bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Frequency of CYP2D6 Ultrarapid Metabolizer Genotype in the Finnish Population
Authors: Pietarinen Paavo , Tornio Aleksi , Niemi Mikko 
Published: April 2016

AbstractCYP2D6 participates in the biotransformation of many commonly used drugs. Large genetic variability in CYP2D6 results in a wide interindividual variability in the response to CYP2D6 substrate drugs. Previous studies have assessed the phenotype and genotype distributions of CYP2D6 in relatively small Finnish population samples. The aim of our study was to investigate the frequencies of CYP2D6 genotypes in a larger Finnish population cohort of 857 healthy volunteers. The volunteers were genotyped for 10 CYP2D6 genetic variants (*2, *3, *4, *5, *6, *9, *10, *17, *39, *41) and copy number variation performed with TaqMan genotyping assays and copy number assay targeting exon 9. CYP2D6 phenotypes were inferred from the genotype data with the classical and activity score methods. According to the classical method, a large majority of the study cases were extensive metabolizers (EM; 87.3%; 95% confidence interval 84.9–89.3) and the second largest group was ultrarapid metabolizers (UM; 7.2%; 5.7–9.2%). Intermediate (IM) and poor metabolizers (PM) were in clear minority (3.0%; 2.1–4.4% and 2.3%; 1.5–3.6%, respectively). The activity score method yielded similar phenotype predictions. These results show that the frequency of UM genotype is higher and that of PM and IM genotype is lower in the Finnish population than in other North European populations. Accordingly, CYP2D6 genetic profile of the Finnish population differs from its geographically close neighbours, which has implications for the effective and safe use of drugs metabolized by CYP2D6.
Robust Risk Prediction with Biomarkers Under Two-Phase Stratified Cohort Design
Authors: Payne Rebecca , Yang Ming , Zheng Yingye , Jensen Majken K. , Cai Tianxi 
Published: April 2016

Summary
Identification of novel biomarkers for risk prediction is important for disease prevention and optimal treatment selection. However, studies aiming to discover which biomarkers are useful for risk prediction often require the use of stored biological samples from large assembled cohorts, and thus the depletion of a finite and precious resource. To make efficient use of such stored samples, two-phase sampling designs are often adopted as resource-efficient sampling strategies, especially when the outcome of interest is rare. Existing methods for analyzing data from two-phase studies focus primarily on single marker analysis or fitting the Cox regression model to combine information from multiple markers. However, the Cox model may not fit the data well. Under model misspecification, the composite score derived from the Cox model may not perform well in predicting the outcome. Under a general two-phase stratified cohort sampling design, we present a novel approach to combining multiple markers to optimize prediction by fitting a flexible nonparametric transformation model. Using inverse probability weighting to account for the outcome-dependent sampling, we propose to estimate the model parameters by maximizing an objective function which can be interpreted as a weighted C-statistic for survival outcomes. Regardless of model adequacy, the proposed procedure yields a sensible composite risk score for prediction. A major obstacle for making inference under two phase studies is due to the correlation induced by the finite population sampling, which prevents standard inference procedures such as the bootstrap from being used for variance estimation. We propose a resampling procedure to derive valid confidence intervals for the model parameters and the C-statistic accuracy measure. We illustrate the new methods with simulation studies and an analysis of a two-phase study of high-density lipoprotein cholesterol (HDL-C) subtypes for predicting the risk of coronary heart disease.
PCAN: Probabilistic Correlation Analysis of Two Non-Normal Data Sets
Authors: Zoh Roger S. , Mallick Bani , Ivanov Ivan , Baladandayuthapani Veera , Manyam Ganiraju , Chapkin Robert S. , Lampe Johanna W. , Carroll Raymond J. 
Published: April 2016

