bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of neonatal verbal autopsy using physician review versus algorithm‐based cause‐of‐death assignment in rural Nepal
Authors: Freeman James V. , Christian Parul , Khatry Subarna K. , Adhikari Ramesh K. , LeClerq Steven C. , Katz Joanne , Darmstadt Gary L. 
Published: June 2005

SummaryVerbal autopsy (VA) is used to ascertain cause‐specific neonatal mortality using parental/familial recall. We sought to compare agreement between causes of death obtained from the VA by physician review vs. computer‐based algorithms. Data were drawn from a cluster‐randomised trial involving 4130 live‐born infants and 167 neonatal deaths in the rural Sarlahi District of Nepal. We examined the agreement between causes ascertained by physician review and algorithm assignment by the kappa (κ) statistic. We also compared responses to identical questions posed posthumously during neonatal VA interviews with those obtained during maternal interviews and clinical examinations regarding condition of newborns soon after birth.Physician reviewers assigned prematurity or acute lower respiratory infection (ALRI) as causes of 48% of neonatal deaths; 41% were assigned as uncertain. The algorithm approach assigned sepsis (52%), ALRI (31%), birth asphyxia (29%), and prematurity (24%) as the most common causes of neonatal death. Physician review and algorithm assignment of causes of death showed high κ for prematurity (0.73), diarrhoea (0.81) and ALRI (0.68), but was low for congenital malformation (0.44), birth asphyxia (0.17) and sepsis (0.00). Sensitivity and specificity of VA interview questions varied by symptom, with positive predictive values ranging from 50% to 100%, when compared with maternal interviews and examinations of neonates soon after birth. Analysis of the VA data by physician review and computer‐based algorithms yielded disparate results for some causes but not for others. We recommend an analysis technique that combines both methods, and further validation studies to improve performance of the VA for assigning causes of neonatal death.
The search for genenotype/phenotype associations and the phenome scan
Authors: Jones Richard , Pembrey Marcus , Golding Jean , Herrick David 
Published: June 2005

SummaryAll the approaches to the search for genotype/phenotype associations have their share of problems. Comparing the genome scan and candidate gene approaches, the former makes fewer assumptions at the genetic level or about mechanism but has greater statistical difficulties while the latter partially solves the statistical problem but makes more assumptions at both genetic and mechanistic levels. Among current difficulties is a lack of information about the nature of gene variant/phenotype associations: the frequency with which different classes of gene or sequence are involved; the type of genetic variation most commonly involved; the appropriate genetic models to apply to analysis. The overarching problem is that of multiple testing, one solution to which is to integrate genetic information to create a smaller number of compound variables. At the other end of the scale, decisions about the level of complexity at which to pitch the identification of phenotypes also affect the multiple testing problem: whether to pitch them at the level of disease outcomes, or at any of the multiple levels of intermediate phenotypes or traits. The third issue is how best to deal with gene/gene or gene/environment interactions, or whether to ignore them. Only as more genotype/phenotype associations emerge, by whatever means, will the numbers of results allow these questions to be answered. We describe here a new approach to genotype/phenotype association studies, the phenome scan, in which dense phenotypic information in human cohorts is scanned for associations with individual genetic variants. We believe that this approach can generate data that will be useful in answering generic questions about genotype/phenotype associations as well as in discovering novel ones.
The effect of terminations of pregnancy for fetal abnormalities on trends in mortality to one year of age in Western Australia
Authors: Bourke Jenny , Bower Carol , Blair Eve , Charles Adrian , Knuiman Matthew 
Published: June 2005

