bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Gene–Environment Interactions for Colorectal Cancer Susceptibility Loci
Authors: Hutter Carolyn M. , Chang-Claude Jenny , Slattery Martha L. , Pflugeisen Bethann M. , Lin Yi , Duggan David , Nan Hongmei , Lemire Mathieu , Rangrej Jagadish , Figueiredo Jane C. , Jiao Shuo , Harrison Tabitha A. , Liu Yan , Chen Lin S. , Stelling Deanna L. , Warnick Greg S. , Hoffmeister Michael , Küry Sébastien , Fuchs Charles S. , Giovannucci Edward , Hazra Aditi , Kraft Peter , Hunter David J. , Gallinger Steven , Zanke Brent W. , Brenner Hermann , Frank Bernd , Ma Jing , Ulrich Cornelia M. , White Emily , Newcomb Polly A. , Kooperberg Charles , LaCroix Andrea Z. , Prentice Ross L. , Jackson Rebecca D. , Schoen Robert E. , Chanock Stephen J. , Berndt Sonja I. , Hayes Richard B. , Caan Bette J. , Potter John D. , Hsu Li , Bézieau Stéphane , Chan Andrew T. , Hudson Thomas J. , Peters Ulrike 
Published: February 2012

Abstract
Genome-wide association studies (GWAS) have identified more than a dozen loci associated with colorectal cancer (CRC) risk. Here, we examined potential effect-modification between single-nucleotide polymorphisms (SNP) at 10 of these loci and probable or established environmental risk factors for CRC in 7,016 CRC cases and 9,723 controls from nine cohort and case–control studies. We used meta-analysis of an efficient empirical-Bayes estimator to detect potential multiplicative interactions between each of the SNPs [rs16892766 at 8q23.3 (EIF3H/UTP23), rs6983267 at 8q24 (MYC), rs10795668 at 10p14 (FLJ3802842), rs3802842 at 11q23 (LOC120376), rs4444235 at 14q22.2 (BMP4), rs4779584 at 15q13 (GREM1), rs9929218 at 16q22.1 (CDH1), rs4939827 at 18q21 (SMAD7), rs10411210 at 19q13.1 (RHPN2), and rs961253 at 20p12.3 (BMP2)] and select major CRC risk factors (sex, body mass index, height, smoking status, aspirin/nonsteroidal anti-inflammatory drug use, alcohol use, and dietary intake of calcium, folate, red meat, processed meat, vegetables, fruit, and fiber). The strongest statistical evidence for a gene–environment interaction across studies was for vegetable consumption and rs16892766, located on chromosome 8q23.3, near the EIF3H and UTP23 genes (nominal Pinteraction = 1.3 × 10−4; adjusted P = 0.02). The magnitude of the main effect of the SNP increased with increasing levels of vegetable consumption. No other interactions were statistically significant after adjusting for multiple comparisons. Overall, the association of most CRC susceptibility loci identified in initial GWAS seems to be invariant to the other risk factors considered; however, our results suggest potential modification of the rs16892766 effect by vegetable consumption. Cancer Res; 72(8); 2036–44. ©2012 AACR.
Predictors of Long-Term Survival After Coronary Artery Bypass Grafting Surgery
Authors: Shahian David M. , O'Brien Sean M. , Sheng Shubin , Grover Frederick L. , Mayer John E. , Jacobs Jeffrey P. , Weiss Jocelyn M. , DeLong Elizabeth R. , Peterson Eric D. , Weintraub William S. , Grau-Sepulveda Maria V. , Klein Lloyd W. , Shaw Richard E. , Garratt Kirk N. , Moussa Issam D. , Shewan Cynthia M. , Dangas George D. , Edwards Fred H. 
Published: February 2012

Background—
Most survival prediction models for coronary artery bypass grafting surgery are limited to in-hospital or 30-day end points. We estimate a long-term survival model using data from the Society of Thoracic Surgeons Adult Cardiac Surgery Database and Centers for Medicare and Medicaid Services.