SummaryMost cancer research now involves one or more assays profiling various biological molecules, e.g., messenger RNA and micro RNA, in samples collected on the same individuals. The main interest with these genomic data sets lies in the identification of a subset of features that are active in explaining the dependence between platforms. To quantify the strength of the dependency between two variables, correlation is often preferred. However, expression data obtained from next-generation sequencing platforms are integer with very low counts for some important features. In this case, the sample Pearson correlation is not a valid estimate of the true correlation matrix, because the sample correlation estimate between two features/variables with low counts will often be close to zero, even when the natural parameters of the Poisson distribution are, in actuality, highly correlated. We propose a model-based approach to correlation estimation between two non-normal data sets, via a method we call Probabilistic Correlations ANalysis, or PCAN. PCAN takes into consideration the distributional assumption about both data sets and suggests that correlations estimated at the model natural parameter level are more appropriate than correlations estimated directly on the observed data. We demonstrate through a simulation study that PCAN outperforms other standard approaches in estimating the true correlation between the natural parameters. We then apply PCAN to the joint analysis of a microRNA (miRNA) and a messenger RNA (mRNA) expression data set from a squamous cell lung cancer study, finding a large number of negative correlation pairs when compared to the standard approaches.
Chromogranin A and neurone‐specific enolase serum levels as predictors of treatment outcome in patients with metastatic castration‐resistant prostate cancer undergoing abiraterone therapy
Authors: Heck Matthias M. , Thaler Markus A. , Schmid Sebastian C. , Seitz Anna‐Katharina , Tauber Robert , Kübler Hubert , Maurer Tobias , Thalgott Mark , Hatzichristodoulou Georgios , Höppner Michael , Nawroth Roman , Luppa Peter B. , Gschwend Jürgen E. , Retz Margitta 
Published: April 2016

ObjectiveTo determine the impact of elevated neuroendocrine serum markers on treatment outcome in patients with metastatic castration‐resistant prostate cancer (mCRPC) undergoing treatment with abiraterone in a post‐chemotherapy setting.Patients and MethodChromogranin A (CGa) and neurone‐specific enolase (NSE) were determined in serum drawn before treatment with abiraterone from 45 patients with mCRPC. Outcome measures were overall survival (OS), prostate‐specific antigen (PSA) response defined by a PSA level decline of ≥50%, PSA progression‐free survival (PSA‐PFS), and clinical or radiographic PFS.ResultsThe CGa and NSE serum levels did not correlate (P = 0.6). Patients were stratified in to low‐ (nine patients), intermediate‐ (18) or high‐risk (18) groups according to elevation of none, one, or both neuroendocrine markers, respectively. The risk groups correlated with decreasing median OS (median OS not reached vs 15.3 vs 6.6 months; P < 0.001), decreasing median clinical or radiographic PFS (8.3 vs 4.4 vs 2.7 months; P = 0.001) and decreasing median PSA‐PFS (12.0 vs 3.2 vs 2.7 months; P = 0.012). In multivariate Cox regression analysis the combination of CGa and NSE (≥1 marker positive vs both markers negative) remained significant predictors of OS, clinical or radiographic PFS, and PSA‐PFS. We did not observe a correlation with PSA response (63% vs 35% vs 31%; P = 0.2).ConclusionChromogranin A and NSE did not predict PSA response in patients with mCRPC treated with abiraterone. However, we observed a correlation with shorter PSA‐PFS, clinical or radiographic PFS, and OS. This might be due to an elevated risk of developing resistance under abiraterone treatment related to neuroendocrine differentiation.
Tree Height Reduction After Selective Logging in a Tropical Forest
Authors: Rutishauser Ervan , Hérault Bruno , Petronelli Pascal , Sist Plinio 
Published: April 2016

AbstractBy harvesting scattered large trees, selective logging increases light availability and thereby stimulates growth and crown expansion at early‐life stage among remnant trees. We assessed the effects of logging on total and merchantable bole (i.e., lowest branch at crown base) heights on 952 tropical canopy trees in French Guiana. We observed reductions in both total (mean, −2.3 m) and bole (mean, −2.0 m) heights more than a decade after selective logging. Depending on local logging intensity, height reductions resulted in 2–13 percent decreases in aboveground tree biomass and 3–17 percent decreases in bole volume. These results highlight the adverse effects of logging at both tree and stand levels. This decrease in height is a further threat to future provision of key environmental services, such as timber production and carbon sequestration.
Readability of clinical letters sent from a young people's department
Authors: McAndie Elena , Gilchrist Anne , Ahamat Boolang 
Published: April 2016

