bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global burden of all-cause and cause-specific mortality due to smokeless tobacco use: systematic review and meta-analysis
Authors: Sinha Dhirendra N , Suliankatchi Rizwan A , Gupta Prakash C , Thamarangsi Thaksaphon , Agarwal Naveen , Parascandola Mark , Mehrotra Ravi 
Published: December 2016

ObjectivesTo systematically review and meta-analyse the studies investigating the association between smokeless tobacco (SLT) use and all-cause mortality and cause-specific mortality outcomes among adult users of SLT and estimate the number of attributable deaths worldwide.MethodsRandom-effects meta-analysis was used to estimate the pooled risk of death due to SLT use. Population attributable fractions were derived and used to calculate the number of attributable deaths. Observational studies published upto 2015 were identified through MEDLINE, IndMED, Google Scholar and other databases. Data on the prevalence of SLT use was obtained from latest reports or national surveys. Data on the disease burden were obtained from the Global Burden of Disease Study. Hospital-based or community-based case–control and cohort studies that adjusted for the smoking status were included.Results16 studies that provided estimates for mortality due to all cause, all cancer, upper aerodigestive tract (UADT) cancer, stomach cancer, cervical cancer, ischaemic heart disease (IHD) and stroke were included. A significant association was found for mortality due to all cause (1.22; 1.11–1.34), all cancer (1.31; 1.16–1.47), UADT cancer (2.17; 1.47–3.22), stomach cancer (1.33; 1.12–1.59), cervical cancer (2.07; 1.64–2.61), IHD (1.10; 1.04–1.17) and stroke (1.37; 1.24–1.51). Subgroup analysis showed major regional differences. Globally, the number of attributable deaths from all-cause mortality was 652 494 (234 008–1 081 437), of which 88% was borne by the South-East Asian region.ConclusionsSLT is responsible for a large number of deaths worldwide with the South-East Asian region bearing a substantial share of the burden.
Electronic and optical properties of pentagonal-B2C monolayer: A first-principles calculation
Authors: Naseri Mosayeb , Jalilian Jafar , Reshak A. H. 
Published: December 2016

The electronic and optical properties of pentagonal B2C (penta-B2C) monolayer are investigated by means of the first-principles calculations in the framework of the density functional theory. The cohesive energy consideration confirms the good stability of the B2C nanostructure in this phase. The electronic band structure reveals that the valence band maximum (VBM) is located at [Formula: see text]-point of the first Brillouin zone (BZ) whereas the conduction band minimum (CBM) is situated at the center of the BZ, resulting in an indirect energy bandgap of about 1.5 eV. Furthermore, a calculated low absorption and low reflection of the material in low energy ranges denote the transparency of the B2C monolayer in the investigated range for normal light incidence. The obtained results may find application in fabrication of future opto-electronic devices.
The origin and occurrence of subaqueous sedimentary cracks
Authors: McMahon Sean , van Smeerdijk Hood Ashleigh , McIlroy Duncan 
Published: December 2016

Abstract
The rock record attests that sediments have cracked at or below the sediment–water interface in strictly subaqueous settings throughout Earth history. In recent decades, a number of hypotheses have been advanced to explain this phenomenon, but these are widely regarded as being mutually exclusive and there is little consensus about which model is correct. In this paper, we first review the geometries, lithologies and range of facies in which subaqueous sedimentary cracks occur in the geological record, with particular attention to cracks in carbonates. We then evaluate current models for subaqueous cracking, emphasizing that different models may be correct with respect to different sets of cracks, but that cracking is generally a two-step process involving sediment stabilization prior to disruption. We also present the results of some simple new experiments designed to test the dominant models of crack formation. These results demonstrate for the first time that microbial mats can produce thin, shallow cracks at the sediment–water interface. We conclude that the presence of cracks in marine, brackish and lacustrine rocks should not be used uncritically to infer fluctuations in salinity in the depositional environment.

