Science translational medicine Journal Impact Factor & Information

Publisher: American Association for the Advancement of Science

Journal description

Current impact factor: 14.41

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 14.414
2012 Impact Factor 10.757
2011 Impact Factor 7.804
2010 Impact Factor 3.511

Impact factor over time

Impact factor
Year

Additional details

5-year impact 10.48
Cited half-life 1.80
Immediacy index 3.69
Eigenfactor 0.04
Article influence 5.18
ISSN 1946-6242

Publisher details

American Association for the Advancement of Science

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Pre-print may be considered prior publication
    • Pre-print on not-for-profit preprint servers where allowed, please contact editors for clarification
    • Cannot archive until publication
    • Authors retain copyright
    • On author's personal website or institutional repository
    • Publisher's version/PDF cannot be used
    • Must link to publisher version
    • Set statement must accompany post-print (see policy)
    • Published source must be acknowledged with DOI
    • Authors covered by funding agency rules, may post author's post-print in PubMed Central or funder's designated repository after a 6 month embargo
    • Authors covered by funding agency rules, must state on submission, for article to be released in PubMed Central or funder's designated repository after 6 months after publication.
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Clinical and Translational Science Awards-funded institutions are naturally equipped to drive research on human phenotyping and, in turn, shape the practice of precision medicine in the clinic of the future. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 04/2015; 7(284):284fs15. DOI:10.1126/scitranslmed.aab1596
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    ABSTRACT: IFNλ restores blood-brain barrier integrity after disruption by West Nile virus, reducing virus invasion of the brain and increasing survival of infected mice (Lazear et al., this issue). Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 04/2015; 7(284):284fs16. DOI:10.1126/scitranslmed.aaa2817
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    ABSTRACT: Regulatory T cells (Tregs) are essential to prevent autoimmunity, but excessive Treg function contributes to cancer progression by inhibiting antitumor immune responses. Tregs exert contact-dependent inhibition of immune cells through the production of active transforming growth factor-β1 (TGF-β1). On the Treg cell surface, TGF-β1 is in an inactive form bound to membrane protein GARP and then activated by an unknown mechanism. We demonstrate that GARP is involved in this activation mechanism. Two anti-GARP monoclonal antibodies were generated that block the production of active TGF-β1 by human Tregs. These antibodies recognize a conformational epitope that requires amino acids GARP137-139 within GARP/TGF-β1 complexes. A variety of antibodies recognizing other GARP epitopes did not block active TGF-β1 production by Tregs. In a model of xenogeneic graft-versus-host disease in NSG mice, the blocking antibodies inhibited the immunosuppressive activity of human Tregs. These antibodies may serve as therapeutic tools to boost immune responses to infection or cancer via a mechanism of action distinct from that of currently available immunomodulatory antibodies. Used alone or in combination with tumor vaccines or antibodies targeting the CTLA4 or PD1/PD-L1 pathways, blocking anti-GARP antibodies may improve the efficiency of cancer immunotherapy. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 04/2015; 7(284):284ra56. DOI:10.1126/scitranslmed.aaa1983
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    ABSTRACT: Two different devices show that delivery of cancer drugs directly into tumors in vivo can indicate cancer sensitivity; if implemented in clinical practice, these devices have the potential to reduce indiscriminate drug use, to improve survival, and to reduce unnecessary adverse effects (Jonas et al. and Klinghoffer et al., this issue). Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 04/2015; 7(284):284ps10. DOI:10.1126/scitranslmed.aab1214
