bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation analysis of the WNT4 gene in Han Chinese women with premature ovarian failure
Authors: Chen Beili , Suo Peisu , Wang Binbin , Wang Jing , Yang Lu , Zhou Sirui , Zhu Ying , Ma Xu , Cao Yunxia 
Published: May 2011

Abstract

Background
The WNT4 gene plays an important role in female sex determination and differentiation. It also contributes to maintaining of the ovaries and the survival of follicles.

Methods
We sequenced the coding region and splice sites of WNT4 in 145 Han Chinese women with premature ovarian failure (POF) and 200 healthy controls.

Results
Only one novel variation, in Exon 2 (195C > T), was detected among the women with POF. However, this synonymous variation did not result in a change in amino acid sequence (65 Asp > Asp). No further variants were found in any of the samples.

Conclusion
Although we cannot provide any evidence that it is a possible disease-causing gene, this study is the first attempt to investigate the possible role of WNT4 in Han Chinese women with POF.
Predicting streptococcal pharyngitis in adults in primary care: a systematic review of the diagnostic accuracy of symptoms and signs and validation of the Centor score
Authors: Aalbers Jolien , O'Brien Kirsty K , Chan Wai-Sun , Falk Gavin A , Teljeur Conor , Dimitrov Borislav D , Fahey Tom 
Published: June 2011

AbstractBackgroundStratifying patients with a sore throat into the probability of having an underlying bacterial or viral cause may be helpful in targeting antibiotic treatment. We sought to assess the diagnostic accuracy of signs and symptoms and validate a clinical prediction rule (CPR), the Centor score, for predicting group A β-haemolytic streptococcal (GABHS) pharyngitis in adults (> 14 years of age) presenting with sore throat symptoms.MethodsA systematic literature search was performed up to July 2010. Studies that assessed the diagnostic accuracy of signs and symptoms and/or validated the Centor score were included. For the analysis of the diagnostic accuracy of signs and symptoms and the Centor score, studies were combined using a bivariate random effects model, while for the calibration analysis of the Centor score, a random effects model was used.ResultsA total of 21 studies incorporating 4,839 patients were included in the meta-analysis on diagnostic accuracy of signs and symptoms. The results were heterogeneous and suggest that individual signs and symptoms generate only small shifts in post-test probability (range positive likelihood ratio (+LR) 1.45-2.33, -LR 0.54-0.72). As a decision rule for considering antibiotic prescribing (score ≥ 3), the Centor score has reasonable specificity (0.82, 95% CI 0.72 to 0.88) and a post-test probability of 12% to 40% based on a prior prevalence of 5% to 20%. Pooled calibration shows no significant difference between the numbers of patients predicted and observed to have GABHS pharyngitis across strata of Centor score (0-1 risk ratio (RR) 0.72, 95% CI 0.49 to 1.06; 2-3 RR 0.93, 95% CI 0.73 to 1.17; 4 RR 1.14, 95% CI 0.95 to 1.37).ConclusionsIndividual signs and symptoms are not powerful enough to discriminate GABHS pharyngitis from other types of sore throat. The Centor score is a well calibrated CPR for estimating the probability of GABHS pharyngitis. The Centor score can enhance appropriate prescribing of antibiotics, but should be used with caution in low prevalence settings of GABHS pharyngitis such as primary care.
Autosomal dominant cerebellar ataxia type I: A review of the phenotypic and genotypic characteristics
Authors: Whaley Nathaniel Robb , Fujioka Shinsuke , Wszolek Zbigniew K 
Published: May 2011

