bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fusobacterium Nucleatum Subspecies Animalis Influences Proinflammatory Cytokine Expression and Monocyte Activation in Human Colorectal Tumors
Authors: Ye Xiangcang , Wang Rui , Bhattacharya Rajat , Boulbes Delphine R. , Fan Fan , Xia Ling , Adoni Harish , Ajami Nadim J. , Wong Matthew C. , Smith Daniel P. , Petrosino Joseph F. , Venable Susan , Qiao Wei , Baladandayuthapani Veera , Maru Dipen , Ellis Lee M. 
Published: May 2017

Abstract
Chronic infection and associated inflammation have long been suspected to promote human carcinogenesis. Recently, certain gut bacteria, including some in the Fusobacterium genus, have been implicated in playing a role in human colorectal cancer development. However, the Fusobacterium species and subspecies involved and their oncogenic mechanisms remain to be determined. We sought to identify the specific Fusobacterium spp. and ssp. in clinical colorectal cancer specimens by targeted sequencing of Fusobacterium 16S ribosomal RNA gene. Five Fusobacterium spp. were identified in clinical colorectal cancer specimens. Additional analyses confirmed that Fusobacterium nucleatum ssp. animalis was the most prevalent F. nucleatum subspecies in human colorectal cancers. We also assessed inflammatory cytokines in colorectal cancer specimens using immunoassays and found that expression of the cytokines IL17A and TNFα was markedly increased but IL21 decreased in the colorectal tumors. Furthermore, the chemokine (C-C motif) ligand 20 was differentially expressed in colorectal tumors at all stages. In in vitro co-culture assays, F. nucleatum ssp. animalis induced CCL20 protein expression in colorectal cancer cells and monocytes. It also stimulated the monocyte/macrophage activation and migration. Our observations suggested that infection with F. nucleatum ssp. animalis in colorectal tissue could induce inflammatory response and promote colorectal cancer development. Further studies are warranted to determine if F. nucleatum ssp. animalis could be a novel target for colorectal cancer prevention and treatment. Cancer Prev Res; 10(7); 398–409. ©2017 AACR.
A STING Agonist Given with OX40 Receptor and PD-L1 Modulators Primes Immunity and Reduces Tumor Growth in Tolerized Mice
Authors: Foote Jeremy B. , Kok Marleen , Leatherman James M. , Armstrong Todd D. , Marcinkowski Bridget C. , Ojalvo Laureen S. , Kanne David B. , Jaffee Elizabeth M. , Dubensky Thomas W. , Emens Leisha A. 
Published: May 2017

Abstract
Stimulator of interferon genes (STING) signaling induces IFNβ production by intratumoral dendritic cells (DC), driving T-cell priming and recruitment into the tumor microenvironment (TME). We examined to what extent preexisting antigen-specific tolerance influenced the efficacy of in situ delivery of a potent STING-activating cyclic dinucleotide (CDN), ADU S-100, against established HER-2+ breast tumors. ADU S-100 induced HER-2–specific CD8+ T-cell priming and durable tumor clearance in 100% of nontolerant parental FVB/N mice. In contrast, ADU S-100 did not sufficiently prime HER-2–specific CD8+ T cells in tolerant neu/N mice, resulting in only delayed tumor growth and tumor clearance in 10% of the mice. No differences in IFNβ production, DC priming, or HER-2–specific CD8+ T-cell trafficking were detected between FVB/N and neu/N mice. However, activation and expansion of HER-2–specific CD8+ T cells were defective in neu/N mice. Immune cell infiltrates of untreated tumor-bearing neu/N mice expressed high numbers of PD1 and OX40 receptors on their CD8+ T cells, and PD-L1 was highly expressed on both myeloid and tumor cells. Modulating PD-L1 and OX40 receptor signaling combined with intratumoral ADU S-100 administration enhanced HER-2–specific CD8+ T-cell activity, clearing tumors in 40% of neu/N mice. Thus, intratumoral STING agonists could potently prime tumor antigen–specific CD8+ T-cell responses, and adding PD-L1 blockade and OX40 receptor activation can overcome antigen-enforced immune tolerance to induce tumor regression. Cancer Immunol Res; 5(6); 468–79. ©2017 AACR.
Notice of Retraction Ethnic vs Math: The Secret inside Borobudur Temple, Indonesia
Authors: Yanuarto Wanda Nugroho 
Published: May 2017

