显示样式:     当前分类: 医药    当前期刊: All 导出
我的关注
我的收藏
您暂时未登录!
登录
  • Interleukin 4 induces apoptosis of acute myeloid leukemia cells in a Stat6-dependent manner
    Leukemia (IF 11.702) Pub Date : September
    P Peña-Martínez, M Eriksson, R Ramakrishnan, M Chapellier, C Högberg, C Orsmark-Pietras, J Richter, A Andersson, T Fioretos, M Järås

    Interleukin 4 induces apoptosis of acute myeloid leukemia cells in a Stat6-dependent mannerLeukemia advance online publication, September 22 2017. doi:10.1038/leu.2017.261Authors: P Peña-Martínez, M Eriksson, R Ramakrishnan, M Chapellier, C Högberg, C Orsmark-Pietras, J Richter, A Andersson, T Fioretos & M Järås

    更新日期:2017-09-23
  • Results of NOPHO ALL2008 treatment for patients aged 1–45 years with acute lymphoblastic leukemia
    Leukemia (IF 11.702) Pub Date : September
    N Toft, H Birgens, J Abrahamsson, L Griškevičius, H Hallböök, M Heyman, T W Klausen, ÓG Jónsson, K Palk, K Pruunsild, P Quist-Paulsen, G Vaitkeviciene, K Vettenranta, A Åsberg, T L Frandsen, H V Marquart, H O Madsen, U Norén-Nyström, K Schmiegelow

    Results of NOPHO ALL2008 treatment for patients aged 1–45 years with acute lymphoblastic leukemiaLeukemia advance online publication, September 22 2017. doi:10.1038/leu.2017.265Authors: N Toft, H Birgens, J Abrahamsson, L Griškevičius, H Hallböök, M Heyman, T W Klausen, ÓG Jónsson, K Palk, K Pruunsild, P Quist-Paulsen, G Vaitkeviciene, K Vettenranta, A Åsberg, T L Frandsen, H V Marquart, H O Madsen, U Norén-Nyström & K Schmiegelow

    更新日期:2017-09-23
  • Activation of RHOA–VAV1 signaling in angioimmunoblastic T-cell lymphoma
    Leukemia (IF 11.702) Pub Date : September
    M Fujisawa, M Sakata-Yanagimoto, S Nishizawa, D Komori, P Gershon, M Kiryu, S Tanzima, K Fukumoto, T Enami, M Muratani, K Yoshida, S Ogawa, K Matsue, N Nakamura, K Takeuchi, K Izutsu, K Fujimoto, T Teshima, H Miyoshi, P Gaulard, K Ohshima, S Chiba

    Activation of RHOA–VAV1 signaling in angioimmunoblastic T-cell lymphomaLeukemia advance online publication, September 22 2017. doi:10.1038/leu.2017.273Authors: M Fujisawa, M Sakata-Yanagimoto, S Nishizawa, D Komori, P Gershon, M Kiryu, S Tanzima, K Fukumoto, T Enami, M Muratani, K Yoshida, S Ogawa, K Matsue, N Nakamura, K Takeuchi, K Izutsu, K Fujimoto, T Teshima, H Miyoshi, P Gaulard, K Ohshima & S Chiba

    更新日期:2017-09-23
  • Multiple productive IGH rearrangements denote oligoclonality even in immunophenotypically monoclonal CLL
    Leukemia (IF 11.702) Pub Date : 
    K Brazdilova, K Plevova, H S Francova, H Kockova, M Borsky, V Bikos, J Malcikova, A Oltova, J Kotaskova, B Tichy, Y Brychtova, J Mayer, M Doubek, S Pospisilova

    Multiple productive IGH rearrangements denote oligoclonality even in immunophenotypically monoclonal CLLLeukemia advance online publication, September 22 2017. doi:10.1038/leu.2017.274Authors: K Brazdilova, K Plevova, H Skuhrova Francova, H Kockova, M Borsky, V Bikos, J Malcikova, A Oltova, J Kotaskova, B Tichy, Y Brychtova, J Mayer, M Doubek & S Pospisilova

    更新日期:2017-09-23
  • Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia
    Leukemia (IF 11.702) Pub Date : 
    S Degryse, C E de Bock, S Demeyer, I Govaerts, S Bornschein, D Verbeke, K Jacobs, S Binos, D A Skerrett-Byrne, H C Murray, N M Verrills, P Van Vlierberghe, J Cools, M D Dun

    Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemiaLeukemia advance online publication, September 22 2017. doi:10.1038/leu.2017.276Authors: S Degryse, C E de Bock, S Demeyer, I Govaerts, S Bornschein, D Verbeke, K Jacobs, S Binos, D A Skerrett-Byrne, H C Murray, N M Verrills, P Van Vlierberghe, J Cools & M D Dun

    更新日期:2017-09-23
  • Extracellular vesicles as potential biomarkers of acute graft-vs.-host-disease
    Leukemia (IF 11.702) Pub Date : 
    G Lia, L Brunello, S Bruno, A Carpanetto, P Omedè, M Festuccia, L Tosti, E Maffini, L Giaccone, M Arpinati, G Ciccone, M Boccadoro, A Evangelista, G Camussi, B Bruno

    Extracellular vesicles as potential biomarkers of acute graft-vs-host diseaseLeukemia advance online publication, September 22 2017. doi:10.1038/leu.2017.277Authors: G Lia, L Brunello, S Bruno, A Carpanetto, P Omedè, M Festuccia, L Tosti, E Maffini, L Giaccone, M Arpinati, G Ciccone, M Boccadoro, A Evangelista, G Camussi & B Bruno

    更新日期:2017-09-23
  • Johannes Joseph van Rood Pioneer in immuno-genetics (April 7, 1926-July 21, 2017)
    Leukemia (IF 11.702) Pub Date : 
    W Fibbe, R P Gale

