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https://www.readbyqxmd.com/read/29989854/ado-trastuzumab-emtansine-for-patients-with-her2-mutant-lung-cancers-results-from-a-phase-ii-basket-trial
#1
Bob T Li, Ronglai Shen, Darren Buonocore, Zachary T Olah, Ai Ni, Michelle S Ginsberg, Gary A Ulaner, Michael Offin, Daniel Feldman, Todd Hembrough, Fabiola Cecchi, Sarit Schwartz, Nick Pavlakis, Stephen Clarke, Helen H Won, Edyta B Brzostowski, Gregory J Riely, David B Solit, David M Hyman, Alexander Drilon, Charles M Rudin, Michael F Berger, Jose Baselga, Maurizio Scaltriti, Maria E Arcila, Mark G Kris
Purpose Human epidermal growth factor receptor 2 ( HER2, ERBB2)-activating mutations occur in 2% of lung cancers. We assessed the activity of ado-trastuzumab emtansine, a HER2-targeted antibody-drug conjugate, in a cohort of patients with HER2-mutant lung cancers as part of a phase II basket trial. Patients and Methods Patients received ado-trastuzumab emtansine at 3.6 mg/kg intravenously every 3 weeks until progression. The primary end point was overall response rate using Response Evaluation Criteria in Solid Tumors (RECIST) version 1...
July 10, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29906251/randomized-double-blind-phase-ii-study-of-temozolomide-in-combination-with-either-veliparib-or-placebo-in-patients-with-relapsed-sensitive-or-refractory-small-cell-lung-cancer
#2
M Catherine Pietanza, Saiama N Waqar, Lee M Krug, Afshin Dowlati, Christine L Hann, Alberto Chiappori, Taofeek K Owonikoko, Kaitlin M Woo, Robert J Cardnell, Junya Fujimoto, Lihong Long, Lixia Diao, Jing Wang, Yevgeniva Bensman, Brenda Hurtado, Patricia de Groot, Erik P Sulman, Ignacio I Wistuba, Alice Chen, Martin Fleisher, John V Heymach, Mark G Kris, Charles M Rudin, Lauren Averett Byers
Purpose Both temozolomide (TMZ) and poly (ADP-ribose) polymerase (PARP) inhibitors are active in small-cell lung cancer (SCLC). This phase II, randomized, double-blind study evaluated whether addition of the PARP inhibitor veliparib to TMZ improves 4-month progression-free survival (PFS). Patients and Methods A total of 104 patients with recurrent SCLC were randomly assigned 1:1 to oral veliparib or placebo 40 mg twice daily, days 1 to 7, and oral TMZ 150 to 200 mg/m2 /day, days 1 to 5, of a 28-day cycle until disease progression, unacceptable toxicity, or withdrawal of consent...
June 15, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29873538/phosphorus-mining-efficiency-declines-with-decreasing-soil-p-concentration-and-varies-across-crop-species
#3
Stephanie Schelfhout, An De Schrijver, Kris Verheyen, Robbe De Beelde, Geert Haesaert, Jan Mertens
High soil P concentrations hinder ecological restoration of biological communities typical for nutrient-poor soils. Phosphorus mining, i.e., growing crops with fertilization other than P, might reduce soil P concentrations. However, crop species have different P-uptake rates and can affect subsequent P removal in crop rotation, both of which may also vary with soil P concentration. In a pot experiment with three soil-P-levels (High-P: 125-155 mg POlsen /kg; Mid-P: 51-70 mg POlsen /kg; Low-P: 6-21 mg POlsen /kg), we measured how much P was removed by five crop species (buckwheat, maize, sunflower, flax, and triticale)...
July 29, 2018: International Journal of Phytoremediation
https://www.readbyqxmd.com/read/29844198/can-physiological-engineering-programming-increase-multi-generational-thermal-tolerance-to-extreme-temperature-events
#4
Kris L Sorby, Mark P Green, Tim D Dempster, Tim S Jessop
Organisms increasingly encounter higher frequencies of extreme weather events as a consequence of global climate change. Currently, few strategies are available to mitigate climate change effects on animals arising from acute extreme high temperature events. We tested the capacity of physiological engineering to influence the intra- and multi-generational upper thermal tolerance capacity of a model organism Artemia , subjected to extreme high temperatures. Enhancement of specific physiological regulators during development could affect thermal tolerances or life-history attributes affecting subsequent fitness...