SummaryMany studies documenting the decline in all‐cause infant mortality rates over the past 20 years have highlighted the contribution of birth defects. Over this time there has also been an increasing number of terminations of pregnancy for fetal abnormality. However, the effect of these terminations on mortality rates in Australia has not yet been estimated. The Western Australian Birth Defects Registry (BDR) records all birth defects that are diagnosed in stillbirths, livebirths and in pregnancies terminated because of a fetal abnormality. All cases on the BDR over the period 1980–98 were categorised into one of eight main birth defect groups and analysed in four time periods to show trends. Linkage provided information on deaths to one year of age, defined as perinatal plus postneonatal deaths. The proportion of terminations for fetal abnormality that would have resulted in a death before one year of age was estimated in two ways. The first method used the proportion of births with a birth defect in each diagnostic category that resulted in a death. The second method involved determination of likelihood of survival to one year of all terminations for fetal abnormality through independent review by two experts. Whilst mortality to one year of age for all birth defects has declined from 4.36/1000 births in 1980–84 to 2.75/1000 births in 1995–98, terminations of pregnancies for fetal abnormalities increased from 1.19/1000 births to 4.70/1000 births. After including the estimated mortality associated with terminations for fetal abnormality, the decline in mortality to one year of age associated with birth defects from 1980 to 1998 changed from a 37% reduction to a 15% reduction based on observed mortality 1980–84, and an 11% increase in mortality based on individual case review, highlighting the importance of considering terminations in mortality analyses.
Multilingual home environment and specific language impairment: a case–control study in Chinese children
Authors: Cheuk Daniel Ka Leung , Wong Virginia , Leung Gabriel Matthew 
Published: June 2005

SummarySpecific language impairment (SLI) is a common developmental disorder in young children. To investigate the association between multilingual home environment and SLI, we conducted a case–control study in Hong Kong Chinese children over a 4‐year period in the Duchess of Kent Children's Hospital. Consecutive medical records of all new referrals below 5 years of age were reviewed and children diagnosed with SLI (case) were compared with those referred with other developmental and behavioural problems who had been assessed as having normal language and overall development (control) using the Griffiths Mental Developmental Scale. SLI was defined as those with a language quotient more than one standard deviation below the mean and below the general developmental quotient in children with normal general developmental quotient, but without neurological or other organic diseases. We used binary and ordinal logistic regression to assess any association between SLI and multilingual exposure at home, adjusting for age and gender of subjects, parental age, education level and occupational status, number of siblings, family history of language delay and main caregiver at home. Multivariable linear regression was used to examine the effect of covariates on the language comprehension and expression standard scores assessed by the Reynell Developmental Language Scale.A total of 326 cases and 304 controls were included. The mean ages of cases and controls were 2.56 and 2.89 years respectively. Boys predominated in both groups (cases, 75.2%; controls, 60.2%). The children were exposed to between one and four languages at home, the major ones being Cantonese Chinese followed by English. The adjusted odds ratio (OR) of SLI was 2.94; [95% confidence interval (CI) 1.82, 4.74] for multilingual compared with monolingual exposure. A significant linear dose–response relationship was found (OR of SLI = 2.58 [1.72, 3.88] for each additional language to which the child was exposed). Male gender (OR = 1.88 [1.24, 2.87]), positive family history (OR = 2.01 [1.17, 3.47]), lower education levels of parents (P = 0.028 for father,P = 0.038 for mother) and lower occupational status of father (P = 0.005) were also risk factors for SLI. Multilingual exposure also significantly reduced the language quotient (P = 0.012) and language comprehension standard score (P = 0.016) of children with SLI, but not of normal children.We concluded that multilingual home environment is associated with SLI with a dose‐response relationship. Exposure to multiple languages might adversely affect subsequent language ability.
Variation in pathogen aggressiveness within a metapopulation of the Cakile maritima–Alternaria brassicicola host–pathogen association
Authors: Thrall P. H. , Barrett L. G. , Burdon J. J. , Alexander H. M. 
Published: June 2005

Variation in aggressiveness and its consequences for disease epidemiology were studied in the Cakile maritima–Alternaria brassicicola host–pathogen association. Variability in pathogen growth rates and spore production in vitro, as well as disease severity and lesion growth rate on C. maritima in glasshouse inoculation trials, were investigated. Substantial variation was found in growth rates among individual A. brassicicola isolates, as well as among pathogen populations. A significant trade‐off also existed between growth and spore production, such that faster‐growing isolates produced fewer spores per unit area. While there was little evidence for a link between growth in vitro and either disease severity or lesion development among fast‐ vs slow‐growth isolate classes at the individual isolate level, the results suggest that variation in pathogen fitness components associated with aggressiveness may influence disease dynamics in nature. An analysis using an independent data set of disease prevalence in the associated host populations found a significant positive relationship between the average growth rate of pathogen populations in vitro and disease progress over the growing season in wild host populations. Trade‐offs such as those demonstrated between growth rate and spore production may contribute to the maintenance of variation in quantitatively based host–pathogen interactions.
Normal ICOS, ICOSL and AID Alleles in Danish Patients with Common Variable Immunodeficiency
Authors: Ohm‐Laursen L. , Schjebel L. , Jacobsen K. , Permin H. , Svejgaard A. , Barington T. 
Published: June 2005