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    ABSTRACT: Deciphering whether actionable driver mutations are found in all or a subset of tumor cells will likely be required to improve drug development and precision medicine strategies. We analyzed nine cancer types to determine the subclonal frequencies of driver events, to time mutational processes during cancer evolution, and to identify drivers of subclonal expansions. Although mutations in known driver genes typically occurred early in cancer evolution, we also identified later subclonal "actionable" mutations, including BRAF (V600E), IDH1 (R132H), PIK3CA (E545K), EGFR (L858R), and KRAS (G12D), which may compromise the efficacy of targeted therapy approaches. More than 20% of IDH1 mutations in glioblastomas, and 15% of mutations in genes in the PI3K (phosphatidylinositol 3-kinase)-AKT-mTOR (mammalian target of rapamycin) signaling axis across all tumor types were subclonal. Mutations in the RAS-MEK (mitogen-activated protein kinase kinase) signaling axis were less likely to be subclonal than mutations in genes associated with PI3K-AKT-mTOR signaling. Analysis of late mutations revealed a link between APOBEC-mediated mutagenesis and the acquisition of subclonal driver mutations and uncovered putative cancer genes involved in subclonal expansions, including CTNNA2 and ATXN1. Our results provide a pan-cancer census of driver events within the context of intratumor heterogeneity and reveal patterns of tumor evolution across cancers. The frequent presence of subclonal driver mutations suggests the need to stratify targeted therapy response according to the proportion of tumor cells in which the driver is identified. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 04/2015; 7(283):283ra54. DOI:10.1126/scitranslmed.aaa1408
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    ABSTRACT: The immunosurveillance mechanisms governing high-risk neuroblastoma (HR-NB), a major pediatric malignancy, have been elusive. We identify a potential role for natural killer (NK) cells, in particular the interaction between the NK receptor NKp30 and its ligand, B7-H6, in the metastatic progression and survival of HR-NB after myeloablative multimodal chemotherapy and stem cell transplantation. NB cells expressing the NKp30 ligand B7-H6 stimulated NK cells in an NKp30-dependent manner. Serum concentration of soluble B7-H6 correlated with the down-regulation of NKp30, bone marrow metastases, and chemoresistance, and soluble B7-H6 contained in the serum of HR-NB patients inhibited NK cell functions in vitro. The expression of distinct NKp30 isoforms affecting the polarization of NK cell functions correlated with 10-year event-free survival in three independent cohorts of HR-NB in remission from metastases after induction chemotherapy (n = 196, P < 0.001), adding prognostic value to known risk factors such as N-Myc amplification and age >18 months. We conclude that the interaction between NKp30 and B7-H6 may contribute to the fate of NB patients and that both the expression of NKp30 isoforms on circulating NK cells and the concentration of soluble B7-H6 in the serum may be clinically useful as biomarkers for risk stratification. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 04/2015; 7(283):283ra55. DOI:10.1126/scitranslmed.aaa2327
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    ABSTRACT: Massively parallel sequencing approaches are beginning to be used clinically to characterize individual patient tumors and to select therapies based on the identified mutations. A major question in these analyses is the extent to which these methods identify clinically actionable alterations and whether the examination of the tumor tissue alone is sufficient or whether matched normal DNA should also be analyzed to accurately identify tumor-specific (somatic) alterations. To address these issues, we comprehensively evaluated 815 tumor-normal paired samples from patients of 15 tumor types. We identified genomic alterations using next-generation sequencing of whole exomes or 111 targeted genes that were validated with sensitivities >95% and >99%, respectively, and specificities >99.99%. These analyses revealed an average of 140 and 4.3 somatic mutations per exome and targeted analysis, respectively. More than 75% of cases had somatic alterations in genes associated with known therapies or current clinical trials. Analyses of matched normal DNA identified germline alterations in cancer-predisposing genes in 3% of patients with apparently sporadic cancers. In contrast, a tumor-only sequencing approach could not definitively identify germline changes in cancer-predisposing genes and led to additional false-positive findings comprising 31% and 65% of alterations identified in targeted and exome analyses, respectively, including in potentially actionable genes. These data suggest that matched tumor-normal sequencing analyses are essential for precise identification and interpretation of somatic and germline alterations and have important implications for the diagnostic and therapeutic management of cancer patients. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 04/2015; 7(283):283ra53. DOI:10.1126/scitranslmed.aaa7161
