-advanced-non-small-cell-lung-cancer
#5
L Fehrenbacher, J von Pawel, K Park, A Rittmeyer, D R Gandara, S Ponce Aix, J-Y Han, S M Gadgeel, T Hida, D L Cortinovis, M Cobo, D M Kowalski, F De Marinis, M Gandhi, B Danner, C Matheny, M Kowanetz, P He, F Felizzi, H Patel, A Sandler, M Ballinger, F Barlesi
INTRODUCTION: The efficacy and safety of atezolizumab vs docetaxel as second- or third-line treatment in patients with advanced non-small cell lung cancer in the primary (n=850; ITT850) and secondary (n=1225; ITT1225) efficacy populations of the randomized phase III OAK study at an updated data cutoff were assessed. METHODS: Patients received atezolizumab 1200mg or docetaxel 75mg/m2 intravenously every 3 weeks until loss of clinical benefit or disease progression, respectively...
May 16, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29777742/a-functional-glycoproteomics-approach-identifies-cd13-as-a-novel-e-selectin-ligand-in-breast-cancer
#6
M A Carrascal, M Silva, J A Ferreira, R Azevedo, D Ferreira, A M N Silva, D Ligeiro, L L Santos, R Sackstein, P A Videira
BACKGROUND: The glycan moieties sialyl-Lewis-X and/or -A (sLeX/A ) are the primary ligands for E-selectin, regulating subsequent tumor cell extravasation into distant organs. However, the nature of the glycoprotein scaffolds displaying these glycans in breast cancer remains unclear and constitutes the focus of the present investigation. METHODS: We isolated glycoproteins that bind E-selectin from the CF1_T breast cancer cell line, derived from a patient with ductal carcinoma...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777713/development-and-psychometric-validation-of-capacity-assessment-of-prosthetic-performance-for-the-upper-limb-cappful
#7
Nathan T Kearns, Jennifer K Peterson, Lisa Smurr Walters, Warren T Jackson, John M Miguelez, Tiffany Ryan
OBJECTIVES: (1) Develop a performance-based measure for adult upper limb (UL) prosthetic functioning through broad (i.e. overall performance) and functional domain-specific (e.g., control skills) assessment of commonplace activities; (2) conduct initial psychometric evaluation of the Capacity Assessment of Prosthetic Performance for the Upper Limb (CAPPFUL). DESIGN: Internal consistency of CAPPFUL and interrater reliability for task, functional domain, and full scale (sub)scores among three independent raters were estimated...
May 16, 2018: Archives of Physical Medicine and Rehabilitation
https://www.readbyqxmd.com/read/29777671/surgical-management-and-outcomes-of-ebstein-anomaly-in-neonates-and-infants-a-society-of-thoracic-surgeons-congenital-heart-surgery-database-analysis
#8
Kimberly A Holst, Joseph A Dearani, Sameh M Said, Ryan R Davies, Christian Pizarro, Christopher Knott-Craig, T K Susheel Kumar, Vaughn Starnes, S Ram Kumar, Sara K Pasquali, Dylan P Thibault, James M Meza, Kevin D Hill, Karen Chiswell, Jeffrey P Jacobs, Marshall L Jacobs
BACKGROUND: Ebstein anomaly (EA) encompasses a broad spectrum of morphology and clinical presentation. Those who are symptomatic early in infancy are generally at highest risk, but there are limited data regarding multi-centric practice patterns and outcomes. We analyzed multi-institutional data concerning operations and outcomes in neonates and infants with EA. METHODS: Index operations reported in the STS Congenital Heart Surgery Database (2010-2016) were potentially eligible for inclusion...
May 16, 2018: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/29777657/mcv-mir-m1-targets-the-host-cell-immune-response-resulting-in-the-attenuation-of-neutrophil-chemotaxis
#9
P Akhbari, D Tobin, K Poterlowicz, W Roberts, J R Boyne
Virus-encoded miRNAs are emerging as key regulators of persistent infection and host-cell immune evasion. Merkel cell polyomavirus (MCPyV), the predominant aetiological agent of Merkel cell carcinoma (MCC), encodes a single miRNA, MCV-miR-M1, which targets the oncogenic MCPyV large T antigen (LT). MCV-miR-M1 has previously been shown to play an important role in establishment of long-term infection, however, the underlying mechanism is not fully understood. A key unanswered question is whether, in addition to auto-regulating LT, MCV-miR-M1 also targets cellular transcripts to orchestrate an environment conducive for persistent infection...
May 16, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29777563/cognitive-and-functional-deficits-in-bipolar-disorder-and-schizophrenia-as-a-function-of-the-presence-and-history-of-psychosis
#10
Christopher R Bowie, Michael W Best, Colin Depp, Brent T Mausbach, Thomas L Patterson, Ann E Pulver, Philip D Harvey
OBJECTIVES: Schizophrenia and bipolar disorder overlap considerably. Schizophrenia is a primary psychotic disorder, whereas approximately half of people with bipolar disorder will experience psychosis. In this study, we examined the extent to which cognitive and functional impairments are related to the presence and history of psychosis across the two disorders. METHOD: A total of 633 participants with bipolar disorder I, schizophrenia, and schizoaffective disorder were recruited for a study on the genetics of cognition and functioning in bipolar disorder and schizophrenia...
