bluuebunny/crossref_metadata_2025_split huggingface dataset:
The temporal program of peripheral blood gene expression in the response of nonhuman primates to Ebola hemorrhagic fever
Authors: Rubins Kathleen H , Hensley Lisa E , Wahl-Jensen Victoria , Daddario DiCaprio Kathleen M , Young Howard A , Reed Douglas S , Jahrling Peter B , Brown Patrick O , Relman David A , Geisbert Thomas W 
Published: August 2007

Abstract
Background
Infection with Ebola virus (EBOV) causes a fulminant and often fatal hemorrhagic fever. In order to improve our understanding of EBOV pathogenesis and EBOV-host interactions, we examined the molecular features of EBOV infection in vivo.

Results
Using high-density cDNA microarrays, we analyzed genome-wide host expression patterns in sequential blood samples from nonhuman primates infected with EBOV. The temporal program of gene expression was strikingly similar between animals. Of particular interest were features of the data that reflect the interferon response, cytokine signaling, and apoptosis. Transcript levels for tumor necrosis factor-α converting enzyme (TACE)/α-disintegrin and metalloproteinase (ADAM)-17 increased during days 4 to 6 after infection. In addition, the serum concentration of cleaved Ebola glycoprotein (GP2 delta) was elevated in late-stage EBOV infected animals. Of note, we were able to detect changes in gene expression of more than 300 genes before symptoms appeared.

Conclusion
These results provide the first genome-wide ex vivo analysis of the host response to systemic filovirus infection and disease. These data may elucidate mechanisms of viral pathogenesis and host defense, and may suggest targets for diagnostic and therapeutic development.
Neutrophil transepithelial migration in response to the chemoattractant fMLP but not C5a is phospholipase D-dependent and related to the use of CD11b/CD18
Authors: Carrigan Svetlana O , Pink Desmond B S , Stadnyk Andrew W 
Published: August 2007

AbstractIn Crohn’s disease and ulcerative colitis patients, the numbers of neutrophils recovered from stool directly correlates with the severity of disease, implying that neutrophils in the lumen contribute to the tissue destruction; therefore, it is important to understand the mechanisms behind transintestinal epithelial migration. Neutrophil transintestinal epithelial migration to fMLP is appreciated to be CD11b/CD18 integrin (Mac-1)-dependent, while we recently reported that migration to C5a is Mac-1-independent. Here, we investigated whether phospholipase D (PLD), a signaling molecule linked to chemoattractant activation of neutrophils, is necessary for both Mac-1-dependent and Mac-1-independent migration. Both fMLP and C5a increased neutrophil expression of the Mac-1 activation epitope, indicating PLD was activated. This up-regulation was dose-dependently prevented by incubation of neutrophils in 1-butanol, an inhibitor of PLD activity. Despite this effect on Mac-1, 1-butanol did not prevent neutrophil migration across acellular filters. Incubation in 1-butanol did inhibit fMLP but not C5a-mediated migration across intestinal epithelial cell monolayers, showing that transepithelial migration to fMLP but not C5a is dependent on PLD. The addition of phosphatidic acid, a reaction product of PLD, partially restored fMLP-mediated transepithelial migration in the presence of 1-butanol but not the migration of Mac-1-deficient neutrophil-differentiated HL-60 cells. Thus PLD control over expression of the Mac-1 activation epitope is critical for neutrophil migration to fMLP but not C5a. Moreover, as PLD controls other neutrophil functions, such as the oxidative response, degranulation, and protease release, we could exclude these functions as being important in neutrophil transepithelial migration to C5a.
Single Nucleotide Polymorphisms in the NOD2/CARD15 Gene Are Associated With an Increased Risk of Relapse and Death for Patients With Acute Leukemia After Hematopoietic Stem-Cell Transplantation With Unrelated Donors
Authors: Mayor Neema P. , Shaw Bronwen E. , Hughes Derralynn A. , Maldonado-Torres Hazael , Madrigal J. Alejandro , Keshav Satish , Marsh Steven G.E. 
Published: August 2007