AbstractCommon variable immunodeficiency, CVID, is a primary antibody deficiency characterized by decreased levels of serum immunoglobulin G (IgG), decreased IgA and/or IgM and recurrent infections. It is assumed to be heterogeneous group of disorders caused by different genetic defects. Some patients have decreased levels of class switched memory B cells and/or decreased levels of somatic hypermutation which points to defects in the germinal centre (GC) reactions as cause of the disease in these patients. The inducible costimulator, ICOS, and its' ligand, ICOSL, are both involved in and necessary for the GC reaction and so is activation‐induced cytidine deaminase, AID. Therefore, we sequenced the ICOS, ICOSL and AID genes in a cohort of 34 Danish CVID patients. We found 13 new single nucleotide polymorphisms (SNP) in the intron regions of the ICOSL gene as well as one SNP in exon 3. However, none of these polymorphisms were associated with CVID. We did not find a previously reported CVID‐causing ICOS gene deletion or any other unique mutations in the ICOS or AID genes.
Infection of Human Endothelial Cells with Staphylococcus aureus Induces Transcription of Genes Encoding an Innate Immunity Response
Authors: Matussek A. , Strindhall J. , Stark L. , Rohde M. , Geffers R. , Buer J. , Kihlström E. , Lindgren P.‐E. , Löfgren S. 
Published: June 2005

Abstract Staphylococcus aureus is a gram‐positive bacterium frequently isolated from patients with bloodstream infections. Endothelial cells (EC) play an important role in host defence against bacteria, and recent reports have shown that infection of EC with S. aureus induces expression of cytokines and cell surface receptors involved in activating the innate immune response. The ability of S. aureus to invade nonphagocytic cells, including EC, has been documented. However, the knowledge of the role of EC in pathogenesis of S. aureus infection is still limited. In this study, we investigate the gene‐expression program in human EC initiated by internalized S. aureus, using microarray analysis. We found 156 genes that were differentially regulated at least threefold, using arrays representing 14,239 genes. Many of the upregulated genes code for proteins involved in innate immunity, such as cytokines, chemokines and cell adhesion proteins. Other upregulated genes encode proteins involved in antigen presentation, cell signalling and metabolism. Furthermore, intracellular bacteria survived for days without inducing EC death.
AUXIN RESPONSE FACTOR 2 (ARF2): a pleiotropic developmental regulator
Authors: Okushima Yoko , Mitina Irina , Quach Hong L. , Theologis Athanasios 
Published: June 2005

SummaryAUXIN RESPONSE FACTORS (ARFs) regulate auxin‐mediated transcriptional activation/repression. They are encoded by a gene family in Arabidopsis, and each member is thought to play a central role in various auxin‐mediated developmental processes. We have characterized three arf2 mutant alleles, arf2‐6, arf2‐7 and arf2‐8. The mutants exhibit pleiotropic developmental phenotypes, including large, dark green rosette leaves, delayed flowering, thick and long inflorescence, abnormal flower morphology and sterility in early formed flowers, large organ size and delayed senescence and abscission, compared with wild‐type plants. In addition, arf2 mutant seedlings have elongated hypocotyls with enlarged cotyledons under various light conditions. The transcription of ACS2, ACS6 and ACS8 genes is impaired in the developing siliques of arf2‐6. The phenotypes of all three alleles are similar to those of the loss‐of‐function mutants obtained by RNA interference or co‐suppression. There is no significant effect of the mutation on global auxin‐regulated gene expression in young seedlings, suggesting that ARF2 does not participate in auxin signaling at that particular developmental stage of the plant life cycle. Because ARF2 is thought to function as a transcriptional repressor, the prospect arises that its pleiotropic effects may be mediated by negatively modulating the transcription of downstream genes in signaling pathways that are involved in cell growth and senescence.
Spontaneously occurring mutations in the cyclobutane pyrimidine dimer photolyase gene cause different sensitivities to ultraviolet‐B in rice
Authors: Hidema Jun , Teranishi Mika , Iwamatsu Yutaka , Hirouchi Tokuhisa , Ueda Tadamasa , Sato Tadashi , Burr Benjamin , Sutherland Betsy M. , Yamamoto Kazuo , Kumagai Tadashi 
Published: June 2005

