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https://www.readbyqxmd.com/read/29160310/cyclin-d-cdk4-kinase-destabilizes-pd-l1-via-cul3-spop-to-control-cancer-immune-surveillance
#1
Jinfang Zhang, Xia Bu, Haizhen Wang, Yasheng Zhu, Yan Geng, Naoe Taira Nihira, Yuyong Tan, Yanpeng Ci, Fei Wu, Xiangpeng Dai, Jianping Guo, Yu-Han Huang, Caoqi Fan, Shancheng Ren, Yinghao Sun, Gordon J Freeman, Piotr Sicinski, Wenyi Wei
Treatments that target immune checkpoints, such as the one mediated by programmed cell death protein 1 (PD-1) and its ligand PD-L1, have been approved for treating human cancers with durable clinical benefit(1,2). However, many cancer patients fail to respond to anti-PD-1/PD-L1 treatment, and the underlying mechanism(s) is not well understood(3-5). Recent studies revealed that response to PD-1/PD-L1 blockade might correlate with PD-L1 expression levels in tumor cells(6,7). Hence, it is important to mechanistically understand the pathways controlling PD-L1 protein expression and stability, which can offer a molecular basis to improve the clinical response rate and efficacy of PD-1/PD-L1 blockade in cancer patients...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29158379/energy-decomposition-analysis-of-single-bonds-within-kohn-sham-density-functional-theory
#2
Daniel S Levine, Martin Head-Gordon
An energy decomposition analysis (EDA) for single chemical bonds is presented within the framework of Kohn-Sham density functional theory based on spin projection equations that are exact within wave function theory. Chemical bond energies can then be understood in terms of stabilization caused by spin-coupling augmented by dispersion, polarization, and charge transfer in competition with destabilizing Pauli repulsions. The EDA reveals distinguishing features of chemical bonds ranging across nonpolar, polar, ionic, and charge-shift bonds...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29155947/dementia-after-moderate-severe-traumatic-brain-injury-coexistence-of-multiple-proteinopathies
#3
Kimbra Kenney, Diego Iacono, Brian L Edlow, Douglas I Katz, Ramon Diaz-Arrastia, Kristen Dams-O'Connor, Daniel H Daneshvar, Allison Stevens, Allison L Moreau, Lee S Tirrell, Ani Varjabedian, Anastasia Yendiki, Andre van der Kouwe, Azma Mareyam, Jennifer A McNab, Wayne A Gordon, Bruce Fischl, Ann C McKee, Daniel P Perl
We report the clinical, neuroimaging, and neuropathologic characteristics of 2 patients who developed early onset dementia after a moderate-severe traumatic brain injury (TBI). Neuropathological evaluation revealed abundant β-amyloid neuritic and cored plaques, diffuse β-amyloid plaques, and frequent hyperphosphorylated-tau neurofibrillary tangles (NFT) involving much of the cortex, including insula and mammillary bodies in both cases. Case 1 additionally showed NFTs in both the superficial and deep cortical layers, occasional perivascular and depth-of-sulci NFTs, and parietal white matter rarefaction, which corresponded with decreased parietal fiber tracts observed on ex vivo MRI...
November 16, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29154277/potential-of-low-dose-leuco-methylthioninium-bis-hydromethanesulphonate-lmtm-monotherapy-for-treatment-of-mild-alzheimer-s-disease-cohort-analysis-as-modified-primary-outcome-in-a-phase-iii-clinical-trial
#4
Gordon K Wilcock, Serge Gauthier, Giovanni B Frisoni, Jianping Jia, Jiri H Hardlund, Hans J Moebius, Peter Bentham, Karin A Kook, Bjoern O Schelter, Damon J Wischik, Charles S Davis, Roger T Staff, Vesna Vuksanovic, Trevor Ahearn, Luc Bracoud, Kohkan Shamsi, Ken Marek, John Seibyl, Gernot Riedel, John M D Storey, Charles R Harrington, Claude M Wischik
BACKGROUND: LMTM is being developed as a treatment for AD based on inhibition of tau aggregation. OBJECTIVES: To examine the efficacy of LMTM as monotherapy in non-randomized cohort analyses as modified primary outcomes in an 18-month Phase III trial in mild AD. METHODS: Mild AD patients (n = 800) were randomly assigned to 100 mg twice a day or 4 mg twice a day. Prior to unblinding, the Statistical Analysis Plan was revised to compare the 100 mg twice a day as monotherapy subgroup (n = 79) versus 4 mg twice a day as randomized (n = 396), and 4 mg twice a day as monotherapy (n = 76) versus 4 mg twice a day as add-on therapy (n = 297), with strong control of family-wise type I error...