Notice of Retraction-----------------------------------------------------------------------After careful and considered review of the content of this paper by a duly constituted expert committee, this paper has been found to be in violation of UAD-IAES's Publication Principles.We hereby retract the content of this paper. Reasonable effort should be made to remove all past references to this paper.The presenting author of this paper has the option to appeal this decision by contacting edulearn@journal.uad.ac.id.-----------------------------------------------------------------------Mostly in Eastern religions, particularly in Indonesia the ancient Imperial cults of Borobudur temple as Buddhism, ritually celebrate their beliefs as a congregation where prayer and religious addresses are a communal activity. This culture is interesting to study whether building a place of worship is built on the cultural elements or there is a correlation with formula or complicated calculations about how the building is erected . The mathematical study for Borobudur’s architectural design has once related to answer the question about the metric system used by ancient Javanese to build such giant buildings with good measurement. Fractal dimension is calculated by using the cube counting method and found that the dimension is , which is laid between the two-dimensional plane and three dimensional space. The applied fractal geometry and self-similarity of the building is emerged as the building process implement the metric rules, since there is no universal metric standard known in ancient traditional Javanese culture thus the architecture is not based on final master plan. The paper also proposes how the hypothetical algorithmic architecture might be applied computationally in order to see some experimental generations of similar building. The paper ends with some conjectures for further challenge and insights related to fractal geometry in Javanese traditional cultural heritages.
Lipopolysaccharide as trigger of platelet aggregation via eicosanoid over-production
Authors: Nocella Cristina , Carnevale Roberto , Bartimoccia Simona , Novo Marta , Cangemi Roberto , Pastori Daniele , Calvieri Camilla , Pignatelli Pasquale , Violi Francesco 
Published: May 2017

SummaryThe effect of lipopolysaccharide (LPS) on platelet aggregation is still controversial. We performed in vitro and ex vivo studies in controls and in patients with community-acquired pneumonia (CAP) to assess the effect of LPS on platelet activation (PA). LPS (15–100 pg/ml) significantly increased PA only if combined with sub-threshold concentrations (STC) of collagen or ADP; this effect was associated with increased platelet H2O2 production, Nox2 activation, PLA2 phosphorylation, thromboxane (Tx)A2 and 8-iso-PGF2α-III, and was inhibited by aspirin, TxA2 receptor antagonist or by Toll-like receptor 4 blocking peptide (TLR4bp). Analysis of up-stream signalling potentially responsible for Nox2 and PLA2 activation demonstrated that LPS-mediated PA was associated with phosphorylation of AKT, p38 and p47phox translocation. In 10 consecutive CAP patients serum endotoxins were significantly higher compared to 10 controls (145 [115–187] vs 18 [6–21] pg/ml; p<0.01). Ex vivo study showed that agonist-stimulated platelets were associated with enhanced PA (p<0.01), Toll-like receptor 4 (TLR4) expression (p<0.05), TxA2 (p<0.01) and 8-iso-PGF2α-III (p<0.01) production in CAP patients compared to controls. The study provides evidence that LPS amplifies the platelet response to common agonists via TLR4-mediated eicosanoid production and suggests LPS as a potential trigger for PA in CAP.Supplementary Material to this article is available online at www.thrombosis-online.com
CD32 inhibition and high dose of rhFVIII suppress murine FVIII-specific recall response by distinct mechanisms in vitro
Authors: Vollack Nadine , Friese Julia , Bergmann Sabine , Tiede Andreas , Werwitzke Sonja 
Published: May 2017

