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Patrick McGillivray, Russell Ault, Mayur Pawashe, Robert Kitchen, Suganthi Balasubramanian, Mark Gerstein
Upstream open reading frames (uORFs) latent in mRNA transcripts are thought to modify translation of coding sequences by altering ribosome activity. Not all uORFs are thought to be active in such a process. To estimate the impact of uORFs on the regulation of translation in humans, we first circumscribed the universe of all possible uORFs based on coding gene sequence motifs and identified 1.3 million unique uORFs. To determine which of these are likely to be biologically relevant, we built a simple Bayesian classifier using 89 attributes of uORFs labeled as active in ribosome profiling experiments...
March 19, 2018: Nucleic Acids Research
E A Elgindy, H Sibai, M I Mostafa, A Gibreel, E Darwish, H Maghraby
STUDY QUESTION: In ICSI patients with high risk of ovarian hyperstimulation syndrome (OHSS), are antagonist cycles triggered by gonadotropin releasing hormone (GNRH) agonist with a specialized luteal support regimen associated with comparable ongoing pregnancy rate (OPR) and less OHSS than those triggered by hCG? SUMMARY ANSWER: In antagonist ICSI cycles, GnRH agonist triggering with a specialized luteal support regimen is associated with comparable OPR to those triggered by hCG but may be less likely to be associated with OHSS...
March 19, 2018: Human Reproduction
John F Seymour, Thomas J Kipps, Barbara Eichhorst, Peter Hillmen, James D'Rozario, Sarit Assouline, Carolyn Owen, John Gerecitano, Tadeusz Robak, Javier De la Serna, Ulrich Jaeger, Guillaume Cartron, Marco Montillo, Rod Humerickhouse, Elizabeth A Punnoose, Yan Li, Michelle Boyer, Kathryn Humphrey, Mehrdad Mobasher, Arnon P Kater
BACKGROUND: Venetoclax inhibits BCL2, an antiapoptotic protein that is pathologically overexpressed and that is central to the survival of chronic lymphocytic leukemia cells. We evaluated the efficacy of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia. METHODS: In this randomized, open-label, phase 3 trial, we randomly assigned 389 patients to receive venetoclax for up to 2 years (from day 1 of cycle 1) plus rituximab for the first 6 months (venetoclax-rituximab group) or bendamustine plus rituximab for 6 months (bendamustine-rituximab group)...
March 22, 2018: New England Journal of Medicine
Geoffrey H Tison, José M Sanchez, Brandon Ballinger, Avesh Singh, Jeffrey E Olgin, Mark J Pletcher, Eric Vittinghoff, Emily S Lee, Shannon M Fan, Rachel A Gladstone, Carlos Mikell, Nimit Sohoni, Johnson Hsieh, Gregory M Marcus
Importance: Atrial fibrillation (AF) affects 34 million people worldwide and is a leading cause of stroke. A readily accessible means to continuously monitor for AF could prevent large numbers of strokes and death. Objective: To develop and validate a deep neural network to detect AF using smartwatch data. Design, Setting, and Participants: In this multinational cardiovascular remote cohort study coordinated at the University of California, San Francisco, smartwatches were used to obtain heart rate and step count data for algorithm development...
March 21, 2018: JAMA Cardiology
José Eduardo Pelizon Pelino, Alan Passero, Airton Abrahao Martin, Christine Ann Charles
The objective of this study was to evaluate the in vitro effects, including surface morphological characteristics and chemical elemental properties, of different mouthwash formulations on enamel and dental restorative materials, simulating up to 6 months of daily use. Human enamel samples, hydroxyapatite, composite resin, and ceramic surfaces were exposed to 3 different mouthwashes according to label directions - Listerine® Cool Mint®, Listerine® Total Care, and Listerine® Whitening - versus control (hydroalcohol solution) to simulate daily use for up to 6 months...
March 15, 2018: Brazilian Oral Research
Agnieszka Drozd, Dominika Wojewska, Manuel David Peris-Díaz, Piotr Jakimowicz, Artur Krężel
Metallothioneins (MTs), small cysteine-rich proteins, present in four major isoforms, are key proteins involved in zinc and copper homeostasis in mammals. To date, only one X-ray crystal structure of a MT has been solved. It demonstrates seven bivalent metal ions bound in two structurally independent domains with M4S11 (α) and M3S9 (β) clusters. Recent discoveries indicate that Zn(ii) ions are bound with MT2 with the range from nano- to picomolar affinity, which determines its cellular zinc buffering properties that are demonstrated by the presence of partially Zn(ii)-depleted MT2 species...
March 21, 2018: Metallomics: Integrated Biometal Science
Benjamin B Kasten, Patsy G Oliver, Harrison Kim, Jinda Fan, Soldano Ferrone, Kurt R Zinn, Donald J Buchsbaum
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis. There is a clinical need for effective, targeted therapy strategies that destroy both differentiated TNBC cells and TNBC cancer initiating cells (CICs), as the latter are implicated in the metastasis and recurrence of TNBC. Chondroitin sulfate proteoglycan 4 (CSPG4) is overexpressed on differentiated tumor cells and CICs obtained from TNBC patient specimens, suggesting that CSPG4 may be a clinically relevant target for the imaging and therapy of TNBC...