    Johannes Joseph van Rood Pioneer in immuno-genetics (7 April 1926–21 July 2017)Leukemia advance online publication, September 22 2017. doi:10.1038/leu.2017.278Authors: W Fibbe & R P Gale

    更新日期:2017-09-23
  • Overall survival analysis of EXAM, a phase 3 trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma
    Ann. Oncol. (IF 11.855) Pub Date : 2017-09-22
    M. Schlumberger, R. Elisei, S. Müller, P. Schöffski, M. Brose, M. Shah, L. Licitra, J. Krajewska, M. C. Kreissl, B. Niederle, E. E. W. Cohen, L. Wirth, H. Ali, D. O. Clary, Y. Yaron, M. Mangeshkar, D. Ball, B. Nelkin, S. Sherman

    Primary analysis of the double-blind, phase 3 EXAM trial demonstrated significant improvement in progression-free survival (PFS) with cabozantinib versus placebo in patients with progressive medullary thyroid cancer (MTC). Final analysis of overall survival (OS), a key secondary endpoint, was performed after long-term follow-up.

    更新日期:2017-09-23
  • Molecular genomic characterization of tick- and human-derived severe fever with thrombocytopenia syndrome virus isolates from South Korea
    PLOS Negl. Trop. Dis. (IF 3.834) Pub Date : 2017-09-22
    Seok-Min Yun, Su-Jin Park, Sun-Whan Park, WooYoung Choi, Hye Won Jeong, Young-Ki Choi, Won-Ja Lee
    更新日期:2017-09-23
  • Recombinant vaccines of a CD4+ T-cell epitope promote efficient control of Paracoccidioides brasiliensis burden by restraining primary organ infection
    PLOS Negl. Trop. Dis. (IF 3.834) Pub Date : 2017-09-22
    Rodrigo Assunção Holanda, Julián Esteban Muñoz, Lucas Santos Dias, Leandro Buffoni Roque Silva, Julliana Ribeiro Alves Santos, Sthefany Pagliari, Érica Leandro Marciano Vieira, Tatiane Alves Paixão, Carlos Pelleschi Taborda, Daniel Assis Santos, Oscar Bruña-Romero
    更新日期:2017-09-23
  • Household costs of hospitalized dengue illness in semi-rural Thailand
    PLOS Negl. Trop. Dis. (IF 3.834) Pub Date : 2017-09-22
    Yesim Tozan, Pitcha Ratanawong, Maquines Odhiambo Sewe, Annelies Wilder-Smith, Pattamaporn Kittayapong
    更新日期:2017-09-23
  • Structures of foot and mouth disease virus pentamers: Insight into capsid dissociation and unexpected pentamer reassociation
    PLOS Pathog. (IF 6.608) Pub Date : 2017-09-22
    Nayab Malik, Abhay Kotecha, Sarah Gold, Amin Asfor, Jingshan Ren, Juha T. Huiskonen, Tobias J. Tuthill, Elizabeth E. Fry, David I. Stuart
    更新日期:2017-09-23
  • Cell cycle stage-specific transcriptional activation of cyclins mediated by HAT2-dependant H4K10 acetylation of promoters in Leishmania donovani
    PLOS Pathog. (IF 6.608) Pub Date : 2017-09-22
    Udita Chandra, Aarti Yadav, Devanand Kumar, Swati Saha
    更新日期:2017-09-23
  • A highly conserved amino acid in VP1 regulates maturation of enterovirus 71
    PLOS Pathog. (IF 6.608) Pub Date : 2017-09-22
    Yong-Xin Zhang, Yu-Ming Huang, Quan-Jie Li, Xiao-Yu Li, Yong-Dong Zhou, Fei Guo, Jin-Ming Zhou, Shan Cen
    更新日期:2017-09-23
  • The Kaposi's sarcoma-associated herpesvirus (KSHV) non-structural membrane protein K15 is required for viral lytic replication and may represent a therapeutic target
    PLOS Pathog. (IF 6.608) Pub Date : 2017-09-22
    Bizunesh Abere, Tamrat M. Mamo, Silke Hartmann, Naira Samarina, Elias Hage, Jessica Rückert, Sven-Kevin Hotop, Guntram Büsche, Thomas F. Schulz
    更新日期:2017-09-23
  • Your loving mother: the films of Chantal Akerman
    Lancet Psychiatry (IF 11.588) Pub Date : 2017-10-01
    Laura Thomas
    更新日期:2017-09-23
  • Intestinal helminth infection drives carcinogenesis in colitis-associated colon cancer
    PLOS Pathog. (IF 6.608) Pub Date : 2017-09-22
    Eva Pastille, Annika Frede, Henry J. McSorley, Jessica Gräb, Alexandra Adamczyk, Sebastian Kollenda, Wiebke Hansen, Matthias Epple, Jan Buer, Rick M. Maizels, Robert Klopfleisch, Astrid M. Westendorf
    更新日期:2017-09-23
  • Red
    Lancet Psychiatry (IF 11.588) Pub Date : 2017-10-01
    Kelley Swain
    更新日期:2017-09-23
  • ABC294640, a novel sphingosine kinase 2 inhibitor induces oncogenic virus infected cell autophagic death and represses tumor growth
    Mol. Cancer Ther. (IF 5.764) Pub Date : 2017-01-01
    Lu Dai, Aiping Bai, Charles D. Smith, Paulo C. Rodriguez, Fangyou Yu, Zhiqiang Qin

