bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic Lactobacillus reuteri
Authors: Gao Chunxu , Major Angela , Rendon David , Lugo Monica , Jackson Vanessa , Shi Zhongcheng , Mori-Akiyama Yuko , Versalovic James 
Published: December 2015

ABSTRACTProbiotics and commensal intestinal microbes suppress mammalian cytokine production and intestinal inflammation in various experimental model systems. Limited information exists regarding potential mechanisms of probiotic-mediated immunomodulationin vivo. In this report, we demonstrate that specific probiotic strains ofLactobacillus reuterisuppress intestinal inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis model. Only strains that possess thehdcgene cluster, including the histidine decarboxylase and histidine-histamine antiporter genes, can suppress colitis and mucosal cytokine (interleukin-6 [IL-6] and IL-1β in the colon) gene expression. Suppression of acute colitis in mice was documented by diminished weight loss, colonic injury, serum amyloid A (SAA) protein concentrations, and reduced uptake of [18F]fluorodeoxyglucose ([18F]FDG) in the colon by positron emission tomography (PET). The ability of probioticL. reuterito suppress colitis depends on the presence of a bacterial histidine decarboxylase gene(s) in the intestinal microbiome, consumption of a histidine-containing diet, and signaling via the histamine H2 receptor (H2R). Collectively, luminal conversion ofl-histidine to histamine byhdc+L. reuteriactivates H2R, and H2R signaling results in suppression of acute inflammation within the mouse colon.IMPORTANCEProbiotics are microorganisms that when administered in adequate amounts confer beneficial effects on the host. Supplementation with probiotic strains was shown to suppress intestinal inflammation in patients with inflammatory bowel disease and in rodent colitis models. However, the mechanisms of probiosis are not clear. Our current studies suggest that supplementation withhdc+L. reuteri, which can convertl-histidine to histamine in the gut, resulted in suppression of colonic inflammation. These findings link luminal conversion of dietary components (amino acid metabolism) by gut microbes and probiotic-mediated suppression of colonic inflammation. The effective combination of diet, gut bacteria, and host receptor-mediated signaling may result in opportunities for therapeutic microbiology and provide clues for discovery and development of next-generation probiotics.
Common Viral Integration Sites Identified in Avian Leukosis Virus-Induced B-Cell Lymphomas
Authors: Justice James F. , Morgan Robin W. , Beemon Karen L. 
Published: December 2015

ABSTRACT

Avian leukosis virus (ALV) induces B-cell lymphoma and other neoplasms in chickens by integrating within or near cancer genes and perturbing their expression. Four genes—
MYC
,
MYB
,
Mir-155
, and
TERT
—have previously been identified as common integration sites in these virus-induced lymphomas and are thought to play a causal role in tumorigenesis. In this study, we employ high-throughput sequencing to identify additional genes driving tumorigenesis in ALV-induced B-cell lymphomas. In addition to the four genes implicated previously, we identify other genes as common integration sites, including
TNFRSF1A
,
MEF2C
,
CTDSPL
,
TAB2
,
RUNX1
,
MLL5
,
CXorf57
, and
BACH2
. We also analyze the genome-wide ALV integration landscape
in vivo
and find increased frequency of ALV integration near transcriptional start sites and within transcripts. Previous work has shown ALV prefers a weak consensus sequence for integration in cultured human cells. We confirm this consensus sequence for ALV integration
in vivo
in the chicken genome.

IMPORTANCE
Avian leukosis virus induces B-cell lymphomas in chickens. Earlier studies showed that ALV can induce tumors through insertional mutagenesis, and several genes have been implicated in the development of these tumors. In this study, we use high-throughput sequencing to reveal the genome-wide ALV integration landscape in ALV-induced B-cell lymphomas. We find elevated levels of ALV integration near transcription start sites and use common integration site analysis to greatly expand the number of genes implicated in the development of these tumors. Interestingly, we identify several genes targeted by viral insertions that have not been previously shown to be involved in cancer.
Survival analysis of time to uptake of modern contraceptives among sexually active women of reproductive age in Nigeria
Authors: Fagbamigbe Adeniyi Francis , Adebowale Ayo Stephen , Morhason-Bello ImranOludare 
Published: December 2015