Methods and Results—
The final study cohort included 348 341 isolated coronary artery bypass grafting patients aged ≥65 years, discharged between January 1, 2002, and December 31, 2007, from 917 Society of Thoracic Surgeons–participating hospitals, randomly divided into training (n=174 506) and validation (n=173 835) samples. Through linkage with Centers for Medicare and Medicaid Services claims data, we ascertained vital status from date of surgery through December 31, 2008 (1- to 6-year follow-up). Because the proportional hazards assumption was violated, we fit 4 Cox regression models conditional on being alive at the beginning of the following intervals: 0 to 30 days, 31 to 180 days, 181 days to 2 years, and >2 years. Kaplan-Meier–estimated mortality was 3.2% at 30 days, 6.4% at 180 days, 8.1% at 1 year, and 23.3% at 3 years of follow-up. Harrell's C statistic for predicting overall survival time was 0.732. Some risk factors (eg, emergency status, shock, reoperation) were strong predictors of short-term outcome but, for early survivors, became nonsignificant within 2 years. The adverse impact of some other risk factors (eg, dialysis-dependent renal failure, insulin-dependent diabetes mellitus) continued to increase.

Conclusions—
Using clinical registry data and longitudinal claims data, we developed a long-term survival prediction model for isolated coronary artery bypass grafting. This provides valuable information for shared decision making, comparative effectiveness research, quality improvement, and provider profiling.
Effects of Catecholamine Stress on Diastolic Function and Myocardial Energetics in Obesity
Authors: Rider Oliver J. , Francis Jane M. , Ali Mohammed K. , Holloway Cameron , Pegg Tammy , Robson Matthew D. , Tyler Damian , Byrne James , Clarke Kieran , Neubauer Stefan 
Published: February 2012

Background—
Obesity is characterized by impaired cardiac energetics, which may play a role in the development of diastolic dysfunction and inappropriate shortness of breath. We assessed whether, in obesity, derangement of energetics and diastolic function is further altered during acute cardiac stress.

Methods and Results—

Normal-weight (body mass index, 22±2 kg/m
2
; n=9–17) and obese (body mass index, 39±7 kg/m
2
; n=17–46) subjects underwent assessment of diastolic left ventricular function (cine magnetic resonance imaging volume-time curve analysis) and cardiac energetics (phosphocreatine/ATP ratio;
31
P-magnetic resonance spectroscopy) at rest and during dobutamine stress (heart rate increase, 65±22% and 69±14%, respectively;
P
=0.61). At rest, obesity was associated with a 22% lower peak filling rate (
P
<0.001) and a 15% lower phosphocreatine/ATP ratio (1.73±0.40 versus 2.03±0.28;
P
=0.048). Peak filling rate correlated with fat mass, left ventricular mass, leptin, waist-to-hip ratio, and phosphocreatine/ATP ratio. On multivariable analysis, phosphocreatine/ATP was the only independent predictor of peak filling rate (β=0.50;
P
=0.03). During stress, a further reduction in phosphocreatine/ATP occurred in obese (from 1.73±0.40 to 1.53±0.50;
P
=0.03) but not in normal-weight (from 1.98±0.24 to 2.04±0.34;
P
=0.50) subject. For similar levels of inotropic stress, there were smaller increases in peak filling rate in obesity (38% versus 70%;
P
=0.01).

Conclusions—
In obesity, cardiac energetics are further deranged during inotropic stress, in association with continued diastolic dysfunction. Myocardial energetics may play a key role in the impairment of diastolic function in obesity.
Changing Epidemiology of Abdominal Aortic Aneurysms in England and Wales
Authors: Choke Edward , Vijaynagar Badri , Thompson John , Nasim Akhtar , Bown Matthew J. , Sayers Robert D. 
Published: February 2012

Background—
Recent studies from Australia, New Zealand, and Sweden have reported declines in abdominal aortic aneurysm (AAA) incidence, prevalence, and mortality. This finding may have important implications for screening programs. This study determined trends in AAA incidence and mortality in England and Wales.

Methods and Results—

Cause-specific mortality data for England and Wales were obtained from UK Office for National Statistics, and hospital admissions and procedures data for England were obtained from Hospital Episode Statistics from 2001 to 2009. Poisson regression models were constructed to estimate the relative change over time. Age-standardized rates for AAA mortality in England and Wales fell significantly by 35.7% from 2001 to 2009, which was largely due to a 35.3% drop in age-standardized ruptured AAA deaths. During the same period, ruptured AAA admissions and emergency AAA repairs in England declined by 29.3% and 35.5%, respectively. In contrast, nonruptured AAA admissions remained static, and nonemergency AAA repairs increased by 17.2%. The average ages for hospital admissions for nonruptured AAAs and ruptured AAAs increased by 0.19 years of age per annum (
P
<0.001) and 0.09 years of age per annum (
P
<0.001), respectively. Nonruptured AAA admissions increased by 21.4% in age band 75 years or more but declined by 11.7% in ages <75 years.