    Kaposi's Sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several malignancies, including Kaposi's Sarcoma (KS) and primary effusion lymphoma (PEL), which preferentially arise in HIV+ patients and lack effective treatment. Sphingosine kinase 2 (SphK2) is a key factor within sphingolipid metabolism, responsible for the conversion of pro-apoptotic ceramides to anti-apoptotic sphingosine-1-phosphate (S1P). We have previously demonstrated that targeting SphK2 using a novel selective inhibitor, ABC294640, leads to the accumulation of intracellular ceramides and induces apoptosis in KSHV-infected primary endothelial cells and PEL tumor cells but not in uninfected cells. In the current study, we found that ABC294640 induces autophagic death instead of apoptosis in a KSHV long-term-infected immortalized endothelial cell-line, TIVE-LTC, but not in uninfected TIVE cells, through the up-regulation of LC3B protein. Transcriptomic analysis indicates that many genes related to cellular stress responses, cell cycle/proliferation, and cellular metabolic process are altered in TIVE-LTC exposed to ABC294640. One of the candidates, Egr-1, was found to directly regulate LC3B expression and required for the ABC294640-induced autophagic death. By using a KS-like nude mice model with TIVE-LTC, we found that ABC294640 treatment significantly suppressed KSHV-induced tumor growth in vivo, which indicates that targeting sphingolipid metabolism especially SphK2 may represent a promising therapeutic strategy against KSHV-related malignancies.

    更新日期:2017-09-23
  • Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical Activity with the Novel Selective ERK1/2 Inhibitor BVD-523 (ulixertinib)
    Mol. Cancer Ther. (IF 5.764) Pub Date : 2017-01-01
    Ursula A Germann, Brinley F. Furey, William Markland, Russell R Hoover, Alex M Aronov, Jeffrey J Roix, Micheal Hale, Diane M Boucher, David A Sorrell, Gabriel Martinez-Botella, Matthew Fitzgibbon, Paul Shapiro, Michael J Wick, Ramin Samadani, Kathryn Meshaw, Anna Groover, Gary DeCrescenzo, Mark Namchuk, Caroline M Emery, Saurabh Saha, Dean J. Welsch

    Aberrant activation of signaling through the RAS-RAF-MEK-ERK (MAPK) pathway is implicated in numerous cancers, making it an attractive therapeutic target. Although BRAF- and MEK-targeted combination therapy has demonstrated significant benefit beyond single-agent options, the majority of patients develop resistance and disease progression after approximately 12 months. Reactivation of ERK signaling is a common driver of resistance in this setting. Here we report the discovery of BVD-523 (ulixertinib), a novel, reversible, ATP-competitive ERK1/2 inhibitor with high potency and ERK1/2 selectivity. In vitro BVD-523 treatment resulted in reduced proliferation and enhanced caspase activity in sensitive cells. Interestingly, BVD-523 inhibited phosphorylation of target substrates despite increased phosphorylation of ERK1/2. In in vivo xenograft studies, BVD-523 showed dose-dependent growth inhibition and tumor regression. BVD-523 yielded synergistic anti-proliferative effects in a BRAFV600E mutant melanoma cell line xenograft model when used in combination with BRAF inhibition. Antitumor activity was also demonstrated in in vitro and in vivo models of acquired resistance to single-agent and combination BRAF/MEK targeted therapy. Based on these promising results, these studies demonstrate BVD-523 holds promise as a treatment for ERK-dependent cancers, including those whose tumors have acquired resistance to other treatments targeting upstream nodes of the MAPK pathway. Assessment of BVD-523 in clinical trials is underway ([NCT01781429][1], [NCT02296242][2] and [NCT02608229][3]). [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01781429&atom=%2Fmolcanther%2Fearly%2F2017%2F09%2F22%2F1535-7163.MCT-17-0456.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02296242&atom=%2Fmolcanther%2Fearly%2F2017%2F09%2F22%2F1535-7163.MCT-17-0456.atom [3]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02608229&atom=%2Fmolcanther%2Fearly%2F2017%2F09%2F22%2F1535-7163.MCT-17-0456.atom

    更新日期:2017-09-23
  • A novel therapeutic strategy for pancreatic cancer: targeting cell surface glycan using rBC2LC-N lectin-drug conjugate (LDC).
    Mol. Cancer Ther. (IF 5.764) Pub Date : 2017-01-01
    Osamu Shimomura, Tatsuya Oda, Hiroaki Tateno, Yusuke Ozawa, Sota Kimura, Shingo Sakashita, Masayuki Noguchi, Jun Hirabayashi, Makoto Asashima, Nobuhiro Ohkohchi

    Various cancers, including pancreatic ductal adenocarcinoma (PDAC), remain intractable even with costly tumour-targeting antibody drugs. Because the outermost coatings of cancer cells are composed of cell-specific glycan layers (glycocalyx), lectins, proteins with glycan-binding potential, were evaluated for possible use as drug carriers in PDAC treatment. A human PDAC cell line with well-to-moderately differentiated properties (Capan-1) was subjected to lectin microarray analysis to identify specific lectin-glycan pairs. The selected lectin was fused with a bacterial exotoxin for the construction of a lectin-drug conjugate (LDC), and its safety and anti-tumour effects were evaluated. A specific affinity between rBC2LC-N (a recombinant bacterial C-type lectin) and Capan-1 was identified, and its positivity was confirmed in 69 human samples. In contrast to the belief that all lectins mediate harmful haemagglutination, rBC2LC-N did not cause haemagglutination with human erythrocytes and was safely administered to mice. The 50% inhibitory concentration of LDC to Capan-1 (1.04 pg/ml=0.0195 pmol/l) was 1/1000 lower than that reported for conventional immunotoxins. The intraperitoneal administration of LDC reduced the tumour weight from 390 mg to 130.8 mg (P<0.01) in an orthotopic model, and reduced the number of nodules from 48 to 3 (P<0.001) and improved survival from 62 to 105 days in a peritoneal dissemination model (P<0.0001). In addition, the effect of LDC was reproduced in nodules from patient-derived PDAC xenografts through intravenous injection. Herein, we show the concept of utilizing lectins as drug carriers to target glycans on the cancer cell surface, highlighting new insights into cancer treatments.

