bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: Common Genetic Variants in GCK and TCF7L2 Are Associated With Fasting and Postchallenge Glucose Levels in Pregnancy and With the New Consensus Definition of Gestational Diabetes Mellitus From the International Association of Diabetes and Pregnancy Study Groups
Authors: Freathy Rachel M. , Hayes M. Geoffrey , Urbanek Margrit , Lowe Lynn P. , Lee Hoon , Ackerman Christine , Frayling Timothy M. , Cox Nancy J. , Dunger David B. , Dyer Alan R. , Hattersley Andrew T. , Metzger Boyd E. , Lowe William L. ,   for the HAPO Study Cooperative Research Group
Published: August 2010

OBJECTIVE
Common genetic variants in GCK and TCF7L2 are associated with higher fasting glucose and type 2 diabetes in nonpregnant populations. However, their associations with glucose levels from oral glucose tolerance tests (OGTTs) in pregnancy have not been assessed in a large sample. We hypothesized that these variants are associated with quantitative measures of glycemia in pregnancy.

RESEARCH DESIGN AND METHODS
We analyzed the associations between variants rs1799884 (GCK) and rs7903146 (TCF7L2) and OGTT outcomes at 24–32 weeks' gestation in 3,811 mothers of European (U.K. and Australia) and 1,706 mothers of Asian (Thailand) ancestry from the HAPO cohort. We also tested associations with offspring birth anthropometrics.

RESULTS
The maternal GCK variant was associated with higher fasting glucose in Europeans (P = 0.001) and Thais (P &lt; 0.0001), 1-h glucose in Europeans (P = 0.001), and 2-h glucose in Thais (P = 0.005). It was also associated with higher European offspring birth weight, fat mass, and skinfold thicknesses (P &lt; 0.05). The TCF7L2 variant was associated with all three maternal glucose outcomes (P = 0.03, P &lt; 0.0001, and P &lt; 0.0001 for fasting and 1-h and 2-h glucose, respectively) in the Europeans but not in the Thais (P &gt; 0.05). In both populations, both variants were associated with higher odds of gestational diabetes mellitus according to the new International Association of Diabetes and Pregnancy Study Groups recommendations (P = 0.001–0.08).

CONCLUSIONS
Maternal GCK and TCF7L2 variants are associated with glucose levels known to carry an increased risk of adverse pregnancy outcome in women without overt diabetes. Further studies will be important to determine the variance in maternal glucose explained by all known genetic variants.
Incidence of liver cirrhosis in HIV-infected patients with chronic hepatitis B or C in the era of highly active antiretroviral therapy
Authors: Tuma Paula , Medrano Jose , Resino Salvador , Vispo Eugenia , Madejón Antonio , Sánchez-Piedra Carlos , Rivas Pablo , Labarga Pablo , Martín-Carbonero Luz , Barreiro Pablo , Soriano Vincent 
Published: August 2010

Background Longitudinal assessment of liver fibrosis with transient elastometry (TE) in patients with chronic viral hepatitis is becoming routine clinical practice in many clinics, as this procedure is non-invasive, easy to perform and relatively inexpensive, allowing early detection of cirrhosis. Herein, we examine the incidence of cirrhosis, using TE assessment, in HIV-infected individuals with chronic hepatitis B or C receiving highly active anti-retroviral therapy (HAART). Methods A longitudinal study was performed on a cohort of HIV-infected patients with chronic hepatitis B or C who were followed since 2004 at Hospital Carlos III (Madrid, Spain) with periodic TE assessments. The primary outcome was the development of cirrhosis, defined as liver stiffness >12.5 KPa. Results A total of 508 HIV-infected patients were examined, of whom 54 developed liver cirrhosis during a mean ±sd follow-up of 2.6 ±1.0 years (overall incidence was 41.13 cases per 1,000 person-years). The risk of developing cirrhosis was significantly higher in 297 HCV-RNA-positive patients (either untreated or non- responders to hepatitis C therapy) compared with 55 patients who had cleared HCV with therapy (odds ratio 3.73, 95% confidence interval 1.06–13.17; P=0.04). By contrast, the risk of developing cirrhosis was low and similar in 24 HIV–HBV-coinfected patients under long-term suppressive HBV therapy (mainly tenofovir disoproxil fumarate), 132 HIV-infected patients without chronic liver disease and those who had cleared HCV with therapy. Conclusions Development of liver cirrhosis in HIV- infected individuals in the HAART era is mainly associated with active HCV coinfection. The risk of developing cirrhosis is negligible in patients who cleared HCV with therapy, as well as in HIV–HBV-coinfected patients on long-term suppressive tenofovir disoproxil fumarate therapy.
Efficacy of Cognitive-Behavioral Therapies in Fibromyalgia Syndrome — A Systematic Review and Metaanalysis of Randomized Controlled Trials
Authors: BERNARDY KATHRIN , FÜBER NICOLE , KÖLLNER VOLKER , HÄUSER WINFRIED 
Published: August 2010