SummarySensitivity to ultraviolet‐B (UVB) radiation (280–320 nm) varies widely among rice cultivars. We previously indicated that UV‐resistant rice cultivars are better able to repair cyclobutane pyrimidine dimers (CPDs) through photorepair than are UV‐sensitive cultivars. In this paper, we report that UVB sensitivity in rice, in part, is the result of defective CPD photolyase alleles. Surjamkhi (indica) exhibited greater sensitivity to UVB radiation and was more deficient in CPD photorepair ability compared with UV‐resistant Sasanishiki (japonica). The deficiency in CPD photorepair in Surjamkhi resulted from changes in two nucleotides at positions 377 and 888 in the photolyase gene, causing alterations of two deduced amino acids at positions 126 and 296 in the photolyase enzyme. A linkage analysis in populations derived from Surjamkhi and Sasanishiki showed that UVB sensitivity is a quantitative inherited trait and that the CPD photolyase locus is tightly linked with a quantitative trait locus that explains a major portion of the genetic variation for this trait. These results suggest that spontaneously occurring mutations in the CPD photolyase gene cause different degrees of sensitivity to UVB in rice, and that the resistance of rice to UVB radiation could be increased by increasing the photolyase function through conventional breeding or bioengineering.
Repression of light signaling by Arabidopsis SPA1 involves post‐translational regulation of HFR1 protein accumulation
Authors: Yang Jianping , Lin Rongcheng , Hoecker Ute , Liu Bolin , Xu Ling , Wang Haiyang 
Published: June 2005

SummaryArabidopsis uses two major classes of photoreceptors to mediate seedling de‐etiolation. The cryptochromes (cry1 and cry2) absorb blue/ultraviolet‐A light, whereas the phytochromes (phyA–phyE) predominantly regulate responses to red/far‐red light. Arabidopsis COP1 represses light signaling by acting as an E3 ubiquitin ligase in the nucleus, and is responsible for targeted degradation of a number of photomorphogenesis‐promoting factors, including HY5, LAF1, phyA, and HFR1. Distinct light signaling pathways initiated by multiple photoreceptors (including both phytochromes and cryptochromes) eventually converge on COP1, causing its inactivation and nuclear depletion. Arabidopsis SPA1, which encodes a protein structurally related to COP1, also represses light signaling under various light conditions. In this study, we present genetic evidence supporting that HFR1, which encodes a photomorphogenesis‐promoting bHLH transcription factor, acts downstream of SPA1 and is required for different subsets of branch pathways of light signaling controlled by SPA1 under different light conditions. We show that SPA1 physically interacts with HFR1 in a yeast two‐hybrid assay and an in vitro co‐immunoprecipitation assay. We demonstrate that higher levels of HFR1 protein accumulate in the spa1 mutant background under various light conditions, including far‐red, red, blue, and white light, whereas a marginal increase in HFR1 transcript level is only seen in dark‐ and far‐red light‐grown spa1‐100 mutants. Together, our data suggest that repression of light signaling by Arabidopsis SPA1 likely involves post‐translational regulation of HFR1 protein accumulation.
Arabidopsis IQD1, a novel calmodulin‐binding nuclear protein, stimulates glucosinolate accumulation and plant defense
Authors: Levy Maggie , Wang Qiaomei , Kaspi Roy , Parrella Michael P. , Abel Steffen 
Published: June 2005