May 29, 2018: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29769268/pbdes-altered-gut-microbiome-and-bile-acid-homeostasis-in-male-c57bl-6-mice
#5
Cindy Yanfei Li, Joseph L Dempsey, Dongfang Wang, SooWan Lee, Kris M Weigel, Qiang Fei, Deepak Kumar Bhatt, Bhagwat Prasad, Daniel Raftery, Haiwei Gu, Julia Yue Cui
Polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants with well-characterized toxicities in host organs. Gut microbiome is increasingly recognized as an important regulator of xenobiotic biotransformation; however, little is known about its interactions with PBDEs. Primary bile acids (BAs) are metabolized by the gut microbiome into more lipophilic secondary BAs that may be absorbed and interact with certain host receptors. The goal of this study was to test our hypothesis that PBDEs cause dysbiosis and aberrant regulation of BA homeostasis...
May 16, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29688083/localized-delivery-of-therapeutic-doxorubicin-dose-across-the-canine-blood-brain-barrier-with-hyperthermia-and-temperature-sensitive-liposomes
#6
Amy Lee Bredlau, Anjan Motamarry, Chao Chen, M A McCrackin, Kris Helke, Kent E Armeson, Katrina Bynum, Ann-Marie Broome, Dieter Haemmerich
Most drugs cannot penetrate the blood-brain barrier (BBB), greatly limiting the use of anti-cancer agents for brain cancer therapy. Temperature sensitive liposomes (TSL) are nanoparticles that rapidly release the contained drug in response to hyperthermia (>40 °C). Since hyperthermia also transiently opens the BBB, we hypothesized that localized hyperthermia can achieve drug delivery across the BBB when combined with TSL. TSL-encapsulated doxorubicin (TSL-Dox) was infused intravenously over 30 min at a dose of 0...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29684148/antiviral-activity-of-oral-jnj-53718678-in-healthy-adult-volunteers-challenged-with-respiratory-syncytial-virus-a-placebo-controlled-study
#7
Marita Stevens, Sarah Rusch, John DeVincenzo, Young-In Kim, Lisa Harrison, Elizabeth A Meals, Alison Boyers, Juin Fok-Seang, Dymphy Huntjens, Nacer Lounis, Kris Mari N, Bart Remmerie, Dirk Roymans, Anil Koul, René Verloes
Background: Respiratory syncytial virus (RSV) disease has no effective treatment. JNJ-53718678 is a fusion inhibitor with selective activity against RSV. Methods: After confirmation of RSV infection or 5 days post inoculation with RSV, participants (n=69) were randomized to JNJ-53718678 75 mg (n=15), 200 mg (n=17), 500 mg (n=18), or placebo (n=17), orally once-daily for 7 days. Antiviral effects were evaluated by assessing RSV RNA viral load (VL) area-under-the-curve (AUC) from baseline (prior to the first dose) until discharge, time-to-peak VL, duration of viral shedding, clinical symptoms, and quantity of nasal secretions...
April 19, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29597261/dietary-intakes-of-epa-and-dha-omega-3-fatty-acids-among-us-childbearing-age-and-pregnant-women-an-analysis-of-nhanes-2001-2014
#8
Zhiying Zhang, Victor L Fulgoni, Penny M Kris-Etherton, Susan Hazels Mitmesser
BACKGROUND: The 2015–2020 Dietary Guidelines for Americans (DGA) recommend that the general population should consume about 8 ounces (oz.) per week of a variety of seafood, providing approximately 250 mg per day of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and that pregnant and lactating women should consume 8–12 oz. per week of seafood. METHODS: We determined the usual intakes, percentage not meeting recommendations, and trends in EPA and DHA intakes among childbearing-age and pregnant women (15–44 years of age) using the NHANES cycles 2001–2002 through 2013–2014...