ObjectiveTo assess the timing of modern contraceptive uptake among married and never-married women in Nigeria.DesignA retrospective cross-sectional study.Data and methodWe used nationally representative 2013 Demographic and Health Survey data in Nigeria. Modern contraceptive uptake time was measured as the period between first sexual intercourse and first use of a modern contraceptive. Non-users of modern contraceptives were censored on the date of the survey. Kaplan–Meier survival curves were used to determine the rate of uptake. A Cox proportional-hazards model was used to determine variables influencing the uptake at 5% significance level.ParticipantsA total of 33 223 sexually active women of reproductive age.Outcome measureTime of uptake of a modern contraceptive after first sexual intercourse.ResultsThe median modern contraceptive uptake time was 4 years in never-married and 14 years among ever-married women. Significant differences in modern contraceptive uptake existed in respondents’ age, location, education and wealth status. Never-married women were about three times more likely to use a modern contraceptive than ever-married women (aHR=3.24 (95% CI 2.82 to 3.65)). Women with higher education were six times more likely to use a modern contraceptive than those without education (aHR=6.18 (95% CI 5.15 to 7.42)).ConclusionsThe rate of modern contraceptive uptake is low, and timing of contraceptive uptake during or after first sexual intercourse differed according to marital status. Age and number of children ever born influenced modern contraceptive uptake among the never-married women, but religion and place of residence were associated with the probability of modern contraceptive uptake among ever-married women.
Long-term risk of cardiovascular and cerebrovascular disease after removal of the colonic microbiota by colectomy: a cohort study based on the Danish National Patient Register from 1996 to 2014
Authors: Jensen Anders Boeck , Ajslev Teresa Adeltoft , Brunak Søren , Sørensen Thorkild I A 
Published: December 2015

ObjectivesThe hypothesis of the study was that if the gut microbiota is involved in the development of atherosclerotic cardiovascular and cerebrovascular diseases (CVDs), total colectomy may reduce the long-term risk of CVDs. The aim was therefore to investigate the risk of CVD in patients after a total colectomy compared with patients undergoing other types of surgery, which are not expected to alter the gut microbiota or the CVD risk.SettingThe Danish National Patient Register including all hospital discharges in Denmark from 1996 to 2014.ParticipantsPatients (n=1530) aged 45 years and above and surviving 1000 days after total colectomy without CVDs were selected and matched with five control patients who were also free of CVD 1000 days after other types of surgery. The five control patients were randomly selected from each of the three surgical groups: orthopaedic surgery, surgery in the gastrointestinal tract leaving it intact and other surgeries not related to the gastrointestinal tract or CVD (n=22 950).Primary and secondary outcome measuresThe primary outcome was the first occurring CVD event in any of the seven diagnostic domains (hypertensive disorders, acute ischaemic heart diseases, chronic ischaemic heart disease, cardiac arrhythmias, heart failure, cerebrovascular diseases and other arterial diseases) and the secondary outcomes were the first occurring event within each of these domains.ResultsEstimated by Cox proportional hazard models, the HRs of the composite CVD end point for patients with colectomy compared with the control patients were not significantly reduced (HR=0.94, 95% confidence limits 0.85 to 1.04). Among the seven CVD domains, only the risk of hypertensive disorders was significantly reduced (HR=0.85, 0.73 to 0.98).ConclusionsColectomy did not reduce the general risk of CVD, but reduced the risk of hypertensive disorders, most likely due to salt and water depletion induced by colectomy. These results encourage a reappraisal of the associations between gut microbiota and CVD.
Ethnic differences in cognitive development in the first 7 years: does maternal generational status matter?
Authors: Smith Neil R , Kelly Yvonne J , Nazroo James Y 
Published: December 2015

BackgroundDifferences in cognitive development have been observed across a variety of ethnic minority groups but relatively little is known about the persistence of these developmental inequalities over time or generations.MethodsA repeat cross-sectional analysis assessed cognitive ability scores of children aged 3, 5 and 7 years from the longitudinal UK Millennium Cohort Study (white UK born n=7630; Indian n=248; Pakistani n=328; Bangladeshi n=87; black Caribbean n=172; and black African n=136). Linear regression estimated ethnic differences in age normed scores at each time point. Multivariable logistic regression estimated within-group generational differences in test scores at each age adjusting stepwise for sociodemographic factors, maternal health behaviours, indicators of the home learning environment and parenting styles.ResultsThe majority of ethnic minority groups scored lower than the white UK born reference group at 3 years with these differences narrowing incrementally at ages 5 and 7 years. However, the black Caribbean group scored significantly lower than the white UK born reference group throughout early childhood. At 3 years, Pakistani, black Caribbean and black African children with UK born mothers had significantly higher test scores than those with foreign born mothers after baseline adjustment for maternal age and child gender. Controlling for social, behavioural and parenting factors attenuated this generational advantage. By 7 years there were no significant generational differences in baseline models.ConclusionsEthnic differences in cognitive development diminish throughout childhood for the majority of groups. Cumulative exposure to the UK environment may be associated with higher cognitive development scores.
Natural IgM Blockade Limits Infarct Expansion and Left Ventricular Dysfunction in a Swine Myocardial Infarct Model
Authors: Sihag Smita , Haas Michael S. , Kim Karen M. , Guerrero J. Luis , Beaudoin Jonathan , Alicot Elisabeth M. , Schuerpf Franziska , Gottschall James D. , Puro Robyn J. , Madsen Joren C. , Sachs David H. , Newman Walter , Carroll Michael C. , Allan James S. 
Published: December 2015

