bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatotoxicity of isotretinoin in patients with acne and Gilbert's syndrome: a comparative study
Authors: Fernández-Crehuet Pablo , Fernández-Crehuet José Luis , Allam Mohamed Farouk , Fernández-Crehuet Navajas Rafael 
Published: March 2014

ObjectivesThe objective of our follow-up study is to evaluate liver function tests (LFTs) and lipid profiles in patients with Gilbert's syndrome treated with isotretinoin because of severe acne.SettingDermatology outpatient clinics of three regional hospitals of Jaén (Spain).ParticipantsOver 4 years, we included all patients diagnosed with severe acne. Only 37 patients were identified, of which 11 had Gilbert's syndrome.InterventionsAll patients were treated with isotretinoin and followed-up in our outpatient clinics after 10 and 20 weeks. Patients were subjected to an interview questionnaire which included data on age, gender, complete blood count, coagulation profile, fasting blood glucose, LFTs and lipid profiles. Data and results of patients with severe acne and Gilbert's syndrome were compared with those of 26 patients with only severe acne (control group).Primary outcomeBlood analyses were repeated in the follow-up visits.ResultsIn patients with Gilbert's syndrome, bilirubin levels showed substantial decrease over the 20-week follow-up, with more decrease after 10 weeks. None of the control group patients had significant increase in total bilirubin levels after 10 and 20 weeks of follow-up. Liver enzymes were maintained within normal levels in both groups. Both study groups did not show significant pathological increase in lipid profile levels. LDL levels were increased in the two study groups, but this increase was less substantial in patients with Gilbert's syndrome.ConclusionsOur preliminary results suggest that oral isotretinoin could be an effective, safe treatment for patients with Gilbert's syndrome, and may lower bilirubin levels in the first 10 weeks of treatment. Limitations of the study include the small numbers of participants and the fact that it is restricted to one region of Spain.
Comparative effectiveness of microdecompression and laminectomy for central lumbar spinal stenosis: study protocol for an observational study
Authors: Nerland Ulf S , Jakola Asgeir S , Solheim Ole , Weber Clemens , Rao Vidar , Lønne Greger , Solberg Tore K , Salvesen Øyvind , Carlsen Sven M , Nygaard Øystein P , Gulati Sasha 
Published: March 2014

IntroductionThis observational study is designed to test the equivalence between the clinical effectiveness of microdecompression and laminectomy in the surgical treatment of central lumbar spinal stenosis. Lumbar spinal stenosis is the most frequent indication for spinal surgery in the elderly, and as the oldest segment of the population continues to grow its prevalence is likely to increase. However, data on surgical outcomes are limited. Open or wide decompressive laminectomy, often combined with medial facetectomy and foraminotomy, was formerly the standard treatment. In recent years a growing tendency towards less invasive decompressive procedures has emerged. At present, many spine surgeons perform microdecompression for central lumbar spinal stenosis.Methods and analysisProspectively registered treatment and outcome data are obtained from the Norwegian Registry for Spine Surgery. The primary outcome measure is change in Oswestry disability index between baseline and 12-month follow-up. Secondary outcome measures are changes in health-related quality of life measured by the Euro-Qol-5D between baseline and 12-month follow-up, perioperative complications, and duration of surgical procedures and length of hospital stay.Ethics and disseminationThe study has been evaluated and approved by the regional committee for medical research in central Norway and all participants provided written informed consent. The findings of this study will be disseminated through peer-reviewed publications.Trial registration numberClinicaltrials.gov (NCT02006901).
DIFFERENCES BETWEEN REAL AND PARTICLE-IN-CELL PLASMAS: EFFECTS OF COARSE-GRAINING
Authors: MELZANI MICKAËL , WALDER ROLF , FOLINI DORIS , WINISDOERFFER CHRISTOPHE 
Published: March 2014