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    ABSTRACT: The surge in computing power and mobile connectivity have fashioned a foundation for mobile health (mHealth) technologies that can transform the mode and quality of clinical research and health care on a global scale. Unimpeded by geographical boundaries, smartphone-linked wearable sensors, point-of-need diagnostic devices, and medical-grade imaging, all built around real-time data streams and supported by automated clinical decision-support tools, will enable care and enhance our understanding of physiological variability. However, the path to mHealth incorporation into clinical care is fraught with challenges. We currently lack high-quality evidence that supports the adoption of many new technologies and have financial, regulatory, and security hurdles to overcome. Fortunately, sweeping efforts are under way to establish the true capabilities and value of the evolving mHealth field. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 04/2015; 7(283):283rv3. DOI:10.1126/scitranslmed.aaa3487
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    ABSTRACT: Hepatitis C virus (HCV) infection affects an estimated 185 million people worldwide, with chronic infection often leading to liver cirrhosis and hepatocellular carcinoma. Although HCV is curable, there is an unmet need for the development of effective and affordable treatment options. Through a cell-based high-throughput screen, we identified chlorcyclizine HCl (CCZ), an over-the-counter drug for allergy symptoms, as a potent inhibitor of HCV infection. CCZ inhibited HCV infection in human hepatoma cells and primary human hepatocytes. The mode of action of CCZ is mediated by inhibiting an early stage of HCV infection, probably targeting viral entry into host cells. The in vitro antiviral effect of CCZ was synergistic with other anti-HCV drugs, including ribavirin, interferon-α, telaprevir, boceprevir, sofosbuvir, daclatasvir, and cyclosporin A, without significant cytotoxicity, suggesting its potential in combination therapy of hepatitis C. In the mouse pharmacokinetic model, CCZ showed preferential liver distribution. In chimeric mice engrafted with primary human hepatocytes, CCZ significantly inhibited infection of HCV genotypes 1b and 2a, without evidence of emergence of drug resistance, during 4 and 6 weeks of treatment, respectively. With its established clinical safety profile as an allergy medication, affordability, and a simple chemical structure for optimization, CCZ represents a promising candidate for drug repurposing and further development as an effective and accessible agent for treatment of HCV infection. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 04/2015; 7(282):282ra49. DOI:10.1126/scitranslmed.3010286
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    ABSTRACT: Infiltration by macrophages represents a characteristic morphological hallmark in high-grade lymphatic malignancies such as Burkitt's lymphoma (BL). Although macrophages can, in principle, target neoplastic cells and mediate antibody-dependent cellular cytotoxicity (ADCC), tumor-associated macrophages (TAMs) regularly fail to exert direct cytotoxic functions. The underlying mechanisms responsible for this observation remain unclear. We demonstrate that inflammatory M1 macrophages kill proliferating high-grade B cell lymphoma cells by releasing the antimicrobial peptide cathelicidin in a vitamin D-dependent fashion. We show that cathelicidin directly induces cell death by targeting mitochondria of BL cells. In contrast, anti-inflammatory M2 macrophages and M2-like TAMs in BL exhibit an altered vitamin D metabolism, resulting in a reduced production of cathelicidin and consequently in inability to lyse BL cells. However, treatment of M2 macrophages with the bioactive form of vitamin D, 1,25D3, or a vitamin D receptor agonist effectively induces cathelicidin production and triggers tumoricidal activity against BL cells. Furthermore, rituximab-mediated cytotoxicity of vitamin D-treated M2 macrophages is cathelicidin-dependent. Finally, vitamin D treatment of 25-hydroxyvitamin D (25D)-deficient volunteers in vivo or primary TAMs in vitro improves rituximab-mediated ADCC against B cell lymphoma cells. These data indicate that activation of the vitamin D signaling pathway activates antitumor activity of TAMs and improves the efficacy of ADCC. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 04/2015; 7(282):282ra47. DOI:10.1126/scitranslmed.aaa3230
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    ABSTRACT: Translation in an academic environment requires a support system-people, goals, models, partnerships, and infrastructures-that will push promising basic science and technology projects forward into the clinic. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 04/2015; 7(282):282cm2. DOI:10.1126/scitranslmed.aaa2049