March 28, 2018: Nutrients
https://www.readbyqxmd.com/read/29525501/the-isotopic-exchangeability-of-phosphate-in-mg-al-layered-double-hydroxides
#9
Maarten Everaert, Kris Slenders, Kris Dox, Simon Smolders, Dirk De Vos, Erik Smolders
Layered double hydroxides (LDH) of Mg/Al are anion exchangers that are candidate materials for phosphate (PO4 ) recovery and recycling from waste streams. However, PO4 recycling in agriculture might be limited by incomplete desorption of PO4 from the minerals. This study was set up to identify the factors explaining irreversible PO4 sorption ("fixation") on LDHs by comparing the isotopic exchangeability (33 PO4 ) with the PO4 desorption from LDH materials and from boehmite as a P fixing reference mineral...
June 15, 2018: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/29313216/chemical-speciation-and-fate-of-tripolyphosphate-after-application-to-a-calcareous-soil
#10
Jordan G Hamilton, Jay Grosskleg, David Hilger, Kris Bradshaw, Trevor Carlson, Steven D Siciliano, Derek Peak
Adsorption and precipitation reactions often dictate the availability of phosphorus in soil environments. Tripolyphosphate (TPP) is considered a form of slow release P fertilizer in P limited soils, however, investigations of the chemical fate of TPP in soils are limited. It has been proposed that TPP rapidly hydrolyzes in the soil solution before adsorbing or precipitating with soil surfaces, but in model systems, TPP also adsorbs rapidly onto mineral surfaces. To study the adsorption behavior of TPP in calcareous soils, a short-term (48 h) TPP spike was performed under laboratory conditions...
January 8, 2018: Geochemical Transactions
https://www.readbyqxmd.com/read/29274396/transplant-conditioning-with-treosulfan-fludarabine-with-or-without-total-body-irradiation-a-randomized-phase-ii-trial-in-patients-with-myelodysplastic-syndrome-and-acute-myeloid-leukemia
#11
H Joachim Deeg, Emily A Stevens, Rachel B Salit, Ralph P Ermoian, Min Fang, Boglarka Gyurkocza, Mohamed L Sorror, Giancarlo Fatobene, Joachim Baumgart, Lauri M Burroughs, Colleen Delaney, Kris Doney, Daniel N Egan, Mary E D Flowers, Filippo Milano, Jerry P Radich, Bart L Scott, Eileen J Sickle, Brent L Wood, Cecilia Yeung, Barry E Storer
In this prospective, randomized, phase II "pick the winner" trial we assessed the efficacy of transplant conditioning with treosulfan/fludarabine ± 2 Gy total body irradiation (TBI) in reducing post-transplant relapse in 100 patients, aged 2 to 70 years (median, 57), with myelodysplastic syndrome (MDS)/chronic myelomonocytic leukemia (n = 51) or acute myeloid leukemia (AML; n = 49). Patients received i.v. treosulfan, 14 g/m2 /day on days -6 to -4 and i.v. fludarabine, 30 mg/m2 /day on days -6 to -2, alone or combined with 2 Gy TBI (day 0)...
May 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29210808/prophylactic-use-of-haloperidol-and-changes-in-glucose-levels-in-hospitalized-older-patients
#12
RANDOMIZED CONTROLLED TRIAL
Kris van Keulen, Wilma Knol, Edmée J M Schrijver, Rob J van Marum, Astrid M van Strien, Prabath W B Nanayakkara
BACKGROUND: Treatment with antipsychotic drugs has been associated with glucose dysregulation in older outpatients, especially in the early stage of therapy. The underlying mechanism is, however, unclear. The aim of this study was to investigate changes in glucose levels during haloperidol use compared with the use of placebo among older hospitalized patients. METHODS: This substudy was part of a larger multicenter, randomized, double blind, placebo-controlled clinical trial among hospitalized patients aged 70 years and older who had an increased risk of in-hospital delirium...