    更新日期:2017-09-23
  • Dinesh Bhugra: sunken hearts and attics of mind
    Lancet Psychiatry (IF 11.588) Pub Date : 2017-10-01
    Dara Mohammadi
    更新日期:2017-09-23
  • Targeting Phosphatidylserine with Calcium-dependent Protein-Drug Conjugates for the Treatment of Cancer
    Mol. Cancer Ther. (IF 5.764) Pub Date : 2017-01-01
    Ran Li, Srinivas Chiguru, Li Li, Dongyoung Kim, Ramraj Velmurugan, David Kim, Siva Charan Devanaboyina, Hong Tian, Alan Schroit, Ralph Mason, Raimund J Ober, E. Sally Ward

    In response to cellular stress, phosphatidylserine (PS) is exposed on the outer membrane leaflet of tumor blood vessels and cancer cells, motivating the development of PS-specific therapies. The generation of drug-conjugated PS-targeting agents represents an unexplored therapeutic approach, for which anti-tumor effects are critically dependent on efficient internalization and lysosomal delivery of the cytotoxic drug. In the current study, we have generated PS-targeting agents by fusing PS-binding domains to a human IgG1-derived Fc fragment. The tumor localization and pharmacokinetics of several PS-specific Fc fusions have been analyzed in mice and demonstrate that Fc-Syt1, a fusion containing the synaptotagmin 1 C2A domain, effectively targets tumor tissue. Conjugation of Fc-Syt1 to the cytotoxic drug, monomethyl auristatin E, results in a protein-drug conjugate (PDC) that is internalized into target cells and, due to the Ca²⁺-dependence of PS binding, dissociates from PS in early endosomes. The released PDC is efficiently delivered to lysosomes and has potent anti-tumor effects in mouse xenograft tumor models. Interestingly, whilst an engineered, tetravalent Fc-Syt1 fusion shows increased binding to target cells, this higher avidity variant demonstrates reduced persistence and therapeutic effects compared with bivalent Fc-Syt1. Collectively, these studies show that finely tuned, Ca²⁺-switched PS-targeting agents can be therapeutically efficacious.

    更新日期:2017-09-23
  • A chemical modulator of p53 transactivation that acts as a radioprotective agonist
    Mol. Cancer Ther. (IF 5.764) Pub Date : 2017-01-01
    Akinori Morita, Ippei Takahashi, Megumi Sasatani, Shin Aoki, Bing Wang, Shinya Ariyasu, Kaoru Tanaka, Tetsuji Yamaguchi, Akiko Sawa, Yurie Nishi, Tatsuro Teraoka, Shohei Ujita, Yosuke Kawate, Chihiro Yanagawa, Keiji Tanimoto, Atsushi Enomoto, Mitsuru Nenoi, Kenji Kamiya, Yasushi Nagata, Yoshio Hosoi, Toshiya Inaba

    Inhibiting p53-dependent apoptosis by inhibitors of p53 is an effective strategy for preventing radiation-induced damage in hematopoietic lineages, while p53 and p21 also play radioprotective roles in the gastrointestinal epithelium. We previously identified some zinc(II) chelators, including 8-quinolinol derivatives that suppress apoptosis in attempts to discover compounds that target the zinc-binding site in p53. We found that 5-chloro-8-quinolinol (5CHQ) has a unique p53-modulating activity that shifts its transactivation from proapoptotic to protective responses including enhancing p21 induction and suppressing PUMA induction. This p53-modulating activity also influenced p53 and p53-target gene expression in unirradiated cells without inducing DNA damage. The specificity of 5CHQ for p53 and p21 was demonstrated by silencing the expression of each protein. These effects seems to be attributable to the sequence-specific alteration of p53 DNA-binding, as evaluated by chromatin immunoprecipitation and electrophoretic mobility shift assays. In addition, 5-chloro-8-methoxyquinoline itself had no antiapoptotic activity, indicating that the hydroxyl group at the 8-position is required for its antiapoptotic activity. We applied this remarkable agonistic activity to protecting the hematopoietic and gastrointestinal system in mouse irradiation models. The dose-reduction factors of 5CHQ in total-body and abdominally irradiated mice were about 1.2 and 1.3, respectively. 5CHQ effectively protected mouse epithelial stem cells from a lethal dose of abdominal irradiation. Furthermore, the specificity of 5CHQ for p53 in reducing the lethality induced by abdominal irradiation was revealed in Trp53-KO mice. These results indicate that the pharmacological upregulation of radioprotective p53-target genes is an effective strategy for addressing the gastrointestinal syndrome.

    更新日期:2017-09-23
  • Research round-up
    Lancet Psychiatry (IF 11.588) Pub Date : 2017-10-01
    Seema Kang
    更新日期:2017-09-23
  • Mapping mental health priorities in London with real-world data
    Lancet Psychiatry (IF 11.588) Pub Date : 2017-10-01
    Antonis A Kousoulis, Isabella Goldie
    更新日期:2017-09-23
  • mHealth: bridging the mental health gap in central and eastern Europe
    Lancet Psychiatry (IF 11.588) Pub Date : 2017-10-01
    Aaron Poppleton, Nadeem Gire

    In The Lancet Psychiatry, Petr Winkler and colleagues1 expertly account for challenges facing central and eastern European (CEE) psychiatric service reform and stakeholder engagement. Building on this, we propose that efforts to develop culturally appropriate mental health care in CEE can benefit from wider global partnerships specifically concerned with mHealth.

    更新日期:2017-09-23
  • Institutional discrimination against psychiatric patients in Poland
    Lancet Psychiatry (IF 11.588) Pub Date : 2017-10-01
    Jacek Gierus, Anna Mosiołek, Tytus Koweszko, Agata Szulc
    更新日期:2017-09-23
  • Corrections
    Lancet Psychiatry (IF 11.588) Pub Date : 2017-10-01

    Hincapie-Castillo JM, Daniels PF. Use of lithium in patients with unipolar depression. Lancet Psychiatry 2017; 4: 662—The first sentence of this Correspondence should read “Jari Tiihonen and colleagues1 presented a retrospective cohort study on the comparative effectiveness of various pharmacological treatments for unipolar depression in the prevention of hospital readmissions.” This correction has been made to the online version as of September 22.