March 21, 2018: International Journal of Molecular Sciences
Sicheng Tang, Yang Zhang, Pravat Dhakal, Laura Ravelo, Cheyenne L Anderson, Kevin M Collins, Françisco M Raymo
A photochemical strategy to encode fluorescence signals in vivo with spatial control was designed around the unique properties of a photoactivatable borondipyrromethene (BODIPY). The photoinduced disconnection of two oxazines, flanking a single BODIPY, in two consecutive steps produces a mixture of three emissive molecules with resolved fluorescence inside polymer beads. The relative amounts and emission intensities of the three fluorophores can be regulated precisely in each bead by adjusting the dose of activating photons to mark individual particles with distinct codes of fluorescence signals...
March 21, 2018: Journal of the American Chemical Society
Dong-Min Kim, Dong Ho Kim, Woong Jung, Kye Young Lee, Dong-Eun Kim
Mutations in epidermal growth factor receptor (EGFR) are known as biomarkers that cause non-small cell lung cancer. Particularly, approximately 45% of non-small cell lung cancer patients possess a deletion in exon 19 of the EGFR gene. A less invasive method for detecting the EGFR mutation is required; thus, we developed a simple polymerase chain reaction (PCR)-based method for detecting EGFR exon 19 deletion by using a quencher-free fluorescent probe DNA and graphene oxide (GO). In the presence of the exon 19 deletion mutation, the fluorophore-labeled DNA probe was designed to be fully complementary to the mutant sequences...
March 21, 2018: Analyst
Roxanne C Oriel, Julie Wang
PURPOSE OF REVIEW: The aim of this review is to describe effective management strategies in nursery or school based upon research findings. RECENT FINDINGS: The prevalence of food allergy and number of emergency department visits for food-related anaphylaxis are increasing in children and adolescents. As there is currently no cure, the most effective strategy to decrease allergic reactions is food allergen avoidance. However, allergic reactions are inevitable in both food allergic children as well as in first-time reactors...
March 20, 2018: Current Opinion in Allergy and Clinical Immunology
Robert Strohal, Martina Mittlböck, Gilbert Hämmerle
OBJECTIVE: Critical colonization or local infection is very common in chronic wounds, but clinically problematic. Because therapeutic options for these conditions are limited in number and efficacy, the study authors tested a new acid-oxidizing solution (AOS [Nexodyn]; APR Applied Pharma Research S.A., Balerna, Switzerland) to determine its ancillary antimicrobial properties and potential support for wound healing. DESIGN AND SETTING: This open-label clinical case series was conducted with a prospective, single-arm design at the Federal County Hospital in Bregenz, Austria...
April 2018: Advances in Skin & Wound Care
Kei Nakashima, Masahiro Aoshima, Satoko Ohfuji, Satoshi Yamawaki, Masahiro Nemoto, Shinya Hasegawa, Satoshi Noma, Masafumi Misawa, Naoto Hosokawa, Makito Yaegashi, Yoshihito Otsuka
It is unclear whether simultaneous administration of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a quadrivalent influenza vaccine (QIV) produces immunogenicity in older individuals. This study tested the hypothesis that the pneumococcal antibody response elicited by simultaneous administration of PPSV23 and QIV in older individuals is not inferior to that elicited by sequential administration of PPSV23 and QIV. We performed a single-center, randomized, open-label, non-inferiority trial comprising 162 adults aged ≥65 years randomly assigned to either the simultaneous (simultaneous injections of PPSV23 and QIV) or sequential (control; PPSV23 injected 2 weeks after QIV vaccination) groups...
March 21, 2018: Human Vaccines & Immunotherapeutics
Paul Glue, Shona M Neehoff, Natalie J Medlicott, Andrew Gray, Guy Kibby, Neil McNaughton
OBJECTIVE: In this maintenance treatment study, we sought to evaluate the effect on anxiety ratings, safety and tolerability of 3 months of weekly ketamine in 20 patients with treatment-refractory DSM IV generalised anxiety disorder (GAD) and/or social anxiety disorder (SAD), and subsequent assessment of remission post-treatment. METHODS: This was an uncontrolled open-label study in 20 patients who had been responders in an ascending dose ketamine study. The study was undertaken in a university clinic...
