bluuebunny/crossref_metadata_2025_split huggingface dataset:
End point prick test: could this new test be used to predict the outcome of oral food challenge in children with cow's milk allergy?
Authors: Bellini Federica , Ricci Giampaolo , Dondi Arianna , Piccinno Valentina , Angelini Federico , Pession Andrea 
Published: November 2011

Abstract

Background
Cow's milk allergy (CMA) is the most frequent food allergy in childhood; the trend of CMA is often characterized by a progressive improvement to achieve tolerance in the first 4 to 5 years of life.
It has been observed that specific IgE (sIgE) towards cow's milk proteins decrease when the age increases.
Although food allergy can be easily diagnosed, it is difficult to predict the outcome of the oral food challenge (OFC), that remains the gold standard in the diagnosis of food allergy, by allergometric tests.

Methods
We considered 44 children with CMA diagnosed through OFC who returned to our Allergy and Immunology Pediatric Department between January to December 2010 to evaluate the persistence of allergy or the achievement of tolerance.
On the basis of the history, we performed both allergometric skin tests and OFC in children that were still following a milk-free diet, whereas only allergometric skin tests those that had already undergone spontaneous introduction of milk protein at home without presenting symptoms.

Objective
The aim of this study was to investigate the relationship between the persistence of CMA or the acquisition of tolerance and the results of the end point prick test (EPT).

Results and Discussion
The OFC with cow's milk was performed on 30 children, 4 children were excluded because of a history of severe reactions to cow's milk, and 10 because they had spontaneously already taken milk food derivates at home without problems. 16/30 (53%) children showed clinical reactions and the challenge was stopped, 14/30 (47%) did not have any reaction.
Comparing the mean wheal diameter of every EPT's dilution between the group of allergic children and the tolerant ones, we obtained a significant difference (p < 0.05) for the first 4 dilutions.
We have also calculated sensitivity (SE), specificity (SP), the positive predictive value (PPV) and the negative predictive value (NPV) for each EPT dilution.

Conclusions
EPT is a safe and cheap test, easy to be executed and that could provide good prediction of the outcome of OFC; so it might be used to avoid OFC-induced anaphylaxis in children affected by CMA. It can also help avoiding dietetic restrictions in tolerant children who show sensitization towards cow's milk proteins.
Neutrophil-derived matrix metalloproteinase-9 is a potent activator of trypsinogen in acinar cells in acute pancreatitis
Authors: Awla Darbaz , Abdulla Aree , Syk Ingvar , Jeppsson Bengt , Regnér Sara , Thorlacius Henrik 
Published: November 2011

ABSTRACT
MMPs are generally considered to regulate degradation and remodeling of the ECM. Convincing data also implicate a role for MMPs in inflammatory conditions, such as AP, although the mechanisms are not known. The aim of this study was to define the role of MMPs in regulating activation of trypsinogen and tissue damage in AP, which was induced by infusion of taurocholate into the pancreatic duct in mice. A broad-spectrum MMP inhibitor (BB-94) and MMP-9 gene-deficient mice were used. Neutrophil secretions and rMMP-9 were used to stimulate trypsinogen activation in isolated acinar cells. Taurocholate challenge increased serum amylase, neutrophil infiltration, MIP-2 (CXCL2) formation, trypsinogen activation, and tissue damage in the pancreas. Treatment with the broad-spectrum inhibitor of MMPs, BB-94, markedly reduced activation of trypsinogen, levels of CXCL2, infiltration of neutrophils, and tissue damage in AP. Taurocholate challenge increased serum levels of MMP-9 but not MMP-2. Taurocholate-induced amylase levels, neutrophil accumulation, production of CXCL2, trypsinogen activation, and tissue damage in the pancreas were abolished in MMP-9-deficient mice. Moreover, secretions from activated neutrophils isolated from WT but not from MMP-9-deficient animals stimulated trypsinogen activation in acinar cells. Notably, rMMP-9 greatly enhanced activation of trypsinogen in acinar cells. These findings demonstrate that neutrophil-derived MMP-9 is a potent activator of trypsinogen in acinar cells and regulates pathological inflammation and tissue damage in AP.
White matter in autism spectrum disorders – evidence of impaired fiber formation
Authors: Bode Michaela K , Mattila Marja-Leena , Kiviniemi Vesa , Rahko Jukka , Moilanen Irma , Ebeling Hanna , Tervonen Osmo , Nikkinen Juha 
Published: November 2011