February 2018: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/29187388/effects-of-dark-chocolate-and-almonds-on-cardiovascular-risk-factors-in-overweight-and-obese-individuals-a-randomized-controlled-feeding-trial
#13
Yujin Lee, Claire E Berryman, Sheila G West, C-Y Oliver Chen, Jeffrey B Blumberg, Karen G Lapsley, Amy G Preston, Jennifer A Fleming, Penny M Kris-Etherton
BACKGROUND: Consumption of almonds or dark chocolate and cocoa has favorable effects on markers of coronary heart disease; however, the combined effects have not been evaluated in a well-controlled feeding study. The aim of this study was to examine the individual and combined effects of consumption of dark chocolate and cocoa and almonds on markers of coronary heart disease risk. METHODS AND RESULTS: A randomized controlled, 4-period, crossover, feeding trial was conducted in overweight and obese individuals aged 30 to 70 years...
November 29, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29042835/double-blind-randomized-placebo-controlled-trial-of-single-dose-intravenous-acetaminophen-for-pain-associated-with-adenotonsillectomy-in-pediatric-patients-with-sleep-disordered-breathing
#14
Arlyne K Thung, Charles A Elmaraghy, N'Diris Barry, Dmitry Tumin, Kris R Jatana, Julie Rice, Vidya Raman, Tarun Bhalla, David P Martin, Marco Corridore, Joseph D Tobias
OBJECTIVES: Adequate pain control is an important component in the postoperative outcome for pediatric adenotonsillectomy patients with sleep-disordered breathing (SDB). Intravenous acetaminophen appears to be a favorable analgesic adjunct owing to its predictable pharmacokinetics and opioid-sparing effects; however, its role in pediatric adenotonsillectomy pain management remains unclear. METHODS: In this prospective, randomized, double-blinded, controlled study, subjects with the diagnosis of SDB, aged 2 to 8 years, who required extended postoperative admission, received intravenous acetaminophen (15 mg/kg) or saline placebo intraoperatively in addition to morphine (0...
September 2017: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/29023915/a-randomized-trial-of-obeticholic-acid-monotherapy-in-patients-with-primary-biliary-cholangitis
#15
Kris V Kowdley, Velimir Luketic, Roger Chapman, Gideon M Hirschfield, Raoul Poupon, Christoph Schramm, Catherine Vincent, Christian Rust, Albert Parés, Andrew Mason, Hanns-Ulrich Marschall, David Shapiro, Luciano Adorini, Cathi Sciacca, Tessa Beecher-Jones, Olaf Böhm, Richard Pencek, David Jones
Obeticholic acid (OCA), a potent farnesoid X receptor agonist, was studied as monotherapy in an international, randomized, double-blind, placebo-controlled phase 2 study in patients with primary biliary cholangitis who were then followed for up to 6 years. The goals of the study were to assess the benefit of OCA in the absence of ursodeoxycholic acid, which is relevant for patients who are intolerant of ursodeoxycholic acid and at higher risk of disease progression. Patients were randomized and dosed with placebo (n = 23), OCA 10 mg (n = 20), or OCA 50 mg (n = 16) given as monotherapy once daily for 3 months (1 randomized patient withdrew prior to dosing)...
May 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28951228/efficacy-of-glecaprevir-pibrentasvir-for-8-or-12-weeks-in-patients-with-hepatitis-c-virus-genotype-2-4-5-or-6-infection-without-cirrhosis
#16
Tarik Asselah, Kris V Kowdley, Neddie Zadeikis, Stanley Wang, Tarek Hassanein, Yves Horsmans, Massimo Colombo, Filipe Calinas, Humberto Aguilar, Victor de Ledinghen, Parvez S Mantry, Christophe Hezode, Rui Tato Marinho, Kosh Agarwal, Frederik Nevens, Magdy Elkhashab, Jens Kort, Ran Liu, Teresa I Ng, Preethi Krishnan, Chih-Wei Lin, Federico J Mensa
BACKGROUND & AIMS: Hepatitis C virus (HCV) has high genotypic diversity and global distribution. Agents that are effective against all major HCV genotypes, with shorter treatment duration, are needed to reduce disease burden. Glecaprevir (an NS3/4A protease inhibitor) and pibrentasvir (an NS5A inhibitor) have a high barrier to resistance and synergistic antiviral activity. We evaluated the safety and efficacy of 8 and 12 weeks' treatment with glecaprevir/pibrentasvir in patients with HCV genotype 2, 4, 5, or 6 infection without cirrhosis in 3 separate phase 3 trials...
