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https://www.readbyqxmd.com/read/29355559/evaluation-of-pharmacokinetics-pharmacodynamics-and-efficacy-of-one-month-depots-of-tak-448-and-tak-683-investigational-kisspeptin-analogs-in-male-rats-and-an-androgen-dependent-prostate-cancer-model
#1
Akira Tanaka, Daisuke Nakata, Tsuneo Masaki, Masami Kusaka, Tatsuya Watanabe, Hisanori Matsui
TAK-448 and TAK-683 are kisspeptin agonist analogs with improved in vivo stability and activity. Previous studies showed that continuous subcutaneous administration of TAK-448 or TAK-683 caused rapid and profound reductions in plasma testosterone levels in various species, including male healthy volunteers, suggesting their therapeutic potential as anti-prostate cancer agents. For clinical drug development, one-month sustained-release depots of TAK-448 and TAK-683, TAK-448-SR(1M) and TAK-683-SR(1M), were designed to improve usability in clinical practice...
January 17, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29348645/a-global-perspective-on-the-trophic-geography-of-sharks
#2
Christopher S Bird, Ana Veríssimo, Sarah Magozzi, Kátya G Abrantes, Alex Aguilar, Hassan Al-Reasi, Adam Barnett, Dana M Bethea, Gérard Biais, Asuncion Borrell, Marc Bouchoucha, Mariah Boyle, Edward J Brooks, Juerg Brunnschweiler, Paco Bustamante, Aaron Carlisle, Diana Catarino, Stéphane Caut, Yves Cherel, Tiphaine Chouvelon, Diana Churchill, Javier Ciancio, Julien Claes, Ana Colaço, Dean L Courtney, Pierre Cresson, Ryan Daly, Leigh de Necker, Tetsuya Endo, Ivone Figueiredo, Ashley J Frisch, Joan Holst Hansen, Michael Heithaus, Nigel E Hussey, Johannes Iitembu, Francis Juanes, Michael J Kinney, Jeremy J Kiszka, Sebastian A Klarian, Dorothée Kopp, Robert Leaf, Yunkai Li, Anne Lorrain, Daniel J Madigan, Aleksandra Maljković, Luis Malpica-Cruz, Philip Matich, Mark G Meekan, Frédéric Ménard, Gui M Menezes, Samantha E M Munroe, Michael C Newman, Yannis P Papastamatiou, Heidi Pethybridge, Jeffrey D Plumlee, Carlos Polo-Silva, Katie Quaeck-Davies, Vincent Raoult, Jonathan Reum, Yassir Eden Torres-Rojas, David S Shiffman, Oliver N Shipley, Conrad W Speed, Michelle D Staudinger, Amy K Teffer, Alexander Tilley, Maria Valls, Jeremy J Vaudo, Tak-Cheung Wai, R J David Wells, Alex S J Wyatt, Andrew Yool, Clive N Trueman
Sharks are a diverse group of mobile predators that forage across varied spatial scales and have the potential to influence food web dynamics. The ecological consequences of recent declines in shark biomass may extend across broader geographic ranges if shark taxa display common behavioural traits. By tracking the original site of photosynthetic fixation of carbon atoms that were ultimately assimilated into muscle tissues of 5,394 sharks from 114 species, we identify globally consistent biogeographic traits in trophic interactions between sharks found in different habitats...
January 18, 2018: Nature Ecology & Evolution
https://www.readbyqxmd.com/read/29348128/pevonedistat-a-first-in-class-nedd8-activating-enzyme-nae-inhibitor-combined-with-azacitidine-in-patients-with-aml
#3
Ronan T Swords, Steven Coutre, Michael B Maris, Joshua F Zeidner, James M Foran, Jose Cruz, Harry P Erba, Jesus G Berdeja, Wayne Tam, Saran Vardhanabhuti, Iwona Pawlikowska-Dobler, Hélène M Faessel, Ajeeta B Dash, Farhad Sedarati, Bruce J Dezube, Douglas V Faller, Michael R Savona
Pevonedistat (TAK-924/MLN4924) is a novel inhibitor of NEDD8-activating enzyme (NAE) with single-agent activity in relapsed/refractory acute myeloid leukemia (AML). We performed a phase 1b study (NCT01814826) of pevonedistat (PEV) with azacitidine (AZA) based on synergistic activity seen preclinically. Primary objectives included safety and tolerability, and secondary objectives included pharmacokinetics (PK) and disease response. Patients ≥60 years with treatment-naïve AML, unfit for standard induction therapy, received PEV 20 or 30 mg/m2 IV on days 1, 3, and 5, combined with fixed-dose AZA (75 mg/m2 IV/SC) on days 1-5, 8, and 9, every 28 days...