BackgroundWriting directly to patients or copying letters to them is common practice in Child and Adolescent Mental Health Services (CAMHS). If the intention is to increase young people's understanding and collaboration in their health care, then the readability of such letters is important. The aim of this study was to reassess the readability of letters sent to patients from the Young People's Department at Royal Cornhill Hospital since it adopted the choice and partnership approach (CAPA).MethodReadability of clinical letters was measured using indices available in Microsoft Word. Results were compared to readability thresholds.ResultsMost letters sent to patients were still not easily readable.ConclusionsAwareness of easily accessible readability formulae has not led to acceptable levels of readability in letters. More needs to be done to investigate patients’ views and improve communication.
Pituitary apoplexy – bespoke patient management allows good clinical outcome
Authors: Giritharan Sumithra , Gnanalingham Kanna , Kearney Tara 
Published: April 2016

SummaryObjectiveTo describe the clinical presentation, management and outcome of pituitary apoplexy from a single centre and retrospectively apply the Pituitary Apoplexy Score (PAS).DesignRetrospective review of patients presenting with classical pituitary apoplexy to a single neurosurgical centre in the Greater Manchester region.ResultsA total of 31 cases with classical pituitary apoplexy were identified between 2005 and 2014. The mean age at presentation was 55 years, and there were 19 men. In only one patient was there prior knowledge of a pituitary adenoma. Eleven (35%) patients were managed conservatively and 20 (65%) patients managed surgically. Emergency surgery was carried out in 11 patients. At presentation, visual symptoms were present in a higher proportion of patients in the surgical group (90%) compared to the conservatively managed group (64%). At final follow‐up, visual recovery was apparent in most patients in both the surgical (100%) and conservatively (86%) managed groups. The proportion of patients with hypopituitarism was high in both the surgical (86%) and conservative (73%) groups at presentation, and this failed to improve at final follow‐up (90% vs 73%, respectively). The median PAS scores were higher in the surgical (PAS 2), compared to the conservatively managed group (PAS 0).ConclusionIn pituitary apoplexy patients managed conservatively or surgically, there is good recovery of visual symptoms but not endocrine function. Patients should be managed on a case‐by‐case basis based on the severity of symptoms at presentation, progression of disease and surgical expertise available. Further prospective studies using the PAS are required to determine its usefulness in clinical practice.
Formation of the circle of Willis during human embryonic development
Authors: Takakuwa Tetsuya , Koike Teppei , Muranaka Taiga , Uwabe Chigako , Yamada Shigehito 
Published: April 2016

AbstractThe circle of Willis (CW) is a circulatory anastomosis that supplies blood to the brain and adjacent structures. We examined the timing of formation of CW in 20 Japanese human embryo samples by using 3‐dimensional reconstruction of serial histological sections. The CW was closed in 1 (n = 6), 2 (n = 8), 2 (n = 3) and 2 (n = 3) samples at Carnegie stages 20, 21, 22, and 23, respectively. The CW was unclosed in 13 samples (unclosed at ACOM alone, 6 samples; ACOM and bilateral P1, 4; left PCOM and right P1, 1; right PCOM and right P1, 1; ACOM and left PCOM, 1). It was difficult to predict whether the circle would close during further development, as such variations frequently exist in adults.
A Survey of Cardiac 4D PC‐MRI Data Processing
Authors: Köhler Benjamin , Born Silvia , van Pelt Roy F. P. , Hennemuth Anja , Preim Uta , Preim Bernhard 
Published: April 2016

AbstractCardiac four‐dimensional phase‐contrast magnetic resonance imaging (4D PC‐MRI) acquisitions have gained increasing clinical interest in recent years. They allow to non‐invasively obtain extensive information about patient‐specific hemodynamics, and thus have a great potential to improve the diagnosis, prognosis and therapy planning of cardiovascular diseases. A dataset contains time‐resolved, three‐dimensional blood flow directions and strengths, making comprehensive qualitative and quantitative data analysis possible. Quantitative measures, such as stroke volumes, help to assess the cardiac function and to monitor disease progression. Qualitative analysis allows to investigate abnormal flow characteristics, such as vortices, which are correlated to different pathologies. Processing the data comprises complex image processing methods, as well as flow analysis and visualization. In this work, we mainly focus on the aorta. We provide an overview of data measurement and pre‐processing, as well as current visualization and quantification methods. This allows other researchers to quickly catch up with the topic and take on new challenges to further investigate the potential of 4D PC‐MRI data.
Protective benefit of predominant breastfeeding against otitis media may be limited to early childhood: results from a prospective birth cohort study
Authors: Brennan‐Jones C.G. , Eikelboom R.H. , Jacques A. , Swanepoel D. , Atlas M.D. , Whitehouse A.J.O. , Jamieson S.E. , Oddy W.H. 
Published: April 2016