SummaryGlucosinolates are a class of secondary metabolites with important roles in plant defense and human nutrition. To uncover regulatory mechanisms of glucosinolate production, we screened Arabidopsis thaliana T‐DNA activation‐tagged lines and identified a high‐glucosinolate mutant caused by overexpression of IQD1 (At3g09710). A series of gain‐ and loss‐of‐function IQD1 alleles in different accessions correlates with increased and decreased glucosinolate levels, respectively. IQD1 encodes a novel protein that contains putative nuclear localization signals and several motifs known to mediate calmodulin binding, which are arranged in a plant‐specific segment of 67 amino acids, called the IQ67 domain. We demonstrate that an IQD1‐GFP fusion protein is targeted to the cell nucleus and that recombinant IQD1 binds to calmodulin in a Ca2+‐dependent fashion. Analysis of steady‐state messenger RNA levels of glucosinolate pathway genes indicates that IQD1 affects expression of multiple genes with roles in glucosinolate metabolism. Histochemical analysis of tissue‐specific IQD1::GUS expression reveals IQD1 promoter activity mainly in vascular tissues of all organs, consistent with the expression patterns of several glucosinolate‐related genes. Interestingly, overexpression of IQD1 reduces insect herbivory, which we demonstrated in dual‐choice assays with the generalist phloem‐feeding green peach aphid (Myzus persicae), and in weight‐gain assays with the cabbage looper (Trichoplusia ni), a generalist‐chewing lepidopteran. As IQD1 is induced by mechanical stimuli, we propose IQD1 to be novel nuclear factor that integrates intracellular Ca2+ signals to fine‐tune glucosinolate accumulation in response to biotic challenge.
In vitro metabolism of progesterone by canine hair follicle cells
Authors: BAMBERG ELMAR , AICHINGER AMANDA , WÜNSCH GERDA 
Published: June 2005

Abstract  Dermal papilla cells (DPC) and dermal fibroblasts (DFB) derived from hair follicles from two different body sites (head, flank) of four male, castrated beagle dogs were incubated for 24 h with radioactive progesterone (P4). Thin‐layer chromatography was used for separation and autoradiography for identification of the radioactive metabolites. In DFB the main metabolites were cortisol and 4‐pregnene‐11β‐ol‐3,20‐dione, whereas in DPC they were 5α‐pregnane‐3,20‐dione and cortisol. The highest percentage of metabolism of P4 was found in DFB of the head. Smaller amounts of other metabolites were found in both cell types of both locations.
Comparison of the clinical efficacy of oral terbinafine and ketoconazole combined with cephalexin in the treatment ofMalasseziadermatitis in dogs – a pilot study
Authors: ROSALES MILLIE S. , MARSELLA ROSANNA , KUNKLE GAIL , HARRIS BRADLEY L. , NICKLIN CONSTANCE F. , LOPEZ JENNIFER 
Published: June 2005

Abstract The purpose of this randomized, single blinded clinical trial was to evaluate cytologically and clinically the efficacy of oral cephalexin alone and its combination with terbinafine or ketoconazole for the treatment ofMalasseziadermatitis in dogs. Twenty‐two client‐owned dogs withMalasseziadermatitis completed the 3‐week study. All received cephalexin (generic, 250 mg or 500 mg) at 22–30 mg kg−1twice daily. Eight dogs received terbinafine at 30 mg kg−1once daily and seven dogs received ketoconazole (generic, 200 mg) at 5–10 mg kg−1twice daily. The remaining seven dogs received cephalexin alone. At week 0 (visit 1) and week 3 (visit 2), mean yeast counts were determined from three affected areas using tape‐strip cytology, a clinical index score (CIS) was assigned to the affected areas, and owners evaluated pruritus using a visual analogue scale. All groups showed reduction in mean yeast counts, CIS and pruritus. There was an 86.8%, 80.2% and 28.8% reduction in mean yeast counts from visit 1 to visit 2 for the terbinafine, ketoconazole and cephalexin‐only groups, respectively. However, within treatment group comparisons a significant reduction in mean yeast count was only evident for the terbinafine (P < 0.002) and ketoconazole (P < 0.01) groups. Pruritus reduction was only significant for the terbinafine group. These preliminary results suggest that terbinafine should be further assessed for the treatment of canineMalasseziadermatitis.