January 18, 2018: Blood
https://www.readbyqxmd.com/read/29346614/influenza-vaccine-effectiveness-against-influenza-a-h3n2-hospitalizations-in-children-in-hong-kong-in-a-prolonged-season-2016-17
#4
Susan S Chiu, Mike Y W Kwan, Shuo Feng, Joshua S C Wong, Chi-Wai Leung, Eunice L Y Chan, Kwok-Hung Chan, Tak-Keung Ng, Wing-Kin To, Benjamin J Cowling, J S Malik Peiris
Background: Influenza A(H3N2) viruses circulated for 12 consecutive months in Hong Kong in 2016-2017, peaking in late June and July 2017. The objective of our study was to estimate the effectiveness of influenza vaccination in preventing hospitalizations in children in Hong Kong. Methods: We conducted a test-negative study between September 1 2016 and August 31 2017, enrolling children 6 months to 17 years of age hospitalized for an acute respiratory infection. Influenza was diagnosed by PCR on nasopharyngeal aspirates...
January 16, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29345044/preclinical-characterisation-of-absorption-distribution-metabolism-and-excretion-properties-of-tak-063
#5
Kimio Tohyama, Miyako Sudo, Akio Morohashi, Suguru Kato, Junzo Takahashi, Yoshihiko Tagawa
TAK-063 is currently being developed to treat schizophrenia. In this study, we investigated the absorption, distribution, metabolism and excretion (ADME) properties of TAK-063 using several paradigms. Following oral administration of TAK-063 at 0.3 mg/kg, bioavailability of TAK-063 was 27.4% in rats and 49.5% in dogs with elimination half-lives of 3.1 hr in rats and 3.7 hr in dogs. TAK-063 is a highly permeable compound without P-glycoprotein (P-gp) or breast cancer resistance protein substrate liability and can be readily absorbed into systemic circulation via the intestine...
January 17, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29341582/in-plane-channel-structured-catalyst-layer-for-polymer-electrolyte-membrane-fuel-cells
#6
Dong-Hyun Lee, Wonhee Jo, Seongmin Yuk, Jaeho Choi, Sungyu Choi, Gisu Doo, Dong Wook Lee, Hee-Tak Kim
In this study, we present a novel catalyst layer (CL) with in-plane flow channels to enhance the mass transports in polymer electrolyte membrane fuel cells (PEMFCs). The CL with in-plane channels on its surface is fabricated by coating a CL slurry onto a surface-treated substrate with the inverse line pattern and transferring the dried CL from the substrate to a membrane. The membrane electrode assembly (MEA) with the in-plane channel-patterned CL (IC-CL) has superior power performances in high current densities compared with an un-patterned, flat CL (FCL), demonstrating a significant enhancement of the mass transport property by the in-plane channels carved in the CL...
January 17, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29334402/noninvasive-reconstruction-of-placental-methylome-from-maternal-plasma-dna-potential-for-prenatal-testing-and-monitoring
#7
Kun Sun, Fiona M F Lun, Tak Y Leung, Rossa W K Chiu, Y M Dennis Lo, Hao Sun
OBJECTIVE: During human pregnancy, the DNA methylation of placental tissue is highly relevant to the normal growth and development of the fetus, therefore methylomic analysis of the placental tissue possesses high research and clinical value in prenatal testing and monitoring. Thus our aim is to develop an approach for reconstruction of the placental methylome, which should be completely noninvasive and achieve high accuracy and resolution. RESULTS: We propose a novel size-based algorithm, FEMER, to noninvasively reconstruct the placental methylome by genomewide bisulfite sequencing and size-based analysis of maternal plasma DNA...