Objective.We performed the first systematic review with metaanalysis of the efficacy of cognitive-behavioral therapies (CBT) in fibromyalgia syndrome (FM).Methods.We screened Cochrane Library, Medline, PsychINFO, and Scopus (through June 2009) and the reference sections of original studies and systematic reviews for CBT in FM. Randomized controlled trials (RCT) comparing CBT to controls were analyzed. Primary outcomes were pain, sleep, fatigue, and health-related quality of life (HRQOL). Secondary outcomes were depressed mood, self-efficacy pain, and healthcare-seeking behavior. Effects were summarized using standardized mean differences (SMD).Results.A total of 14 out of 27 RCT with 910 subjects with a median treatment time of 27 hours (range 6–75) over a median of 9 weeks (range 5–15) were included. CBT reduced depressed mood (SMD −0.24, 95% CI −0.40, −0.08; p = 0.004) at posttreatment. Sensitivity analyses showed that the positive effect on depressed mood could not be distinguished from some risks of bias. There was no significant effect on pain, fatigue, sleep, and HRQOL at posttreatment and at followup. There was a significant effect on self-efficacy pain posttreatment (SMD 0.85, 95% CI 0.25, 1.46; p = 0.006) and at followup (SMD 0.90, 95% CI 0.14, 1.66; p = 0.02). Operant behavioral therapy significantly reduced the number of physician visits at followup (SMD −1.57, 95% CI −2.00, −1.14; p < 0.001).Conclusion.CBT can be considered to improve coping with pain and to reduce depressed mood and healthcare-seeking behavior in FM.
Ral Isoforms Are Implicated in FcγR-Mediated Phagocytosis: Activation of Phospholipase D by RalA
Authors: Corrotte Matthias , Tran Nyguyen An Phu , Harlay Marie Line , Vitale Nicolas , Bader Marie-France , Grant Nancy J. 
Published: August 2010

AbstractPhagocytosis is an essential element of the immune response permitting the elimination of pathogens, cellular debris, apoptotic cells, and tumor cells. Recently, both phospholipase D (PLD) isoforms, PLD1 and PLD2, were shown to be necessary for efficient FcγR-mediated phagocytosis. In this study, we investigated the role of a potential PLD regulator, the Ral GTPases RalA and RalB, in murine RAW 264.7 macrophages. Both Ral isoforms are expressed in macrophages and are transiently activated following FcγR stimulation. When Ral expression levels were varied using Ral mutants or interference RNA, phagocytosis assays revealed that Ral isoforms have antagonistic effects; RalA is a positive modulator, whereas RalB plays a negative role. We then focused on RalA and its possible relationship with PLD. The increase in PLD activity that occurs when phagocytosis is stimulated was inhibited in cells with reduced RalA protein, but it was unaffected by reduced levels of RalB. Furthermore, in macrophages transfected with dsRed-RalA and GFP-PLD1 or GFP-PLD2, RalA colocalized with PLD1 and PLD2 at the phagocytic cup during phagosome formation. Additional results obtained from immunoprecipitation of PLD from macrophages transfected with myc-RalA and hemagglutinin-tagged PLD1 or PLD2 indicated an enhanced interaction of RalA with both PLD isoforms during phagocytic stimulation. The increase in RalA and PLD1 interaction was transient and correlated with the time course of RalA activation. These findings reveal a novel pathway involving RalA and PLD in the regulation of FcγR-mediated phagocytosis.
A Proinflammatory Role for Proteolytically Cleaved Annexin A1 in Neutrophil Transendothelial Migration
Authors: Williams Samantha L. , Milne Ian R. , Bagley Christopher J. , Gamble Jennifer R. , Vadas Mathew A. , Pitson Stuart M. , Khew-Goodall Yeesim 
Published: August 2010