March 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28940498/twice-weekly-pulse-and-daily-continuous-dose-erlotinib-as-initial-treatment-for-patients-with-epidermal-growth-factor-receptor-mutant-lung-cancers-and-brain-metastases
#17
Kathryn C Arbour, Mark G Kris, Gregory J Riely, Ai Ni, Kathryn Beal, Mariza Daras, Sara A Hayes, Robert J Young, Christopher R Rodriguez, Linda Ahn, William Pao, Helena A Yu
BACKGROUND: In a phase 1 study of pulse/continuous-dose erlotinib, no patient had disease progression in the central nervous system (CNS). This expansion cohort of the phase 1 study tested the same regimen in a cohort of individuals with epidermal growth factor receptor (EGFR)-mutant lung cancers with untreated brain metastases. METHODS: Patients had not received EGFR tyrosine kinase inhibitors or radiation for brain metastases. All received 1200 mg of erlotinib on days 1 and 2 and 50 mg on days 3 to 7 weekly...
January 1, 2018: Cancer
https://www.readbyqxmd.com/read/28833331/a-randomized-placebo-controlled-trial-of-cenicriviroc-for-treatment-of-nonalcoholic-steatohepatitis-with-fibrosis
#18
Scott L Friedman, Vlad Ratziu, Stephen A Harrison, Manal F Abdelmalek, Guruprasad P Aithal, Juan Caballeria, Sven Francque, Geoffrey Farrell, Kris V Kowdley, Antonio Craxi, Krzysztof Simon, Laurent Fischer, Liza Melchor-Khan, Jeffrey Vest, Brian L Wiens, Pamela Vig, Star Seyedkazemi, Zachary Goodman, Vincent Wai-Sun Wong, Rohit Loomba, Frank Tacke, Arun Sanyal, Eric Lefebvre
The aim of this study was to evaluate cenicriviroc (CVC), a dual antagonist of CC chemokine receptor types 2 and 5, for treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis (LF). A randomized, double-blind, multinational phase 2b study enrolled subjects with NASH, a nonalcoholic fatty liver disease activity score (NAS) ≥4, and LF (stages 1-3, NASH Clinical Research Network) at 81 clinical sites. Subjects (N = 289) were randomly assigned CVC 150 mg or placebo. Primary outcome was ≥2-point improvement in NAS and no worsening of fibrosis at year 1...
May 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28803054/decolorization-of-reactive-azo-dyes-using-a-sequential-chemical-and-activated-sludge-treatment
#19
Ken Meerbergen, Sam Crauwels, Kris A Willems, Raf Dewil, Jan Van Impe, Lise Appels, Bart Lievens
Textile wastewater contains high concentrations of organic substances derived from diverse dyes and auxiliary chemicals, some of which are non-biodegradable and/or toxic. Therefore, it is essential that textile wastewater is treated and that these substances are removed before being discharged into the environment. A combination of advanced oxidation processes (AOPs) to obtain partial dye degradation followed by a biological treatment has been suggested as a promising method for cost-effective decolorization of wastewater...
December 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28801864/isolation-and-characterization-of-iron-chelators-from-turmeric-curcuma-longa-selective-metal-binding-by-curcuminoids
#20
Donald J Messner, Christine Surrago, Celia Fiordalisi, Wing Yin Chung, Kris V Kowdley
Iron overload disorders may be treated by chelation therapy. This study describes a novel method for isolating iron chelators from complex mixtures including plant extracts. We demonstrate the one-step isolation of curcuminoids from turmeric, the medicinal food spice derived from Curcuma longa. The method uses iron-nitrilotriacetic acid (NTA)-agarose, to which curcumin binds rapidly, specifically, and reversibly. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin each bound iron-NTA-agarose with comparable affinities and a stoichiometry near 1...
October 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
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