bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of phosphorus in the pathophysiology of chronic kidney disease
Authors: Geddes Rebecca F. , Finch Natalie C. , Syme Harriet M. , Elliott Jonathan 
Published: March 2013

AbstractObjectiveTo review the human and veterinary literature on the role of phosphorus in the pathophysiology of chronic kidney disease (CKD) and to explore why control of plasma phosphorus concentration is an important goal in the management of patients with this disease.Data SourcesHuman and veterinary studies, reviews, clinical reports, textbooks, and recent research findings focused on phosphate homeostasis andCKDpatient management.Human Data SynthesisRecent studies using rodent models and human patients withCKDhave focused on trying to elucidate the role of the phosphatonins, predominantly fibroblast growth factor‐23, in phosphate homeostasis and the pathophysiology of secondary renal hyperparathyroidism (SRHP). Fibroblast growth factor‐23 is now considered to be a key regulator of plasma phosphorus concentration in people but has only recently been investigated in companion animal species.Veterinary Data SynthesisCross‐sectional studies of naturally occurringCKDin dogs and cats have shown hyperphosphatemia andSRHPto be highly prevalent and associated with increased morbidity and mortality in these patients. Experimental studies of surgically induced renal impairment in the dog and cat, and cases of naturally occurringCKDhave emphasized the ability of renal care diets to modify plasma phosphorus and parathyroid hormone concentrations. Evidence from these studies indicates that maintaining plasma phosphorus concentrations to within the International Renal Interest Society targets forCKDpatients improves survival time and reduces clinical manifestations of hyperphosphatemia andSRHP.ConclusionsThe maintenance of plasma phosphorus concentrations in to within the International Renal Interest Society targets is recommended in management ofCKDpatients. The discovery of the phosphatonins has improved understanding of the mechanisms involved in phosphorus homeostasis andSRHPand may lead to improved ability to monitor and manage these patients.
Vertical Transmission of a
Drosophila
Endosymbiont Via Cooption of the Yolk Transport and Internalization Machinery
Authors: Herren Jeremy K. , Paredes Juan C. , Schüpfer Fanny , Lemaitre Bruno 
Published: March 2013

ABSTRACT

Spiroplasma
is a diverse bacterial clade that includes many vertically transmitted insect endosymbionts, including
Spiroplasma poulsonii
, a natural endosymbiont of
Drosophila melanogaster
. These bacteria persist in the hemolymph of their adult host and exhibit efficient vertical transmission from mother to offspring. In this study, we analyzed the mechanism that underlies their vertical transmission, and here we provide strong evidence that these bacteria use the yolk uptake machinery to colonize the germ line. We show that
Spiroplasma
reaches the oocyte by passing through the intercellular space surrounding the ovarian follicle cells and is then endocytosed into oocytes within yolk granules during the vitellogenic stages of oogenesis. Mutations that disrupt yolk uptake by oocytes inhibit vertical
Spiroplasma
transmission and lead to an accumulation of these bacteria outside the oocyte. Impairment of yolk secretion by the fat body results in
Spiroplasma
not reaching the oocyte and a severe reduction of vertical transmission. We propose a model in which
Spiroplasma
first interacts with yolk in the hemolymph to gain access to the oocyte and then uses the yolk receptor, Yolkless, to be endocytosed into the oocyte. Cooption of the yolk uptake machinery is a powerful strategy for endosymbionts to target the germ line and achieve vertical transmission. This mechanism may apply to other endosymbionts and provides a possible explanation for endosymbiont host specificity.

IMPORTANCE
Most insect species, including important disease vectors and crop pests, harbor vertically transmitted endosymbiotic bacteria. Studies have shown that many facultative endosymbionts, including
Spiroplasma
, confer protection against different classes of parasites on their hosts and therefore are attractive tools for the control of vector-borne diseases. The ability to be efficiently transmitted from females to their offspring is the key feature shaping associations between insects and their inherited endosymbionts, but to date, little is known about the mechanisms involved. In oviparous animals, yolk accumulates in developing eggs and serves to meet the nutritional demands of embryonic development. Here we show that
Spiroplasma
coopts the yolk transport and uptake machinery to colonize the germ line and ensure efficient vertical transmission. The uptake of yolk is a female germ line-specific feature and therefore an attractive target for cooption by endosymbionts that need to maintain high-fidelity maternal transmission.
EvolutionaryGenomics of Salmonellaenterica Subspecies
Authors: Desai Prerak T. , Porwollik Steffen , Long Fred , Cheng Pui , Wollam Aye , Clifton Sandra W. , Weinstock George M. , McClelland Michael 
Published: March 2013

