bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacogenetic warfarin dose refinements remain significantly influenced by genetic factors after one week of therapy
Authors: Lenzini Petra , Wadelius Mia , Jorgensen Andrea , Kimmel Stephen , Ridker Paul , Eriksson Niclas , Anderson Jeffrey , Pirmohamed Munir , Limdi Nita , Pendleton Robert , McMillin Gwendolyn , Burmester James , Kurnik Daniel , Stein C. , Caldwell Michael , Eby Charles , Rane Anders , Lindh Jonatan , Shin Jae-Gook , Kim Ho-Sook , Angchaisuksiri Pantep , Glynn Robert , Kronquist Kathryn , Carlquist John , Grice Gloria , Barrack Robert , Li Juan , Gage Brian , Horne Benjamin 
Published: December 2011

SummaryBy guiding initial warfarin dose, pharmacogenetic (PGx) algorithms may improve the safety of warfarin initiation. However, once international normalised ratio (INR) response is known, the contribution of PGx to dose refinements is uncertain. This study sought to develop and validate clinical and PGx dosing algorithms for warfarin dose refinement on days 6–11 after therapy initiation. An international sample of 2,022 patients at 13 medical centres on three continents provided clinical, INR, and genetic data at treatment days 6–11 to predict therapeutic warfarin dose. Independent derivation and retrospective validation samples were composed by randomly dividing the population (80%/20%). Prior warfarin doses were weighted by their expected effect on S-warfarin concentrations using an exponential-decay pharmacokinetic model. The INR divided by that “effective” dose constituted a treatment response index. Treatment response index, age, amiodarone, body surface area, warfarin indication, and target INR were associated with dose in the derivation sample. A clinical algorithm based on these factors was remarkably accurate: in the retrospective validation cohort its R2 was 61.2% and median absolute error (MAE) was 5.0 mg/week. Accuracy and safety was confirmed in a prospective cohort (N=43). CYP2C9 variants and VKORC1–1639 G→A were significant dose predictors in both the derivation and validation samples. In the retrospective validation cohort, the PGx algorithm had: R2= 69.1% (p<0.05 vs. clinical algorithm), MAE= 4.7 mg/week. In conclusion, a pharmacogenetic warfarin dose-refinement algorithm based on clinical, INR, and genetic factors can explain at least 69.1% of therapeutic warfarin dose variability after about one week of therapy.
BLACK AND WHITE LIBERATION
Authors: LAGERWERF LENY 
Published: December 2011

AbstractSome time ago the department of missiology received a position paper from Mindolo Ecumenical Foundation dealing with "The Churches and Change in Southern Africa". This paper has been an incentive to this review of some (Third World) Christian Literature on Southern Africa, and more particularly on the subject of violence/nonviolence.
Chapter 1 deals with the general question "What is violence?" and with the legitimacy of the use of power. Chapter 2 gives an account of the various (violent or nonviolent) ways that people within or outside these Southern African countries are propagating or practising in their struggle to combat violence.
On the Use of Reanalysis Data for Downscaling
Authors: Brands S. , Gutiérrez J. M. , Herrera S. , Cofiño A. S. 
Published: December 2011

Abstract
In this study, a worldwide overview on the expected sensitivity of downscaling studies to reanalysis choice is provided. To this end, the similarity of middle-tropospheric variables—which are important for the development of both dynamical and statistical downscaling schemes—from 40-yr European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA-40) and NCEP–NCAR reanalysis data on a daily time scale is assessed. For estimating the distributional similarity, two comparable scores are used: the two-sample Kolmogorov–Smirnov statistic and the probability density function (PDF) score. In addition, the similarity of the day-to-day sequences is evaluated with the Pearson correlation coefficient. As the most important results demonstrated, the PDF score is found to be inappropriate if the underlying data follow a mixed distribution. By providing global similarity maps for each variable under study, regions where reanalysis data should not assumed to be “perfect” are detected. In contrast to the geopotential and temperature, significant distributional dissimilarities for specific humidity are found in almost every region of the world. Moreover, for the latter these differences not only occur in the mean, but also in higher-order moments. However, when considering standardized anomalies, distributional and serial dissimilarities are negligible over most extratropical land areas. Since transformed reanalysis data are not appropriate for regional climate models—in opposition to statistical approaches—their results are expected to be more sensitive to reanalysis choice.
An Examination of Model Track Forecast Errors for Hurricane Ike (2008) in the Gulf of Mexico
Authors: Brennan Michael J. , Majumdar Sharanya J. 
Published: December 2011