January 15, 2018: Prenatal Diagnosis
https://www.readbyqxmd.com/read/29334375/a-small-molecule-inhibitor-of-the-ubiquitin-activating-enzyme-for-cancer-treatment
#8
Marc L Hyer, Michael A Milhollen, Jeff Ciavarri, Paul Fleming, Tary Traore, Darshan Sappal, Jessica Huck, Judy Shi, James Gavin, Jim Brownell, Yu Yang, Bradley Stringer, Robert Griffin, Frank Bruzzese, Teresa Soucy, Jennifer Duffy, Claudia Rabino, Jessica Riceberg, Kara Hoar, Anya Lublinsky, Saurabh Menon, Michael Sintchak, Nancy Bump, Sai M Pulukuri, Steve Langston, Stephen Tirrell, Mike Kuranda, Petter Veiby, John Newcomb, Ping Li, Jing Tao Wu, Josh Powe, Lawrence R Dick, Paul Greenspan, Katherine Galvin, Mark Manfredi, Chris Claiborne, Benjamin S Amidon, Neil F Bence
The ubiquitin-proteasome system (UPS) comprises a network of enzymes that is responsible for maintaining cellular protein homeostasis. The therapeutic potential of this pathway has been validated by the clinical successes of a number of UPS modulators, including proteasome inhibitors and immunomodulatory imide drugs (IMiDs). Here we identified TAK-243 (formerly known as MLN7243) as a potent, mechanism-based small-molecule inhibitor of the ubiquitin activating enzyme (UAE), the primary mammalian E1 enzyme that regulates the ubiquitin conjugation cascade...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29332540/using-the-woman-abuse-screening-tool-to-screen-for-and-assess-dating-violence-in-college-students
#9
Janet Yuen-Ha Wong, Daniel Yee-Tak Fong, Jessie Ho-Yin Yau, Edmond Pui-Hang Choi, Anna Wai-Man Choi, Judith Belle Brown
The study aimed to evaluate the measurement properties of the Woman Abuse Screening Tool (WAST) in Chinese college students. A cross-sectional survey was conducted in Hong Kong. A cutoff score of 10 was found to be able to discriminate between abused and nonabused Chinese young adults. The total score was significantly correlated with total scores for anxiety and depression on the Chinese version of the Hospital Anxiety and Depression Scale. Two-factor structure of the WAST was supported by exploratory and confirmatory factor analyses...
October 1, 2017: Violence Against Women
https://www.readbyqxmd.com/read/29330875/performance-of-the-early-access-ampliseq%C3%A2-mitochondrial-panel-with-degraded-dna-samples-using-the-ion-torrent%C3%A2-platform
#10
Ka Tak Wai, Mark Barash, Peter Gunn
The Early Access AmpliSeq™ Mitochondrial Panel amplifies whole mitochondrial genomes for phylogenetic and kinship identifications, using Ion Torrent™ technology. There is currently limited information on its performance with degraded DNA, a common occurrence in forensic samples. This study evaluated the performance of the Panel with DNA samples degraded in vitro, to mimic conditions commonly found in forensic investigations. Purified DNA from five individuals was heat-treated at five time points each (125°C for 0, 30, 60, 120 and 240 minutes; total n = 25)...
January 13, 2018: Electrophoresis
https://www.readbyqxmd.com/read/29330245/impact-of-pharmacist-previsit-input-to-providers-on-chronic-opioid-prescribing-safety
#11
Nicholas Cox, Casey R Tak, Susan E Cochella, Eric Leishman, Karen Gunning
INTRODUCTION: Primary care providers (PCPs) account for half of opioid prescriptions, often feel chronic pain patients are challenging to manage, and there is wide variability in practice patterns. The purpose of this pilot study was to evaluate the impact of a previsit pharmacist review of high-risk patients treated with opioids for chronic pain on compliance to guideline recommendations at a family medicine residency clinic. METHODS: All adult patients with an appointment for chronic pain who were prescribed >50 morphine milligram equivalents (MMEs)/day had charts reviewed by a pharmacist before each appointment; recommendations were sent electronically to the provider before the appointment...