November 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29152419/supradapedon-revisited-geological-explorations-in-the-triassic-of-southern-tanzania
#5
Max C Langer, Átila A S da Rosa, Felipe C Montefeltro
The upper Triassic deposits of the Selous Basin in south Tanzania have not been prospected for fossil tetrapods since the middle of last century, when Gordon M. Stockley collected two rhynchosaur bone fragments from the so called "Tunduru beds". Here we present the results of a field trip conducted in July 2015 to the vicinities of Tunduru and Msamara, Ruvuma Region, Tanzania, in search for similar remains. Even if unsuccessful in terms of fossil discoveries, the geological mapping conducted during the trip improved our knowledge of the deposition systems of the southern margin of the Selous Basin during the Triassic, allowing tentative correlations to its central part and to neighbouring basins...
2017: PeerJ
https://www.readbyqxmd.com/read/29152243/effect-of-pomegranate-extract-on-blood-pressure-and-anthropometry-in-adults-a-double-blind-placebo-controlled-randomised-clinical-trial
#6
A Stockton, G Farhat, Gordon J McDougall, E A S Al-Dujaili
Pomegranate (Punica granatum), a polyphenol-rich fruit, has been suggested to reduce cardiovascular risk due to its antioxidant properties. Hypertension and obesity are the most preventable cardiovascular risk factors. Few studies on blood pressure and/or body-weight status have been conducted in human subjects. Previous investigations have tended to focus on pomegranate juice. The aim of the present study was to investigate the effect of pomegranate extract (PE) on blood pressure and anthropometric measures in adults with no symptomatic disease...
2017: Journal of Nutritional Science
https://www.readbyqxmd.com/read/29151137/blood-brain-barrier-transport-and-neuroprotective-potential-of-blackberry-digested-polyphenols-an-in-vitro-study
#7
Inês Figueira, Lucélia Tavares, Carolina Jardim, Inês Costa, Ana P Terrasso, Andreia F Almeida, Coen Govers, Jurriaan J Mes, Rui Gardner, Jörg D Becker, Gordon J McDougall, Derek Stewart, Augusto Filipe, Kwang S Kim, Dora Brites, Catarina Brito, M Alexandra Brito, Cláudia N Santos
PURPOSE: Epidemiological and intervention studies have attempted to link the health effects of a diet rich in fruits and vegetables with the consumption of polyphenols and their impact in neurodegenerative diseases. Studies have shown that polyphenols can cross the intestinal barrier and reach concentrations in the bloodstream able to exert effects in vivo. However, the effective uptake of polyphenols into the brain is still regarded with some reservations. Here we describe a combination of approaches to examine the putative transport of blackberry-digested polyphenols (BDP) across the blood-brain barrier (BBB) and ultimate evaluation of their neuroprotective effects...