Background Diffusion tensor imaging (DTI) enables measurements and visualization of the microstructure of neural fiber tracts. The existing literature on autism spectrum disorders (ASDs) and DTI is heterogenous both regarding methodology and results. Purpose To compare brain white matter of high-functioning individuals with ASDs and controls. Material and Methods Tract-based spatial statistics (TBSS), a voxel-based approach to DTI, was used to compare 27 subjects with ASDs (mean age 14.7 years, range 11.4–17.6 years, 20 boys, 7 girls) and 26 control subjects (mean age 14.5 years, range 11.7–17.3 years, 17 boys, 9 girls). Mean fractional anisotropy (FA) image (skeleton) was created and each subject's aligned FA data were then projected onto this skeleton. Voxelwise cross-subject statistics on the skeletonized FA data, mean diffusivity (MD), and measures of diffusion direction were calculated. Importantly, the data were corrected across the whole image instead of using ROI-based methods. Results The ASD group showed significantly greater FA ( P < 0.05, corrected) in the area containing clusters of optic radiation and the right inferior fronto-occipital fasciculus (iFOF). In the same area, λ3 (representing transverse diffusion) was significantly reduced in the ASD group. No age-related changes were found. Conclusion The results suggest that the reduced transverse diffusion within the iFOF is related to abnormal information flow between the insular salience processing areas and occipital visual areas.
Troponin T Measurements by High-Sensitivity vs Conventional Assays for Risk Stratification in Acute Dyspnea
Authors: van Wijk Sandra , Jacobs Leo , Eurlings Luc W , van Kimmenade Roland , Lemmers Roosmarijn , Broos Pieter , Bekers Otto , Prins Martin H , Crijns Harry J , Pinto Yigal M , van Dieijen-Visser Marja P , Brunner-La Rocca Hans-Peter 
Published: November 2011

Abstract

BACKGROUND
Cardiac troponin T measured by a high-sensitivity assay (hs-cTnT) recently proved to be of prognostic value in several populations. The hs-cTnT assay may also improve risk stratification in acute dyspnea.

METHODS
We prospectively studied the prognostic value of hs-cTnT in 678 consecutive patients presenting to the emergency department with acute dyspnea. On the basis of conventional cardiac troponin T assay (cTnT) and hs-cTnT assay measurements, patients were divided into 3 categories: (1) neither assay increased (cTnT &lt;0.03 μg/L, hs-cTnT &lt;0.016 μg/L), (2) only hs-cTnT increased ≥0.016 μg/L (cTnT &lt;0.03 μg/L), and (3) both assays increased (cTnT ≥0.03 μg/L, hs-cTnT ≥0.016 μg/L). Moreover, the prognostic value of hs-cTnT was investigated if cTnT was not detectable (&lt;0.01).

RESULTS
One hundred seventy-two patients were in the lowest, 282 patients in the middle, and 223 patients in the highest troponin category. Patients in the second and third categories had significantly higher mortality compared to those in the first category (90-day mortality rate 2%, 10%, and 26% in groups 1, 2, and 3, respectively, P &lt; 0.001; 1-year mortality rate 9%, 21%, and 39%, P &lt; 0.001). Importantly, in patients with undetectable cTnT (n = 347, 51%), increased hs-cTnT indicated worse outcome [90-day mortality, odds ratio 4.26 (95% CI 1.19–15.21); 1-year mortality, hazard ratio 2.27 (1.19–4.36), P = 0.013], whereas N-terminal pro–brain-type natriuretic peptide (NT-proBNP) was not predictive of short-term outcome.

CONCLUSIONS
hs-cTnT is associated with mortality in patients presenting with acute dyspnea. hs-cTnT concentrations provide additional prognostic information to cTnT and NT-proBNP testing in patients with cTnT concentrations below the detection limit. In particular, the hs-cTnT cutoff of 0.016 μg/L enables identification of low-risk patients.
Shaping the CD4+ memory immune response against tuberculosis: the role of antigen persistence, location and multi-functionality
Authors: Ancelet Lindsay , Kirman Joanna 
Published: November 2011

AbstractEffective vaccination against intracellular pathogens, such as tuberculosis (TB), relies on the generation and maintenance of CD4 memory T cells. An incomplete understanding of the memory immune response has hindered the rational design of a new, more effective TB vaccine. This review discusses how the persistence of antigen, the location of memory cells, and their multifunctional ability shape the CD4 memory T cell response against TB.
Stickbreaking: A Novel Fitness Landscape Model That Harbors Epistasis and Is Consistent with Commonly Observed Patterns of Adaptive Evolution
Authors: Nagel Anna C , Joyce Paul , Wichman Holly A , Miller Craig R 
Published: November 2011