The PIC model relies on two building blocks. The first stems from the capability of computers to handle only up to ~ 1010 particles, while real plasmas contain from 104 to 1020 particles per Debye sphere: a coarse-graining step must be used, whereby of the order of p ~ 1010 real particles are represented by a single computer superparticle. The second is field storage on a grid with its subsequent finite superparticle size. We introduce the notion of coarse-graining dependent quantities, i.e. physical quantities depending on the number p. They all derive from the plasma parameter Λ, which we show to be proportional to 1/p. We explore three examples: the rapid collision- and fluctuation-induced thermalization of plasmas with different temperatures, that scale with the number of superparticles per grid cell and are a factor p ~ 1010 faster than in real plasmas; the high level of electrostatic fluctuations in a thermal plasma, with corrections due to the finite superparticle sizes; and the blurring of the linear spectrum of the filamentation instability, where the fastest growing modes do not dominate the total energy because of a high level of fluctuations. We stress that the enhanced collisions and correlations of PIC plasmas must be kept negligible toward kinetic physics.
Lymphocyte Telomere Length Is Long in BRCA1 and BRCA2 Mutation Carriers Regardless of Cancer-Affected Status
Authors: Pooley Karen A. , McGuffog Lesley , Barrowdale Daniel , Frost Debra , Ellis Steve D. , Fineberg Elena , Platte Radka , Izatt Louise , Adlard Julian , Bardwell Julian , Brewer Carole , Cole Trevor , Cook Jackie , Davidson Rosemarie , Donaldson Alan , Dorkins Huw , Douglas Fiona , Eason Jacqueline , Houghton Catherine , Kennedy M. John , McCann Emma , Miedzybrodzka Zosia , Murray Alex , Porteous Mary E. , Rogers Mark T. , Side Lucy E. , Tischkowitz Marc , Walker Lisa , Hodgson Shirley , Eccles Diana M. , Morrison Patrick J. , Evans D. Gareth , Eeles Rosalind A. , Antoniou Antonis C. , Easton Douglas F. , Dunning Alison M. 
Published: March 2014

Abstract
Background: Telomere length has been linked to risk of common diseases, including cancer, and has previously been proposed as a biomarker for cancer risk. Germline BRCA1 and BRCA2 mutations predispose to breast, ovarian, and other cancer types.
Methods: We investigated telomere length in BRCA mutation carriers and their non-carrier relatives and further examined whether telomere length is a modifier of cancer risk in mutation carriers. We measured mean telomere length in DNA extracted from whole blood using high-throughput quantitative PCR. Participants were from the EMBRACE study in United Kingdom and Eire (n = 4,822) and comprised BRCA1 (n = 1,628) and BRCA2 (n = 1,506) mutation carriers and their non-carrier relatives (n = 1,688).
Results: We find no significant evidence that mean telomere length is associated with breast or ovarian cancer risk in BRCA mutation carriers. However, we find mutation carriers to have longer mean telomere length than their non-carrier relatives (all carriers vs. non-carriers, Ptrend = 0.0018), particularly in families with BRCA2 mutations (BRCA2 mutation carriers vs. all non-carriers, Ptrend = 0.0016).
Conclusions: Our findings lend little support to the hypothesis that short mean telomere length predisposes to cancer. Conversely, our main and unexpected finding is that BRCA mutation carriers (regardless of cancer status) have longer telomeres than their non-mutation carrier, non–cancer-affected relatives. The longer telomere length in BRCA2 mutation carriers is consistent with its role in DNA damage response. Overall, it seems that increased telomere length may be a consequence of these mutations, but is not itself directly related to the increased cancer risk in carriers.
Impact: The finding that mutation carriers have longer mean telomere lengths than their non-carrier relatives is unexpected but biologically plausible and could open up new lines of research into the functions of the BRCA proteins. To our knowledge, this is the largest study of telomere length in BRCA mutation carriers and their relatives. The null cancer-risk association supports recent large prospective studies of breast and ovarian cancer and indicates that mean telomere length would not be a useful biomarker in these cancers. Cancer Epidemiol Biomarkers Prev; 23(6); 1018–24. ©2014 AACR.
Tailoring Peptidomimetics for Targeting Protein–Protein Interactions
Authors: Akram Omar N. , DeGraff David J. , Sheehan Jonathan H. , Tilley Wayne D. , Matusik Robert J. , Ahn Jung-Mo , Raj Ganesh V. 
Published: March 2014