Abstract
Type I autosomal dominant cerebellar ataxia (ADCA) is a type of spinocerebellar ataxia (SCA) characterized by ataxia with other neurological signs, including oculomotor disturbances, cognitive deficits, pyramidal and extrapyramidal dysfunction, bulbar, spinal and peripheral nervous system involvement. The global prevalence of this disease is not known. The most common type I ADCA is SCA3 followed by SCA2, SCA1, and SCA8, in descending order. Founder effects no doubt contribute to the variable prevalence between populations. Onset is usually in adulthood but cases of presentation in childhood have been reported. Clinical features vary depending on the SCA subtype but by definition include ataxia associated with other neurological manifestations. The clinical spectrum ranges from pure cerebellar signs to constellations including spinal cord and peripheral nerve disease, cognitive impairment, cerebellar or supranuclear ophthalmologic signs, psychiatric problems, and seizures. Cerebellar ataxia can affect virtually any body part causing movement abnormalities. Gait, truncal, and limb ataxia are often the most obvious cerebellar findings though nystagmus, saccadic abnormalities, and dysarthria are usually associated. To date, 21 subtypes have been identified: SCA1-SCA4, SCA8, SCA10, SCA12-SCA14, SCA15/16, SCA17-SCA23, SCA25, SCA27, SCA28 and dentatorubral pallidoluysian atrophy (DRPLA). Type I ADCA can be further divided based on the proposed pathogenetic mechanism into 3 subclasses: subclass 1 includes type I ADCA caused by CAG repeat expansions such as SCA1-SCA3, SCA17, and DRPLA, subclass 2 includes trinucleotide repeat expansions that fall outside of the protein-coding regions of the disease gene including SCA8, SCA10 and SCA12. Subclass 3 contains disorders caused by specific gene deletions, missense mutation, and nonsense mutation and includes SCA13, SCA14, SCA15/16, SCA27 and SCA28. Diagnosis is based on clinical history, physical examination, genetic molecular testing, and exclusion of other diseases. Differential diagnosis is broad and includes secondary ataxias caused by drug or toxic effects, nutritional deficiencies, endocrinopathies, infections and post-infection states, structural abnormalities, paraneoplastic conditions and certain neurodegenerative disorders. Given the autosomal dominant pattern of inheritance, genetic counseling is essential and best performed in specialized genetic clinics. There are currently no known effective treatments to modify disease progression. Care is therefore supportive. Occupational and physical therapy for gait dysfunction and speech therapy for dysarthria is essential. Prognosis is variable depending on the type of ADCA and even among kindreds.
Improved host defense against septic peritonitis in mice lacking MyD88 and TRIF is linked to a normal interferon response
Authors: Reim Daniel , Rossmann-Bloeck Tanja , Jusek Gabriela , Prazeres da Costa Olivia , Holzmann Bernhard 
Published: June 2011

ABSTRACTThe signaling adapters MyD88 and TRIF are engaged by TLRs and/or receptors of the IL-1 family and are considered important for innate immune responses that combat bacterial infections. Here, the consequences of a combined MyD88 and TRIF deficiency for the innate immune response against severe septic peritonitis was examined. We demonstrate that Myd88−/−;TrifLps2/Lps2 mice had markedly reduced bacterial numbers in the peritoneal cavity and peripheral blood, indicating that bacterial clearance in this model is improved in the absence of MyD88/TRIF signals. Survival of Myd88−/−; TrifLps2/Lps2 mice was improved significantly. The lack of MyD88/TRIF signaling prevented the excessive production of inflammatory cytokines and of IL-10. In contrast, Ifng mRNA was expressed at WT levels, and induction of Ifnb mRNA was reduced only by one-half. Consistent with these findings, numerous IFN-regulated genes, including p47 and p65 GTPases, as well as CXCL10, were expressed in a MyD88/TRIF-independent manner. In support of the in vivo data, Myd88−/−; TrifLps2/Lps2 macrophages stimulated with live intestinal bacteria produced normal amounts of CXCL10. The production of p47 GTPases and CXCL10 in septic peritonitis was found to be dependent on the presence of IFNAR1, but not IFN-γ, indicating a normal induction of the type I IFN response in Myd88−/−;TrifLps2/Lps2 mice, despite attenuated IFN-β production. Together, these results provide evidence that in severe septic peritonitis, the absence of MyD88 and TRIF balances the innate immune response in a favorable manner by attenuating deleterious responses such as excessive cytokine release, while leaving intact protective IFN responses.
Suppressor of cytokine signaling (SOCS)1 is a key determinant of differential macrophage activation and function
Authors: Whyte Claire S , Bishop Eileen T , Rückerl Dominik , Gaspar-Pereira Silvia , Barker Robert N , Allen Judith E , Rees Andrew J , Wilson Heather M 
Published: June 2011