Abstract
Sources of dynamical model track error for Hurricane Ike (2008) in the Gulf of Mexico are examined. Deterministic and ensemble model output are compared against National Centers for Environmental Prediction (NCEP) Global Forecast System (GFS) analyses to identify potential critical features associated with the motion of Ike and its eventual landfall along the upper Texas coast. Several potential critical features were identified, including the subtropical ridge north of Ike and several synoptic-scale short-wave troughs and ridges over central and western North America, and Tropical Storm Lowell in the eastern North Pacific. Using the NCEP Gridpoint Statistical Interpolation (GSI) data assimilation scheme, the operational GSI analysis from the 0000 UTC 9 September 2008 cycle was modified by perturbing each of these features individually, and then integrating the GFS model using the perturbed initial state. The track of Ike from each of the perturbed runs was compared to the operational GFS and it was found that the greatest improvements to the track forecast were associated with weakening the subtropical ridge north of Ike and strengthening a midlevel short-wave trough over California. A GFS run beginning with an analysis where both of these features were perturbed produced a greater track improvement than either did individually. The results suggest that multiple sources of error exist in the initial states of the operational models, and that the correction of these errors in conjunction with reliable ensemble forecasts would lead to improved forecasts of tropical cyclone tracks and their accompanying uncertainty.
Serotonin 5-HT2B receptors are required for bone-marrow contribution to pulmonary arterial hypertension
Authors: Launay Jean-Marie , Hervé Philippe , Callebert Jacques , Mallat Ziad , Collet Corinne , Doly Stéphane , Belmer Arnauld , Diaz Silvina L. , Hatia Sarah , Côté Francine , Humbert Marc , Maroteaux Luc 
Published: December 2011

Abstract
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by lung endothelial dysfunction and vascular remodeling. Recently, bone marrow progenitor cells have been localized to PAH lungs, raising the question of their role in disease progression. Independently, serotonin (5-HT) and its receptors have been identified as contributors to the PAH pathogenesis. We hypothesized that 1 of these receptors, 5-HT2B, is involved in bone marrow stem cell mobilization that participates in the development of PAH and pulmonary vascular remodeling. A first study revealed expression of 5-HT2B receptors by circulating c-kit+ precursor cells, whereas mice lacking 5-HT2B receptors showed alterations in platelets and monocyte-macrophage numbers, and in myeloid lineages of bone marrow. Strikingly, mice with restricted expression of 5-HT2B receptors in bone marrow cells developed hypoxia or monocrotaline-induced increase in pulmonary pressure and vascular remodeling, whereas restricted elimination of 5-HT2B receptors on bone marrow cells confers a complete resistance. Moreover, ex vivo culture of human CD34+ or mice c-kit+ progenitor cells in the presence of a 5-HT2B receptor antagonist resulted in altered myeloid differentiation potential. Thus, we demonstrate that activation of 5-HT2B receptors on bone marrow lineage progenitors is critical for the development of PAH.
Transformation of Botrytis cinerea by direct hyphal blasting or by wound-mediated transformation of sclerotia
Authors: Ish - Shalom Shahar , Gafni Aviva , Lichter Amnon , Levy Maggie 
Published: December 2011

Abstract

Background

Botrytis cinerea is a haploid necrotrophic ascomycete which is responsible for 'grey mold' disease in more than 200 plant species. Broad molecular research has been conducted on this pathogen in recent years, resulting in the sequencing of two strains, which has generated a wealth of information toward developing additional tools for molecular transcriptome, proteome and secretome investigations. Nonetheless, transformation protocols have remained a significant bottleneck for this pathogen, hindering functional analysis research in many labs.