Supplementary material:
A video showing a micro-CT scan of a hand-sample from the Monteville Formation, South Africa is available at
https://doi.org/10.6084/m9.figshare.c.3580673
Filling the Tank: Keeping Antitumor T Cells Metabolically Fit for the Long Haul
Authors: Delgoffe Greg M. 
Published: December 2016

Abstract
Discoveries in tumor immunology and subsequent clinical advances in cancer immunotherapy have revealed that the immune system is not oblivious to tumor progression but heavily interacts with developing neoplasia and malignancy. A major factor preventing immune destruction is the establishment of a highly immunosuppressive tumor microenvironment (TME), which provides architecture to the tumor, supports indirect means of immunosuppression such as the recruitment of tolerogenic cells like regulatory T cells and myeloid-derived suppressor cells (MDSC), and represents a zone of metabolically dearth conditions. T-cell activation and consequent effector function are cellular states characterized by extreme metabolic demands, and activation in the context of insufficient metabolic substrates results in anergy or regulatory differentiation. Thus, T cells must endure both immunosuppression (co-inhibitory molecule ligation, regulatory T cells, and suppressive cytokines) but also a sort of metabolic suppression in the TME. Here I will review the general features of the TME, identify the metabolic demands of activated effector T cells, discuss the known metabolic checkpoints associated with intratumoral T cells, and propose strategies for generating superior antitumor T cells, whether in vitro for adoptive cell therapy or through in vivo reinvigoration of the existing immune response. Cancer Immunol Res; 4(12); 1001–6. ©2016 AACR.
Effect of ticagrelor on endothelial calcium signalling and barrier function
Authors: Gündüz Dursun , Tanislav Christian , Schluter Klaus-Dieter , Schulz Rainer , Hamm Christian , Aslam Muhammad 
Published: December 2016

SummaryThe P2Y12 receptor is a Gi-coupled receptor whose activation inhibits adenylyl cyclase and thereby reduces the concentration of intracellular cAMP. Here the hypothesis was tested whether AR-C 66096 or ticagrelor, two direct-acting and reversibly binding P2Y12 receptor antagonists, protect endothelial cell (EC) barrier function by raising intracellular cAMP in ECs. The study was carried out on primary human umbilical vein ECs (HUVECs) and human pulmonary microvascular ECs (hPMECs). AR-C66096 (10 µM) induced a 50 % increase in cAMP in ECs whereas ticagrelor (2–10 µM) had no effect. Likewise, AR-C666096 antagonised thrombin-induced hyperpermeability in both HUVECs and hPMECs, but ticagrelor had no effect on basal EC monolayer permeability. Ticagrelor, however, sensitised ECs for thrombin-induced hyperpermeability and potentiated the thrombin effect. Ticagrelor but not AR-C66096 caused an increase in cytosolic calcium ([Ca2+]i). This increase in [Ca2+]i was abrogated by LaCl3 (Ca2+ influx inhibitor) but not by xestospongin C (IP3 receptor antagonist) or by depletion of intracellular stores with thapsigargin, suggesting a Ca2+ influx from the extracellular space. Accordingly, ticagrelor caused an increase in myosin light chain (MLC) phosphorylation, an important regulator of EC contractile machinery and thus permeability, which was abrogated by LaCl3. The ability of ticagrelor to potentiate EC permeability was abrogated by a MLC kinase inhibitor (ML-7; 10 µM). Our data demonstrate that the P2Y12 receptor antagonist AR-C66096 exerts a protective effect on ECs in vitro, possibly by raising intracellular cAMP, whereas ticagrelor sensitises EC barrier function by inducing Ca2+ influx and activating downstream EC contractile machinery.Supplementary Material to this article is available online at www.thrombosis-online.com.
A novel hirudin derivative inhibiting thrombin without bleeding for subcutaneous injection
Authors: Zhao Bing , Zhang Yanling , Huang Yinong , Yu Jinchao , Li Yaran , Wang Qi , Ma Yixin , Song Hou-Yan , Yu Min , Mo Wei 
Published: December 2016