November 18, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/29151048/early-vasopressor-use-following-traumatic-injury-a-systematic-review
#8
Mathieu Hylands, Augustin Toma, Nicolas Beaudoin, Anne Julie Frenette, Frédérick D'Aragon, Émilie Belley-Côté, Emmanuel Charbonney, Morten Hylander Møller, Jon Henrik Laake, Per Olav Vandvik, Reed Alexander Siemieniuk, Bram Rochwerg, François Lauzier, Robert S Green, Ian Ball, Damon Scales, Srinivas Murthy, Joey S W Kwong, Gordon Guyatt, Sandro Rizoli, Pierre Asfar, François Lamontagne
OBJECTIVES: Current guidelines suggest limiting the use of vasopressors following traumatic injury; however, wide variations in practice exist. Although excessive vasoconstriction may be harmful, these agents may help reduce administration of potentially harmful resuscitation fluids. This systematic review aims to compare early vasopressor use to standard resuscitation in adults with trauma-induced shock. DESIGN: Systematic review. DATA SOURCES: We searched MEDLINE, EMBASE, ClinicalTrials...
November 17, 2017: BMJ Open
https://www.readbyqxmd.com/read/29151036/combination-therapy-is-superior-to-sequential-monotherapy-for-the-initial-treatment-of-hypertension-a-double-blind-randomized-controlled-trial
#9
Thomas M MacDonald, Bryan Williams, David J Webb, Steve Morant, Mark Caulfield, J Kennedy Cruickshank, Ian Ford, Peter Sever, Isla S Mackenzie, Sandosh Padmanabhan, Gerald P McCann, Jackie Salsbury, Gordon McInnes, Morris J Brown
BACKGROUND: Guidelines for hypertension vary in their preference for initial combination therapy or initial monotherapy, stratified by patient profile; therefore, we compared the efficacy and tolerability of these approaches. METHODS AND RESULTS: We performed a 1-year, double-blind, randomized controlled trial in 605 untreated patients aged 18 to 79 years with systolic blood pressure (BP) ≥150 mm Hg or diastolic BP ≥95 mm Hg. In phase 1 (weeks 0-16), patients were randomly assigned to initial monotherapy (losartan 50-100 mg or hydrochlorothiazide 12...
November 18, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29150084/radiology-led-lung-escalation-pathway-a-streamlined-innovative-service-expediting-the-diagnosis-of-lung-cancer
#10
J Cox, J Spratt, A Ajith, S Haydar, G Gordon, S Elwell, R Marsh
No abstract text is available yet for this article.
November 14, 2017: Clinical Radiology
https://www.readbyqxmd.com/read/29149497/perceptions-of-general-and-postpresidential-election-discrimination-are-associated-with-loss-of-control-eating-among-racially-ethnically-diverse-young-men
#11
Nichole R Kelly, Tasia M Smith, Gordon C N Hall, Claire Guidinger, Gina Williamson, Elizabeth L Budd, Nicole R Giuliani
OBJECTIVE: The purpose of this study was to examine the association between young men's perceived experiences with discrimination, both general and following the 2016 presidential election, and their loss of control (LOC) eating. The degree to which men identified with their ethnic identity was evaluated as a moderator. METHOD: The sample included 798 men (18-30 years; M = 24.0 ± 3.6) who identified as African American (n = 261), Asian/Asian American (n = 266), or Hispanic/Latino (n = 271)...
November 17, 2017: International Journal of Eating Disorders
https://www.readbyqxmd.com/read/29149259/pancreatic-cancer-incidence-trends-evidence-from-the-surveillance-epidemiology-and-end-results-seer-population-based-data
#12
Vanessa L Gordon-Dseagu, Susan S Devesa, Michael Goggins, Rachael Stolzenberg-Solomon
Background: Annual pancreatic cancer incidence rates have been increasing. We examine pancreatic cancer incidence trends by demographics and histologic type. Methods: Data from the Surveillance, Epidemiology and End Results (SEER) registries were available to assess temporal trends and pancreatic cancer rates from 1974 to 2013. Results: Pancreatic cancer incidence rates declined between the 1970s and 1990s but increased from 1994 to 2013 among White males...