January 2018: Journal of the American Board of Family Medicine: JABFM
https://www.readbyqxmd.com/read/29329808/structural-and-energetic-basis-for-the-molecular-recognition-of-dual-synthetic-vs-natural-inhibitors-of-egfr-her2
#12
Bello Martiniano, Saldaña-Rivero Lucia, Correa-Basurto José, García Benjamín, Sánchez-Espinosa Víctor Armando
Activation of EGFR starts by ligand binding at the extracellular domain which results in homo and heterodimerization, leading to phosphorylation, activation of downstream signaling pathways which upregulate expression of genes, proliferation and angiogenesis. Abnormalities in the expression of EGFR play a critical role in the development of different types of cancer. HER2 is the preferred heterodimerization partner for EGFR; this biological characteristic together with the high percentage of structural homology has been exploited in the design of dual synthetic inhibitors against EGFR/HER2...
January 9, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29329354/palmitate-induced-er-stress-and-inhibition-of-protein-synthesis-in-cultured-myotubes-does-not-require-toll-like-receptor-4
#13
Ben D Perry, Jill A Rahnert, Yang Xie, Bin Zheng, Myra E Woodworth-Hobbs, S Russ Price
Saturated fatty acids, such as palmitate, are elevated in metabolically dysfunctional conditions like type 2 diabetes mellitus. Palmitate has been shown to impair insulin sensitivity and suppress protein synthesis while upregulating proteolytic systems in skeletal muscle. Increased sarco/endoplasmic reticulum (ER) stress and subsequent activation of the unfolded protein response may contribute to the palmitate-induced impairment of muscle protein synthesis. In some cell types, ER stress occurs through activation of the Toll-like receptor 4 (TLR4)...
2018: PloS One
https://www.readbyqxmd.com/read/29329305/evaluating-the-efficacy-of-switching-from-lamivudine-plus-adefovir-to-tenofovir-disoproxil-fumarate-monotherapy-in-lamivudine-resistant-stable-hepatitis-b-patients
#14
Heon Ju Lee, Sang Jin Kim, Young Oh Kweon, Soo Young Park, Jeong Heo, Hyun Young Woo, Jae Seok Hwang, Woo Jin Chung, Chang Hyeong Lee, Byung Seok Kim, Jeong Ill Suh, Won Young Tak, Byoung Kuk Jang
BACKGROUND: The efficacy of switching to tenofovir disoproxil fumarate (TDF) monotherapy from lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy (stable switching) in patients with LAM-resistant chronic hepatitis B (CHB) and undetectable hepatitis B virus (HBV) DNA is not clear. METHODS: In this non-inferiority trial, patients with LAM-resistant CHB and undetectable serum HBV DNA (<20 IU/mL) for >6 months after initiating LAM+ADV combination therapy were randomized (1:2) either to continue the combination therapy (LAM+ADV group, n = 58) or switched to TDF monotherapy (TDF group, n = 111)...
2018: PloS One
https://www.readbyqxmd.com/read/29323433/electrically-driven-microengineered-bioinspired-soft-robots
#15
Su Ryon Shin, Bianca Migliori, Beatrice Miccoli, Yi-Chen Li, Pooria Mostafalu, Jungmok Seo, Serena Mandla, Alessandro Enrico, Silvia Antona, Ram Sabarish, Ting Zheng, Lorenzo Pirrami, Kaizhen Zhang, Yu Shrike Zhang, Kai-Tak Wan, Danilo Demarchi, Mehmet R Dokmeci, Ali Khademhosseini
To create life-like movements, living muscle actuator technologies have borrowed inspiration from biomimetic concepts in developing bioinspired robots. Here, the development of a bioinspired soft robotics system, with integrated self-actuating cardiac muscles on a hierarchically structured scaffold with flexible gold microelectrodes is reported. Inspired by the movement of living organisms, a batoid-fish-shaped substrate is designed and reported, which is composed of two micropatterned hydrogel layers. The first layer is a poly(ethylene glycol) hydrogel substrate, which provides a mechanically stable structure for the robot, followed by a layer of gelatin methacryloyl embedded with carbon nanotubes, which serves as a cell culture substrate, to create the actuation component for the soft body robot...