AbstractProtein–protein interactions (PPI) are a hallmark of cellular signaling. Such interactions occur abundantly within the cellular milieu and encompass interactions involved in vital cellular processes. Understanding the various types, mechanisms, and consequences of PPIs with respect to cellular signaling and function is vital for targeted drug therapy. Various types of small-molecule drugs and targeted approaches to drug design have been developed to modulate PPIs. Peptidomimetics offer an exciting class of therapeutics as they can be designed to target specific PPIs by mimicking key recognition motifs found at critical points in the interface of PPIs (e.g., hotspots). In contrast to peptides, peptidomimetics do not possess a natural peptide backbone structure but present essential functional groups in a required three-dimensional pattern complimentary to the protein-binding pocket. This design feature overcomes many limitations of peptide therapeutics including limited stability toward peptidases, poor transport across biologic membranes, and poor target specificity. Equally important is deciphering the structural requirements and amino acid residues critical to PPIs. This review provides an up-to-date perspective of the complexity of cellular signaling and strategies for targeting PPIs in disease states, particularly in cancer, using peptidomimetics, and highlights that the rational design of agents that target PPIs is not only feasible but is of the utmost clinical importance. Mol Cancer Res; 12(7); 967–78. ©2014 AACR.
Circulating Osteoglycin and NGAL/MMP9 Complex Concentrations Predict 1-Year Major Adverse Cardiovascular Events After Coronary Angiography
Authors: Cheng Jin M. , Akkerhuis K. Martijn , Meilhac Olivier , Oemrawsingh Rohit M. , Garcia-Garcia Hector M. , van Geuns Robert-Jan , Piquer Dominique , Merle Delphine , du Paty Emilie , Galéa Pascale , Jaisser Frederic , Rossignol Patrick , Serruys Patrick W. , Boersma Eric , Fareh Jeannette , Kardys Isabella 
Published: March 2014

Objective—
Previous proteomics experiments have demonstrated that several proteins are differentially expressed in vulnerable human carotid plaques compared with stable plaques. This study aims to investigate the prognostic value of 13 such circulating biomarkers in patients with coronary artery disease.

Approach and Results—

Between 2008 and 2011, 768 patients who underwent coronary angiography for acute coronary syndrome or stable angina pectoris were included in a prospective biomarker study. Plasma concentrations of 13 biomarkers were measured in 88 patients who experienced a major adverse cardiovascular event (MACE) within 1 year and 176 control patients without MACE who were matched on age, sex, and number of diseased coronary vessels. MACE comprised all-cause mortality, acute coronary syndrome, unplanned coronary revascularization, and stroke. After adjustment for established cardiovascular risk factors, osteoglycin (OGN; odds ratio per SD increase in ln-transformed OGN, 1.53; 95% confidence interval, 1.11–2.11;
P
=0.010) and neutrophil gelatinase–associated lipocalin/matrix metalloproteinase 9 (NGAL/MMP9; odds ratio per SD increase in ln-transformed NGAL/MMP9, 1.37; 95% confidence interval, 1.01–1.85;
P
=0.042) complex were independently associated with MACE during follow-up. These associations were independent of C-reactive protein levels. Adding OGN or NGAL/MMP9 to a model containing conventional risk factors did not significantly improve discriminatory power (OGN: area under receiver operating characteristic curve, 0.75 versus 0.67; NGAL/MMP9: 0.73 versus 0.67) but did significantly improve risk reclassification (OGN: net reclassification index=0.29; 95% confidence interval, 0.05–0.53;
P
<0.019; NGAL/MMP9: net reclassification index=0.44; 95% confidence interval, 0.20–0.69;
P
<0.001).

Conclusions—
Circulating OGN and NGAL/MMP9 complex are promising biomarkers that are expressed in vulnerable atherosclerotic plaques and may have incremental value for prediction of MACE within 1 year after coronary angiography.
Incidence and Clinical Impact of Stent Fracture After the Nobori Biolimus‐Eluting Stent Implantation
Authors: Kuramitsu Shoichi , Iwabuchi Masashi , Yokoi Hiroyoshi , Domei Takenori , Sonoda Shinjo , Hiromasa Takashi , Morinaga Takashi , Kobayashi Yohei , Ohe Kensuke , Goya Kaoru , Yamaji Kyohei , Hyodo Makoto , Soga Yoshimitsu , Kondo Katsuhiro , Shirai Shinichi , Ando Kenji , Sakai Koyu , Nobuyoshi Masakiyo 
Published: March 2014

Background

Stent fracture (
SF
) after drug‐eluting stent implantation has become an important concern. The aim of this study was to assess the incidence, predictors, and clinical impact of
SF
after biolimus‐eluting stent.