Conclusions—
AAA mortality, ruptured AAA admission, and emergency AAA repair have declined in England and Wales. However, nonruptured AAA admission has remained steady, with an increasing rate in older population offsetting a decreasing rate in younger population. This suggests a shift in AAA presentation to the older population. Present screening strategies may need reassessment to include consideration for increasing the age at which to screen men for AAAs.
Endothelial Cells Overexpressing Interleukin-8 Receptors Reduce Inflammatory and Neointimal Responses to Arterial Injury
Authors: Xing Dongqi , Li Peng , Gong Kaizheng , Yang Zhengqin , Yu Hao , Hage Fadi G. , Oparil Suzanne , Chen Yiu-Fai 
Published: February 2012

Background—
Interleukin-8 (IL8) receptors IL8RA and IL8RB on neutrophil membranes bind to IL8 and direct neutrophil recruitment to sites of inflammation, including acutely injured arteries. This study tested whether administration of IL8RA- and/or IL8RB-transduced rat aortic endothelial cells (ECs) accelerates adhesion of ECs to the injured surface, thus suppressing inflammation and neointima formation in balloon-injured rat carotid arteries. We tested the hypothesis that targeted delivery of ECs by overexpressing IL8RA and IL8RB receptors prevents inflammatory responses and promotes structural recovery of arteries after endoluminal injury.

Methods and Results—

Young adult male rats received balloon injury of the right carotid artery and were transfused intravenously with ECs (total, 1.5×10
6
cells at 1, 3, and 5 hours after injury) transduced with adenoviral vectors carrying IL8RA, IL8RB, and IL8RA/RB (dual transduction) genes, AdNull (empty vector), or vehicle (no EC transfusion). ECs overexpressing IL8Rs inhibited proinflammatory mediators expression significantly (by 60% to 85%) and reduced infiltration of neutrophils and monocytes/macrophages into injured arteries at 1 day after injury, as well as stimulating a 2-fold increase in reendothelialization at 14 days after injury. IL8RA-EC, IL8RB-EC, and IL8RA/RB-EC treatment reduced neointima formation dramatically (by 80%, 74%, and 95%) at 28 days after injury.

Conclusions—
ECs with overexpression of IL8RA and/or IL8RB mimic the behavior of neutrophils that target and adhere to injured tissues, preventing inflammation and neointima formation. Targeted delivery of ECs to arteries with endoluminal injury provides a novel strategy for the prevention and treatment of cardiovascular disease.
An Admission Bioclinical Score to Predict 1-Year Outcomes in Patients Undergoing Aneurysm Coiling
Authors: Degos Vincent , Apfel Christian C. , Sanchez Paola , Colonne Chantal , Renuit Isabelle , Clarençon Frédéric , Nouet Aurélien , Boch Anne Laure , Pourmohamad Tony , Kim Helen , Gourraud Pierre Antoine , Young William L. , Puybasset Louis 
Published: February 2012

Background and Purpose—
A number of scores were developed to predict outcomes after clipping for subarachnoid hemorrhages, yet there is no score for patients undergoing endovascular treatment. Our goal was to develop, compare, and validate a predictive score for 1-year outcomes in patients with coiled subarachnoid hemorrhage.

Methods—
We studied 526 patients for 1 year after intensive care unit discharge. We developed an admission bioclinical score (ABC score), which integrated biomarkers such as troponin I and S100β, with the Glasgow Coma Scale. Using the receiver operating characteristic curve (95% CI), the ABC score was compared with the Glasgow Coma Scale, World Federation of Neurosurgical Societies score, and Fisher score in the derivation cohort and further validated in an independent cohort.

Results—

In the derivation cohort (from 2003–2007, n=368), multivariate logistic regression analysis showed that only Glasgow Coma Scale (
P
<0.001), high S100β (
P
<0.001), and high troponin (
P
<0.02) were independently associated with 1-year mortality. Troponin, S100β, and Glasgow Coma Scale were thus integrated to derive the ABC score. In the derivation cohort, the ABC score reached an receiver operating characteristic curve of 0.82 (0.77–0.88,
P
<0.001) and was significantly greater than the receiver operating characteristic curves of the Glasgow Coma Scale, World Federation of Neurosurgical Societies, and Fisher scores for predicting 1-year mortality. In the validation cohort (from 2008–2009, n=158), the ABC score's receiver operating characteristic curve of 0.76 (0.67–0.86,
P
<0.001) remained superior to the 3 other scores for predicting 1-year mortality.