AbstractIn relating genotypes to fitness, models of adaptation need to both be computationally tractable and qualitatively match observed data. One reason that tractability is not a trivial problem comes from a combinatoric problem whereby no matter in what order a set of mutations occurs, it must yield the same fitness. We refer to this as the bookkeeping problem. Because of their commutative property, the simple additive and multiplicative models naturally solve the bookkeeping problem. However, the fitness trajectories and epistatic patterns they predict are inconsistent with the patterns commonly observed in experimental evolution. This motivates us to propose a new and equally simple model that we call stickbreaking. Under the stickbreaking model, the intrinsic fitness effects of mutations scale by the distance of the current background to a hypothesized boundary. We use simulations and theoretical analyses to explore the basic properties of the stickbreaking model such as fitness trajectories, the distribution of fitness achieved, and epistasis. Stickbreaking is compared to the additive and multiplicative models. We conclude that the stickbreaking model is qualitatively consistent with several commonly observed patterns of adaptive evolution.
A Screen for X-Linked Mutations Affecting Drosophila Photoreceptor Differentiation Identifies Casein Kinase 1α as an Essential Negative Regulator of Wingless Signaling
Authors: Legent Kevin , Steinhauer Josefa , Richard Magali , Treisman Jessica E 
Published: November 2011

Abstract
The Wnt and Hedgehog signaling pathways are essential for normal development and are misregulated in cancer. The casein kinase family of serine/threonine kinases regulates both pathways at multiple levels. However, it has been difficult to determine whether individual members of this family have distinct functions in vivo, due to their overlapping substrate specificities. In Drosophila melanogaster, photoreceptor differentiation is induced by Hedgehog and inhibited by Wingless, providing a sensitive system in which to identify regulators of each pathway. We used a mosaic genetic screen in the Drosophila eye to identify mutations in genes on the X chromosome required for signal transduction. We recovered mutations affecting the transcriptional regulator CREB binding protein, the small GTPase dynamin, the cytoskeletal regulator Actin-related protein 2, and the protein kinase Casein kinase 1α. Consistent with its reported function in the β-Catenin degradation complex, Casein Kinase 1α mutant cells accumulate β-Catenin and ectopically induce Wingless target genes. In contrast to previous studies based on RNA interference, we could not detect any effect of the same Casein Kinase 1α mutation on Hedgehog signaling. We thus propose that Casein kinase 1α is essential to allow β-Catenin degradation and prevent inappropriate Wingless signaling, but its effects on the Hedgehog pathway are redundant with other Casein kinase 1 family members.
The Double-Bromodomain Proteins Bdf1 and Bdf2 Modulate Chromatin Structure to Regulate S-Phase Stress Response in Schizosaccharomyces pombe
Authors: Garabedian Mikael V , Noguchi Chiaki , Ziegler Melissa A , Das Mukund M , Singh Tanu , Harper Logan J , Leman Adam R , Khair Lyne , Moser Bettina A , Nakamura Toru M , Noguchi Eishi 
Published: November 2011

Abstract
Bromodomain proteins bind acetylated histones to regulate transcription. Emerging evidence suggests that histone acetylation plays an important role in DNA replication and repair, although its precise mechanisms are not well understood. Here we report studies of two double bromodomain-containing proteins, Bdf1 and Bdf2, in fission yeast. Loss of Bdf1 or Bdf2 led to a reduction in the level of histone H4 acetylation. Both bdf1Δ and bdf2Δ cells showed sensitivity to DNA damaging agents, including camptothecin, that cause replication fork breakage. Consistently, Bdf1 and Bdf2 were important for recovery of broken replication forks and suppression of DNA damage. Surprisingly, deletion of bdf1 or bdf2 partially suppressed sensitivity of various checkpoint mutants including swi1Δ, mrc1Δ, cds1Δ, crb2Δ, chk1Δ, and rad3Δ, to hydroxyurea, a compound that stalls replication forks and activates the Cds1-dependent S-phase checkpoint. This suppression was not due to reactivation of Cds1. Instead, we found that bdf2 deletion alleviates DNA damage accumulation caused by defects in the DNA replication checkpoint. We also show that hydroxyurea sensitivity of mrc1Δ and swi1Δ was suppressed by mutations in histone H4 acetyltransferase subunits or histone H4. These results suggest that the double bromodomain-containing proteins modulate chromatin structure to coordinate DNA replication and S-phase stress response.
Multiple Roles of the Cox20 Chaperone in Assembly of Saccharomyces cerevisiae Cytochrome c Oxidase
Authors: Elliott Leah E , Saracco Scott A , Fox Thomas D 
Published: November 2011