Results
In this study, we tested three different transformation methods for B. cinerea: electroporation, air-pressure-mediated and sclerotium-mediated transformation. We demonstrate successful transformation with three different DNA constructs using both air-pressure- and sclerotium-mediated transformation.

Conclusions
These transformation methods, which are fast, simple and reproducible, can expedite functional gene analysis of B. cinerea.
Ultrasonographic median nerve cross-section areas measured by 8-point "inching test" for idiopathic carpal tunnel syndrome: a correlation of nerve conduction study severity and duration of clinical symptoms
Authors: Chen Shu-Fang , Lu Cheng-Hsien , Huang Chi-Ren , Chuang Yao-Chung , Tsai Nai-Wen , Chang Chiung-Chih , Chang Wen-Neng 
Published: December 2011

AbstractBackgroundIncremental palmar stimulation of the median nerve sensory conduction at the wrist, the "inching test", provides an assessment with reference to segments proximal and distal to the entrapment. This study used high-resolution ultrasonography (US) to measure the median nerve's cross-section areas (CSAs) like the "inching test" and to correlate with the nerve conduction study (NCS) severity and duration of carpal tunnel syndrome (CTS).MethodsTwo hundred and twelve (212) "CTS-hands" from 135 CTS patients and 50 asymptomatic hands ("A-hands") from 25 control individuals were enrolled. The median nerve CSAs were measured at the 8-point marked asi4,i3,i2,i1,w,o1,o2, and03 in inching test. The NCS severities were classified into six groups based on motor and sensory responses (i.e., negative, minimal, mild, moderate, severe, and extreme). Results of US studies were compared in terms of NCS severity and duration of clinical CTS symptoms.ResultsThere was significantly larger CSA of the NCS negative group of "CTS-hands" than of "A-hands". The cut-off values of the CSAs of the NCS negative CTS group were 12.5 mm2, 11.5 mm2and 10.1 mm2at the inlet, wrist crease, and outlet, respectively. Of the 212 "CTS-hands", 32 were NCS negative while 40 had minimal, 43 mild, 85 moderate, 10 severe, and two extreme NCS severities. The CSAs of "CTS-hands" positively correlated with different NCS severities and with the duration of CTS symptoms. By duration of clinical symptoms, 12 of the 212 "CTS-hands" were in the 1 month group; 82 in >1 month and ≤12 months group, and 118 in >12 months group. In "inching test", segmentsi4-i3 andi3-i2 were the most common "positive-site". The corresponding CSAs measured ati4 andi3, but not ati2, were significantly larger than those measured at points that were not "positive-site".ConclusionsUsing the 8-point measurement of the median nerve CSA from inlet to outlet similar to the "inching test" has positive correlations with NCS severity and duration of CTS clinical symptoms, and can provide more information on anatomic changes. Combined NCS and US studies using the 8-point measurement may have a higher positive rate than NCS alone for diagnosing CTS.
Genome-wide association study identifies PERLD1 as asthma candidate gene
Authors: Anantharaman Ramani , Andiappan Anand Kumar , Nilkanth Pallavi Parate , Suri Bani Kaur , Wang De Yun , Chew Fook Tim 
Published: December 2011

Abstract

Background
Recent genome-wide association studies (GWAS) for asthma have been successful in identifying novel associations which have been well replicated. The aim of this study is to identify the genetic variants that influence predisposition towards asthma in an ethnic Chinese population in Singapore using a GWAS approach.

Methods
A two-stage GWAS was performed in case samples with allergic asthma, and in control samples without asthma and atopy. In the discovery stage, 490 case and 490 control samples were analysed by pooled genotyping. Significant associations from the first stage were evaluated in a replication cohort of 521 case and 524 control samples in the second stage. The same 980 samples used in the discovery phase were also individually genotyped for purposes of a combined analysis. An additional 1445 non-asthmatic atopic control samples were also genotyped.