Abstract
Neutrophil extravasation, a critical component of innate immunity must be tightly regulated to prevent inadvertent or prolonged inflammation and subsequent tissue damage. We have shown previously that endothelial ERK1/2 signaling essential for neutrophil transendothelial migration is induced by a soluble factor produced by activated neutrophils. In this study, we demonstrate that the soluble neutrophil factor is a truncated form of annexin A1 (AnxA1) that can be generated by calpain 1 cleavage of the N terminus, thus identifying a novel proinflammatory function to AnxA1. In contrast, neither the full-length protein nor the N-terminal 26 aa peptide, previously shown to be antiinflammatory, were able to activate Erk. Our data suggest that two different fragments of AnxA1 have opposing functions in inflammation. We also provide evidence that C-terminal AnxA1 functions by increasing ICAM1 clustering around adherent neutrophils to anchor them to the endothelium and promote transmigration through the transcellular route.
Cutting Edge: All-Trans Retinoic Acid Sustains the Stability and Function of Natural Regulatory T Cells in an Inflammatory Milieu
Authors: Zhou Xiaohui , Kong Ning , Wang Julie , Fan Huiming , Zou Hejian , Horwitz David , Brand David , Liu Zhongmin , Zheng Song Guo 
Published: August 2010

Abstract
Recent studies have demonstrated that plasticity of naturally occurring CD4+Foxp3+ regulatory T cells (nTregs) may account for their inability to control chronic inflammation in established autoimmune diseases. All-trans retinoic acid (atRA), the active derivative of vitamin A, has been demonstrated to promote Foxp3+ Treg differentiation and suppress Th17 development. In this study, we report a vital role of atRA in sustaining the stability and functionality of nTregs in the presence of IL-6. We found that nTregs treated with atRA were resistant to Th17 and other Th cell conversion and maintained Foxp3 expression and suppressive activity in the presence of IL-6 in vitro. atRA decreased IL-6R expression and signaling by nTregs. Of interest, adoptive transfer of nTregs even from arthritic mice treated with atRA suppressed progression of established collagen-induced arthritis. We suggest that nTregs treated with atRA may represent a novel treatment strategy to control established chronic immune-mediated inflammatory diseases.
Neutrophils Influence the Level of Antigen Presentation during the Immune Response to Protein Antigens in Adjuvants
Authors: Yang Chiao-Wen , Strong Beverly S. I. , Miller Mark J. , Unanue Emil R. 
Published: August 2010

Abstract
Neutrophils modulated Ag presentation following immunization with Ags in CFA or IFA or alum. The neutrophils had an important negative role in the CD4 T cell and B cell responses to three protein Ags: hen egg white lysozyme, OVA, and listeriolysin O. In their absence (by depleting with Abs for only the first 24 h, or using genetically neutropenic mice), the cellular responses increased several-fold. The CD8 response was not affected or slightly decreased. Competition for Ag between the presenting cells and the neutrophils, as well as an effect on the response to Ag-bearing dendritic cells (DCs), was documented. Neutrophils entered the draining lymph nodes rapidly and for a brief period of several hours, localizing mainly to the marginal sinus and superficial cortex. There they established brief contact with DCs and macrophages. Moreover, neutrophils imprinted on the quality of the subsequent DC–T cell interactions, despite no physical contact with them; by intravital microscopy, the clustering of Ag-specific T cells and DCs was improved in neutropenic mice. Thus, neutrophils are obligate cells that briefly enter sites of immunization and set the level of Ag presentation. A brief depletion may have a considerably positive impact on vaccination.
Biological behavior of preneoplastic conditions of the endometrium: A retrospective 16-year study in south India
Authors: Rao Shalinee , Sundaram Sandhya , Narasimhan Raghavan 
Published: August 2010