Abstract
The Cox2 subunit of Saccharomyces cerevisiae cytochrome c oxidase is synthesized in the mitochondrial matrix as a precursor whose leader peptide is rapidly processed by the inner membrane protease following translocation to the intermembrane space. Processing is chaperoned by Cox20, an integral inner membrane protein whose hydrophilic domains are located in the intermembrane space, and Cox20 remains associated with mature, unassembled Cox2. The Cox2 C-tail domain is exported post-translationally by the highly conserved translocase Cox18 and associated proteins. We have found that Cox20 is required for efficient export of the Cox2 C-tail. Furthermore, Cox20 interacts by co-immune precipitation with Cox18, and this interaction requires the presence of Cox2. We therefore propose that Cox20 binding to Cox2 on the trans side of the inner membrane accelerates dissociation of newly exported Cox2 from the Cox18 translocase, promoting efficient cycling of the translocase. The requirement for Cox20 in cytochrome c oxidase assembly and respiratory growth is partially bypassed by yme1, mgr1 or mgr3 mutations, each of which reduce i-AAA protease activity in the intermembrane space. Thus, Cox20 also appears to stabilize unassembled Cox2 against degradation by the i-AAA protease. Pre-Cox2 leader peptide processing by Imp1 occurs in the absence of Cox20 and i-AAA protease activity, but is greatly reduced in efficiency. Under these conditions some mature Cox2 is assembled into cytochrome c oxidase allowing weak respiratory growth. Thus, the Cox20 chaperone has important roles in leader peptide processing, C-tail export, and stabilization of Cox2.
Age-Specific Administration of Chemotherapy and Long-Term Quality of Life in Stage II and III Colorectal Cancer Patients: A Population-Based Prospective Cohort
Authors: Jansen Lina , Hoffmeister Michael , Chang-Claude Jenny , Koch Moritz , Brenner Hermann , Arndt Volker 
Published: November 2011

Abstract

Learning Objectives
After completing this course, the reader will be able to: Critically appraise the current pattern of administration of chemotherapy in older patients with colorectal cancer.Describe the survival benefits associated with chemotherapy as well as its long-term effects on quality of life in stage II/III colorectal cancer patients.
CME This article is available for continuing medical education credit at CME.TheOncologist.com

Purpose.
To investigate the age-specific pattern of administration of chemotherapy and its association with long-term survival and quality of life (QoL) in stage II and III colorectal cancer patients.

Methods.
Chemotherapy allocation according to disease and patient characteristics was investigated in a population-based cohort of 562 stage II and III colorectal cancer patients. Five years after diagnosis, survival was determined and QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Items and a tumor specific module. The association among chemotherapy, survival, and QoL was examined while controlling for potential confounders.

Results.
Chemotherapy was administered in 71% of patients aged &lt;60 years and in only 20% of patients aged ≥80 years. A significant association between chemotherapy and longer survival time was found for stage III cancer only. Chemotherapy was associated with higher symptom levels for trouble with taste, anxiety, and hair loss. In age-specific analyses, younger survivors (&lt;70 years at time of follow-up) with a history of chemotherapy reported significantly lower physical, role, and cognitive functioning and higher pain, appetite loss, hair loss, and trouble with taste symptom levels. In contrast, for older survivors (≥70 years), only two (hair loss and dry mouth) out of 38 QoL scores were significantly associated with chemotherapy.

Discussion.
Chemotherapy is associated with lower long-term QoL, especially in younger survivors. In cases of uncertain survival benefits of chemotherapy, consideration of its long-term effects on QoL should be incorporated into final decisions on treatment.
Size at Birth, Weight Gain in Infancy and Childhood, and Adult Diabetes Risk in Five Low- or Middle-Income Country Birth Cohorts
Authors: Norris Shane A. , Osmond Clive , Gigante Denise , Kuzawa Christopher W. , Ramakrishnan Lakshmy , Lee Nanette R. , Ramirez-Zea Manual , Richter Linda M. , Stein Aryeh D. , Tandon Nikhil , Fall Caroline H.D. ,   the COHORTS Group
Published: November 2011

OBJECTIVE
We examined associations of birth weight and weight gain in infancy and early childhood with type 2 diabetes (DM) risk in five cohorts from low- and middle-income countries.

RESEARCH DESIGN AND METHODS
Participants were 6,511 young adults from Brazil, Guatemala, India, the Philippines, and South Africa. Exposures were weight at birth, at 24 and 48 months, and adult weight, and conditional weight gain (CWG, deviation from expected weight gain) between these ages. Outcomes were adult fasting glucose, impaired fasting glucose or DM (IFG/DM), and insulin resistance homeostasis model assessment (IR-HOMA, three cohorts).