Methods and Results

A total of 1026 patients with 1407 lesions undergoing the Nobori biolimus‐eluting stent implantation and follow‐up angiography within 9 months after index procedure were analyzed.
SF
was defined as complete or partial separation of the stent, as assessed by using plain fluoroscopy, intravascular ultrasound, or optical coherence tomography during the follow‐up. We assessed the rate of
SF
and the cumulative incidence of clinically driven target lesion revascularization and definite stent thrombosis within 9 months.
SF
was observed in 58 (4.1%) of 1407 lesions and 57 (5.5%) of 1026 patients. Lesions with hinge motion (
OR
8.90, 95%
CI
3.84 to 20.6,
P
<0.001), tortuosity (
OR
4.16, 95%
CI
1.75 to 9.88,
P
=0.001), and overlapping stents (
OR
2.41, 95%
CI
0.95 to 6.10,
P
=0.06) were predictors of
SF
. Cumulative incidence of clinically driven target lesion revascularization within 9 months was numerically higher in the
SF
group than that in the non‐
SF
group (12.0% versus 1.0%). Cumulative incidence of definite stent thrombosis within 9 months tended to be higher in the
SF
group than that in the non‐
SF
group (1.7% versus 0.5%).

Conclusions

SF
after biolimus‐eluting stent occurs in 4.1% of lesions and appears to be associated with clinically driven target lesion revascularization.
A Randomized Pilot Study of Aortic Waveform Guided Therapy in Chronic Heart Failure
Authors: Borlaug Barry A. , Olson Thomas P. , Abdelmoneim Mohamed Sahar , Melenovsky Vojtech , Sorrell Vincent L. , Noonan Kelly , Lin Grace , Redfield Margaret M. 
Published: March 2014

Background

Medication treatment decisions in heart failure (
HF
) are currently informed by measurements of brachial artery pressure, but ventricular afterload is more accurately represented by central aortic pressure, which differs from brachial pressure. We sought to determine whether aggressive titration of vasoactive medicines beyond goal‐directed heart failure medical therapy (
GDMT
) based upon aortic pressure improves exercise capacity and cardiovascular structure‐function.

Methods and Results

Subjects with chronic
HF
(n=50) underwent cardiopulmonary exercise testing, echocardiography, and arterial tonometry to measure aortic pressure and augmentation index, and were then randomized to aortic pressure‐guided treatment (active, n=23) or conventional therapy (control, n=27). Subjects returned for 6 monthly visits wherein
GDMT
was first optimized. Additional vasoactive therapies were then sequentially added with the goal to reduce aortic augmentation index to 0% (active) or if brachial pressure remained elevated (control). Subjects randomized to active treatment experienced greater improvement in peak oxygen consumption compared with controls (1.37±3.76 versus −0.65±2.21 mL min
−1
kg
−1
,
P
=0.025) though reductions in aortic augmentation index were similar (−7±9% versus −5±6%,
P
=0.46). Forward stroke volume increased while arterial elastance and left ventricular volumes decreased in all participants, with no between‐group difference. Subjects randomized to active treatment were more likely to receive additional vasoactive therapies including nitrates, aldosterone antagonists and hydralazine, with no increased risk of hypotension or worsening renal function.

Conclusions
Maximization of goal‐directed medical therapy in heart failure patients may enhance afterload reduction and lead to reverse remodeling, while additional medicine titration based upon aortic pressure data improves exercise capacity in patients with heart failure.
Difference in Aneurysm Characteristics Between Ruptured and Unruptured Aneurysms in Patients With Multiple Intracranial Aneurysms
Authors: Backes Daan , Vergouwen Mervyn D.I. , Velthuis Birgitta K. , van der Schaaf Irene C. , Bor A. Stijntje E. , Algra Ale , Rinkel Gabriel J.E. 
Published: March 2014

Background and Purpose—
Prediction of the risk of rupture of unruptured intracranial aneurysms is mainly based on aneurysm size and location. Previous studies identified features of aneurysm shape and flow angles as additional risk factors for aneurysm rupture, but these studies were at risk for confounding by patient-specific risk factors such as hypertension and age. In this study, we avoided this risk by comparing characteristics of ruptured and unruptured aneurysms in patients with both aneurysmal subarachnoid hemorrhage and multiple intracranial aneurysms.

Methods—
We included patients with aneurysmal subarachnoid hemorrhage and multiple aneurysms who presented to our hospital between 2003 and 2013. We identified the ruptured aneurysm based on bleeding pattern on head computed tomography or surgical findings. Aneurysm characteristics (size, location, shape, aspect ratio [neck-to-dome length / neck-width], flow angles, sidewall or bifurcation type, and contact with bone) were evaluated on computed tomographic angiograms. We calculated odds ratios with 95% confidence intervals with conditional univariable logistic regression analysis. Analyses were repeated after adjustment for aneurysm size and location.