Background—
Acute coronary syndrome is the leading cause of mortality worldwide. However, treatment of acute coronary occlusion inevitably results in ischemia-reperfusion injury. Circulating natural IgM has been shown to play a significant role in mouse models of ischemia-reperfusion injury. A highly conserved self-antigen, nonmuscle myosin heavy chain II, has been identified as a target of pathogenic IgM. We hypothesized that a monoclonal antibody (m21G6) directed against nonmuscle myosin heavy chain II may inhibit IgM binding and reduce injury in a preclinical model of myocardial infarction. Thus, our objective was to evaluate the efficacy of intravenous m21G6 treatment in limiting infarct expansion, troponin release, and left ventricular dysfunction in a swine myocardial infarction model.

Methods and Results—

Massachusetts General Hospital miniature swine underwent occlusion of the midleft anterior descending coronary artery for 60 minutes, followed by 1 hour, 5-day, or 21-day reperfusion. Specificity and localization of m21G6 to injured myocardium were confirmed using fluorescently labeled m21G6. Treatment with m21G6 before reperfusion resulted in a 49% reduction in infarct size (
P
<0.005) and a 61% reduction in troponin-T levels (
P
<0.05) in comparison with saline controls at 5-day reperfusion. Furthermore, m21G6-treated animals recovered 85.4% of their baseline left ventricular function as measured by 2-dimensional transthoracic echocardiography in contrast to 67.1% in controls at 21-day reperfusion (
P
<0.05).

Conclusions—
Treatment with m21G6 significantly reduced infarct size and troponin-T release, and led to marked preservation of cardiac function in our study. Overall, these findings suggest that pathogenic IgM blockade represents a valid therapeutic strategy in mitigating myocardial ischemia-reperfusion injury.
Efficacy and Safety of Vorapaxar in Non–ST‐Segment Elevation Acute Coronary Syndrome Patients Undergoing Noncardiac Surgery
Authors: van Diepen Sean , Tricoci Pierluigi , Podder Mohua , Westerhout Cynthia M. , Aylward Philip E. , Held Claes , Van de Werf Frans , Strony John , Wallentin Lars , Moliterno David J. , White Harvey D. , Mahaffey Kenneth W. , Harrington Robert A. , Armstrong Paul W. 
Published: December 2015

Background

Perioperative antiplatelet agents potentially increase bleeding after non–
ST
‐segment elevation (
NSTE
) acute coronary syndromes (
ACS
). The protease‐activated receptor 1 antagonist vorapaxar reduced cardiovascular events and was associated with increased bleeding versus placebo in
NSTE ACS
, but its efficacy and safety in noncardiac surgery (
NCS
) remain unknown. We aimed to evaluate ischemic, bleeding, and long‐term outcomes of vorapaxar in
NCS
after
NSTE ACS
.

Methods and Results

In the
TRACER
trial, 2202 (17.0%) patients underwent major or minor
NCS
after
NSTE ACS
over 1.5 years (median); continuing study treatment perioperatively was recommended. The primary ischemic end point for this analysis was cardiovascular death, myocardial infarction, stent thrombosis, or urgent revascularization within 30 days of
NCS
. Safety outcomes included 30‐day
NCS
bleeding and
GUSTO
moderate/severe bleeding. Overall, 1171 vorapaxar and 1031 placebo patients underwent
NCS
. Preoperative aspirin and thienopyridine use was 96.8% versus 97.7% (
P
=0.235) and 89.1% versus 86.1% (
P
=0.036) for vorapaxar versus placebo, respectively. Within 30 days of
NCS
, no differences were observed in the primary ischemic end point between vorapaxar and placebo groups (3.4% versus 3.9%; adjusted odds ratio 0.81, 95%
CI
0.50 to 1.33,
P
=0.41). Similarly, no differences in
NCS
bleeding (3.9% versus 3.4%; adjusted odds ratio 1.41, 95%
CI
0.87 to 2.31,
P
=0.17) or
GUSTO
moderate/severe bleeding (4.2% versus 3.7%; adjusted odds ratio 1.15, 95%
CI
, 0.72 to 1.83,
P
=0.55) were observed. In a 30‐day landmarked analysis,
NCS
patients had a higher long‐term risk of the ischemic end point (adjusted hazard ratio 1.62, 95%
CI
1.33 to 1.97,
P
<0.001) and
GUSTO
moderate/severe bleeding (adjusted hazard ratio 5.63, 95%
CI
3.98 to 7.97,
P
<0.001) versus patients who did not undergo
NCS
, independent of study treatment.