ABSTRACT

Six subspecies are currently recognized in
Salmonella
enterica
. Subspecies I (subspecies
enterica
) is responsible for nearly
all infections in humans and warm-blooded animals, while five other
subspecies are isolated principally from cold-blooded animals. We
sequenced 21 phylogenetically diverse strains, including two
representatives from each of the previously unsequenced five
subspecies and 11 diverse new strains from
S. enterica
subspecies
enterica
, to put this species into an
evolutionary perspective. The phylogeny of the subspecies was partly
obscured by abundant recombination events between lineages and a
relatively short period of time within which subspeciation took place.
Nevertheless, a variety of different tree-building methods gave
congruent evolutionary tree topologies for subspeciation. A total of
285 gene families were identified that were recruited into subspecies
enterica
, and most of these are of
unknown function. At least 2,807 gene families were identified in one
or more of the other subspecies that are not found in subspecies I or
Salmonella
bongori
. Among these gene families were 13 new
candidate effectors and 7 new candidate fimbrial clusters. A third
complete type III secretion system not present in subspecies
enterica
(I) isolates was found in
both strains of subspecies
salamae
(II). Some gene
families had complex taxonomies, such as the type VI secretion
systems, which were recruited from four different lineages in five of
six subspecies. Analysis of nonsynonymous-to-synonymous substitution
rates indicated that the more-recently acquired regions in
S.
enterica
are undergoing faster fixation rates than the
rest of the genome. Recently acquired AT-rich regions, which often
encode virulence functions, are under ongoing selection to maintain
their high AT content.

IMPORTANCE
We have
sequenced 21 new genomes which encompass the phylogenetic diversity of
Salmonella
, including strains of the previously
unsequenced subspecies
arizonae
,
diarizonae
,
houtenae
,
salamae
, and
indica
as well as new
diverse strains of subspecies
enterica
. We have deduced possible
evolutionary paths traversed by this very important zoonotic pathogen
and identified novel putative virulence factors that are not found in
subspecies I. Gene families gained at the time of the evolution of
subspecies
enterica
are of particular
interest because they include mechanisms by which this subspecies
adapted to warm-blooded hosts.
HEALTH STATUS AND SERVICE USE IN HOMELESS INDIVIDUALS WITH MENTAL ILLNESS: CONSISTENCY BETWEEN SELF-REPORT AND ADMINISTRATIVE HEALTH RECORDS IN THE AT HOME/CHEZ SOI MULTI-SITE TRIAL
Authors: Hinds Aynslie , Distasio Jino , Martens Patricia J , Smith Mark 
Published: March 2013

ObjectiveHomeless individuals with poor health frequently use healthcare services. However, studies using self-reported data may be subject to biases. We examined health status, healthcare and drug use among mentally ill homeless individuals, comparing self-report and administrative data claims to estimate the degree of agreement between the two sources.MethodsBaseline survey data from 100 participants of the Winnipeg site of the Mental Health Commission of Canada's At Home/Chez Soi research project were linked to deidentified administrative health records stored in the Repository at the Manitoba Centre for Health Policy. Demographic characteristics, homelessness histories and health service use were analysed, as well as disease status for asthma, hypertension, arthritis and diabetes (using previously validated definitions). Participants were similarly classified using their survey responses. The degree of agreement between the two data sources was evaluated using cross-tabulations and the κ statistic.ResultsThere was 100% linkage of surveyed homeless people with the Repository data. In 1 year, 97% of participants had at least one ambulatory physician visit, with an age- and sex-adjusted rate of 14.82 per person-year (Manitoba rate=4.99 per person-year). 34% had an inpatient hospitalisation (adjusted hospital separation rate=491 per thousand person-years vs the Manitoba rate of 137 per thousand person-years). 95% filled at least one prescription, with 65% of drugs targeting the nervous system (majority were psycholeptics). The degree of agreement between the data sources ranged from a κ of 0.27 for arthritis to 0.57 for hypertension. Individuals were more likely to be classified as having one of the four conditions based on the administrative data than on the survey data.ConclusionsCompared with the general population, participants had high health service use, and high prescription drug use. There was poor to moderate agreement between the two data sources. Researchers studying homeless persons with mental illness should consider using multiple data sources to estimate disease prevalence and health service use.
IS THERE AN ASSOCIATION BETWEEN BODY MASS INDEX AND MIGRAINE HEADACHES WITHIN THE CANADIAN POPULATION?
Authors: Quach Pauline 
Published: March 2013