ABSTRACTMacrophages become activated by their environment and develop polarized functions: classically activated (M1) macrophages eliminate pathogens but can cause tissue injury, whereas alternatively activated (M2) macrophages promote healing and repair. Mechanisms directing polarized activation, especially in vivo, are not understood completely, and here, we examined the role of SOCS proteins. M2 macrophages activated in vitro or elicited by implanting mice i.p. with the parasitic nematode Brugia malayi display a selective and IL-4-dependent up-regulation of SOCS1 but not SOCS3. Using siRNA-targeted knockdown in BMDM, we reveal that the enhanced SOCS1 is crucial for IL-4-induced M2 characteristics, including a high arginase I:iNOS activity ratio, suppression of T cell proliferation, attenuated responses to IFN-γ/LPS, and curtailed SOCS3 expression. Importantly, SOCS1 was essential in sustaining the enhanced PI3K activity that drives M2 activation, defining a new regulatory mechanism by which SOCS1 controls M2 polarization. By contrast, for M1 macrophages, SOCS1 was not only an important regulator of proinflammatory mediators (IL-6, IL-12, MHC class II, NO), but critically, for M1, we show that SOCS1 also restricted IL-10 secretion and arginase I activity, which otherwise would limit the efficiency of M1 macrophage proinflammatory responses. Together, our results uncover SOCS1, not only as a feedback inhibitor of inflammation but also as a critical molecular switch that tunes key signaling pathways to effectively program different sides of the macrophage balance.
End-of-life treatment and care: General Medical Council good practice guidance
Authors: Tapley Michael , Jolley David 
Published: May 2011

SummaryThe General Medical Council's guidelines on treatment and care towards the end of life, published in May 2010, contain important guidance for all doctors, including psychiatrists, who care for patients and their families towards the end of life. The document is written in the light of the Mental Capacity Act 2005 and complements existing Good Medical Practice and confidentiality guidelines, also from the General Medical Council. Psychiatrists need to be aware of the communication, legal and ethical issues around end-of-life care, including advance directives and clinically assisted nutrition and hydration. This new guidance is compulsory reading for all psychiatrists.
The adverse consequences of mephedrone use: a case series
Authors: Mackay Kirsty , Taylor Mark , Bajaj Neeraj 
Published: May 2011

Aims and methodMephedrone is a cathinone with amphetamine-like stimulant effects, and is a commonly used recreational drug. The adverse effects of mephedrone use have not been extensively studied. All individuals who self-presented between January and June 2010 to the emergency departments and acute mental health services in Edinburgh and Falkirk with adverse effects of self-reported mephedrone use were identified.ResultsTwenty cases were identified and analysed. Severe agitation was the most common presenting problem (70%), with 40% of individuals developing psychotic symptoms and a further 20% reporting low mood and suicidality. One person died by suicide.Clinical implicationsMephedrone can produce amphetamine-like adverse psychological intoxication effects, particularly in those with a history of mental illness. Clinicians should consider advising patients on the adverse effects of mephedrone, where relevant.
Vaccination With Patient-Specific Tumor-Derived Antigen in First Remission Improves Disease-Free Survival in Follicular Lymphoma
Authors: Schuster Stephen J. , Neelapu Sattva S. , Gause Barry L. , Janik John E. , Muggia Franco M. , Gockerman Jon P. , Winter Jane N. , Flowers Christopher R. , Nikcevich Daniel A. , Sotomayor Eduardo M. , McGaughey Dean S. , Jaffe Elaine S. , Chong Elise A. , Reynolds Craig W. , Berry Donald A. , Santos Carlos F. , Popa Mihaela A. , McCord Amy M. , Kwak Larry W. 
Published: June 2011

PurposeVaccination with hybridoma-derived autologous tumor immunoglobulin (Ig) idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) and administered with granulocyte-monocyte colony-stimulating factor (GM-CSF) induces follicular lymphoma (FL) –specific immune responses. To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial.Patients and MethodsTreatment-naive patients with advanced stage FL achieving complete response (CR) or CR unconfirmed (CRu) after chemotherapy were randomly assigned two to one to receive either Id vaccine (Id-KLH + GM-CSF) or control (KLH + GM-CSF). Primary efficacy end points were disease-free survival (DFS) for all randomly assigned patients and DFS for randomly assigned patients receiving at least one dose of Id vaccine or control.ResultsOf 234 patients enrolled, 177 (81%) achieved CR/CRu after chemotherapy and were randomly assigned. For 177 randomly assigned patients, including 60 patients not vaccinated because of relapse (n = 55) or other reasons (n = 5), median DFS between Id-vaccine and control arms was 23.0 versus 20.6 months, respectively (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.16; P = .256). For 117 patients who received Id vaccine (n = 76) or control (n = 41), median DFS after randomization was 44.2 months for Id-vaccine arm versus 30.6 months for control arm (HR, 0.62; 95% CI, 0.39 to 0.99; P = .047) at median follow-up of 56.6 months (range, 12.6 to 89.3 months). In an unplanned subgroup analysis, median DFS was significantly prolonged for patients receiving IgM-Id (52.9 v 28.7 months; P = .001) but not IgG-Id vaccine (35.1 v 32.4 months; P = .807) compared with isotype-matched control-treated patients.ConclusionVaccination with patient-specific hybridoma-derived Id vaccine after chemotherapy-induced CR/CRu may prolong DFS in patients with FL. Vaccine isotype may affect clinical outcome and explain differing results between this and other controlled Id-vaccine trials.
Too Hot to Handle
Authors: Padoongpatt Tanachai Mark 
Published: June 2011