November 14, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/29146906/qtl-mapping-and-molecular-characterization-of-the-classical-d-locus-controlling-seed-and-flower-color-in-linum-usitatissimum-flax
#13
Gurudatt Pavagada Sudarshan, Manoj Kulkarni, Leonid Akhov, Paula Ashe, Hamid Shaterian, Sylvie Cloutier, Gordon Rowland, Yangdou Wei, Gopalan Selvaraj
The flowers of flax (linseed) are blue-hued, ephemeral and self-pollinating, and the seeds are typically brown. A century-old interest in natural yellow seed variants and a historical model point to recessive alleles in B1, D and G loci being responsible, but the functional aspects had remained unknown. Here, we characterized the "D" locus by quantitative trait loci (QTL) mapping and identified a FLAVONOID 3'5' HYDROXYLASE (F3'5'H) gene therein. It does not belong to the F3'5'H clade, but resembles biochemically characterized F3'Hs (flavonoid 3' hydroxylase) but without F3'H activity...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141225/a-comprehensive-patient-derived-xenograft-collection-representing-the-heterogeneity-of-melanoma
#14
Clemens Krepler, Katrin Sproesser, Patricia Brafford, Marilda Beqiri, Bradley Garman, Min Xiao, Batool Shannan, Andrea Watters, Michela Perego, Gao Zhang, Adina Vultur, Xiangfan Yin, Qin Liu, Ioannis N Anastopoulos, Bradley Wubbenhorst, Melissa A Wilson, Wei Xu, Giorgos Karakousis, Michael Feldman, Xiaowei Xu, Ravi Amaravadi, Tara C Gangadhar, David E Elder, Lauren E Haydu, Jennifer A Wargo, Michael A Davies, Yiling Lu, Gordon B Mills, Dennie T Frederick, Michal Barzily-Rokni, Keith T Flaherty, Dave S Hoon, Michael Guarino, Joseph J Bennett, Randall W Ryan, Nicholas J Petrelli, Carol L Shields, Mizue Terai, Takami Sato, Andrew E Aplin, Alexander Roesch, David Darr, Steve Angus, Rakesh Kumar, Ensar Halilovic, Giordano Caponigro, Sebastien Jeay, Jens Wuerthner, Annette Walter, Matthias Ocker, Matthew B Boxer, Lynn Schuchter, Katherine L Nathanson, Meenhard Herlyn
Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29138899/correction-to-potentially-modifiable-factors-contributing-to-outcome-from-acute-respiratory-distress-syndrome-the-lung-safe-study
#15
John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fabiana Madotto, Ednan K Bajwa, Laurent Brochard, Kevin Clarkson, Andres Esteban, Luciano Gattinoni, Frank van Haren, Leo M Heunks, Kiyoyasu Kurahashi, Jon Henrik Laake, Anders Larsson, Daniel F McAuley, Lia McNamee, Nicolas Nin, Haibo Qiu, Marco Ranieri, Gordon D Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Antonio Pesenti
Correction to: Intensive Care Med (2016) 42:1865-1876 DOI 10.1007/s00134-016-4571-5.
November 14, 2017: Intensive Care Medicine
https://www.readbyqxmd.com/read/29136445/effect-of-varying-doses-of-epicutaneous-immunotherapy-vs-placebo-on-reaction-to-peanut-protein-exposure-among-patients-with-peanut-sensitivity-a-randomized-clinical-trial
#16
Hugh A Sampson, Wayne G Shreffler, William H Yang, Gordon L Sussman, Terri F Brown-Whitehorn, Kari C Nadeau, Amarjit S Cheema, Stephanie A Leonard, Jacqueline A Pongracic, Christine Sauvage-Delebarre, Amal H Assa'ad, Frederic de Blay, J Andrew Bird, Stephen A Tilles, Franck Boralevi, Thierry Bourrier, Jacques Hébert, Todd D Green, Roy Gerth van Wijk, André C Knulst, Gisèle Kanny, Lynda C Schneider, Marek L Kowalski, Christophe Dupont
Importance: Epicutaneous immunotherapy may have potential for treating peanut allergy but has been assessed only in preclinical and early human trials. Objective: To determine the optimal dose, adverse events (AEs), and efficacy of a peanut patch for peanut allergy treatment. Design, Setting, and Participants: Phase 2b double-blind, placebo-controlled, dose-ranging trial of a peanut patch in peanut-allergic patients (6-55 years) from 22 centers, with a 2-year, open-label extension (July 31, 2012-July 31, 2014; extension completed September 29, 2016)...