IntroductionObesity (a body mass index ≥30 kg/m2) and migraine headaches are both chronic conditions that have become increasingly common within the Canadian population. Increasing body mass index (BMI) is associated with increased frequency and severity of migraine headaches, but not its prevalence, such that increasing BMI leads to greater disability by exacerbating migraine symptoms among migraneurs. The association between increasing BMI and the prevalence of migraine headaches, however, has provided inconsistent findings. There is uncertainty as to whether there is an association between increasing BMI and an individual's risk of developing and having this condition. Some studies have found that there is an association, whereas other studies have dismissed such a relationship. There has been little to no Canadian studies conducted to determine the association between increasing BMI and the prevalence of migraines, and the Canadian Community Health Survey (CCHS) dataset has not been used as a source population.ObjectiveTo investigate whether increasing BMI (underweight, normal, overweight, obese) was significantly associated with a linear dose-response trend in the prevalence of migraine headaches. It is hypothesized that compared with normal weight, increasing BMI would result in a larger prevalence.MethodsA sample population of 113 235 subjects from the 2007–2008 cross-sectional CCHS, Cycle 4.1 was used. Subjects included those who had responded to questions regarding self-reported height, weight and migraine status. Subjects less than 18 years of age, and those who were pregnant, were excluded. Log binomial modelling was used to derive unadjusted and adjusted prevalence ratio (PR) estimates, with their corresponding 95% CI. Population weights and average design effects were incorporated to adjust for the effects of complex survey designs.ResultsWhen adjusting for covariates compared with normal weight, the PR for migraines was highest and significant only among the obese, 1.19 (95% CI 1.12 to 1.27), followed by underweight which was not significant, 1.09 (95% CI 0.97 to 1.23), and overweight which was marginally significant, 1.06 (95% CI 1.00 to 1.12).ConclusionsObese and overweight BMI were significantly associated with increased prevalence of migraine headaches. Although a U-shaped pattern was observed with obese and underweight at the extremes, when addressing the non-significant PR estimates for underweight, a resulting linear dose-response trend was present, thus, resulting in the obese having the highest PR followed by overweight and normal weight. Small samples of underweight subjects, various biases, and/or an actual plausible mechanism for underweight and migraine prevalence could have accounted for the high PR estimates for underweight. Additional studies to verify results are warranted.
Combined and Interactive Effects of Environmental and GWAS-Identified Risk Factors in Ovarian Cancer
Authors: Pearce Celeste Leigh , Rossing Mary Anne , Lee Alice W. , Ness Roberta B. , Webb Penelope M. ,   for Australian Cancer Study (Ovarian Cancer),   and Australian Ovarian Cancer Study Group, Chenevix-Trench Georgia , Jordan Susan M. , Stram Douglas A. , Chang-Claude Jenny , Hein Rebecca , Nickels Stefan , Lurie Galina , Thompson Pamela J. , Carney Michael E. , Goodman Marc T. , Moysich Kirsten , Hogdall Estrid , Jensen Allan , Goode Ellen L. , Fridley Brooke L. , Cunningham Julie M. , Vierkant Robert A. , Weber Rachel Palmieri , Ziogas Argyrios , Anton-Culver Hoda , Gayther Simon A. , Gentry-Maharaj Aleksandra , Menon Usha , Ramus Susan J. , Brinton Louise , Wentzensen Nicolas , Lissowska Jolanta , Garcia-Closas Montserrat , Massuger Leon F.A.G. , Kiemeney Lambertus A.L.M. , Van Altena Anne M. , Aben Katja K.H. , Berchuck Andrew , Doherty Jennifer A. , Iversen Edwin , McGuire Valerie , Moorman Patricia G. , Pharoah Paul , Pike Malcolm C. , Risch Harvey , Sieh Weiva , Stram Daniel O. , Terry Kathryn L. , Whittemore Alice , Wu Anna H. , Schildkraut Joellen M. , Kjaer Susanne K. ,   for the Ovarian Cancer Association Consortium
Published: March 2013