RESULTS
Birth weight was inversely associated with adult glucose and risk of IFG/DM (odds ratio 0.91[95% CI 0.84–0.99] per SD). Weight at 24 and 48 months and CWG 0–24 and 24–48 months were unrelated to glucose and IFG/DM; however, CWG 48 months–adulthood was positively related to IFG/DM (1.32 [1.22–1.43] per SD). After adjusting for adult waist circumference, birth weight, weight at 24 and 48 months and CWG 0–24 months were inversely associated with glucose and IFG/DM. Birth weight was unrelated to IR-HOMA, whereas greater CWG at 0–24 and 24–48 months and 48 months–adulthood predicted higher IR-HOMA (all P &lt; 0.001). After adjusting for adult waist circumference, birth weight was inversely related to IR-HOMA.

CONCLUSIONS
Lower birth weight and accelerated weight gain after 48 months are risk factors for adult glucose intolerance. Accelerated weight gain between 0 and 24 months did not predict glucose intolerance but did predict higher insulin resistance.
Lower Risk of Cancer in Patients on Metformin in Comparison With Those on Sulfonylurea Derivatives
Authors: Ruiter Rikje , Visser Loes E. , van Herk-Sukel Myrthe P.P. , Coebergh Jan-Willem W. , Haak Harm R. , Geelhoed-Duijvestijn Petronella H. , Straus Sabine M.J.M. , Herings Ron M.C. , Stricker Bruno H.Ch. 
Published: November 2011

OBJECTIVE
Numerous studies have suggested a decreased risk of cancer in patients with diabetes on metformin. Because different comparison groups were used, the effect magnitude is difficult to estimate. Therefore, the objective of this study was to further analyze whether, and to what extent, use of metformin is associated with a decreased risk of cancer in a cohort of incident users of metformin compared with users of sulfonylurea derivatives.

RESEARCH DESIGN AND METHODS
Data for this study were obtained from dispensing records from community pharmacies individually linked to hospital discharge records from 2.5 million individuals in the Netherlands. The association between the risk of cancer in those using metformin compared with those using sulfonylurea derivatives was analyzed using Cox proportional hazard models with cumulative duration of drug use as a time-varying determinant.

RESULTS
Use of metformin was associated with a lower risk of cancer in general (hazard ratio 0.90 [95% CI 0.88–0.91]) compared with use of sulfonylurea derivatives. When specific cancers were used as end points, similar estimates were found. Dosage-response relations were identified for users of metformin but not for users of sulfonylurea derivatives.

CONCLUSIONS
In our study, cumulative exposure to metformin was associated with a lower risk of specific cancers and cancer in general, compared with cumulative exposure to sulfonylurea derivatives. However, whether this should indeed be seen as a decreased risk of cancer for the use of metformin or as an increased risk of cancer for the use sulfonylurea derivatives remains to be elucidated.
Explaining the Increase of Diabetes Prevalence and Plasma Glucose in Mauritius
Authors: Magliano Dianna J. , Söderberg Stefan , Zimmet Paul Z. , Chen Lei , Joonas Noorjehan , Kowlessur Sudhir , Larhubarbe Jose , Gaoneadry Dhanunjaye , Pauvaday Vassen , Tuomilehto Jaakko , Alberti K. George M.M. , Shaw Jonathan E. 
Published: November 2011

OBJECTIVE
Secular trends in the epidemiology of diabetes are best described by studying the same population over time, but few such studies exist. Using surveys from Mauritius in 1987 and 2009, we examined 1) the change in the prevalence of diabetes, 2) the extent to which changes in traditional diabetes risk factors explained the increase, and 3) the change in the distribution of plasma glucose levels over time.

RESEARCH DESIGN AND METHODS
Independent population-based surveys were undertaken in Mauritius in 1987 and 2009 using similar methodology in adults aged 20–74 years. Physical measurements and fasting blood samples were taken, and an oral glucose tolerance test was performed at both surveys.

RESULTS
The age-standardized prevalence of diabetes in 2009 was 22.3% (95% CI 20.0–24.6) among men and 20.2% (18.3–22.3) among women, representing an increase since 1987 of 64 and 62% among men and women, respectively. Concurrent changes in the distribution of age, ethnicity, waist circumference, BMI, physical activity, smoking, family history of diabetes, and hypertension explained more of the increase in the prevalence of diabetes in men than in women. Increases in plasma glucose (especially fasting glucose) were seen across the population but were greater at the upper levels.

CONCLUSIONS
In Mauritius, there has been a marked increase in diabetes prevalence over 22 years. This mainly results from changes in traditional risk factors, leading to population-wide increases in plasma glucose levels. Interventions to control this escalation of diabetes should focus on population-wide strategies.