May 18, 2018: Bipolar Disorders
https://www.readbyqxmd.com/read/29777484/identification-of-differentially-expressed-micrornas-in-sahiwal-bos-indicus-breed-of-cattle-during-thermal-stress
#11
Gyanendra Singh Sengar, Rajib Deb, Umesh Singh, Vivek Junghare, Saugata Hazra, T V Raja, Rani Alex, Ashish Kumar, R R Alyethodi, Rajiv Kant, Subhash Jakshara, C G Joshi
microRNAs (miRNAs) are a class of small non-coding RNAs that play key roles in post transcriptional gene regulation that influence various fundamental cellular processes, including the cellular responses during environmental stresses. However, perusal of literatures revealed few reports on the differential expression of miRNA during thermal stress in Indian native (Bos indicus) cattle breeds. The present investigation aimed to identify differentially expressed miRNAs during thermal stress in Sahiwal (Bos indicus) dairy cattle breed of India, adapted with tropical climate over a long period of time...
May 18, 2018: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/29777411/spatial-environmental-risk-evaluation-of-potential-toxic-elements-in-stream-sediments
#12
I M H R Antunes, M T D Albuquerque, N Roque
Potential toxic elements (PTE), in stream sediments, were used as contamination indicators for the definition of high-/low-grade spatial clusters in the Monfortinho area (Central Portugal). A set of 271 stream sediment samples was used for spatial modelling and further definition of rings of enrichment-high and low rings. A three-step multivariate statistical and geostatistical approach was used: (1) principal components analysis for PTE's association evaluation and dimensionality reduction; (2) ordinary kriging as an unbiased interpolator for content inference and construction of a continuous representation of the considered attributes, at any arbitrary spatial location; (3) G clustering algorithm for the definition of high and low significance clusters...
May 18, 2018: Environmental Geochemistry and Health
https://www.readbyqxmd.com/read/29777368/organizational-context-and-individual-adaptability-in-promoting-perceived-importance-and-use-of-best-practices-for-substance-use
#13
Danica K Knight, George W Joe, David T Morse, Corey Smith, Hannah Knudsen, Ingrid Johnson, Gail A Wasserman, Nancy Arrigona, Larkin S McReynolds, Jennifer E Becan, Carl Leukefeld, Tisha R A Wiley
This study examines associations among organizational context, staff attributes, perceived importance, and use of best practices among staff in community-based, juvenile justice (JJ) agencies. As part of the National Institute on Drug Abuse's Juvenile Justice-Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS) study, 492 staff from 36 JJ agencies were surveyed about the perceived importance and use of best practices within their organization in five substance use practice domains: screening, assessment, standard referral, active referral, and treatment support...
May 18, 2018: Journal of Behavioral Health Services & Research
https://www.readbyqxmd.com/read/29777279/-flap-coverage-using-the-posterior-gluteal-thigh-flap
#14
REVIEW
M K Boyce, T R Mett, R Ipaktchi, P M Vogt
OBJECTIVE: Defect coverage of the sacral, trochanteric or ischial region with durable tissue (gluteal thigh flap). INDICATIONS: Decubital ulcers of the sacral, trochanteric or ischial region after exhaustion of conservative measures. CONTRAINDICATIONS: Moribund or palliative patients who do not benefit from defect coverage and are likely to suffer a life-threatening complication. Noncompliant patients, who cannot follow the postoperative recommendations or protocols in regard to positioning or recurrence prevention...
May 17, 2018: Operative Orthopädie und Traumatologie
https://www.readbyqxmd.com/read/29777137/enhanced-efficacy-of-combined-temozolomide-and-bromodomain-inhibitor-therapy-for-gliomas-using-targeted-nanoparticles
#15
Fred C Lam, Stephen W Morton, Jeffrey Wyckoff, Tu-Lan Vu Han, Mun Kyung Hwang, Amanda Maffa, Elena Balkanska-Sinclair, Michael B Yaffe, Scott R Floyd, Paula T Hammond
Effective treatment for glioblastoma (GBM) is limited by the presence of the blood-brain barrier (BBB) and rapid resistance to single agent therapies. To address these issues, we developed a transferrin-functionalized nanoparticle (Tf-NP) that can deliver dual combination therapies. Using intravital imaging, we show the ability of Tf-NPs to traverse intact BBB in mice as well as achieve direct tumor binding in two intracranial orthotopic models of GBM. Treatment of tumor-bearing mice with Tf-NPs loaded with temozolomide and the bromodomain inhibitor JQ1 leads to increased DNA damage and apoptosis that correlates with a 1...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29776834/bet-bromodomain-ligands-probing-the-wpf-shelf-to-improve-brd4-bromodomain-affinity-and-metabolic-stability
#16
Laura E Jennings, Matthias Schiedel, David S Hewings, Sarah Picaud, Corentine M C Laurin, Paul A Bruno, Joseph P Bluck, Amy R Scorah, Larissa See, Jessica K Reynolds, Mustafa Moroglu, Ishna N Mistry, Amy Hicks, Pavel Guzanov, James Clayton, Charles N G Evans, Giulia Stazi, Philip C Biggin, Anna K Mapp, Ester M Hammond, Philip G Humphreys, Panagis Filippakopoulos, Stuart J Conway
Ligands for the bromodomain and extra-terminal domain (BET) family of bromodomains have shown promise as useful therapeutic agents for treating a range of cancers and inflammation. Here we report that our previously developed 3,5-dimethylisoxazole-based BET bromodomain ligand (OXFBD02) inhibits interactions of BRD4(1) with the RelA subunit of NF-κB, in addition to histone H4. This ligand shows a promising profile in a screen of the NCI-60 panel but was rapidly metabolised (t½  = 39.8 min). Structure-guided optimisation of compound properties led to the development of the 3-pyridyl-derived OXFBD04...