Abstract
Background: There are several well-established environmental risk factors for ovarian cancer, and recent genome-wide association studies have also identified six variants that influence disease risk. However, the interplay between such risk factors and susceptibility loci has not been studied.
Methods: Data from 14 ovarian cancer case–control studies were pooled, and stratified analyses by each environmental risk factor with tests for heterogeneity were conducted to determine the presence of interactions for all histologic subtypes. A genetic “risk score” was created to consider the effects of all six variants simultaneously. A multivariate model was fit to examine the association between all environmental risk factors and genetic risk score on ovarian cancer risk.
Results: Among 7,374 controls and 5,566 cases, there was no statistical evidence of interaction between the six SNPs or genetic risk score and the environmental risk factors on ovarian cancer risk. In a main effects model, women in the highest genetic risk score quartile had a 65% increased risk of ovarian cancer compared with women in the lowest [95% confidence interval (CI), 1.48–1.84]. Analyses by histologic subtype yielded risk differences across subtype for endometriosis (Phet &lt; 0.001), parity (Phet &lt; 0.01), and tubal ligation (Phet = 0.041).
Conclusions: The lack of interactions suggests that a multiplicative model is the best fit for these data. Under such a model, we provide a robust estimate of the effect of each risk factor that sets the stage for absolute risk prediction modeling that considers both environmental and genetic risk factors. Further research into the observed differences in risk across histologic subtype is warranted. Cancer Epidemiol Biomarkers Prev; 22(5); 880–90. ©2013 AACR.
Biomarker Discovery for Heterogeneous Diseases
Authors: Wallstrom Garrick , Anderson Karen S. , LaBaer Joshua 
Published: March 2013

AbstractBackground: Modern genomic and proteomic studies reveal that many diseases are heterogeneous, comprising multiple different subtypes. The common notion that one biomarker can be predictive for all patients may need to be replaced by an understanding that each subtype has its own set of unique biomarkers, affecting how discovery studies are designed and analyzed.Methods: We used Monte Carlo simulation to measure and compare the performance of eight selection methods with homogeneous and heterogeneous diseases using both single-stage and two-stage designs. We also applied the selection methods in an actual proteomic biomarker screening study of heterogeneous breast cancer cases.Results: Different selection methods were optimal, and more than two-fold larger sample sizes were needed for heterogeneous diseases compared with homogeneous diseases. We also found that for larger studies, two-stage designs can achieve nearly the same statistical power as single-stage designs at significantly reduced cost.Conclusions: We found that disease heterogeneity profoundly affected biomarker performance. We report sample size requirements and provide guidance on the design and analysis of biomarker discovery studies for both homogeneous and heterogeneous diseases.Impact: We have shown that studies to identify biomarkers for the early detection of heterogeneous disease require different statistical selection methods and larger sample sizes than if the disease were homogeneous. These findings provide a methodologic platform for biomarker discovery of heterogeneous diseases. Cancer Epidemiol Biomarkers Prev; 22(5); 747–55. ©2013 AACR.
Identification of PTHrP(12-48) as a Plasma Biomarker Associated with Breast Cancer Bone Metastasis
Authors: Washam Charity L. , Byrum Stephanie D. , Leitzel Kim , Ali Suhail M. , Tackett Alan J. , Gaddy Dana , Sundermann Suzanne E. , Lipton Allan , Suva Larry J. 
Published: March 2013