SummaryCurrently, anticoagulants would be used to prevent thrombosis. Thrombin is an effector enzyme for haemostasis and thrombosis. We designed a direct thrombin inhibitor peptide (DTIP) using molecular simulation and homology modelling and demonstrated that the C-terminus of DTIP interacts with exosite I, and N-terminus with the activity site of thrombin, respectively. DTIP interfered with thrombin-mediated coagulation in human, rat and mouse plasma (n=10 per group) and blocked clotting in human whole blood in vitro. When administered subcutaneously, DTIP showed potent and dose-dependent extension of aPTT, PT, TT and CT in rats (n=10 per group). The antithrombotic dose of DTIP induced significantly less bleeding than bivalirudin determined by transecting distal tail assay in rats. Furthermore, DTIP reached peak blood concentration in 0.5–1 hour and did not cause increased bleeding after five days of dosing compared to dabigatran etexilate. The antithrombotic effect of DTIP was evaluated in mice using lethal pulmonary thromboembolism model and FeCl3-induced mesenteric arteriole thrombus model. DTIP (1.0 mg/kg, sc) prevented deep venous thrombosis and increased the survival rate associated with pulmonary thromboembolism from 30 % to 80 %. Intravital microscopy showed that DTIP (1.0 mg/kg, sc) decelerated mesenteric arteriole thrombosis caused by FeCl3 injury. These data establish that DTIP is a novel antithrombotic agent that could be used to prevent thrombosis without conferring an increased bleeding risk.Supplementary Material to this article is available at www.thrombosis-online.com.
The Uzun Hasan Mosque in Tabriz: New Perspectives on a Tabrizi Ceramic Tile Workshop
Authors: Aube Sandra 
Published: December 2016

The recent rediscovery of the mosque erected around 1477–84 (882–89) in Tabriz by the Aq Qoyunlu ruler Uzun Hasan (r. 1457–78]) provides new perspectives on ceramic tile production in the former Turkmen capital. The Blue Mosque and its exceptional tile decoration have long been considered to be the last vestiges of the innovative features of the Qara Qoyunlu workshops in Tabriz. The recovery of the Uzun Hasan Mosque sheds new light on this prestigious artistic center: besides confirming the innovative traits of Tabrizi production, its architectural decoration highlights the strong artistic continuity from Qara Qoyunlu to Aq Qoyunlu workshops. These unusual ceramic tiles also constitute a previously unknown stage in the history of Iranian ceramic tiles.
Intrahepatic distant recurrence after radiofrequency ablation for hepatocellular carcinoma: precursor nodules on pre-procedural gadoxetic acid-enhanced liver magnetic resonance imaging
Authors: Song Kyoung Doo , Rhim Hyunchul , Lee Min Woo , Kim Young-sun , Kang Tae Wook 
Published: December 2016

Background Intrahepatic distant recurrence (IDR) after radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) is associated with poor overall survival outcome. Purpose To evaluate the incidence and findings on pre-procedural gadoxetic acid-enhanced liver magnetic resonance imaging (MRI) of precursor nodules for IDR after RF ablation for HCC. Material and Methods This study was approved by our institutional review board. Among 343 patients treated with RF ablation for HCC between 2009 and 2011, 141 patients who underwent pre-procedural gadoxetic acid-enhanced liver MRI and experienced IDR were enrolled. The presence of precursor nodules for IDR on pre-procedural imaging was assessed. Nodules were categorized based on hypervascularity in the arterial phase and signal intensity on hepatobiliary phase images. Time to recurrence was compared between patients with and without precursor nodules. Results In 46 (32.7%) of 141 patients (50 HCCs), there were precursor nodules on pre-procedural MRIs (median follow-up period, 4.39 years; range, 0.08–6.08). In three patients, HCCs were missed on imaging. In the remaining 43 patients, the 47 precursor nodules identified were non-hypervascular hypointense (n = 26), non-hypervascular isointense (n = 6), non-hypervascular hyperintense (n = 2), hypervascular hypointense (n = 10), and hypervascular isointense (n = 3). The mean time-to-recurrence was significantly shorter for patients with precursor nodules than for those without (16.6 versus 24.0 months, P = 0.011). Conclusion About one-third of patients with IDR after RF ablation for HCC had precursor nodules on pre-procedural gadoxetic acid-enhanced MRI, most commonly non-hypervascular hypointense nodules in the hepatobiliary phase.
Assessing Progress in Implementing Uganda’s Nutrition Action Plan
Authors: Agaba Edgar , Pomeroy-Stevens Amanda , Ghosh Shibani , Griffiths Jeffrey K. 
Published: December 2016