Results
19 promising SNPs which passed our genome-wide P value threshold of 5.52 × 10-8 were individually genotyped. In the combined analysis of 1011 case and 1014 control samples, SNP rs2941504 in PERLD1 on chromosome 17q12 was found to be significantly associated with asthma at the genotypic level (P = 1.48 × 10-6, ORAG = 0.526 (0.369-0.700), ORAA = 0.480 (0.361-0.639)) and at the allelic level (P = 9.56 × 10-6, OR = 0.745 (0.654-0.848)). These findings were found to be replicated in 3 other asthma GWAS studies, thus validating our own results. Analysis against the atopy control samples suggested that the SNP was associated with allergic asthma and not to either the asthma or allergy components. Genotyping of additional SNPs in 100 kb flanking rs2941504 further confirmed that the association was indeed to PERLD1. PERLD1 is involved in the modification of the glycosylphosphatidylinositol anchors for cell surface markers such as CD48 and CD59 which are known to play multiple roles in T-cell activation and proliferation.

Conclusions
These findings reveal the association of a PERLD1 as a novel asthma candidate gene and reinforce the involvement of genes on the 17q12-21 chromosomal region in the etiology of asthma.
Down-regulation of kallikrein-related peptidase 5 (KLK5) expression in breast cancer patients: a biomarker for the differential diagnosis of breast lesions
Authors: Avgeris Margaritis , Papachristopoulou Georgia , Polychronis Athanasios , Scorilas Andreas 
Published: December 2011

AbstractBackgroundKallikrein-related peptidase 5 (KLK5) is a secreted trypsin-like protease of the KLK family, encoded by theKLK5gene. KLK5 has been found to cleave various extracellular matrix components, as well as to activate several other KLK proteases, triggering the stimulation of tissue microenvironment proteolytic cascades.Material and MethodsKLK5expression levels were quantified in 102 cancerous and benign breast tissue specimens, obtained by randomly chosen patients, using RT-qPCR assay. Subsequently, advanced biostatistics were applied in order to analyze theKLK5expression profile in the two patients' cohorts and also to evaluate its clinical significance for the discrimination of breast tumors.ResultsA statistically significant (p < 0.001) down-regulation of theKLK5expression levels were observed in the malignant specimens compared to the benign ones. Logistic regression and ROC curve analysis revealed the significant (p < 0.001) and the independent (p < 0.001) value of theKLK5expression quantification, for the discrimination of the malignant from the benign mammary gland biopsies. Moreover,KLK5expression levels correlate with the pre-menopausal status (p < 0.005) as well as the ER-negative staining (p = 0.028) of women with breast cancer.ConclusionsThe quantification ofKLK5expression in breast tissue biopsies may be considered as a novel and independent biomarker for the differential diagnosis between malignant and benign tumors of the mammary gland.
Minireview: NAD+, a Circadian Metabolite with an Epigenetic Twist
Authors: Sassone-Corsi Paolo 
Published: December 2011

Abstract
A wide variety of endocrine, physiological, and metabolic functions follow daily oscillations. Most of these regulations are controlled at the level of gene expression by the circadian clock and, a remarkably coordinated transcription-translation machinery that exerts its function in virtually all mammalian cells. A large fraction of the genome is under control of the circadian clock, a regulation that is achieved through dynamic changes in chromatin states. Recent findings have demonstrated intimate connections between the circadian clock and epigenetic control. The case of nicotinamide adenine dinucleotide, which modulates the circadian activity of the deacetylase sirtuin 1, constitutes a paradigmatic example of the link between cyclic cellular metabolism and chromatin remodeling. Indeed, the clock transcriptional feedback loop is interlocked with the enzymatic loop of the nicotinamide adenine dinucleotide salvage pathway.
Influence of periodic heartbeat reversal and abdominal movements on hemocoelic and tracheal pressure in resting blowfliesCalliphora vicina
Authors: Wasserthal Lutz Thilo 
Published: December 2011