Results—
The largest aneurysm had not ruptured in 36 (29%) of the 124 included patients with 302 aneurysms. Odds ratios for aspect ratio ≥1.3 was 3.3 (95% confidence intervals [1.3–8.4]) and odds ratios for irregular shape was 3.0 (95% confidence intervals [1.0–8.8]), both after adjustment for aneurysm size and location.

Conclusions—
Aspect ratio ≥1.3 and irregular shape are associated with aneurysm rupture independent of aneurysm size and location, and independent of patient characteristics. Additional studies need to assess to what extent these factors increase the risks of rupture of small aneurysms in absolute terms.
The Increasing Complementarity between Cognitive and Social Skills
Authors: Weinberger Catherine J. 
Published: March 2014

Abstract
Data linking 1972 and 1992 adolescent skill endowments to adult outcomes reveal increasing complementarity between cognitive and social skills. In fact, previously noted growth in demand for cognitive skills affected only individuals with strong endowments of both social and cognitive skills. These findings are corroborated using Census and CPS data matched with Dictionary of Occupational Titles (DOT) job task measures; employment in and earnings premia to occupations requiring high levels of both cognitive and social skill grew substantially compared with occupations that require only one or neither type of skill, and this emerging feature of the labor market has persisted into the new millennium.
A New Sahidic Fragment of the Gospel of Luke from the Michigan Collection
Authors: Jones Brice C. 
Published: March 2014

AbstractThis article publishes for the first time the extant remains of a Sahidic Coptic manuscript containing portions of Luke 17-19. Almost all of the special Lukan pericope concerning Jesus and Zacchaeus is preserved (19:1-10), as well as most of the parable of the Dishonest Judge (18:1-8). The edition includes a transcription, translation, palaeographical analysis, critical apparatus, as well as images of the fragment.
Hapax Legomena and the Idiolect of John
Authors: Mardaga Hellen 
Published: March 2014

AbstractThe present contribution treats hapax legomena in the Fourth Gospel. The author presents three important findings. First, John has few hapaxes in his gospel (84) and only five hapaxes are unique (i.e. these words are mainly used after the composition of the Fourth Gospel). Second, the presence of hapaxes could be an indicator of orality and memory. Third, in several instances John uses hapaxes in conjunction with repetitions in two ways: 1) In John 2:14-16; 12:14; 18:3; 19:39-40 a hapax is followed by a (more) common word that belongs to the same semantic domain as the hapax. The common word repeats and clarifies the meaning of the hapax to the audience; 2) In John 4:7, 11, 15, 20-24; 9:1-2, 6, 8; 11:11-13; 13:5 a hapax is created by means of a stem-related word. The alteration between repetition and hapaxes helps the audience to focus on the narrative and follow the line of thought.
Convection over Tropical Africa and the East Atlantic during the West African Monsoon: Regional and Diurnal Variability
Authors: Janiga Matthew A. , Thorncroft Chris D. 
Published: March 2014

Abstract
The geographic and diurnal variability of moist convection over tropical Africa and the east Atlantic is examined using the Tropical Rainfall Measuring Mission (TRMM) satellite and related to the variability of the convective environment. The stratiform rain fraction is highest within oceanic and continental regions just north of the equator. Both regions have high column relative humidity (CRH). In both monsoon and semiarid continental regions, stratiform rain fractions are significantly higher on days when the CRH is high, which suggests a relationship between these quantities. Large convective systems with high echo tops dominate the rainfall over the Sahel. The importance of CAPE and shear to the development of these types of systems is suggested by the fact these systems are especially common on days when the CAPE and shear are unusually high.
Both deep convective and stratiform conditional rain rates increase with the size and echo-top height of convective systems. According to the TRMM Precipitation Radar (PR) near-surface rain rate, the highest deep convective and stratiform conditional rain rates occur off the coast of West Africa. However, comparisons between the PR near-surface rain rate and rain rates computed from Z–R relationships from the literature suggest that deep convective conditional rain rates over the Sahel are underestimated by the TRMM precipitation algorithm. Over the Sahel, small (large) convective systems produce most of the rainfall in the afternoon (early morning). This is associated with enhanced convective rainfall in the afternoon and stratiform in the early morning. The transition from small to large convective systems as convection propagates away from topographic features is also observed.