Purpose Hematopoietic stem cell transplantation (HSCT) is an important option in the management of acute leukemia, but the risk of disease relapse and death remains appreciable. Recent studies have suggested that nucleotide-binding oligomerization domain 2 (NOD2)/caspase recruitment domain 15 (CARD15) gene single nucleotide polymorphisms (SNPs), implicated in innate immunity and Crohn's disease, may also affect immune function post-HSCT. Patients and Methods NOD2/CARD15 genotypes were analyzed in 196 patients diagnosed with acute leukemia and their unrelated donors. The pairs are part of a previously well-characterized cohort with a median follow-up of 2.2 years (range, 0.42 to 6.61 years). T-cell depletion was used in 83% of pairs. Results NOD2/CARD15 SNPs were associated with a reduction in overall survival (44% v 22%; log-rank P = .0087) due to an increase in disease relapse (32% v 54%; Gray's test P = .001) as compared with wild-type pairs. In multivariate analyses, the two most significant factors impacting outcome were transplantation in relapse and the presence of SNPs. The incidence of acute graft-versus-host disease was low and there was no significant difference due to the presence of SNPs. Conclusion These data indicate an unrecognized role for the NOD2/CARD15 gene in unrelated donor HSCT for acute leukemia. The increased risk of disease relapse suggests that the wild-type gene product may contribute to a graft-versus-leukemia effect. These data suggest that NOD2/CARD15 genotyping before transplantation may contribute to prognosis and influence clinical management.
A Screening Technique for Joint Chance-Constrained Programming for Air-Quality Management
Authors: An Hyunhee , Eheart J. Wayland 
Published: August 2007

This technical note presents a screening technique for using chance-constrained programming to achieve overall system (i.e., joint) reliability when there is statistical dependence between constraints representing an ambient air-quality requirement at different geographical locations. The technique is intended to determine whether the full analysis of row interdependence, which requires more intensive programming and larger computational effort, is warranted, by examining a possible spectrum of solutions at three extreme cases of row dependence. The technique is illustrated for airborne particulate emissions control, in which the overall cost of controlling particulate emissions from two electrostatic precipitators is minimized in a manner that maintains ground-level particulate concentration at all receptors with a prescribed reliability. In accordance with the theory presented here, such screening is achieved by setting the required reliability values of individual constraints according to assumptions of complete codependence, zero codependence, and complete negative codependence. In application, these reliability values represent the probability of achieving the ambient concentration standard at several receptor locations. The results of the screening technique are compared to those of two more computationally intensive methods for achieving overall system reliability. It is found that, for a given example, the screening technique brackets the results of those full-analysis methods for row dependence, as expected.
The Rookwood Driving Battery: Normative older adult performance
Authors: Rees Janice. , McKenna Pat. , Bell Vaughan. , Skucek Emily. , Nichols E. , Fisher P. 
Published: August 2007

ObjectivesThe current study aimed to obtain older adult normative data on a neuropsychological battery in relation to functions underlying driving ability. The effect of age on performance on the battery was previously unknown; normative data revision was necessary to enable more appropriate use of the battery with older clients.DesignCross‐sectional cohort study.MethodsVolunteers were sought from healthy older people living independently in the community to complete the Rookwood Driving Battery. A group of 202 volunteers above the age of 70 were recruited from local social groups to complete the battery. Of these, 184 completed a screening test of cognitive integrity (Mini Mental State Examination, MMSE). The age ranged from 70 to 96 (mean age=81 years,SD= 5.438). In the total sample, 155 (77%) were females.ResultsResults of the MMSE indicated that 161 (87.5%) of the group fell above a cut‐off (25/30) typically used in epidemiological studies to identify age‐related cognitive decline. Of these cognitively intact volunteers, performance was marked by higher battery error scores (mean=5.12,SD= 3.75) than those observed in an earlier normative study using younger volunteers below 70 years of age (mean=1.41,SD= 1.87). The two age groups differed significantly on all 10 battery subtests; in all cases the level of significance was .002 or less; for nine subtests, significance fell below .001. In the ‘intact’ older group, battery performance was observed to be closely related to score on the MMSE, a test of general cognitive integrity (r= .558,p= .01).ConclusionsPerformance on the Rookwood Battery differs for the over 70s and under 70s. The authors suggest essential modifications in its use with older people.
Low Dietary Riboflavin but Not Folate Predicts Increased Fracture Risk in Postmenopausal Women Homozygous for the MTHFR 677 T Allele
Authors: Yazdanpanah Nahid , Uitterlinden André G , Zillikens M Carola , Jhamai Mila , Rivadeneira Fernando , Hofman Albert , de Jonge Robert , Lindemans Jan , Pols Huibert AP , van Meurs Joyce B 
Published: August 2007