SummaryDevelopment of neutralising antibodies (inhibitors) against factor VIII (FVIII) is a frequent and severe complication of replacement therapy in haemophilia A. Previous data from haemophilia A mouse model demonstrates that both CD32 inhibition and high doses of rhFVIII prevent the differentiation of FVIII-specific memory B cells (MBCs) into antibody secreting cells (ASCs). Here, cellular targets responsible for the suppression of ASC formation by means of CD32 inhibition and high dose of rhFVIII were analysed. We investigated apoptosis on FVIII-specific MBCs using a pan caspases inhibitor, and screened for defects in rhFVIII presentation by analysing T cell release of Th1- and Th2-cytokines in vitro. Although high dose of rhFVIII suppressed ASC formation, cytokine response was not affected. Upon re-stimulation of splenocytes with high dose of rhFVIII, prevention of apoptosis fully restored the FVIII-specific recall response. In contrast, genetic deletion or inhibition of CD32 significantly altered Th1- and Th2-response. CD32 blockade and inhibition of apoptosis resulted in a partial rescue of FVIII-specific ASCs. Normal cytokine secretion could not be restored. In conclusion, suppression of FVIII-specific recall response by CD32 and high doses of rhFVIII is mediated by distinct mechanisms. High dose of rhFVIII induces apoptosis in FVIII-specific MBCs but does not influence FVIII-specific T cell response. CD32 blockade, however, may suppress the FVIII-specific recall response by two ways: i) increasing apoptosis of FVIII-specific MBCs and ii) disturbing FVIII-specific T cell response by modulating presentation of rhFVIII to CD4+ T cells in vitro.Supplementary Material to this article is available online at www.thrombosis-online.com.
Coronary Plaque Characterization in Psoriasis Reveals High-Risk Features That Improve After Treatment in a Prospective Observational Study
Authors: Lerman Joseph B. , Joshi Aditya A. , Chaturvedi Abhishek , Aberra Tsion M. , Dey Amit K. , Rodante Justin A. , Salahuddin Taufiq , Chung Jonathan H. , Rana Anshuma , Teague Heather L. , Wu Jashin J. , Playford Martin P. , Lockshin Benjamin A. , Chen Marcus Y. , Sandfort Veit , Bluemke David A. , Mehta Nehal N. 
Published: May 2017

Background:
Psoriasis, a chronic inflammatory disease associated with an accelerated risk of myocardial infarction, provides an ideal human model to study inflammatory atherogenesis in vivo. We hypothesized that the increased cardiovascular risk observed in psoriasis would be partially attributable to an elevated subclinical coronary artery disease burden composed of noncalcified plaques with high-risk features. However, inadequate efforts have been made to directly measure coronary artery disease in this vulnerable population. As such, we sought to compare total coronary plaque burden and noncalcified coronary plaque burden (NCB) and high-risk plaque (HRP) prevalence between patients with psoriasis (n=105), patients with hyperlipidemia eligible for statin therapy under National Cholesterol Education Program-Adult Treatment Panel III guidelines (n=100) who were ≈10 years older, and healthy volunteers without psoriasis (n=25).

Methods:
Patients underwent coronary computed-tomography angiography for total coronary plaque burden and NCB quantification and HRP identification, defined as low attenuation (<30 hounsfield units), positive remodeling (>1.10), and spotty calcification. A consecutive sample of the first 50 patients with psoriasis was scanned again 1 year after therapy.

Results:

Despite being younger and at lower traditional risk than patients with hyperlipidemia, patients with psoriasis had increased NCB (mean±SD: 1.18±0.33 versus 1.11±0.32,
P
=0.02) and similar HRP prevalence (
P
=0.58). Furthermore, compared to healthy volunteers, patients with psoriasis had increased total coronary plaque burden (1.22±0.31 versus 1.04±0.22,
P
=0.001), NCB (1.18±0.33 versus 1.03±0.21,
P
=0.004), and HRP prevalence beyond traditional risk (odds ratio, 6.0; 95% confidence interval, 1.1–31.7;
P
=0.03). Last, among patients with psoriasis followed for 1 year, improvement in psoriasis severity was associated with improvement in total coronary plaque burden (β=0.45, 0.23–0.67;
P
<0.001) and NCB (β=0.53, 0.32–0.74;
P
<0.001) beyond traditional risk factors.

Conclusions:
Patients with psoriasis had greater NCB and increased HRP prevalence than healthy volunteers. In addition, patients with psoriasis had elevated NCB and equivalent HRP prevalence as older patients with hyperlipidemia. Last, modulation of target organ inflammation (eg, skin) was associated with an improvement in NCB at 1 year, suggesting that control of remote sites of inflammation may translate into reduced coronary artery disease risk.
Race‐Sex Differences in Statin Use and Low‐Density Lipoprotein Cholesterol Control Among People With Diabetes Mellitus in the Reasons for Geographic and Racial Differences in Stroke Study
Authors: Gamboa Christopher M. , Colantonio Lisandro D. , Brown Todd M. , Carson April P. , Safford Monika M. 
Published: May 2017

Background
Statin therapy is a cornerstone of cardiovascular disease risk reduction for people with diabetes mellitus. Past reports have shown race‐sex differences in statin use in general populations, but statin patterns by race and sex in those with diabetes mellitus have not been thoroughly studied.