May 15, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29776780/racial-disparities-in-cardiovascular-health-behaviors-the-coronary-artery-risk-development-in-young-adults-study
#17
Kara M Whitaker, David R Jacobs, Kiarri N Kershaw, Ryan T Demmer, John N Booth, April P Carson, Cora E Lewis, David C Goff, Donald M Lloyd-Jones, Penny Gordon-Larsen, Catarina I Kiefe
INTRODUCTION: There are known racial differences in cardiovascular health behaviors, including smoking, physical activity, and diet quality. A better understanding of these differences may help identify intervention targets for reducing cardiovascular disease disparities. This study examined whether socioeconomic, psychosocial, and neighborhood environmental factors, in isolation or together, mediate racial differences in health behaviors. METHODS: Participants were 3,081 men and women from the Coronary Artery Risk Development in Young Adults study who were enrolled in 1985-1986 (Year 0) and completed a follow-up examination in 2015-2016 (Year 30)...
May 15, 2018: American Journal of Preventive Medicine
https://www.readbyqxmd.com/read/29776626/insomnia-symptoms-and-their-association-with-workplace-productivity-cross-sectional-and-pre-post-intervention-analyses-from-a-large-multinational-manufacturing-company
#18
Colin A Espie, Brent Pawlecki, Dickon Waterfield, Kit Fitton, Michael Radocchia, Annemarie I Luik
BACKGROUND: Symptoms of insomnia are common and might impact work productivity. We investigated the relationship between insomnia symptoms and workplace productivity in a global manufacturing company. METHODS: Within an uncontrolled, cross-sectional study, employees from a US-based company were invited to participate in an online evaluation comprising the Sleep Condition Indicator (SCI) measuring symptoms of insomnia (high score indicating better sleep), 2 items of the Work Productivity and Impairment Index (WPAI) measuring 'presenteeism' and 'absenteeism' (high score indicating loss of work productivity) and 1 item of the Perceived Stress Scale (PSS) from January 2015 onwards...
June 2018: Sleep Health
https://www.readbyqxmd.com/read/29776473/surgeons-experience-and-perceived-barriers-with-outpatient-shoulder-arthroplasty
#19
Tyler J Brolin, Ryan M Cox, Benjamin M Zmistowski, Surena Namdari, Gerald R Williams, Joseph A Abboud
BACKGROUND: Recently, outpatient total shoulder arthroplasty (TSA) has been proposed as a safe and cost-effective alternative to the inpatient setting. This study evaluated the expert shoulder surgeon's experience with and perceived barriers to outpatient TSA. METHODS: A secure web application was used to perform an online survey of 484 active American Shoulder and Elbow Surgeons members. The survey assessed surgeon practice demographics, experience with TSA/outpatient TSA, and perceived barriers to successful outpatient TSA...
June 2018: Journal of Shoulder and Elbow Surgery
https://www.readbyqxmd.com/read/29776444/mediastinal-staging-of-non-small-cell-lung-cancer-by-endobronchial-and-endoscopic-ultrasonography-with-or-without-additional-surgical-mediastinoscopy-mediastrial-study-protocol-of-a-multicenter-randomised-controlled-trial
#20
Jelle E Bousema, Marcel G W Dijkgraaf, Nicole E Papen-Botterhuis, Hermien W Schreurs, Jos G Maessen, Erik H van der Heijden, Willem H Steup, Jerry Braun, Valentin J J M Noyez, Fieke Hoeijmakers, Naomi Beck, Martijn van Dorp, Niels J M Claessens, Birgitta I Hiddinga, Johannes M A Daniels, David J Heineman, Harmen R Zandbergen, Ad F T M Verhagen, Paul E van Schil, Jouke T Annema, Frank J C van den Broek
BACKGROUND: In case of suspicious lymph nodes on computed tomography (CT) or fluorodeoxyglucose positron emission tomography (FDG-PET), advanced tumour size or central tumour location in patients with suspected non-small cell lung cancer (NSCLC), Dutch and European guidelines recommend mediastinal staging by endosonography (endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS)) with sampling of mediastinal lymph nodes. If biopsy results from endosonography turn out negative, additional surgical staging of the mediastinum by mediastinoscopy is advised to prevent unnecessary lung resection due to false negative endosonography findings...
May 18, 2018: BMC Surgery
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