Abstract
The MTHFR C677T polymorphism is associated with mildly elevated homocysteine levels when folate and/or riboflavin status is low. Furthermore, a mildly elevated homocysteine level is a risk factor for osteoporotic fractures. We studied whether dietary intake of riboflavin and folate modifies the effects of the MTHFR C677T variant on fracture risk in 5035 men and women from the Rotterdam Study. We found that the MTHFR C677T variant interacts with dietary riboflavin intake to influence fracture risk in women.
Introduction: The MTHFR C677T polymorphism is associated with mildly elevated homocysteine (Hcy) levels in the presence of low folate and/or riboflavin status. A mildly elevated Hcy level was recently identified as a modifiable risk factor for osteoporotic fracture. We studied whether dietary intake of riboflavin and folate modifies the effects of the MTHFR C677T polymorphism on BMD and fracture risk.
Materials and Methods: We studied 5035 individuals from the Rotterdam Study, ≥55 yr of age, who had data available on MTHFR, nutrient intake, and fracture risk. We performed analysis on Hcy levels in a total of 666 individuals, whereas BMD data were present for 4646 individuals (2692women).
Results: In the total population, neither the MTHFR C677T polymorphism nor low riboflavin intake was associated with fracture risk and BMD. However, in the lowest quartile of riboflavin intake, female 677-T homozygotes had a 1.8 (95% CI: 1.1-2.9, p = 0.01) times higher risk for incident osteoporotic fractures and a 2.6 (95% CI: 1.3-5.1, p = 0.01) times higher risk for fragility fractures compared with the 677-CC genotype (interaction, p = 0.0002). This effect was not seen for baseline BMD in both men and women. No significant influence was found for dietary folate intake on the association between the MTHFR C677T genotype and fracture risk or BMD. In the lowest quartile of dietary riboflavin intake, T-homozygous individuals (men and women combined) had higher (22.5%) Hcy levels compared with C-homozygotes (mean difference = 3.44 νM, p = 0. 01; trend, p = 0.02).
Conclusions: In this cohort of elderly whites, the MTHFR C677T variant interacts with dietary riboflavin intake to influence fracture risk in women.
Development of American National Standards for Sustainable Building Products
Authors: Wilson Jane M. , Bowen Jaclyn M. 
Published: August 2007

Abstract
Numerous interior furnishing products have been introduced into the market claiming a variety of environmental attributes. End users are requesting access to information other than marketing claims to help understand the environmental benefits of each product and to be able to compare products using a consistent basis of measurement. Developing responses to these requests is time-consuming and expensive for manufacturers. Having a consensus set of attributes that define and identify sustainable products in the form of American National Standards will assist both manufacturers and end users in communicating environmental and sustainability related product benefits. NSF International, an ANSI-accredited standards development organization, is working with stakeholders in the contract textile, carpet and rug, and resilient flooring sectors to initiate separate sustainability standardization efforts for these product categories. By working with multiple industries that affect the indoor environment, NSF intends to promote the sharing of best sustainability practices across standards committees, so that the standards are developed in a consistent and cohesive manner. Establishment of these standards will serve to directly support and inform the end user decision-making process for the evaluation of products in these categories with respect to identifying the desired sustainability performance for products to be utilized within specific indoor environments.
HLA-DPB1*0402 Protects Against Type 1A Diabetes Autoimmunity in the Highest Risk DR3-DQB1*0201/DR4-DQB1*0302 DAISY Population
Authors: Baschal Erin E. , Aly Theresa A. , Babu Sunanda R. , Fernando Maria S. , Yu Liping , Miao Dongmei , Barriga Katherine J. , Norris Jill M. , Noble Janelle A. , Erlich Henry A. , Rewers Marian J. , Eisenbarth George S. 
Published: August 2007