March 1, 2018: Journal of Psychopharmacology
Tomas Lorant, Mats Bengtsson, Torsten Eich, Britt-Marie Eriksson, Lena Winstedt, Sofia Järnum, Yvonne Stenberg, Anna-Karin Robertson, Kristina Mosén, Lars Björck, Lars Bäckman, Erik Larsson, Kathryn Wood, Gunnar Tufveson, Christian Kjellman
Safety, immunogenicity, pharmacokinetics and efficacy of the immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS, Imlifidase) was assessed in a single centre, open label ascending dose study in highly sensitised chronic kidney disease patients. Eight patients with cytotoxic panel-reactive antibodies (median cytotoxic PRA of 64%) at enrolment received 1 or 2 intravenous infusions of IdeS on consecutive days (0.12 mg/kg body weight x2 (n=3); 0.25 mg/kg x1 (n=3) or 0.25 mg/kg x2 (n=2)). IgG degradation was observed in all subjects after IdeS treatment, with <1% plasma IgG remaining within 48 hours and remaining low up to 7 days...
March 21, 2018: American Journal of Transplantation
Forough Ghasemi, M Reza Hormozi-Nezhad, Morteza Mahmoudi
Monitoring the ratio of 40- and 42-residue amyloid β peptides (i.e., Aβ40 and Aβ42) in human plasma is considered one of the hallmarks of detection of the early stage of Alzheimer's disease (AD). Therefore, development of a specific, yet non-antibody-based method for simultaneous detection of Aβ40 and Aβ42 may have considerable clinical applications. Here, we developed a 'nanoparticle-based colorimetric sensor array' utilizing label-free gold and silver nanoparticles for visual detection of Aβ42 and Aβ40...
March 21, 2018: Nanoscale
Damir Klepac, Hana Kostková, Svetlana Petrova, Petr Chytil, Tomáš Etrych, Sami Kereïche, Ivan Raška, David A Weitz, Sergey K Filippov
In this paper, we revised the current understanding of the protein corona that is created on the surface of nanoparticles in blood plasma after an intravenous injection. We have focused on nanoparticles that have a proven therapeutic outcome. These nanoparticles are based on two types of biocompatible amphiphilic copolymers based on N-(2-hydroxypropyl)methacrylamide (HPMA): a block copolymer, poly(ε-caprolactone) (PCL)-b-poly(HPMA), and a statistical HPMA copolymer bearing cholesterol moieties, which have been tested both in vitro and in vivo...
March 21, 2018: Nanoscale
Vikram Subramanian, Sabine Borchard, Omid Azimzadeh, Wolfgang Sievert, Juliane Merl-Pham, Mariateresa Mancuso, Emanuela Pasquali, Gabriele Multhoff, Bastian Popper, Hans Zischka, Michael J Atkinson, Soile Tapio
High-dose ionizing radiation is known to induce adverse effects such as inflammation and fibrosis in the heart. Transcriptional regulators PPARα and TGFβ are known to be involved in this radiation response. PPARα, an anti-inflammatory transcription factor controlling cardiac energy metabolism, is inactivated by irradiation. The pro-inflammatory and pro-fibrotic TGFβ is activated by irradiation via SMAD-dependent and SMAD-independent pathways. The goal of this study was to investigate how altering the level of PPARα influences the radiation response of these signaling pathways...
March 21, 2018: Journal of Proteome Research
Yin-Qiu Fan, Jing-Cheng Cui, Jun Yang, Pin Wang
OBJECTIVE: To observe the effect of "Huayu Tongluo"(Blood-stasis Dispersing and Meridian-collateral Dredging) moxibustion on the delayed memory and expression of Nestin and Doublecortin (DCX) proteins in the hippocampus in vascular dementia (VD) rats in the view of neurogenesis produced by intracerebral transplantation of neural stem cells (NSCs) and endothelial progenitor cells (EPCs). METHODS: Healthy male Wistar rats were randomized into control group, VD model group,NSCs+EPCs group and NSCs+EPCs moxibustion group...
March 25, 2018: Zhen Ci Yan Jiu, Acupuncture Research
Yang Zhang, Yang Wang, Wei-Wei Cao, Ke-Tao Ma, Wei Ji, Zi-Wei Han, Jun-Qiang Si, Li Li
Significant autofluorescence (AF) of renal tissue is one of the major causes restricting the use of immunofluorescent staining. This study aimed at controlling renal tissue AF and testing an effective method for optimizing specific signals. In the present study, we observed emergence of strong AF in all renal cells under different fluorescent channels. Significant concentration-dependent reduction in AF of kidney tissue was observed with the use of sodium borohydride (NaBH4 ) and Sudan black B (SBB) alone (p < 0...
March 20, 2018: Journal of Fluorescence
Satoshi Nozaki, Aya Mawatari, Yuka Nakatani, Emi Hayashinaka, Yasuhiro Wada, Yukihiro Nomura, Takahito Kitayoshi, Kouji Akimoto, Shinji Ninomiya, Hisashi Doi, Yasuyoshi Watanabe
PURPOSE: Thiamine is an essential component of glucose metabolism and energy production. The disulfide derivative, thiamine tetrahydrofurfuryl disulfide (TTFD), is better absorbed than readily-available water-soluble thiamine salts because it does not require the rate-limiting transport system required for thiamine absorption. However, the detailed pharmacokinetics of thiamine and TTFD under normal and pathological conditions have not yet been clarified. C-11-labeled thiamine and TTFD were recently synthesized by our group...
March 20, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
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