    更新日期:2017-09-23
  • The future of psychiatry in Africa—thinking outside the box
    Lancet Psychiatry (IF 11.588) Pub Date : 2017-10-01
    Dixon Chibanda
    更新日期:2017-09-23
  • Renegotiating the contract
    Lancet Psychiatry (IF 11.588) Pub Date : 2017-10-01
    Sarah Carr
    更新日期:2017-09-23
  • More than one scenario exists for the future of psychiatry
    Lancet Psychiatry (IF 11.588) Pub Date : 2017-10-01
    Norman Sartorius
    更新日期:2017-09-23
  • New wave
    Lancet Psychiatry (IF 11.588) Pub Date : 2017-10-01
    The Lancet Psychiatry
    更新日期:2017-09-23
  • Prebiotic galacto-oligosaccharides mitigate the adverse effects of iron fortification on the gut microbiome: a randomised controlled study in Kenyan infants
    Ann. Rheum. Dis. (IF 12.811) Pub Date : 2017-08-03
    Daniela Paganini, Mary A Uyoga, Guus A M Kortman, Colin I Cercamondi, Diego Moretti, Tanja Barth-Jaeggi, Clarissa Schwab, Jos Boekhorst, Harro M Timmerman, Christophe Lacroix, Simon Karanja, Michael B Zimmermann

    Objective Iron-containing micronutrient powders (MNPs) reduce anaemia in African infants, but the current high iron dose (12.5 mg/day) may decrease gut Bifidobacteriaceae and Lactobacillaceae , and increase enteropathogens, diarrhoea and respiratory tract infections (RTIs). We evaluated the efficacy and safety of a new MNP formula with prebiotic galacto-oligosaccharides (GOS) combined with a low dose (5 mg/day) of highly bioavailable iron.Design In a 4-month, controlled, double-blind trial, we randomised Kenyan infants aged 6.5–9.5 months (n=155) to receive daily (1) a MNP without iron (control); (2) the identical MNP but with 5 mg iron (2.5 mg as sodium iron ethylenediaminetetraacetate and 2.5 mg as ferrous fumarate) (Fe group); or (3) the identical MNP as the Fe group but with 7.5 g GOS (FeGOS group).Results Anaemia decreased by ≈50% in the Fe and FeGOS groups (p<0.001). Compared with the control or FeGOS group, in the Fe group there were (1) lower abundances of Bifidobacterium and Lactobacillus and higher abundances of Clostridiales (p<0.01); (2) higher abundances of virulence and toxin genes (VTGs) of pathogens (p<0.01); (3) higher plasma intestinal fatty acid-binding protein (a biomarker of enterocyte damage) (p<0.05); and (4) a higher incidence of treated RTIs (p<0.05). In contrast, there were no significant differences in these variables comparing the control and FeGOS groups, with the exception that the abundance of VTGs of all pathogens was significantly lower in the FeGOS group compared with the control and Fe groups (p<0.01).Conclusion A MNP containing a low dose of highly bioavailable iron reduces anaemia, and the addition of GOS mitigates most of the adverse effects of iron on the gut microbiome and morbidity in African infants.Trial registration number NCT02118402.

    更新日期:2017-09-23
  • Serrated pathway: a paradigm shift in CRC prevention
    Ann. Rheum. Dis. (IF 12.811) Pub Date : 2017-08-01
    Evelien Dekker, Joep Evert Godfried IJspeert

    In the prevention of colorectal cancer (CRC), hyperplastic polyps have long been regarded as innocent bystanders and only adenomas were thought to be precursors for CRC. Therefore, focus during colonoscopy was on adenomas only. In the past decade, evidence has accumulated that serrated polyps might progress to cancer as well via the serrated neoplasia pathway. On the one hand, patients with multiple serrated polyps, nowadays classified as having serrated polyposis syndrome, demonstrated an increased risk of CRC development, and small cancers were detected within serrated lesions. On the other hand, a growing body of circumstantial evidence suggests that at least 15% of all CRCs arise through the serrated neoplasia pathway, and an even larger proportion of postcolonoscopy CRCs arise from serrated polyps.1This growing body of evidence has gradually led to a paradigm shift in both cancer prevention as well as treatment strategies. To reduce the number of postcolonoscopy CRCs and to optimise current clinical care for patients with serrated polyps, several issues are at stake. The new British Society of Gastroenterology (BSG) position statement on serrated polyps in the colon and rectum is therefore timely as well as important.2 It discusses current knowledge on serrated polyps and provides recommendations for daily clinical practice as well as research. We hope that this publication will increase the awareness among clinicians on this topic and will be an incentive for appropriate management of these lesions. In the light of rapidly developing evidence on this topic, we would like to comment on this excellent work of the BSG.As the terminology of serrated polyps is confusing, and does not help to bring a clear message to the general gastrointestinal practice, the BSG proposes new terminology. We support the proposal of the BSG to simplify the WHO classification slightly by renaming ‘sessile serrated adenomas/polyps’ …

    更新日期:2017-09-23
  • A New Series of Succinimido-ferrociphenols and Related Heterocyclic Species Induce Strong Antiproliferative Effects, Especially against Ovarian Cancer Cells Resistant to Cisplatin
    J. Med. Chem. (IF 6.259) Pub Date : 2017-09-22
    Pascal Pigeon, Yong Wang, Siden Top, Feten Najlaoui, Maria Concepcion Garcia Alvarez, Jérôme Bignon, Michael J. McGlinchey, Gérard Jaouen
    更新日期:2017-09-23
  • Annexin A11 is targeted by IgG4 and IgG1 autoantibodies in IgG4-related disease
    Ann. Rheum. Dis. (IF 12.811) Pub Date : 2017-08-01
    Lowiek M Hubers, Harmjan Vos, Alex R Schuurman, Robin Erken, Ronald P Oude Elferink, Boudewijn Burgering, Stan F J van de Graaf, Ulrich Beuers