Abstract
Background: Breast cancer bone metastasis is a complication that significantly compromises patient survival due, in part, to the lack of disease-specific biomarkers that allow early and accurate diagnosis.
Methods: Using mass spectrometry protein profiling, plasma samples were screened from three independent breast cancer patient cohorts with and without clinical evidence of bone metastasis.
Results: The results identified 13 biomarkers that classified all 110 patients with a sensitivity of 91% and specificity of 93% [receiver operating characteristics area under the curve (AUC = 1.00)]. The most discriminatory protein was subsequently identified as a unique 12-48aa peptide fragment of parathyroid hormone-related protein (PTHrP). PTHrP(12-48) was significantly increased in plasma of patients with bone metastasis compared with patients without bone metastasis (P &lt; 0.0001). Logistic regression models were used to evaluate the diagnostic potential of PTHrP(12-48) as a single biomarker or in combination with the measurement of the clinical marker N-telopeptide of type I collagen (NTx). The PTHrP(12-48) and NTx logistic regression models were not significantly different and classified the patient groups with high accuracy (AUC = 0.85 and 0.95), respectively. Interestingly, in combination with serum NTx, the plasma concentration of PTHrP(12-48) increased diagnostic specificity and accuracy (AUC = 0.99).
Conclusions: These data show that PTHrP(12-48) circulates in plasma of patient with breast cancer and is a novel and predictive biomarker of breast cancer bone metastasis. Importantly, the clinical measurement of PTHrP(12-48) in combination with NTx improves the detection of breast cancer bone metastasis.
Impact: In summary, we present the first validated, plasma biomarker signature for diagnosis of breast cancer bone metastasis that may improve the early diagnosis of high-risk individuals. Cancer Epidemiol Biomarkers Prev; 22(5); 972–83. ©2013 AACR.
Risk Assessment of Upper Tract Urothelial Carcinoma Related to Aristolochic Acid
Authors: Wu Felicia , Wang Tianxiu 
Published: March 2013

Abstract
Background: Aristolochic acid is a toxin found in plants of the genus Aristolochia, to which humans can be exposed either through certain Chinese herbal medicines or through inadvertent commingling with food crops. Our objective was to estimate cumulative exposures of aristolochic acid associated with increased risk of end-stage renal disease (ESRD), and to conduct a systematic review and meta-analysis on aristolochic acid-induced upper tract urothelial carcinoma (UUC).
Methods: Using epidemiologic studies on aristolochic acid-related disease from multiple different regions of the world, a systematic review was conducted in which relative risks (RR), HRs, and ORs were derived or extracted directly, and a meta-analysis was conducted. One study was used to estimate a benchmark dose lower confidence limit (BMDL) for aristolochic acid-related ESRD.
Results: Mean values for risk ratios, ORs, RRs, or HRs, of UUC caused by aristolochic acid ranged from 1 to 49. A meta-analysis of these studies resulted in a pooled OR of 5.97 [95% confidence interval (CI), 2.78–12.84] for this aristolochic acid-related cancer. The obtained BMDL for aristolochic acid-related ESRD was 0.42 g cumulative aristolochic acid exposure.
Conclusions: Aristolochic acid exposure is significantly associated with an increased risk of UUC, and there is a dose-dependent relationship between cumulative aristolochic acid exposure and ESRD risk.
Impact: Individuals who use certain Chinese herbal medicines may significantly increase their risk of developing UUC and/or ESRD, as would individuals who are inadvertently exposed to aristolochic acid through commingling of Aristolochia plants with harvested food crops. Cancer Epidemiol Biomarkers Prev; 22(5); 812–20. ©2013 AACR.
Cultivating Cohort Studies for Observational Translational Research
Authors: Ransohoff David F. 
Published: March 2013

Abstract
Background: “Discovery” research about molecular markers for diagnosis, prognosis, or prediction of response to therapy has frequently produced results that were not reproducible in subsequent studies. What are the reasons, and can observational cohorts be cultivated to provide strong and reliable answers to those questions?
Experimental Methods: Selected examples are used to illustrate: (i) what features of research design provide strength and reliability in observational studies about markers of diagnosis, prognosis, and response to therapy? (ii) How can those design features be cultivated in existing observational cohorts, for example, within randomized controlled clinical trial (RCT), other existing observational research studies, or practice settings like health maintenance organization (HMOs)?
Results: Examples include a study of RNA expression profiles of tumor tissue to predict prognosis of breast cancer, a study of serum proteomics profiles to diagnose ovarian cancer, and a study of stool-based DNA assays to screen for colon cancer. Strengths and weaknesses of observational study design features are discussed, along with lessons about how features that help assure strength might be “cultivated” in the future.
Conclusions and Impact: By considering these examples and others, it may be possible to develop a process of “cultivating cohorts” in ongoing RCTs, observational cohort studies, and practice settings like HMOs that have strong features of study design. Such an effort could produce sources of data and specimens to reliably answer questions about the use of molecular markers in diagnosis, prognosis, and response to therapy. Cancer Epidemiol Biomarkers Prev; 22(4); 481–4. ©2013 AACR.