Background: The 2011 Uganda Nutrition Action Plan (UNAP) established 2016 maternal and child nutrition targets. However, there is a lack of routine district-level data collection to assess UNAP implementation. Objective: To use Nutrition Innovation Lab (NIL) data to inform policy makers on the progress of UNAP-related indicators. Methods: The NIL collected serial household-level survey data (n = 3600) in 6 districts, including 2 UNAP implementation districts, in 2012 and 2014. Questionnaires focused on food security, nutrition, and health, among others, and included specific indicators relevant to UNAP’s targets. Results: In 2012, outcomes in Kisoro and Lira districts were below national average for some UNAP key indicators, including dietary diversity and anemia prevalence, but above average for others (exclusive breastfeeding and underweight among women and children). The prevalence of child stunting was higher than national averages in Kisoro but below national averages in Lira. In 2014, anemia among women and children decreased significantly. Kisoro also saw improvements in several other UNAP target indicators including underweight, breastfeeding, and stunting. Conclusion: Although the study showed improvements in key UNAP indicators, there is a need to invest in appropriate methods to gauge its progress because the NIL was not designed to assess UNAP. Since the quality of implementation of complex multisectoral programs can differ widely across different contexts, it is critical that effective monitoring of progress be part of such programs. National endorsement of nutrition plans doesn’t in itself result in desired outcomes, hence, the allocation of scarce resources has to be based on rigorous evidence.
Identification and validation of clinically meaningful benchmarks in the 12-item Multiple Sclerosis Walking Scale
Authors: Goldman Myla D , Ward Melanie D , Motl Robert W , Jones David E , Pula John H , Cadavid Diego 
Published: December 2016

Background: The 12-item Multiple Sclerosis Walking Scale (12-MSWS) is a validated questionnaire which assessed walking function; it has been widely adopted in multiple sclerosis (MS) clinical research. Objective: Identify and validate clinically meaningful 12-MSWS benchmarks in MS. Methods: Cross-sectional study of 159 MS patients permitted identification of clinically meaningful 12-MSWS benchmarks based on their relationship to real-life anchors. Identified 12-MSWS benchmarks were then validated in a second population of 96 subjects using measures of ambulation, cognition, and patient-reported outcomes. Results: 12-MSWS score of 0–24.99 was associated with working outside the home and assistance-free mobility; 25–49.99 was associated with gait disability and difficulty doing housework; 50–74.99 was associated with unemployment, government healthcare, cane use, and difficulty performing instrumental activities of daily living (IADLs); and 75–100 was associated with change in occupation due to walking, mobility impairment requiring bilateral assistance, and inability to perform IADLs. During the validation step, strong linear associations were identified between 12-MSWS benchmarks and other MS-related disability outcome measures, including ambulatory and non-ambulatory measures. Conclusion: We have identified clinically meaningful 12-MSWS benchmarks which define four groups differentiated by increasing levels of mobility impairment and associated loss of functional independence. These data provide insight into how 12-MSWS translate to meaningful functional limitations in MS.
Large differences in adiponectin levels have no clear effect on multiple sclerosis risk: A Mendelian randomization study
Authors: Devorak Julia , Mokry Lauren E , Morris John A , Forgetta Vincenzo , Davey Smith George , Sawcer Stephen , Richards J Brent 
Published: December 2016