    Objective Immunoglobulin G4-related disease (IgG4-RD) is a multiorgan immune-mediated disease that predominantly affects the biliary tract (IgG4-associated cholangitis, IAC) and pancreas (autoimmune pancreatitis, AIP). We recently identified highly expanded IgG4+ B-cell receptor clones in blood and affected tissues of patients with IAC/AIP suggestive of specific (auto)antigenic stimuli involved in initiating and/or maintaining the inflammatory response. This study aimed to identify (auto)antigen(s) that are responsible for the clonal expansion of IgG4+ B cells in IgG4-RD.Design We screened sera of patients with IAC/AIP (n=50), in comparison to control sera of patients with primary sclerosing cholangitis (PSC) and pancreatobiliary malignancies (n=47), for reactivity against human H69 cholangiocyte lysates on immunoblot. Subsequently, target antigens were immunoprecipitated and analysed by mass spectrometry.Results Prominent reactivity against a 56 kDa protein was detected in human H69 cholangiocyte lysates exposed to sera of nine patients with IAC/AIP. Affinity purification and mass spectrometry analysis identified annexin A11, a calcium-dependent phospholipid-binding protein. Annexin A11-specific IgG4 and IgG1 antibodies were only detected in serum of patients with IgG4-RD of the biliary tract/pancreas/salivary glands and not in disease mimickers with PSC and pancreatobiliary malignancies. Epitope analysis showed that two annexin A11 epitopes targeted by IgG1 and IgG4 autoantibodies were shared between patients with IAC/AIP and IgG4 antibodies blocked binding of IgG1 antibodies to the shared annexin A11 epitopes.Conclusion Our data suggest that IgG1-mediated pro-inflammatory autoreactivity against annexin A11 in patients with IgG4-RD may be attenuated by formation of annexin A11-specific IgG4 antibodies supporting an anti-inflammatory role of IgG4 in IgG4-RD.

    更新日期:2017-09-23
  • Fat: so much more than just fat
    Lancet Diabetes Endocrinol. (IF 19.742) Pub Date : 2017-09-22
    Robert Stirrups
    更新日期:2017-09-23
  • Bollywood's dialogue with diabetes: sweet and subtle
    Lancet Diabetes Endocrinol. (IF 19.742) Pub Date : 2017-09-22
    Sanghamitra Pati

    Mainstream Indian cinema fails to engage with the country's increasing burden of diabetes. Sanghamitra Pati reports.

    更新日期:2017-09-23
  • Distinct Tumor-Immune Microenvironments Occur at Different Tumor Sites
    Cancer Discov. (IF 20.011) Pub Date : 2017-09-01
    American Association for Cancer Research

    Tumor regression was linked to immune infiltration in a patient with chemotherapy-treated ovarian cancer.

    更新日期:2017-09-23
  • Oseltamivir, amantadine, and ribavirin combination antiviral therapy versus oseltamivir monotherapy for the treatment of influenza: a multicentre, double-blind, randomised phase 2 trial
    Lancet Infect. Dis. (IF 19.864) Pub Date : 2017-09-22
    John H Beigel, Yajing Bao, Joy Beeler, Weerawat Manosuthi, Alex Slandzicki, Sadia M Dar, John Panuto, Richard L Beasley, Santiago Perez-Patrigeon, Gompol Suwanpimolkul, Marcelo H Losso, Natalie McClure, Dawn R Bozzolo, Christopher Myers, H Preston Holley, Justin Hoopes, H Clifford Lane, Michael D Hughes, Richard T Davey, Michael Winnie, Dinh V Dinh, Raghu Seethala, Hiram Garcia, Joe Pouzar, Michael Seep, Ernie Riffer, Belinda Bart, Sadia Dar, Melanie Hoppers, John Panuto, Heather Rowe, Alex Slandzicki, Cameron Wolfe, Donna Desantis, Barr Baynton, Richard L Beasley, Norman Markowitz, Zebediah A Stearns, Josalyn Cho, Marcy Goisse, Thomas A Wolf, Jennifer Kay, Nila Dharan, William Fitzgibbons, Mark Woodruff, Todd Bell, Thomas Lenzmeier, Robert Schooley, Marie-Carmelle Elie, Patricia Winokur, Robert Finberg, Christopher Hurt, Pablo Tebas, Fred R Sattler, Madhavi Ampajwala, Donald Batts, Mark Bloch, Richard Moore, Dominic Dwyer, Javier Romo-Garcia, Santiago Perez Patrigeon, Ana Patricia Rodríguez Zulueta, Weerawat Manosuthi, Ploenchan Chetchotisakd, Kiat Ruxrungtham, Anchalee Avihingsanon, Gompol Suwanpimolkul, Winai Ratanasuwan, Sergio Lupo, Liliana Trape, Marcelo H Losso, Laura M Macias, Gustavo Lopardo, Laura Barcelona, Analia Mykietuk, Maria F Alzogaray
    更新日期:2017-09-23
  • Finding the right combination antiviral therapy for influenza
    Lancet Infect. Dis. (IF 19.864) Pub Date : 2017-09-22
    Michael G Ison
    更新日期:2017-09-23
  • NHS bosses reject GPs’ request to close patient lists
    BMJ (IF 20.7) Pub Date : 2017-09-22
    Gareth Iacobucci