This article explores the historical roots of the relationship among Thai food, politics, and community formation within the context of global capitalism. It asks why and how Thai food evolved into a powerful community building force for Thai Americans in Los Angeles. Putting the history of Thai Americans in the context of U.S. empire in the Pacific and Southeast Asia, I argue that Thai food is one of the best ways not only to uncover the transnational experiences of Thai Americans but also to understand the way post–World War II U.S. empire has turned foodways into a critical site of racial and ethnic identity formation. Food practices are significant, because they show us that food, as a practice of everyday life, helps people make sense of and imagine their relationship to the world around them. This is an inherently political act.
Drawing from oral histories, Thai- and English-language newspapers, menus, cookbooks, federal and city documents, I discuss the significance of Thai food to Thai Americans in four parts. First, I show how the origins of the Thai culinary scene in Los Angeles spawned not from the arrival of Thai immigrants to U.S. soil but from U.S. intervention in Thailand and the global intensification of tourism during the Cold War. Second, I trace the migration of Thais to Los Angeles and the creation of Thai restaurants as the primary social and community spaces in a period of reindustrialization—or the growth of Los Angeles's service sector economy. Third, I look at how Thai restaurateurs, chefs, and white food critics used Thai food to define the racial, class, and gendered contours of a Thai American identity that was distinct from other Asian groups. Finally, I explain how community leaders tapped into an emerging political discourse of multiculturalism by making Thai food central to Thai American political activism, as well as discuss the limitations of this expression.
Hadp1, a newly identified pleckstrin homology domain protein, is required for cardiac contractility in zebrafish
Authors: Wythe Joshua D. , Jurynec Michael J. , Urness Lisa D. , Jones Christopher A. , Sabeh M. Khaled , Werdich Andreas A. , Sato Mariko , Yost H. Joseph , Grunwald David J. , MacRae Calum A. , Li Dean Y. 
Published: June 2011

SUMMARYThe vertebrate heart is one of the first organs to form, and its early function and morphogenesis are crucial for continued embryonic development. Here we analyze the effects of loss of Heart adaptor protein 1 (Hadp1), which we show is required for normal function and morphogenesis of the embryonic zebrafish heart. Hadp1 is a pleckstrin homology (PH)-domain-containing protein whose expression is enriched in embryonic cardiomyocytes. Knockdown of hadp1 in zebrafish embryos reduced cardiac contractility and altered late myocyte differentiation. By using optical mapping and submaximal levels of hadp1 knockdown, we observed profound effects on Ca2+ handling and on action potential duration in the absence of morphological defects, suggesting that Hadp1 plays a major role in the regulation of intracellular Ca2+ handling in the heart. Hadp1 interacts with phosphatidylinositol 4-phosphate [PI4P; also known as PtdIns(4)P] derivatives via its PH domain, and its subcellular localization is dependent upon this motif. Pharmacological blockade of the synthesis of PI4P derivatives in vivo phenocopied the loss of hadp1 in zebrafish. Collectively, these results demonstrate that hadp1 is required for normal cardiac function and morphogenesis during embryogenesis, and suggest that hadp1 modulates Ca2+ handling in the heart through its interaction with phosphatidylinositols.
Unbound (bioavailable) IGF1 enhances somatic growth
Authors: Elis Sebastien , Wu Yingjie , Courtland Hayden-William , Cannata Dara , Sun Hui , Beth-On Mordechay , Liu Chengyu , Jasper Hector , Domené Horacio , Karabatas Liliana , Guida Clara , Basta-Pljakic Jelena , Cardoso Luis , Rosen Clifford J. , Frystyk Jan , Yakar Shoshana 
Published: June 2011