Conclusion

NCS
after
NSTE ACS
is common and associated with more ischemic outcomes and bleeding. Vorapaxar after
NSTE ACS
was not associated with increased perioperative ischemic or bleeding events in patients undergoing
NCS
.
Admission Hyperglycemia and Clinical Outcome in Cerebral Venous Thrombosis
Authors: Zuurbier Susanna M. , Hiltunen Sini , Tatlisumak Turgut , Peters Guusje M. , Silvis Suzanne M. , Haapaniemi Elena , Kruyt Nyika D. , Putaala Jukka , Coutinho Jonathan M. 
Published: December 2015

Background and Purpose—
Admission hyperglycemia is associated with poor clinical outcome in ischemic and hemorrhagic stroke. Admission hyperglycemia has not been investigated in patients with cerebral venous thrombosis.

Methods—
Consecutive adult patients with cerebral venous thrombosis were included at the Academic Medical Center, The Netherlands (2000–2014) and the Helsinki University Central Hospital, Finland (1998–2014). We excluded patients with known diabetes mellitus and patients without known admission blood glucose. We defined admission hyperglycemia as blood glucose ≥7.8 mmol/L (141 mg/dL) and severe hyperglycemia as blood glucose ≥11.1 mmol/L (200 mg/dL). We used logistic regression analysis to determine if admission hyperglycemia was associated with modified Rankin Scale (mRS) score of 3 to 6 or mortality at last follow-up. We adjusted for: age, sex, coma, malignancy, infection, intracerebral hemorrhage, deep cerebral venous thrombosis, and location of recruitment.

Results—

Of 380 patients with cerebral venous thrombosis, 308 were eligible. Of these, 66 (21.4%) had admission hyperglycemia with 8 (2.6%) having severe admission hyperglycemia. Coma (31.3% versus 5.0%,
P
<0.001) and intracerebral hemorrhage (53.0% versus 32.6%,
P
=0.002) at presentation were more common among patients with admission hyperglycemia than normoglycemic patients. Patients with admission hyperglycemia had a higher risk of mRS score of 3 to 6 (adjusted odds ratio, 3.10; 95% confidence interval, 1.35–7.12) and mortality (adjusted odds ratio, 4.13; 95% confidence interval, 1.41–12.09). Severe hyperglycemia was even more strongly associated with mRS score of 3 to 6 (adjusted odds ratio, 11.59; 95% confidence interval, 1.74–77.30) and mortality (adjusted odds ratio, 33.36; 95% confidence interval, 3.87–287.28) compared with normoglycemic patients.

Conclusions—
Admission hyperglycemia is a strong predictor of poor clinical outcome in patients with cerebral venous thrombosis.
Early Detection and Quantification of Cerebral Venous Thrombosis by Magnetic Resonance Black-Blood Thrombus Imaging
Authors: Yang Qi , Duan Jiangang , Fan Zhaoyang , Qu Xiaofeng , Xie Yibin , Nguyen Christopher , Du Xiangying , Bi Xiaoming , Li Kuncheng , Ji Xunming , Li Debiao 
Published: December 2015

Background and Purpose—
Early diagnosis of cerebral venous thrombosis (CVT) is currently a major clinical challenge. We proposed a novel magnetic resonance black-blood thrombus imaging technique (MRBTI) for detection and quantification of CVT.

Methods—
MRBTI was performed on 23 patients with proven CVT and 24 patients with negative CVT confirmed by conventional imaging techniques. Patients were divided into 2 groups based on the duration of clinical onset: ≤7 days (group 1) and between 7 and 30 days (group 2). Signal/noise ratio was calculated for the detected thrombus, and contrast/noise ratio was measured between thrombus and lumen and also between thrombus and brain tissue. The feasibility of using MRBTI for thrombus volume measurement was explored, and total thrombus volume was calculated for each patient.