SUMMARYIn Calliphoridae and Drosophilidae, the dorsal vessel (heart and aorta with associated venous channels) is the only connection between the thorax and the abdomen. Hemolymph oscillates between the compartments by periodic heartbeat reversal, but both the mechanism and its influence on hemocoelic and tracheal pressure have remained unclear. The pumping direction of the heart regularly reverses, with a higher pulse rate during backward compared with forward pumping. A sequence of forward and backward pulse periods lasts approximately 34 s. Pulse rate, direction, velocity and the duration of heartbeat periods were determined by thermistor and electrophysiological measurements. For the first time, heartbeat-induced pressure changes were measured in the hemocoel and in the tracheal system of the thorax and the abdomen. The tracheal pressure changed from sub-atmospheric during backward heartbeat to supra-atmospheric during forward heartbeat in the thorax and inversely in the abdomen. The heartbeat reversals were coordinated with slow abdominal movements with a pumping stroke at the beginning of the forward pulse period. The pressure effect of the pumping stroke was visible only in the abdomen. Periodic hemolymph shift and abdominal movements resulted in pressure changes in the hemocoel and tracheal system alternating in the thorax and abdomen, suggesting an effect on respiratory gas exchange.
Impact of media reporting of cervical cancer in a UK celebrity on a population-based cervical screening programme
Authors: Macarthur Georgina J , Wright Melissa , Beer Helen , Paranjothy Shantini 
Published: December 2011

Objectives To determine the impact of media reporting of cervical cancer in a UK celebrity on cervical screening uptake, response time and colposcopy referral and attendance. Setting Population-based national cervical screening programme for women in Wales, UK. Methods A time series regression analysis of the Welsh national cervical screening and colposcopy databases was used to examine the number of smear tests carried out between 2000 and 2010, stratified by age group and deprivation indicators. Logistic regression was used to analyse colposcopy attendance. Results Over 33,000 more cervical screening tests than expected were carried out in the year of media reporting (2008/9), 11,539 (35%) of which were in the month of Jade Goody's death. The largest increase was evident in women aged 35–39 years (475 additional tests per month, 95% CI 331–619). Impacts were similar across deprivation quintiles. Colposcopy referrals increased by 18% during the year of media reporting. Increases were observed for all smear test results in 2008/9, particularly among younger women, and further rises were evident in 2009/10 for smear tests showing borderline changes and mild dyskaryosis. The proportion of women attending colposcopy appointments rose in the year of media reporting (χ 2 = 45.8, P < 0.001). Conclusions Mass media reporting of cervical cancer in a UK celebrity was associated with a significant, but transient, increase in screening uptake and colposcopy referral and attendance. Mass media reporting can play a role in enhanced detection of abnormalities, but public health messages must be communicated effectively to minimize anxiety whilst maximizing case-finding and uptake among non-responders.
Treatment of Municipal Landfill Leachate with Organically Modified Bentonite
Authors: Ling Hui , Lu Anhuai , Wang Changqiu , Li Yan , Chen Peng , Zhou Jiangong , Wang Jian 
Published: December 2011

AbstractLandfill leachate is one of the most difficult effluents with which to deal from an environmental perspective because of its concentration and complex composition, including refractory and toxic components such as heavy metals or xenobiotic organic compounds. The objective of the present study was to use organically modified bentonite (OMB) to dispose of landfill leachate >10 y old. The OMB was synthesized using a new method, which removed four steps (filtering, washing, drying, and grinding) from the traditional process. After treatment using OMB, the chemical oxygen demand concentration (COD concentration, an index of the organic pollutants in the landfill leachate, was determined using the potassium dichromate method) of the landfill leachate sample decreased from 2400 to 245 mg/L in 5 h, i.e. the organic pollutants reduction efficiency was as high as 90%. Gas chromatography-mass spectrometry results indicated that most of the organic compounds were removed during the process. The modified and unmodified bentonite contained in the OMB deal with the hydrophobic and hydrophilic organic pollutants, respectively, resulting in significant degradation of the leachate. The study results have provided a new cost-effective method for treatment of landfill leachate.