Background: Mendelian randomization (MR) studies have demonstrated strong support for an association between genetically increased body mass index and risk of multiple sclerosis (MS). The adipokine adiponectin may be a potential mechanism linking body mass to risk of MS. Objective: To evaluate whether genetically increased adiponectin levels influence risk of MS. Methods: Using genome-wide significant single nucleotide polymorphisms (SNPs) for adiponectin, we undertook an MR study to estimate the effect of adiponectin on MS. This method prevents bias due to reverse causation and minimizes bias due to confounding. Sensitivity analyses were performed to evaluate the assumptions of MR. Results: MR analyses did not support a role for genetically elevated adiponectin in risk of MS (odds ratio (OR) = 0.93 per unit increase in natural-log-transformed adiponectin, equivalent to a two-standard deviation increase in adiponectin on the absolute scale; 95% confidence interval (CI) = 0.66–1.33; p = 0.61). Further MR analysis suggested that genetic variation at the adiponectin gene, which influences adiponectin level, does not impact MS risk. Sensitivity analyses, including MR-Egger regression, suggested no bias due to pleiotropy. Conclusion: Lifelong genetically increased adiponectin levels in humans have no clear effect on risk of MS. Other biological factors driving the association between body mass and MS should be investigated.
Translocator positron-emission tomography and magnetic resonance spectroscopic imaging of brain glial cell activation in multiple sclerosis
Authors: Datta Gourab , Violante Ines R , Scott Gregory , Zimmerman Karl , Santos-Ribeiro Andre , Rabiner Eugenii A , Gunn Roger N , Malik Omar , Ciccarelli Olga , Nicholas Richard , Matthews Paul M 
Published: December 2016

Background: Multiple sclerosis (MS) is characterised by a diffuse inflammatory response mediated by microglia and astrocytes. Brain translocator protein (TSPO) positron-emission tomography (PET) and [myo-inositol] magnetic resonance spectroscopy (MRS) were used together to assess this. Objective: To explore the in vivo relationships between MRS and PET [11C]PBR28 in MS over a range of brain inflammatory burden. Methods: A total of 23 patients were studied. TSPO PET imaging with [11C]PBR28, single voxel MRS and conventional magnetic resonance imaging (MRI) sequences were undertaken. Disability was assessed by Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC). Results: [11C]PBR28 uptake and [ myo-inositol] were not associated. When the whole cohort was stratified by higher [11C]PBR28 inflammatory burden, [ myo-inositol] was positively correlated to [11C]PBR28 uptake (Spearman’s ρ = 0.685, p = 0.014). Moderate correlations were found between [11C]PBR28 uptake and both MRS creatine normalised N-acetyl aspartate (NAA) concentration and grey matter volume. MSFC was correlated with grey matter volume (ρ = 0.535, p = 0.009). There were no associations between other imaging or clinical measures. Conclusion: MRS [ myo-inositol] and PET [11C]PBR28 measure independent inflammatory processes which may be more commonly found together with more severe inflammatory disease. Microglial activation measured by [11C]PBR28 uptake was associated with loss of neuronal integrity and grey matter atrophy.
Operationalising cognitive fatigability in multiple sclerosis: A Gordian knot that can be cut?
Authors: Harrison Anthony Mark , das Nair Roshan , Moss-Morris Rona 
Published: December 2016

Background: Researchers have attempted to operationalise objective measures of cognitive fatigability in multiple sclerosis (MS) to overcome the perceived subjectivity of patient-reported outcomes of fatigue (PROs). Measures of cognitive fatigability examine decrements in performance during sustained neurocognitive tasks. Objective: This personal viewpoint briefly summarises available evidence for measures of cognitive fatigability in MS and considers their overall utility. Results: Studies suggest there may be a construct that is distinct from self-reported fatigue, reflecting a new potential intervention target. However, assessments vary and findings across and within measures are inconsistent. Few measures have been guided by a coherent theory, and those identified are likely to be influenced by other confounds, such as cognitive impairment caused more directly by disease processes, depression and assessment biases. Conclusion: Future research may benefit from (a) developing a guiding theory of cognitive fatigability, (b) examining ecological and construct validity of existing assessments and (c) exploring whether the more promising cognitive fatigability measures are correlated with impaired functioning after accounting for possible confounds. Given the issues raised, we caution that our purposes as researchers may be better served by continuing our search for a more objective cognitive fatigability construct that runs in parallel with improving, rather than devaluing, current PROs.