OBJECTIVE— A major goal in genetic studies of type 1A diabetes is prediction of anti-islet autoimmunity and subsequent diabetes in the general population, as &gt;85% of patients do not have a first-degree relative with type 1A diabetes. Given prior association studies, we hypothesized that the strongest candidates for enhancing diabetes risk among DR3-DQB1*0201/DR4-DQB1*0302 individuals would be alleles of DP and DRB1*04 subtypes and, in particular, the absence of reportedly protective alleles DPB1*0402 and/or DRB1*0403.
RESEARCH DESIGN AND METHODS— We genotyped 457 DR3-DQB1*0201/DR4-DQB1*0302 Diabetes Autoimmunity Study of the Young (DAISY) children (358 general population and 99 siblings/offspring of type 1 diabetic patients) at the DPB1, DQB1, and DRB1 loci using linear arrays of immobilized sequence-specific oligonucleotides, with direct sequencing to differentiate DRB1*04 subtypes.
RESULTS— By survival curve analysis of DAISY children, the risk of persistently expressing anti-islet autoantibodies is ∼55% for relatives (children with a parent or sibling with type 1 diabetes) in the absence of these two protective alleles vs. 0% (P = 0.02) with either protective allele, and the risk is 20 vs. 2% (P = 0.004) for general population children. Even when the population analyzed is limited to DR3-DQB1*0201/DR4-DQB1*0302 children with DRB1*0401 (the most common DRB1*04 subtype), DPB1*0402 influences development of anti-islet autoantibodies.
CONCLUSIONS— The ability to identify a major group of general population newborns with a 20% risk of anti-islet autoimmunity should enhance both studies of the environmental determinants of type 1A diabetes and the design of trials for the primary prevention of anti-islet autoimmunity.
Impairment of the Ubiquitin-Proteasome Pathway Is a Downstream Endoplasmic Reticulum Stress Response Induced by Extracellular Human Islet Amyloid Polypeptide and Contributes to Pancreatic β-Cell Apoptosis
Authors: Casas Sílvia , Gomis Ramon , Gribble Fiona M. , Altirriba Jordi , Knuutila Sakari , Novials Anna 
Published: August 2007

OBJECTIVE—Human islet amyloid polypeptide (hIAPP) aggregation plays a major role in the development of islet amyloidosis in type 2 diabetes. It is known that extracellular hIAPP oligomers are toxic to pancreatic β-cells and associated with apoptosis. We therefore investigated the molecular mechanism by which extracellular hIAPP mediates pancreatic β-cell apoptosis.
RESEARCH DESIGN AND METHODS—MIN6 cells and primary cultures of human pancreatic islets were treated with freshly dissolved hIAPP peptide. Morphology of the cultures was evaluated by electron microscopy. Gene expression was analyzed by microarray, RT-PCR, and immunoblot. Calcium levels were measured in fura-2–loaded cells. Apoptosis was quantified by cytometry.
RESULTS—Increased expression of several heat shock proteins and activation of the spliced form of XBP-1, a transcription factor for overexpression of chaperones during endoplasmic reticulum (ER) stress, were detected together with morphological evidence of ER dysfunction. Intracellular calcium overload was detected in association with this process. Moreover, reduction in the proteasome activity, which was detected over time, contributed to the intracellular accumulation of ubiquitinated proteins, leading to a functional suppression of the ubiquitin-proteasome pathway. In addition, impairment of the proteasome function contributed to apoptosis, while, despite the presence of hIAPP, cell viability improved when a proteasome activator was overexpressed. The key cytotoxic events induced by extracellular hIAPP were also observed in treated human islets.
CONCLUSIONS—Our data suggest that ER stress responses are intracellular signaling mechanisms induced by extracellular hIAPP aggregation and that impairment of the ubiquitin-proteasome pathway is implicated in ER stress–mediated pancreatic β-cell apoptosis.
Bone Marrow Is a Preferential Homing Site for Autoreactive T-Cells in Type 1 Diabetes
Authors: Li Ruobing , Perez Nicolas , Karumuthil-Melethil Subha , Vasu Chenthamarakshan 
Published: August 2007