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    ABSTRACT: Efficient and persisting immune memory is essential for long-term protection from infectious and malignant diseases. The yellow fever (YF) vaccine is a live attenuated virus that mediates lifelong protection, with recent studies showing that the CD8(+) T cell response is particularly robust. Yet, limited data exist regarding the long-term CD8(+) T cell response, with no studies beyond 5 years after vaccination. We investigated 41 vaccinees, spanning 0.27 to 35 years after vaccination. YF-specific CD8(+) T cells were readily detected in almost all donors (38 of 41), with frequencies decreasing with time. As previously described, effector cells dominated the response early after vaccination. We detected a population of naïve-like YF-specific CD8(+) T cells that was stably maintained for more than 25 years and was capable of self-renewal ex vivo. In-depth analyses of markers and genome-wide mRNA profiling showed that naïve-like YF-specific CD8(+) T cells in vaccinees (i) were distinct from genuine naïve cells in unvaccinated donors, (ii) resembled the recently described stem cell-like memory subset (Tscm), and (iii) among all differentiated subsets, had profiles closest to naïve cells. Our findings reveal that CD8(+) Tscm are efficiently induced by a vaccine in humans, persist for decades, and preserve a naïveness-like profile. These data support YF vaccination as an optimal mechanistic model for the study of long-lasting memory CD8(+) T cells in humans. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 04/2015; 7(282):282ra48. DOI:10.1126/scitranslmed.aaa3700
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    ABSTRACT: Cardiorespiratory collapse after a seizure is the leading cause of sudden unexpected death in epilepsy (SUDEP) in young persons, but why only certain individuals are at risk is unknown. To identify a mechanism for this lethal cardiorespiratory failure, we examined whether genes linked to increased SUDEP risk lower the threshold for spreading depolarization (SD), a self-propagating depolarizing wave that silences neuronal networks. Mice carrying mutations in Kv1.1 potassium channels (-/-) and Scn1a sodium ion channels (+/R1407X) phenocopy many aspects of human SUDEP. In mutant, but not wild-type mice, seizures initiated by topical application of 4-aminopyridine to the cortex led to a slow, negative DC potential shift recorded in the dorsal medulla, a brainstem region that controls cardiorespiratory pacemaking. This irreversible event slowly depolarized cells and inactivated synaptic activity, producing cardiorespiratory arrest. Local initiation of SD in this region by potassium chloride microinjection also elicited electroencephalographic suppression, apnea, bradycardia, and asystole, similar to the events seen in monitored human SUDEP. In vitro study of brainstem slices confirmed that mutant mice had a lower threshold for SD elicited by metabolic substrate depletion and that immature mice were at greater risk than adults. Deletion of the gene encoding tau, which prolongs life in these mutants, also restored the normal SD threshold in Kv1.1-mutant mouse brainstem. Thus, brainstem SD may be a critical threshold event linking seizures and SUDEP. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 04/2015; 7(282):282ra46. DOI:10.1126/scitranslmed.aaa4050
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    ABSTRACT: Granulocyte colony-stimulating factor (G-CSF) is routinely used to collect peripheral blood stem cells (PBSCs) from healthy donors for allogeneic hematopoietic stem cell transplantation (allo-HSCT). We show that, in both humans and mice, G-CSF mobilizes a subset of CD34(+) cells with mature monocyte features. These cells, which are phenotypically and functionally conserved in mice and humans, are transcriptionally distinct from myeloid and monocytic precursors but similar to mature monocytes and endowed with immunosuppressive properties. In response to interferon-γ released by activated T cells, these cells produce nitric oxide, which induces allogeneic T cell death both in vitro and in vivo. These apoptotic T cells are engulfed by macrophages that release transforming growth factor-β and promote regulatory T cell expansion. Indeed, the fraction of CD34(+) monocytes in peripheral blood CD34(+) cells inversely correlates with the incidence of acute graft-versus-host disease (GVHD) in humans. Therefore, G-CSF-mobilized cells are an attractive candidate population to be expanded ex vivo for cellular therapy against GVHD. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 04/2015; 7(281):281ra42. DOI:10.1126/scitranslmed.3010435
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    ABSTRACT: The inclusion of engineering ideas and approaches makes medicine a quantitative and systems-based discipline that facilitates precision diagnostics and therapeutics to improve health care delivery for all. Copyright © 2015, American Association for the Advancement of Science.
    Science translational medicine 04/2015; 7(281):281fs13. DOI:10.1126/scitranslmed.aaa4325