ObjectivesTo examine the long‐term effects of predominant breastfeeding on incidence of otitis media.DesignProspective birth cohort study.SettingThe West Australian Pregnancy Cohort (Raine) Study recruited 2900 mothers through antenatal clinics at the major tertiary obstetric hospital in Perth, Western Australia, between 1989 and 1992.ParticipantsIn total, 2237 children participated in a 6‐year cohort follow‐up, and a subset of 1344 were given ear and hearing assessments.Main outcome measuresOM diagnosis at 6 years of age (diagnosed by low‐compliance tympanograms, 0–0.1 mmho). This was compared to OM diagnosed at the 3‐year cohort follow‐up using parent‐report measures. Main exposure measures were duration of predominant breastfeeding (defined as the age other milk was introduced) and duration of partial (any) breastfeeding (defined as the age breastfeeding was stopped).ResultsThere was a significant, independent association between predominant breastfeeding (OR = 1.33 [1.04, 1.69]; P = 0.02) and OM, and breastfeeding duration (OR = 1.35 [1.08, 1.68]; P = 0.01) with OM at 3 years of age. However, at 6 years of age, this relationship was no longer statistically significant (predominant breastfeeding OR = 0.78 [0.48, 1.06]; P = 0.09; duration of breastfeeding, OR = 1.34 [0.81, 2.23]; P = 0.25).ConclusionsOur findings are in line with a number of epidemiological studies which show a positive association between breastfeeding and OM in early childhood. However, the long‐term follow‐up of these children revealed that by 6 years of age, there was no significant influence of breastfeeding on presence of OM. These results suggest that the protective effect of predominant breastfeeding for at least 6 months does not extend to school‐age children, where other social and environmental factors may be stronger predictors of OM.
The clinical diagnostic value of target biopsy using narrow‐band imaging endoscopy and accurate laryngeal carcinoma pathologic specimen acquisition
Authors: Yang Y. , Liu J. , Song F. , Zhang S. 
Published: April 2016

ObjectiveTo estimate the clinical significance of target biopsy for clinical diagnosis and determine accurate laryngeal lesion pathologic specimen acquisition via narrow‐band imaging (NBI) endoscopy.MethodsA total of 138 samples from patients with laryngeal lesions (carcinoma, 118; hyperplasia, 3; mild dysplasia, 2; moderate dysplasia, 5; severe dysplasia, 5; vocal cord polyp, 1; and inflammatory lesion, 4) were collected from the Department of Otolaryngology Head and Neck Surgery of Tianjin Union Medical Center from 1 January 2013 to 1 February 2015. All patients were divided into the regular biopsy and NBI target biopsy groups; the imaging data were recorded and patient samples were biopsied. Pathologic diagnoses were used to evaluate the accuracies of regular and target biopsy.ResultsBased on the pathologic diagnosis, NBI target pathology yielded an accurate laryngeal lesion pathologic specimen acquisition rate of 95.6% (65/68), significantly higher than that yielded by regular biopsy (75.7%, 53/70; χ2 = 10.99, P = 0.001). In the NBI target pathology group, the correct accurate pathologic specimen acquisition rates at laryngeal cancer diagnostic stages 0 (Tis), I and II were 100%, 100% and 85.71%, respectively, which were higher than the corresponding rates in the regular biopsy group (0%, χ2 = 10.000, P = 0.002; 25%, χ2 = 5.625, P = 0.018; and 38.46%, χ2 = 6.454, P = 0.011, respectively).ConclusionsIn cases of laryngeal carcinoma, NBI endoscopy plays an important role in clinical diagnosis and accurate pathologic specimen acquisition and could be a regular clinical method for laryngeal lesion detection.
GAMDB: a web resource to connect microRNAs with autophagy in gerontology
Authors: Zhang Lan , Xie Tao , Tian Mao , Li Jingjing , Song Sicheng , Ouyang Liang , Liu Bo , Cai Haoyang 
Published: April 2016