Methods and Results

Our sample of 4288 adults ≥45 years of age with diagnosed diabetes mellitus who had low‐density lipoprotein cholesterol (
LDL
‐C) >100 mg/dL or were taking statins recruited for the Reasons for Geographic and Racial Differences in Stroke study from 2003 to 2007. Exposures included race‐sex groups (white men [
WM
], black men [
BM
], white women [
WW
], black women [
BW
]) and factors that may influence healthcare utilization. Proportions and prevalence ratios were calculated for statin use and
LDL
‐C control. Statin use for
WM
,
BM
,
WW
, and
BW
was 66.0%, 57.8%, 55.0%, and 53.6%, respectively (
P
<0.001). After adjustment for healthcare utilization factors, statin use was lower for
BM
,
WW
, and
BW
compared with
WM
(prevalence ratios [95%
CI
]: 0.96 [0.89‐1.03], 0.86 [0.80‐0.92], and 0.87 [0.81‐0.93], respectively,
P
<0.001).
LDL
‐C control among those taking statins for
WM
,
BM
,
WW
, and
BW
was 75.3%, 62.7%, 69.0%, and 56.0%, respectively (
P
<0.001). After adjustment,
LDL
‐C control was lower for
BM
,
WW
, and
BW
compared with
WM
(prevalence ratios [95%
CI
]: 0.85 [0.79‐0.93], 0.89 [0.82‐0.96], and 0.73 [0.67‐0.80], respectively,
P
<0.001).

Conclusions

Race‐sex disparities in statin use and
LDL
‐C control were only partly explained by factors influencing health services utilization. Healthcare provider awareness of these disparities may help to close the observed race‐sex gaps in statin use and
LDL
‐C control among people with diabetes mellitus.
Observed Cost and Variations in Short Term Cost‐Effectiveness of Therapy for Ischemic Stroke in Interventional Management of Stroke (IMS) III
Authors: Simpson Kit N. , Simpson Annie N. , Mauldin Patrick D. , Palesch Yuko Y. , Yeatts Sharon D. , Kleindorfer Dawn , Tomsick Thomas A. , Foster Lydia D. , Demchuk Andrew M. , Khatri Pooja , Hill Michael D. , Jauch Edward C. , Jovin Tudor G. , Yan Bernard , von Kummer Rüdiger , Molina Carlos A. , Goyal Mayank , Schonewille Wouter J. , Mazighi Mikael , Engelter Stefan T. , Anderson Craig , Spilker Judith , Carrozzella Janice , Ryckborst Karla J. , Janis L. Scott , Broderick Joseph P. ,   the Interventional Management of Stroke (IMS) III Investigators
Published: May 2017

Background

Examination of linked data on patient outcomes and cost of care may help identify areas where stroke care can be improved. We report on the association between variations in stroke severity, patient outcomes, cost, and treatment patterns observed over the acute hospital stay and through the 12‐month follow‐up for subjects receiving endovascular therapy compared to intravenous tissue plasminogen activator alone in the IMS (Interventional Management of Stroke)
III
Trial.

Methods and Results
Prospective data collected for a prespecified economic analysis of the trial were used. Data included hospital billing records for the initial stroke admission and subsequent detailed resource use after the acute hospitalization collected at 3, 6, 9, and 12 months. Cost of follow‐up care varied 6‐fold for patients in the lowest (0–1) and highest (20+) National Institutes of Health Stroke Scale category at 5 days, and by modified Rankin Scale at 3 months. The kind of resources used postdischarge also varied between treatment groups. Incremental short‐term cost‐effectiveness ratios varied greatly when treatments were compared for patient subgroups. Patient subgroups predefined by stroke severity had incremental cost‐effectiveness ratios of $97 303/quality‐adjusted life year (severe stroke) and $3 187 805/quality‐adjusted life year (moderately severe stroke).