Results—

In 23 patients with proven CVT, MRBTI correctly identified 113 of 116 segments with a sensitivity of 97.4%. Thrombus signal/noise ratio was 153±57 and 261±95 for group 1 (n=10) and group 2 (n=13), respectively (
P
<0.01). Thrombus to lumen contrast/noise ratio was 149±57 and 256±94 for group 1 and group 2, respectively. Thrombus to brain tissue contrast/noise ratio was 41±36 and 120±63 (
P
<0.01), respectively. Quantification of thrombus volume was successfully conducted in all patients with CVT, and mean volume of thrombus was 10.5±6.9 mL.

Conclusions—
The current findings support that with effectively suppressed blood signal, MRBTI allows selective visualization of thrombus as opposed to indirect detection of venous flow perturbation and can be used as a promising first-line diagnostic imaging tool.
Improved Simulation of Tropical Cyclone Responses to ENSO in the Western North Pacific in the High-Resolution GFDL HiFLOR Coupled Climate Model*
Authors: Zhang Wei , Vecchi Gabriel A. , Murakami Hiroyuki , Delworth Thomas , Wittenberg Andrew T. , Rosati Anthony , Underwood Seth , Anderson Whit , Harris Lucas , Gudgel Richard , Lin Shian-Jiann , Villarini Gabriele , Chen Jan-Huey 
Published: December 2015

Abstract
This study aims to assess whether, and the extent to which, an increase in atmospheric resolution of the Geophysical Fluid Dynamics Laboratory (GFDL) Forecast-Oriented Low Ocean Resolution version of CM2.5 (FLOR) with 50-km resolution and the High-Resolution FLOR (HiFLOR) with 25-km resolution improves the simulation of the El Niño–Southern Oscillation (ENSO)–tropical cyclone (TC) connections in the western North Pacific (WNP). HiFLOR simulates better ENSO–TC connections in the WNP including TC track density, genesis, and landfall than FLOR in both long-term control experiments and sea surface temperature (SST)- and sea surface salinity (SSS)-restoring historical runs (1971–2012). Restoring experiments are performed with SSS and SST restored to observational estimates of climatological SSS and interannually varying monthly SST. In the control experiments of HiFLOR, an improved simulation of the Walker circulation arising from more realistic SST and precipitation is largely responsible for its better performance in simulating ENSO–TC connections in the WNP. In the SST-restoring experiments of HiFLOR, more realistic Walker circulation and steering flow during El Niño and La Niña are responsible for the improved simulation of ENSO–TC connections in the WNP. The improved simulation of ENSO–TC connections with HiFLOR arises from a better representation of SST and better responses of environmental large-scale circulation to SST anomalies associated with El Niño or La Niña. A better representation of ENSO–TC connections in HiFLOR can benefit the seasonal forecasting of TC genesis, track, and landfall; improve understanding of the interannual variation of TC activity; and provide better projection of TC activity under climate change.
A Mechanism of Ice-Band Pattern Formation Caused by Resonant Interaction between Sea Ice and Internal Waves: A Theory
Authors: Saiki Ryu , Mitsudera Humio 
Published: December 2015

AbstractIce bands are frequently observed over marginal ice zones in polar seas. A typical ice-band pattern has a regular spacing of about 10 km and extends over 100 km in the marginal ice zone. Further, the long axis of an ice band lies to the left (right) with respect to the wind direction in the Northern (Southern) Hemisphere. Here, the study shows that the resonance between ice-band pattern propagation and internal inertia–gravity waves below the sea ice well explains the ice-band pattern formation. Internal waves are generated by the difference between the stress on the open water and the stress on ice-covered water. This in turn reinforces the formation of an ice-band pattern with a regular band spacing. Specifically, the authors have found the following: 1) A band spacing on the order of 10 km is selected by the resonance condition in which the ice-band pattern propagation speed coincides with the phase speed of internal inertia–gravity waves. 2) The ice bands tend to develop favorably when the wind direction and the band propagation direction are nearly parallel. The velocity acceleration caused by the periodic differential stress associated with the ice bands, driven by the wind parallel to the band propagation direction, is important. The wind direction may turn to the left (right) slightly in the Northern (Southern) Hemisphere as a result of the Coriolis force acting on ice. Satellite images confirmed that the band spacing of the ice-band pattern in the polar seas is consistent with this theory.