Conclusions—
The ABC score improves 1-year outcome prediction at admission for patients with coiled subarachnoid hemorrhage. Our study provides large cohort-based evidence supporting integration of individual biomarkers and clinical characteristics to predict outcomes.

Clinical Trial Registration—

URL:
www.clinicaltrials.gov
. Unique identifier: NCT01357057.
Size and shape of the caudate nucleus in individuals with bipolar affective disorder
Authors: Ong Daniel , Walterfang Mark , Malhi Gin S , Styner Martin , Velakoulis Dennis , Pantelis Christos 
Published: February 2012

Objective: The caudate nucleus (CN) is a crucial component of the ventral striatum, which is part of a prefrontal-striatal-thalamic circuit that is modulated by limbic structures to subserve emotional processing. Bipolar disorder is thought to be underpinned by dysfunctional anterior limbic networks, although MRI studies examining the CN have shown equivocal results. As gross volumetric analyses may not detect subtle regional change, we aimed to clarify the role of the CN in bipolar disorder by undertaking shape analysis to detect regional reductions. Methods: The CN was manually traced on MRI scans from 27 patients with bipolar-I disorder and 24 matched controls. A non-parametric spherical harmonic shape analysis was undertaken using the SPHARM toolkit. Results: Whilst the left CN volume was consistently larger in the sample, there was no effect of group or gender or significant interactions between these variables. Volume did not correlate with illness duration or lithium dosage, but was larger in those with a history of psychosis at trend level. However, left caudate shape differed significantly between groups, with deflation in an area along the ventromedial surface (connecting to dorsolateral prefrontal regions) in bipolar patients. Psychotic patients showed increases in the dorsal head and body at trend level overall, in regions connecting to medial and orbitofrontal regions. Conclusions: These findings suggest that subtle rather than gross structural changes occur in the CN, which may not be detectable by volumetric analysis alone, and reflect alterations in specific frontostriatal circuitry in the disorder.
Writing Manuals for Psychodynamic Group Treatments
Authors: Lorentzen Steinar 
Published: February 2012

Treatment manuals may have different purposes. In clinical work it may be to demonstrate the main feabtures and principles of a treatment method to trainees. In psychotherapy research it may be an attempt to ensure that all patients are influenced in a similar way, thus trying to increase the internal validity of the study. Measures taken to ensure internal validity (randomization, inclusion of patients with similar diagnosis, check of treatment fidelity etc.) often reduce the possibility of generalizing the results from such studies to a regular clinical context (external validity). This article describes how treatment manuals for short- and long-term analytic group psychotherapies (20 and 80 weekly sessions, respectively) were developed. We wanted to study the significance of the treatment length, and potential moderators and mediators of differential change in the treatment of regular patients with mixed disorders (anxiety, affective, and mild to moderate personality disorders) who had been referred to outpatient services. The article presents reflections, choices, and dilemmas encountered in developing these manuals. Brief examples from the manuals are presented, highlighting differences between the two formats.
Regulation of mast cell survival and function by tuberous sclerosis complex 1
Authors: Shin Jinwook , Pan Hongjie , Zhong Xiao-Ping 
Published: February 2012

AbstractMast cells play critical roles in allergic disorders and asthma. The importance of tuberous sclerosis complex 1/2-mammalian target of rapamycin (TSC1/2-mTOR) signaling in mast cells is unknown. Here, we report that TSC1 is a critical regulator for mTOR signaling in mast cells downstream of FcεRI and c-Kit, and differentially controls mast cell degranulation and cytokine production. TSC1-deficiency results in impaired mast cell degranulation, but enhanced cytokine production in vitro and in vivo after FcεRI engagement. Furthermore, TSC1 is critical for mast cell survival through multiple pathways of apoptosis including the down-regulation of p53, miR-34a, reactive oxygen species, and the up-regulation of Bcl-2. Together, these findings reveal that TSC1 is a critical regulator of mast cell activation and survival, suggesting the manipulation of the TSC1/2-mTOR pathway as a therapeutic strategy for mast cell-mediated diseases.
Paediatric CT scan usage and referrals of children to computed tomography in Germany-a cross-sectional survey of medical practice and awareness of radiation related health risks among physicians
Authors: Merzenich Hiltrud , Krille Lucian , Hammer Gael , Kaiser Melanie , Yamashita Shunichi , Zeeb Hajo 
Published: February 2012