Abstract
Background:The biological behavior of endometrial carcinoma differs in epidemiology, presentation, and prognosis, suggesting that there are two fundamentally different pathogenic types of disease: type I (estrogen related, endometrioid type) and type II (non-estrogen related, non-endometrioid type). Untreated hyperplasia can develop into an endometrioid type of adenocarcinoma, hence, it is important to recognize the former type. In contrast to cervical cancers, there are limited studies with respect to the biology of hyperplastic lesions documented from India. This was a 16-year retrospective study, carried out to determine the nature and outcome of proliferative lesions of the endometrium in a referral center from south India.Materials and Methods:A histopathological diagnosis of the endometrial hyperplasia, polyp, and carcinoma, on endometrial biopsy and hysterectomy specimens, over a 16 year period (1983 to 1999), were recorded in a computer and the case slides were reviewed. Using the computer software Foxpro, the patients who had come more than once for a subsequent or previous biopsy were identified. An attempt was made to look for progression, regression or a static nature of the lesion in the follow-up cases.Results:A total of 1778 cases were studied, and only 74 patients with endometrial hyperplasia and five cases of benign endometrial polyp had follow-up endometrial histopathology. Hyperplasia cases included 59 cases of simple hyperplasia, 10 cases of complex hyperplasia without atypia, and five cases with atypia. The predominant age for patients with all types of hyperplasias was 41 - 50 years. Progression to a higher grade was seen in 8.10%, regression to a lower grade was seen in 9.45%, lesions reverted to a normal pattern in 10.81% cases, and lesions persisted in 70.27% of the cases. A mixed pattern was seen in 54 cases, with predominant coexistent lesion being simple and complex hyperplasia without atypia.Conclusion:The fate of the hyperplastic lesion of the endometrium showed a varied pattern. Follow-up cases predominantly showed persistence of the lesion, possibly resulting from a fluctuating but higher level of estrogenic stimulus. Hence, it was not only the high levels of estrogen that influenced the biology, but its sustenance for a prolonged period.
Intestinal mantle cell lymphoma recurring at laparotomy scar region
Authors: Ray Amitabh , Basu Ayan , Goswami Jyotirup , Bhattacharya Kalyan 
Published: August 2010

AbstractMantle cell lymphoma (MCL) is a moderately aggressive variety of non-Hodgkins lymphoma. Extranodal presentation of MCL is well known, the intestine being a common site. The incidence of colorectal involvement is relatively rare. Moreover, the recurrence of the disease at laparotomy scar site is even more rare. We report an unusual case of incision line recurrence in a case of colonic MCL occuring three years after initial treatment.
Non-splitting in Kirchberg's Ideal-relatedKK-Theory
Authors: Eilers Søren , Restorff Gunnar , Ruiz Efren 
Published: August 2010

AbstractA. Bonkat obtained a universal coefficient theorem in the setting of Kirchberg's ideal-relatedKK-theory in the fundamental case of aC*-algebra with one specified ideal. The universal coefficient sequence was shown to split, unnaturally, under certain conditions. Employing certainK-theoretical information derivable from the given operator algebras using a method introduced here, we shall demonstrate that Bonkat's UCT does not split in general. Related methods lead to information on the complexity of theK-theory which must be used to classify ∗-isomorphisms for purely infiniteC*-algebras with one non-trivial ideal.
An Outbreak of Plasmodium falciparum Malaria in U.S. Marines Deployed to Liberia
Authors: Whitman Timothy J. , Coyne Philip E. , Magill Alan J. , Blazes David L. , Green Michael D. , Milhous Wilbur K. , Burgess Timothy H. , Freilich Daniel , Tasker Sybil A. , Azar Ramzy G. , Endy Timothy P. , Clagett Christopher D. , Deye Gregory A. , Shanks G. Dennis , Martin Gregory J. 
Published: August 2010

In 2003, 44 U.S. Marines were evacuated from Liberia with either confirmed or presumed Plasmodium falciparum malaria. An outbreak investigation showed that only 19 (45%) used insect repellent, 5 (12%) used permethrin-treated clothing, and none used bed netting. Adherence with weekly mefloquine (MQ) was reported by 23 (55%). However, only 4 (10%) had serum MQ levels high enough to correlate with protection (> 794 ng/mL), and 9 (22%) had evidence of steady-state kinetics (MQ carboxy metabolite/MQ > 3.79). Tablets collected from Marines met USP identity and dissolution specifications for MQ. Testing failed to identify P. falciparum isolates with MQ resistance. This outbreak resulted from under use of personal protective measures and inadequate adherence with chemophrophylaxis. It is essential that all international travelers make malaria prevention measures a priority, especially when embarking to regions of the world with high transmission intensity such as west Africa.“Good doctors are of no use without good discipline. More than half the battle against disease is not fought by doctors, but by regimental officers. It is they who see that the daily dose of mepacrine (anti-malarial chemoprophylactic drug used in WW II) is taken…if mepacrine was not taken, I sacked the commander. I only had to sack three; by then the rest had got my meaning.”—Lieutenant General William Slim (1891–1970), Burma Campaign, 1943
Infectious Diseases Following Disasters
Authors: Murthy Srinivas , Christian Michael D. 
Published: August 2010