November 14, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/29136007/perinatal-mortality-associated-with-induction-of-labour-versus-expectant-management-in-nulliparous-women-aged-35-years-or-over-an-english-national-cohort-study
#17
Hannah E Knight, David A Cromwell, Ipek Gurol-Urganci, Katie Harron, Jan H van der Meulen, Gordon C S Smith
BACKGROUND: A recent randomised controlled trial (RCT) demonstrated that induction of labour at 39 weeks of gestational age has no short-term adverse effect on the mother or infant among nulliparous women aged ≥35 years. However, the trial was underpowered to address the effect of routine induction of labour on the risk of perinatal death. We aimed to determine the association between induction of labour at ≥39 weeks and the risk of perinatal mortality among nulliparous women aged ≥35 years...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29135255/identification-and-characterization-of-molecular-bonding-structures-by-ab-initio-quasi-atomic-orbital-analyses
#18
Aaron C West, Juan J Duchimaza-Heredia, Mark S Gordon, Klaus Ruedenberg
The quasi-atomic analysis of ab initio electronic wave functions in full valence spaces, which was developed in preceding papers, yields oriented quasi-atomic orbitals in terms of which the ab initio molecular wave function and energy can be expressed. These oriented quasi-atomic orbitals are the rigorous ab initio counterparts to the conceptual bond forming atomic hybrid orbitals of qualitative chemical reasoning. In the present work, the quasi-atomic orbitals are identified as bonding orbitals, lone pair orbitals, radical orbitals, vacant orbitals and orbitals with intermediate character...
November 14, 2017: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/29134193/snowball-earth-climate-dynamics-and-cryogenian-geology-geobiology
#19
Paul F Hoffman, Dorian S Abbot, Yosef Ashkenazy, Douglas I Benn, Jochen J Brocks, Phoebe A Cohen, Grant M Cox, Jessica R Creveling, Yannick Donnadieu, Douglas H Erwin, Ian J Fairchild, David Ferreira, Jason C Goodman, Galen P Halverson, Malte F Jansen, Guillaume Le Hir, Gordon D Love, Francis A Macdonald, Adam C Maloof, Camille A Partin, Gilles Ramstein, Brian E J Rose, Catherine V Rose, Peter M Sadler, Eli Tziperman, Aiko Voigt, Stephen G Warren
Geological evidence indicates that grounded ice sheets reached sea level at all latitudes during two long-lived Cryogenian (58 and ≥5 My) glaciations. Combined uranium-lead and rhenium-osmium dating suggests that the older (Sturtian) glacial onset and both terminations were globally synchronous. Geochemical data imply that CO2 was 10(2) PAL (present atmospheric level) at the younger termination, consistent with a global ice cover. Sturtian glaciation followed breakup of a tropical supercontinent, and its onset coincided with the equatorial emplacement of a large igneous province...
November 2017: Science Advances
https://www.readbyqxmd.com/read/29133948/increased-hippocampal-tail-volume-predicts-depression-status-and-remission-to-anti-depressant-medications-in-major-depression
#20
J J Maller, K Broadhouse, A J Rush, E Gordon, S Koslow, S M Grieve
Studies of patients with major depressive disorder (MDD) have consistently reported reduced hippocampal volumes; however, the exact pattern of these volume changes in specific anatomical subfields and their functional significance is unclear. We sought to clarify the relationship between hippocampal tail volumes and (i) a diagnosis of MDD, and (ii) clinical remission to anti-depressant medications (ADMs). Outpatients with nonpsychotic MDD (n=202) based on DSM-IV criteria and a 17-item Hamilton Rating Scale for Depression (HRSD17) score ⩾16 underwent pretreatment magnetic resonance imaging as part of the international Study to Predict Optimized Treatment for Depression (iSPOT-D)...
November 14, 2017: Molecular Psychiatry
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