AbstractObjectivesMicroRNAs (miRNAs) are endogenous ~23 nucleotides (nt) RNAs, regulating gene expression by pairing to the mRNAs of protein‐coding genes to direct their post‐transcriptional repression. Both in normal and aberrant activities, miRNAs contribute to a recurring paradigm of cellular behaviors in pathological settings, especially in gerontology. Autophagy, a multi‐step lysosomal degradation process with function to degrade long‐lived proteins and damaged organelles, has significant impact on gerontology. Thus, elucidating how miRNAs participate in autophagy may enlarge the scope of miRNA in autophagy and facilitate researches in gerontology.Materials and methodsHerein, based upon the published studies, predicted targets and gerontology‐related diseases, we constructed a web resource named Gerontology‐Autophagic‐MicroRNA Database (GAMDB) (http://gamdb.liu-lab.com/index.php), which contained 836 autophagy‐related miRNAs, 197 targeted genes/proteins and 56 aging‐related diseases such as Parkinson' disease, Alzheimer's disease and Huntington's disease.Results and ConclusionWe made use of large amounts of data to elucidate the intricate relationships between microRNA‐regulated autophagic mechanisms and gerontology. This database will facilitate better understanding of autophagy regulation network in gerontology and thus promoting gerontology‐related therapy in the future.
Hormone resuscitation therapy for brain‐dead donors – is insulin beneficial or detrimental?
Authors: Novitzky Dimitri , Mi Zhibao , Videla Luis A. , Collins Joseph F. , Cooper David K. C. 
Published: April 2016

AbstractHormonal replacement therapy to brain‐dead potential organ donors remains controversial. A retrospective study was carried out of hormonal therapy on procurement of organs in 63 593 donors in whom information on thyroid hormone therapy (triiodothyronine or levothyroxine [T3/T4]) was available. In 40 124 donors, T3/T4 and all other hormonal therapy were recorded. The percentage of all organs procured, except livers, was greater when T3/T4 had been administered. An independent beneficial effect of antidiuretic hormone (ADH) was also clear. Corticosteroids were less consistently beneficial (most frequently when T3/T4 had not been administered), although never detrimental. Insulin was almost never beneficial and at times was associated with a reduced yield of organs, particularly of the pancreas and intestine, an observation that does not appear to have been reported previously. In addition, there was reduced survival at 12 months of recipients of pancreases from T3/T4‐treated donors, but not of pancreas grafts. The possibly detrimental effect observed following insulin therapy is discussed.
Climate change sentinel or false prophet? The case of Aloe dichotoma
Authors: Jack S. L. , Hoffman M. T. , Rohde R. F. , Durbach I. 
Published: April 2016

AbstractAimPrevious research suggests that equatorward populations of the iconic arborescent succulent Aloe dichotoma Masson are contracting in response to recent anthropogenic climate change (ACC) in southern Africa. However, previous studies did not account for small‐scale spatial heterogeneity, latitudinal climatic disjunctions or when mortality occurred. We reassess A. dichotoma's suitability as an indicator species and comment on pitfalls in the selection of species with similar life history characteristics.LocationSouth‐western Africa.MethodsA 15,000 km distribution‐wide roadside visual survey was conducted to capture demographic patterns and provide the means for extracting tightly coupled climate profiles for the species. Rainfall and temperature gradients were assessed for latitudinal discontinuities indicating distinct equatorward‐poleward climate zones. Repeat photographs and reference individuals were used to develop an index for dating the approximate time‐since‐death of dead trees at 14 latitudinally spaced populations.ResultsThe proportion of dead individuals was greatest within the southern third of the latitudinal distribution rather than at the equatorward range limit. The equatorward summer rainfall zone (SRZ) was significantly drier, rainfall more variable and temperatures hotter compared to the poleward winter rainfall zone (WRZ). This difference was associated with a generally greater proportion of dead individuals in the SRZ and greater proportion of juveniles in the WRZ. Furthermore, juveniles appeared more sensitive to drought stress while adults were more resilient. Most mortality occurred several decades ago, was not more recent at the equatorward limit and was drawn from the more drought resilient adult stage class.Main conclusionsAloe dichotoma mortality (and recruitment) patterns reflect prevailing differences in the SRZ and WRZ climate, while differing juvenile and adult drought stress tolerances and windthrow‐mediated mortality reinforces this pattern. This and strong indications of non‐recent death suggest that ACC is not responsible for observed mortality. An alternative hypothesis for current demographic patterns, which incorporates palaeoclimatic evidence and A. dichotoma life history characteristics is proposed. Long‐term climate trends, recruitment‐mortality dynamics and potential climatic discontinuities should be considered before advancing species as indicators of ACC.