ABSTRACTInfectious diseases following natural disasters tend to occur as a result of the prolonged secondary effects of the disaster, mostly when there is an interruption of public health measures resulting from destruction of the local infrastructure. This article will review the infectious risks that occur as a result of natural disasters, with a focus on the mechanism of disease spread, infectious diseases after specific disasters, and various evidence-based interventions.(Disaster Med Public Health Preparedness. 2010;4:232-238)
Phenotypic spectrum of 20 novel patients with molecularly defined supernumerary marker chromosomes 15 and a review of the literature
Authors: Kleefstra Tjitske , de Leeuw Nicole , Wolf Roy , Nillesen Willy M. , Schobers Gaby , Mieloo Hanneke , Willemsen Marjolein , Perrotta Concetta Simona , Poddighe Pino J. , Feenstra Ilse , Draaisma Jos , van Ravenswaaij‐Arts Conny M.A. 
Published: August 2010

AbstractSupernumerary marker chromosomes (SMC) originating from chromosome 15 are the most common SMCs. They encompass clinically irrelevant SMC(15)s containing only heterochromatin and 15p material, and clinically relevant SMC(15)s that consist of both eu‐ and heterochromatic 15q material. On the basis of size, the clinically relevant SMC(15)s can be subdivided into type A, “large” asymmetric and type B, “small” symmetric SMC(15)s. Type B SMC(15)s contain the triplicated 15pter to BP3 (located at 26.5 Mb) region, while type A SMC(15)s consist of 15pter → BP4(28.5 Mb)::BP5(30.5 Mb) → 15pter. In this study, the clinical and molecular features of 18 patients with A and B SMC(15)s and two patients with a partial trisomy 15q were reviewed. Questionnaires (including Child Behavior Check Lists) were used to assess behavior and developmental features in more detail. The marker size and parental origin were determined by multiplex ligation‐dependent probe amplification (MLPA). Based on the MLPA results, the majority of patients (14/18) had type A SMC(15)s. The phenotype observed did not show significant differences between types A and B SMC(15)s. A high prevalence of autistic‐like behavior, attention problems, aggressive behavior, anxiety, and sleeping problems was reported. Motor and speech development varied extensively among the patients. An association was found between positive seizure history and degree of intellectual disability. © 2010 Wiley‐Liss, Inc.
Noonan syndrome associated with both a new Jnk‐activating familial SOS1 and a de novo RAF1 mutations
Authors: Longoni Mauro , Moncini Silvia , Cisternino Mariangela , Morella Ilaria M. , Ferraiuolo Serena , Russo Silvia , Mannarino Savina , Brazzelli Valeria , Coi Paola , Zippel Renata , Venturin Marco , Riva Paola 
Published: August 2010

AbstractNoonan syndrome is a genetic condition characterized by congenital heart defects, short stature, and characteristic facial features. Familial or de novo mutations in PTPN11, RAF1, SOS1, KRAS, and NRAS are responsible for 60–75% of the cases, thus, additional genes are expected to be involved in the pathogenesis. In addition, the genotype–phenotype correlation has been hindered by the highly variable expressivity of the disease. For all these reasons, expanding the genotyped and clinically evaluated case numbers will benefit the clinical community. A mutation analysis has been performed on RAF1, SOS1, and GRB2, in 24 patients previously found to be negative for PTPN11 and KRAS mutations. We identified four mutations in SOS1 and one in RAF1, while no GRB2 variants have been found. Interestingly, the RAF1 mutation was present in a patient also carrying a newly identified p.R497Q familial SOS1 mutation, segregating with a typical Noonan Syndrome SOS1 cutaneous phenotype. Functional analysis demonstrated that the R497Q SOS1 mutation leads to Jnk activation, but has no effect on the Ras effector Erk1. We propose that this variant might contribute to the onset of the peculiar ectodermal traits displayed by the propositus amidst the more classical Noonan syndrome presentation. To our knowledge, this is the first reported case of a patient harboring mutations in two genes, with an involvement of both Ras and Rac1 pathways, indicating that SOS1 may have a role of modifier gene that might contribute the variable expressivity of the disease, evidencing a genotype–phenotype correlation in the family. © 2010 Wiley‐Liss, Inc.
Mental retardation, growth retardation, unusual nose, and open mouth: An autosomal recessive entity
Authors: Alkuraya Fowzan S. 
Published: August 2010

AbstractIn this paper, I describe the investigations in three members of an extended consanguineous family from Saudi Arabia, in which nine members show severe mental retardation, long eyelashes, high nasal bridge, underdeveloped malae, low hanging columella, thin upper vermillion, and everted lower vermillion, retrognathia, and an open mouth apparently caused by mandibular dentoalveolar protrusion. Pedigree analysis makes it likely that this is an autosomal recessively inherited disorder. A detailed literature search failed to show a similar entity. © 2010 Wiley‐Liss, Inc.