    A group of general practices in Folkestone, Kent, that applied to formally close their practice lists because of safety concerns have had their request knocked back by NHS bosses, The BMJ has learnt.Earlier this month seven of eight practices in the town applied for permission to close their patient lists on the basis that they were “unable to take on more patients safely.” The action was triggered after one local practice was forced to hand its contract back to South Kent Coast Clinical Commissioning Group in May, prompting the CCG to order that the practice’s 4700 patients be reallocated to other local practices.But the CCG rejected the practices’ application after a meeting held on Thursday 21 September. …

    更新日期:2017-09-23
  • Last ditch effort to repeal Obamacare gathers steam
    BMJ (IF 20.7) Pub Date : 2017-09-22
    Owen Dyer

    The Affordable Care Act, Barack Obama’s signature health reform, faces a real and fast developing threat from a fourth Senate repeal bill.As September began, Senate Republicans’ efforts to undo Obamacare were given a small chance of success. But the prospect of definitive failure seems to have galvanized the party, and leaders are sounding increasingly confident, with President Donald Trump and the Senate majority leader, Mitch McConnell, asserting that their new version of “Trumpcare” will pass.The bill, called Cassidy-Graham, is effectively the last chance this Congress will have to repeal Obamacare before the midterm elections in November 2018. Under Senate rules, after 30 September it will require an unattainable 60 vote majority to pass. Until 30 September it may pass as a budget measure with a simple majority. In a 50-50 Senate split the vice president, Mike Pence, would …

    更新日期:2017-09-23
  • In cases of serious injury “scoop and run” improves survival compared with ambulance
    BMJ (IF 20.7) Pub Date : 2017-09-22
    Zosia Kmietowicz

    Researchers have discovered what gang members have known all along—that you’re more likely to survive a serious injury if you get yourself to hospital than if you wait for an ambulance.1“Scoop and run” describes the most basic form of prehospital trauma care—transportation with no intervention. A study from 2014 found that patients who used private transportation had improved survival compared with those who waited for an ambulance. But researchers from John Hopkins University School of Medicine …

    更新日期:2017-09-23
  • Distinct clinical and biological implications of various DNMT3A mutations in myeloid neoplasms
    Leukemia (IF 11.702) Pub Date : 
    S K Balasubramanian, M Aly, Y Nagata, T Bat, B P Przychodzen, C M Hirsch, V Adema, V Visconte, T Kuzmanovic, T Radivoyevitch, A Nazha, S Mukherjee, M A Sekeres, J P Maciejewski

    Distinct clinical and biological implications of various DNMT3A mutations in myeloid neoplasms Leukemia, Published online: 22 September 2017; doi:10.1038/leu.2017.295

    更新日期:2017-09-22
  • NOTCH1 mutations are associated with high CD49d expression in chronic lymphocytic leukemia: Link between the NOTCH1 and the NF-kB pathways
    Leukemia (IF 11.702) Pub Date : 
    D Benedetti, E Tissino, F Pozzo, T Bittolo, C Caldana, C Perini, D Martorelli, V Bravin, T D’Agaro, F M Rossi, R Bomben, E Santinelli, F Zaja, G Pozzato, A Chiarenza, F Di Raimondo, G Del Poeta, D Rossi, G Gaidano, M Dal Bo, V Gattei, A Zucchetto

    NOTCH1 mutations are associated with high CD49d expression in chronic lymphocytic leukemia: Link between the NOTCH1 and the NF-kB pathways Leukemia, Published online: 22 September 2017; doi:10.1038/leu.2017.296

    更新日期:2017-09-22
  • Performance of the myelofibrosis secondary to PV and ET-prognostic model (MYSEC-PM) in a series of 262 patients from the Spanish registry of myelofibrosis
    Leukemia (IF 11.702) Pub Date : 
    J-C Hernández-Boluda, A Pereira, J-G Correa, A Alvarez-Larrán, F Ferrer-Marín, J-M Raya, J Martínez-López, M Pérez-Encinas, N Estrada, P Velez, M-L Fox, V García-Gutiérrez, A Payer, A Kerguelen, B Cuevas, M-A Durán, M-J Ramírez, M-T Gómez-Casares, M-I Mata-Vázquez, E Mora, C Martínez-Valverde, M Gómez, F Cervantes

    Performance of the myelofibrosis secondary to PV and ET-prognostic model (MYSEC-PM) in a series of 262 patients from the Spanish registry of myelofibrosis Leukemia, Published online: 22 September 2017; doi:10.1038/leu.2017.297

    更新日期:2017-09-22
  • Fibrotic progression in Polycythemia vera is associated with early concomitant driver-mutations besides JAK2
    Leukemia (IF 11.702) Pub Date : 
    S Bartels, M Faisal, G Büsche, J Schlue, H Kreipe, U Lehmann

    Fibrotic progression in Polycythemia vera is associated with early concomitant driver-mutations besides JAK2 Leukemia, Published online: 22 September 2017; doi:10.1038/leu.2017.298

    更新日期:2017-09-22
  • Inflammation: Cytokines alter inflammatory responses via chromatin changes
    Nat. Rev. Rheumatol. (IF 12.188) Pub Date : 
    Sarah Onuora

    Inflammation: Cytokines alter inflammatory responses via chromatin changes Nature Reviews Rheumatology, Published online: 22 September 2017; doi:10.1038/nrrheum.2017.154

    更新日期:2017-09-22
  • Synovial tissue research: a state-of-the-art review
    Nat. Rev. Rheumatol. (IF 12.188) Pub Date : 
    Carl Orr, Elsa Vieira-Sousa, David L. Boyle, Maya H. Buch, Christopher D. Buckley, Juan D. Cañete, Anca I. Catrina, Ernest H. S. Choy, Paul Emery, Ursula Fearon, Andrew Filer, Danielle Gerlag, Frances Humby, John D. Isaacs, Søren A. Just, Bernard R. Lauwerys, Benoit Le Goff, Antonio Manzo, Trudy McGarry, Iain B. McInnes, Aurélie Najm, Constantino Pitzalis, Arthur Pratt, Malcolm Smith, Paul P. Tak, Rogier Thurlings, João E. Fonseca, Douglas J. Veale