OBJECTIVE—The pancreatic microenvironment is considered to be the primary location of autoreactive T-cells in type 1 diabetes. Diabetogenic T-cells have also been detected in the spleens of NOD mice. However, it is not known whether bone marrow also contains T-cells specific for self-antigens in hosts with autoimmunity. In this study, we investigated whether autoreactive diabetogenic T-cells are present in the bone marrow of NOD mice.RESEARCH DESIGN AND METHODS—Bone marrow and splenic T-cells of female NOD mice were purified and tested for their cytokine secretion and proliferation in response to stimulation with immunodominant peptides of pancreatic β-cells. The diabetogenic nature and homing properties of purified bone marrow T-cells were compared with those of splenic T-cells in NOD-Scid and wild-type mice.RESULTS—The bone marrow T-cells from both hyperglycemic and young euglycemic mice demonstrated profoundly higher proliferation and cytokine production in response to stimulation with β-cell antigens than T-cells from spleen. Bone marrow T-cells showed rapid expansion and aggressive infiltration into pancreatic islets in NOD-Scid mice and induced hyperglycemia earlier than splenic T-cells. Adoptive transfer of bone marrow T-cells resulted in their trafficking predominantly to bone marrow and pancreatic lymph nodes.CONCLUSIONS—Our study demonstrates that a large number of diabetogenic T-cells are present in the bone marrow of female NOD mice and that these autoreactive T-cells can be detected long before clinical onset of the disease.
Depression, Self-Care, and Medication Adherence in Type 2 Diabetes
Authors: Gonzalez Jeffrey S. , Safren Steven A. , Cagliero Enrico , Wexler Deborah J. , Delahanty Linda , Wittenberg Eve , Blais Mark A. , Meigs James B. , Grant Richard W. 
Published: August 2007

OBJECTIVE—We examined the association between depression, measured as either a continuous symptom severity score or a clinical disorder variable, with self-care behaviors in type 2 diabetes.
RESEARCH DESIGN AND METHODS—We surveyed 879 type 2 diabetic patients from two primary care clinics using the Harvard Department of Psychiatry/National Depression Screening Day Scale (HANDS), the Summary of Diabetes Self-Care Activities, and self-reported medication adherence.
RESULTS—Of the patients, 19% met the criteria for probable major depression (HANDS score ≥9), and an additional 66.5% reported at least some depressive symptoms. After controlling for covariates, patients with probable major depression reported significantly fewer days' adherent to diet, exercise, and glucose self-monitoring regimens (P &lt; 0.01) and 2.3-fold increased odds of missing medication doses in the previous week (95% CI 1.5–3.6, P &lt; 0.001) compared with all other respondents. Continuous depressive symptom severity scores were better predictors of nonadherence to diet, exercise, and medications than categorically defined probable major depression. Major depression was a better predictor of glucose monitoring. Among the two-thirds of patients not meeting the criteria for major depression (HANDS score &lt;9, n = 709), increasing HANDS scores were incrementally associated with poorer self-care behaviors (P &lt; 0.01).
CONCLUSIONS—These findings challenge the conceptualization of depression as a categorical risk factor for nonadherence and suggest that even low levels of depressive symptomatology are associated with nonadherence to important aspects of diabetes self-care. Interventions aimed at alleviating depressive symptoms, which are quite common, could result in significant improvements in diabetes self-care.
Software for Reading and Grading Diabetic Retinopathy
Authors: Perumalsamy Namperumalsamy , Prasad Noela M. , Sathya Shankar , Ramasamy Kim 
Published: August 2007

OBJECTIVE—To evaluate the validity and reproducibility of software for reading digital images and grading diabetic retinopathy.
RESEARCH DESIGN AND METHODS—A prospective, comparative observational study was conducted on a series of patients with type 2 diabetes who presented at the retina clinic of a tertiary care center in India. A total of 210 eyes of 105 patients were allocated to one of three ophthalmologists, who performed dilated indirect and direct ophthalmoscopy and subsequently assessed the digital images of the same group of patients who were masked to the patient's identity. The interobserver and intertest agreement between clinical assessments and grading of diabetic retinopathy using the software was estimated.
RESULTS—Moderate nonproliferative diabetic retinopathy (NPDR) was most frequently diagnosed, both clinically and on evaluating digital images. The overall agreement between the clinical grading of diabetic retinopathy and the grading of images was 81.3% (κ = 0.69, SE 0.04, P &lt; 0.0001); there was good agreement (81.3%) for NPDR (κ = 0.61, SE 0.05, P &lt; 0.0001), but agreement was not as good (54.6%) for proliferative diabetic retinopathy (κ = 0.29, SE 0.11, P = 0.005). Clinically significant macular edema was diagnosed in 33.3% (70 of 210) of eyes clinically and in 40.2% (84 of 209) of eyes by grading images, and there was good agreement (89.5%) between the two (κ = 0.77, SE 0.07, P &lt; 0.0001).
CONCLUSIONS—Aravind Diabetic Retinopathy Screening 3.0 is a simple and valid tool to assist in the detection of sight-threatening retinopathy and could supplement dilated fundus examinations by ophthalmologists on patients to detect diabetic retinopathy.