SUMMARYUnderstanding insulin-like growth factor-1 (IGF1) biology is of particular importance because, apart from its role in mediating growth, it plays key roles in cellular transformation, organ regeneration, immune function, development of the musculoskeletal system and aging. IGF1 bioactivity is modulated by its binding to IGF-binding proteins (IGFBPs) and the acid labile subunit (ALS), which are present in serum and tissues. To determine whether IGF1 binding to IGFBPs is necessary to facilitate normal growth and development, we used a gene-targeting approach and generated two novel knock-in mouse models of mutated IGF1, in which the native Igf1 gene was replaced by Des-Igf1 (KID mice) or R3-Igf1 (KIR mice). The KID and KIR mutant proteins have reduced affinity for the IGFBPs, and therefore present as unbound IGF1, or ‘free IGF1’. We found that both KID and KIR mice have reduced serum IGF1 levels and a concomitant increase in serum growth hormone levels. Ternary complex formation of IGF1 with the IGFBPs and the ALS was markedly reduced in sera from KID and KIR mice compared with wild type. Both mutant mice showed increased body weight, body and bone lengths, and relative lean mass. We found selective organomegaly of the spleen, kidneys and uterus, enhanced mammary gland complexity, and increased skeletal acquisition. The KID and KIR models show unequivocally that IGF1-complex formation with the IGFBPs is fundamental for establishing normal body and organ size, and that uncontrolled IGF bioactivity could lead to pathological conditions.
Combined bound water and water vapour diffusion of Norway spruce and European beech in and between the principal anatomical directions
Authors: Sonderegger Walter , Vecellio Manuele , Zwicker Pascal , Niemz Peter 
Published: June 2011

Abstract
The combined bound water and water vapour diffusion of wood is of great interest in the field of building physics. Due to swelling stresses, the steady-state-determined diffusion coefficient clearly differs from the unsteady-state-determined diffusion coefficient. In this study, both diffusion coefficients and the water vapour resistance factor of Norway spruce (Picea abies [L.] Karst.) and European beech (Fagus sylvatica L.) were investigated for the principal anatomical directions (radial, tangential and longitudinal) and in 15° steps between these directions. The values were determined with the cup method as the basic principle. The unsteady-state-determined diffusion coefficient is, independent of the direction, about half that of the steady-state-determined diffusion coefficient. Both diffusion coefficients are about two to three times higher for spruce than for beech. They are up to 12 times higher in the longitudinal direction than perpendicular to the grain for spruce, and up to 15 times higher for beech. With increasing moisture content, the diffusion coefficients exponentially increase. The water vapour resistance factor shows converse values to the diffusion coefficients.
Time-optimal reconstruction of Riemannian manifold via boundary electromagnetic measurements
Authors: Belishev Mikhail I. , Demchenko Maxim N. 
Published: June 2011

Abstract
A dynamical Maxwell system is et
= curl h, ht
= – curl e in Ω × (0, T), e|
t=0 = 0, h|
t=0 = 0 in Ω, eθ
= ƒ in ∂Ω × [0, T], where Ω is a smooth compact oriented 3-dimensional Riemannian manifold with boundary, (·)
θ
is a tangent component of a vector at the boundary, e = e
ƒ (x, t) and h = h
ƒ (x, t) are the electric and magnetic components of the solution. One associates with this system a response operator RT
: ƒ ↦ ν ∧ h
ƒ|
∂Ω×(0,T), where ν is an outward normal to ∂Ω.
The time-optimal setup of the inverse problem, which is relevant to the finiteness of the wave speed propagation, is as follows: given R
2T
to recover the part Ω
T
≔ {x ∈ Ω| dist(x, ∂Ω) < T} of the manifold. As was shown by Belishev, Isakov, Pestov, Sharafutdinov (Doklady Mathematics 61: 353–356, 2000), for T small enough the operator R
2T
determines Ω
T
uniquely up to isometry.
Here we prove that uniqueness holds for arbitrary T > 0 and provide a procedure that recovers Ω
T
from R
2T
. Our approach is a version of the boundary control method (Belishev, 1986).