    Synovial tissue research: a state-of-the-art review Nature Reviews Rheumatology, Published online: 22 September 2017; doi:10.1038/nrrheum.2017.161

    更新日期:2017-09-22
  • Inflammation: Cytokines alter inflammatory responses via chromatin changes
    Nat. Rev. Rheumatol. (IF 12.188) Pub Date : 
    Sarah Onuora

    Inflammation: Cytokines alter inflammatory responses via chromatin changes Nature Reviews Rheumatology, Published online: 22 September 2017; doi:10.1038/nrrheum.2017.154

    更新日期:2017-09-22
  • Synovial tissue research: a state-of-the-art review
    Nat. Rev. Rheumatol. (IF 12.188) Pub Date : 
    Carl Orr, Elsa Vieira-Sousa, David L. Boyle, Maya H. Buch, Christopher D. Buckley, Juan D. Cañete, Anca I. Catrina, Ernest H. S. Choy, Paul Emery, Ursula Fearon, Andrew Filer, Danielle Gerlag, Frances Humby, John D. Isaacs, Søren A. Just, Bernard R. Lauwerys, Benoit Le Goff, Antonio Manzo, Trudy McGarry, Iain B. McInnes, Aurélie Najm, Constantino Pitzalis, Arthur Pratt, Malcolm Smith, Paul P. Tak, Rogier Thurlings, João E. Fonseca, Douglas J. Veale

    Synovial tissue research: a state-of-the-art review Nature Reviews Rheumatology, Published online: 22 September 2017; doi:10.1038/nrrheum.2017.161

    更新日期:2017-09-22
  • Stem cell-derived interneuron transplants functionally integrate within the existing circuitry
    Mol. Psychiatry (IF 13.204) Pub Date : 
    J J Donegan, J A Tyson, S Y Branch, M J Beckstead, S A Anderson, D J Lodge

    Stem cell-derived interneuron transplants functionally integrate within the existing circuitry Molecular Psychiatry 22, 1369 (October 2017). doi:10.1038/mp.2017.198 Authors: J J Donegan, J A Tyson, S Y Branch, M J Beckstead, S A Anderson & D J Lodge

    更新日期:2017-09-22
  • BDNF at the synapse: why location matters
    Mol. Psychiatry (IF 13.204) Pub Date : July 25, 2
    M Song, K Martinowich, F S Lee

    BDNF at the synapse: why location matters Molecular Psychiatry 22, 1370 (October 2017). doi:10.1038/mp.2017.144 Authors: M Song, K Martinowich & F S Lee

    更新日期:2017-09-22
  • Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117)
    Mol. Psychiatry (IF 13.204) Pub Date : July 25, 2
    T-K Clarke, M J Adams, G Davies, D M Howard, L S Hall, S Padmanabhan, A D Murray, B H Smith, A Campbell, C Hayward, D J Porteous, I J Deary, A M McIntosh

    Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117) Molecular Psychiatry 22, 1376 (October 2017). doi:10.1038/mp.2017.153 Authors: T-K Clarke, M J Adams, G Davies, D M Howard, L S Hall, S Padmanabhan, A D Murray, B H Smith, A Campbell, C Hayward, D J Porteous, I J Deary & A M McIntosh

    更新日期:2017-09-22
  • Toward a conceptual framework for early brain and behavior development in autism
    Mol. Psychiatry (IF 13.204) Pub Date : July 25, 2
    J Piven, J T Elison, M J Zylka

    Toward a conceptual framework for early brain and behavior development in autism Molecular Psychiatry 22, 1385 (October 2017). doi:10.1038/mp.2017.131 Authors: J Piven, J T Elison & M J Zylka

    更新日期:2017-09-22
  • Neuropathology of suicide: recent findings and future directions
    Mol. Psychiatry (IF 13.204) Pub Date : July 11, 2
    P-E Lutz, N Mechawar, G Turecki

    Neuropathology of suicide: recent findings and future directions Molecular Psychiatry 22, 1395 (October 2017). doi:10.1038/mp.2017.141 Authors: P-E Lutz, N Mechawar & G Turecki

    更新日期:2017-09-22
  • Reduction of smoking urges with intranasal insulin: a randomized, crossover, placebo-controlled clinical trial
    Mol. Psychiatry (IF 13.204) Pub Date : February 2
    A Hamidovic, M Khafaja, V Brandon, J Anderson, G Ray, A M Allan, M R Burge

    Reduction of smoking urges with intranasal insulin: a randomized, crossover, placebo-controlled clinical trial Molecular Psychiatry 22, 1413 (October 2017). doi:10.1038/mp.2016.234 Authors: A Hamidovic, M Khafaja, V Brandon, J Anderson, G Ray, A M Allan & M R Burge

    更新日期:2017-09-22
  • Cannabinoid CB1 receptors in distinct circuits of the extended amygdala determine fear responsiveness to unpredictable threat
    Mol. Psychiatry (IF 13.204) Pub Date : October 4,
    M D Lange, T Daldrup, F Remmers, H J Szkudlarek, J Lesting, S Guggenhuber, S Ruehle, K Jüngling, T Seidenbecher, B Lutz, H C Pape

    Cannabinoid CB1 receptors in distinct circuits of the extended amygdala determine fear responsiveness to unpredictable threat Molecular Psychiatry 22, 1422 (October 2017). doi:10.1038/mp.2016.156 Authors: M D Lange, T Daldrup, F Remmers, H J Szkudlarek, J Lesting, S Guggenhuber, S Ruehle, K Jüngling, T Seidenbecher, B Lutz & H C Pape

    更新日期:2017-09-22
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
所有期刊列表A-Z