Conclusions

Detailed economic and resource utilization data from
IMS III
provide powerful evidence for the large effect that patient outcome has on the economic value of medical and endovascular reperfusion therapies. These data can be used to inform process improvements for stroke care and to estimate the cost‐effectiveness of endovascular therapy in the US health system for stroke intervention trials.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Registration number:
NCT
00359424.
What Is Actually Affected by the Scrambling of Objects When Localizing the Lateral Occipital Complex?
Authors: Margalit Eshed , Biederman Irving , Tjan Bosco S. , Shah Manan P. 
Published: May 2017

Abstract
The lateral occipital complex (LOC), the cortical region critical for shape perception, is localized with fMRI by its greater BOLD activity when viewing intact objects compared with their scrambled versions (resembling texture). Despite hundreds of studies investigating LOC, what the LOC localizer accomplishes—beyond distinguishing shape from texture—has never been resolved. By independently scattering the intact parts of objects, the axis structure defining the relations between parts was no longer defined. This led to a diminished BOLD response, despite the increase in the number of independent entities (the parts) produced by the scattering, thus indicating that LOC specifies interpart relations, in addition to specifying the shape of the parts themselves. LOC's sensitivity to relations is not confined to those between parts but is also readily apparent between objects, rendering it—and not subsequent “place” areas—as the critical region for the representation of scenes. Moreover, that these effects are witnessed with novel as well as familiar intact objects and scenes suggests that the relations are computed on the fly, rather than being retrieved from memory.
Greenland Clouds Observed in CALIPSO-GOCCP: Comparison with Ground-Based Summit Observations
Authors: Lacour Adrien , Chepfer Helene , Shupe Matthew D. , Miller Nathaniel B. , Noel Vincent , Kay Jennifer , Turner David D. , Guzman Rodrigo 
Published: May 2017

AbstractSpaceborne lidar observations from the Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) satellite provide the first-ever observations of cloud vertical structure and phase over the entire Greenland Ice Sheet. This study leverages CALIPSO observations over Greenland to pursue two investigations. First, the GCM-Oriented CALIPSO Cloud Product (CALIPSO-GOCCP) observations are compared with collocated ground-based radar and lidar observations at Summit, Greenland. The liquid cloud cover agrees well between the spaceborne and ground-based observations. In contrast, ground–satellite differences reach 30% in total cloud cover and 40% in cloud fraction below 2 km above ground level, due to optically very thin ice clouds (IWC < 2.5 × 10−3 g m−3) missed by CALIPSO-GOCCP. Those results are compared with satellite cloud climatologies from the GEWEX cloud assessment. Most passive sensors detect fewer clouds than CALIPSO-GOCCP and the Summit ground observations, due to different detection methods. Second, the distribution of clouds over the Greenland is analyzed using CALIPSO-GOCCP. Central Greenland is the cloudiest area in summer, at +7% and +4% above the Greenland-wide average for total and liquid cloud cover, respectively. Southern Greenland contains free-tropospheric thin ice clouds in all seasons and liquid clouds in summer. In northern Greenland, fewer ice clouds are detected than in other areas, but the liquid cloud cover seasonal cycle in that region drives the total Greenland cloud annual variability with a maximum in summer. In 2010 and 2012, large ice-sheet melting events have a positive liquid cloud cover anomaly (from +1% to +2%). In contrast, fewer clouds (−7%) are observed during low ice-sheet melt years (e.g., 2009).
The Eastern Subtropical Pacific Origin of the Equatorial Cold Bias in Climate Models: A Lagrangian Perspective
Authors: Thomas Matthew D. , Fedorov Alexey V. 
Published: May 2017

AbstractGlobal climate models frequently exhibit cold biases in tropical sea surface temperature (SST) in the central and eastern equatorial Pacific. Here, Lagrangian particle back trajectories are used to investigate the source regions of the water that upwells along the equator in the IPSL climate model to test and confirm the hypothesis that the SST biases are caused by remote biases advected in from the extratropics and to identify the dominant source regions. Water in the model is found to be sourced primarily from localized regions along the western and eastern flanks of the subtropical gyres. However, while the model SST bias is especially large in the northwestern subtropical Pacific (about −5°C), it is found that the eastern subtropics contribute to the equatorial bias the most. This is due to two distinct subsurface pathways connecting these regions to the equator. The first pathway, originating in the northwestern subtropical Pacific, has relatively long advection time scales close to or exceeding 60 yr, wherein particles recirculate around the subtropical gyres while descending to approximately 500 m before then shoaling toward the equatorial undercurrent. The second pathway, from the eastern subtropics, has time scales close to 10 yr, with particles following a shallow and more direct route to the equator within the upper 200 m. The deeper and longer pathway taken by the western subtropical water ensures that vertical mixing can erode the bias. Ultimately, it is estimated that relatively confined regions in the eastern subtropics of both hemispheres control approximately half of the equatorial bias.