January 11, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29318783/tak-063-a-novel-pde10a-inhibitor-with-balanced-activation-of-direct-and-indirect-pathways-provides-a-unique-opportunity-for-the-treatment-of-schizophrenia
#16
REVIEW
Kazunori Suzuki, Haruhide Kimura
The basal ganglia regulates motor, cognitive, and emotional behaviors. Dysfunction of dopamine system in this area is implicated in the pathophysiology of schizophrenia characterized by positive symptoms, negative symptoms, and cognitive deficits. Medium spiny neurons (MSNs) are principal output neurons of striatum in the basal ganglia. Similar to current antipsychotics with dopamine D2 receptor antagonism or partial agonism, phosphodiesterase 10A (PDE10A) inhibitors activate indirect pathway MSNs, leading to the expectation of therapeutic potential for the treatment of psychosis...
January 9, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29317617/author-correction-gene-isoforms-as-expression-based-biomarkers-predictive-of-drug-response-in-vitro
#17
Zhaleh Safikhani, Petr Smirnov, Kelsie L Thu, Jennifer Silvester, Nehme El-Hachem, Rene Quevedo, Mathieu Lupien, Tak W Mak, David Cescon, Benjamin Haibe-Kains
In the original version of this Article, financial support was not fully acknowledged. This error has now been corrected in both the PDF and HTML versions of the Article.
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29314475/suppression-of-targeting-of-dbf4-dependent-kinase-to-pre-replicative-complex-in-g0-nuclei
#18
Takuya Okada, Gaku Okabe, Yon-Soo Tak, Satoru Mimura, Haruhiko Takisawa, Yumiko Kubota
Intact G0 nuclei isolated from quiescent cells are not capable of DNA replication in interphase Xenopus egg extracts, which allow efficient replication of permeabilized G0 nuclei. Previous studies have shown multiple control mechanisms for maintaining the quiescent state, but DNA replication inhibition of intact G0 nuclei in the extracts remains poorly understood. Here, we showed that pre-RC is assembled on chromatin, but its activation is inhibited after incubating G0 nuclei isolated from quiescent NIH3T3 cells in the extracts...
January 4, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/29314186/aggressive-nk-cell-leukaemia-and-extranodal-nk-t-cell-lymphoma-are-two-distinct-diseases-that-differ-in-their-clinical-presentation-and-cytogenetic-findings
#19
Ching-Fen Yang, Chih-Yi Hsu, Donald Ming-Tak Ho
AIMS: Distinguishing between aggressive NK-cell leukaemia (ANKCL) and extranodal NK/T-cell lymphoma (ENKTCL) with secondary bone marrow involvement is challenging, as they are rare bone marrow NK/T-cell neoplasms and share similar features. METHODS AND RESULTS: We studied bone marrow NK/T-cell neoplasms by classifying them into those with no extramedullary mass (group 1, 8 cases) and those with extramedullary mass (group 2, 13 cases). Both groups showed similar clinical presentations and pathological features...
January 4, 2018: Histopathology
https://www.readbyqxmd.com/read/29313811/imaging-modalities-for-the-diagnosis-and-disease-activity-assessment-of-takayasu-s-arteritis-a-systematic-review-and-meta-analysis
#20
REVIEW
Lillian Barra, Tahir Kanji, Jacqueline Malette, Christian Pagnoux, Can Vasc
BACKGROUND: Early diagnosis of Takayasu's Arteritis (TAK) and detection of disease activity may reduce the risk of vascular complications. The objective of this study was to determine the effectiveness of imaging modalities for the management of TAK. METHODS: MEDLINE and EMBASE were searched for studies of patients undergoing various imaging modalities for TAK diagnosis or to assess disease activity. We excluded case reports, reviews and case series with <10 patients...
December 4, 2017: Autoimmunity Reviews
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