Abstract

Background
Computed tomography (CT) is a major source of ionizing radiation exposure in medical diagnostic. Compared to adults, children are supposed to be more susceptible to health risks related to radiation. The purpose of a cross-sectional survey among office-based physicians in Germany was the assessment of medical practice in paediatric CT referrals and to investigate physicians' knowledge of radiation doses and potential health risks of radiation exposure from CT in children.

Methods
A standardized questionnaire was distributed to all paediatricians and surgeons in two defined study areas. Furthermore, the study population included a random sample of general practitioners in the two areas. The questionnaire covered the frequency of referrals for paediatric CT examinations, the medical diagnoses leading to paediatric CT referrals, physicians' knowledge of radiation doses and potential health risks of radiation exposure from CT in children.

Results
A total of 295 (36.4%) physicians responded. 59% of the doctors had not referred a child to CT in the past year, and approximately 30% referred only 1-5 children annually. The most frequent indications for a CT examination in children were trauma or a suspected cancer. 42% of the referrals were related to minor diagnoses or unspecific symptoms. The participants underestimated the radiation exposure due to CT and they overestimated the radiation exposure due to conventional X-ray examinations.

Conclusions
In Germany, the frequency of referrals of children to computed tomography is moderate. The knowledge on the risks from radiation exposure among office-based physicians in our sample varied, but there was a tendency to underestimate potential CT risks. Advanced radiological training might lead to considerable amendments in terms of knowledge and practice of CT referral.
Characterization and specificity of the linear epitope of the enterovirus 71 VP2 protein
Authors: Kiener Tanja K , Jia Qiang , Lim Xiao Fang , He Fang , Meng Tao , Kwong Chow Vincent Tak , Kwang Jimmy 
Published: February 2012

Abstract

Background
Enterovirus 71 (EV71) has emerged as a major causative agent of hand, foot and mouth disease in the Asia-Pacific region over the last decade. Hand, foot and mouth disease can be caused by different etiological agents from the enterovirus family, mainly EV71 and coxsackieviruses, which are genetically closely related. Nevertheless, infection with EV71 may occasionally lead to high fever, neurologic complications and the emergence of a rapidly fatal syndrome of pulmonary edema associated with brainstem encephalitis. The rapid progression and high mortality of severe EV71 infection has highlighted the need for EV71-specific diagnostic and therapeutic tools. Monoclonal antibodies are urgently needed to specifically detect EV71 antigens from patient specimens early in the infection process. Furthermore, the elucidation of viral epitopes will contribute to the development of targeted therapeutics and vaccines.

Results
We have identified the monoclonal antibody 7C7 from a screen of hybridoma cells derived from mice immunized with the EV71-B5 strain. The linear epitope of 7C7 was mapped to amino acids 142-146 (EDSHP) of the VP2 capsid protein and was characterized in detail. Mutational analysis of the epitope showed that the aspartic acid to asparagine mutation of the EV71 subgenogroup A (BrCr strain) did not interfere with antibody recognition. In contrast, the serine to threonine mutation at position 144 of VP2, present in recently emerged EV71-C4 China strains, abolished antigenicity. Mice injected with this virus strain did not produce any antibodies against the VP2 protein. Immunofluorescence and Western blotting confirmed that 7C7 specifically recognized EV71 subgenogroups and did not cross-react to Coxsackieviruses 4, 6, 10, and 16. 7C7 was successfully used as a detection antibody in an antigen-capture ELISA assay.

Conclusions
Detailed mapping showed that the VP2 protein of Enterovirus 71 contains a single, linear, non-neutralizing epitope, spanning amino acids 142-146 which are located in the VP2 protein's E-F loop. The S/T(144) mutation in this epitope confers a loss of VP2 antigenicity to some newly emerged EV71-C4 strains from China. The corresponding monoclonal antibody 7C7 was used successfully in an AC-ELISA and did not cross-react to coxsackieviruses 4, 6, 10, and 16 in immunofluorescence assay and Western blots. 7C7 is the first monoclonal antibody described, that can differentiate Coxsackievirus 16 from Enterovirus 71.