bluuebunny/crossref_metadata_2025_split huggingface dataset:
UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development
Authors: Ahmed S. Faisal , Achermann John C. , Arlt Wiebke , Balen Adam H. , Conway Gerry , Edwards Zoe L. , Elford Sue , Hughes Ieuan A. , Izatt Louise , Krone Nils , Miles Harriet L. , O’Toole Stuart , Perry Les , Sanders Caroline , Simmonds Margaret , Wallace A. Michael , Watt Andrew , Willis Debbie 
Published: April 2011

SummaryIt is paramount that any child or adolescent with a suspected disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD. If there is any doubt, the case should be discussed with the regional team. In most cases, particularly in the case of the newborn, the paediatric endocrinologist within the regional DSD team acts as the first point of contact. The underlying pathophysiology of DSD and the strengths and weaknesses of the tests that can be performed should be discussed with the parents and affected young person and tests undertaken in a timely fashion. This clinician should be part of a multidisciplinary team experienced in management of DSD and should ensure that the affected person and parents are as fully informed as possible and have access to specialist psychological support. Finally, in the field of rare conditions, it is imperative that the clinician shares the experience with others through national and international clinical and research collaboration.
Hyper‐activation of the TCP4 transcription factor inArabidopsis thalianaaccelerates multiple aspects of plant maturation
Authors: Sarvepalli Kavitha , Nath Utpal 
Published: April 2011

SummaryPlant organs are initiated as primordial outgrowths, and require controlled cell division and differentiation to achieve their final size and shape. Superimposed on this is another developmental program that orchestrates the switch from vegetative to reproductive to senescence stages in the life cycle. These require sequential function of heterochronic regulators. Little is known regarding the coordination between organ and organismal growth in plants. TheTCPgene family encodes transcription factors that control diverse developmental traits, and a subgroup of class IITCPgenes regulate leaf morphogenesis. Absence of these genes results in large, crinkly leaves due to excess division, mainly at margins. It has been suggested that these class II TCPs modulate the spatio‐temporal control of differentiation in a growing leaf, rather than regulating cell proliferationper se. However, the link between class II TCP action and cell growth has not been established. As loss‐of‐function mutants of individualTCPgenes in Arabidopsis are not very informative due to gene redundancy, we generated a transgenic line that expressed a hyper‐activated form of TCP4 in its endogenous expression domain. This resulted in premature onset of maturation and decreased cell proliferation, leading to much smaller leaves, with cup‐shaped lamina in extreme cases. Further, the transgenic line initiated leaves faster than wild‐type and underwent precocious reproductive maturation due to a shortened adult vegetative phase. Early senescence and severe fertility defects were also observed. Thus, hyper‐activation of TCP4 revealed its role in determining the timing of crucial developmental events, both at the organ and organism level.
LOV KELCH PROTEIN2 and ZEITLUPE repress Arabidopsis photoperiodic flowering under non‐inductive conditions, dependent on FLAVIN‐BINDING KELCH REPEAT F‐BOX1
Authors: Takase Tomoyuki , Nishiyama Yuuki , Tanihigashi Haruna , Ogura Yasunobu , Miyazaki Yuji , Yamada Yumiko , Kiyosue Tomohiro 
Published: April 2011

SummaryLOV KELCH PROTEIN2 (LKP2), ZEITLUPE (ZTL)/LOV KELCH PROTEIN1 (LKP1) and FLAVIN‐BINDING KELCH REPEAT F‐BOX1 (FKF1) constitute a family of Arabidopsis F‐box proteins that regulate the circadian clock. Over‐expression of LKP2 or ZTL causes arrhythmicity of multiple clock outputs under constant light and in constant darkness. Here, we show the significance of LKP2 and ZTL in the photoperiodic control of flowering time in Arabidopsis. In plants over‐expressing LKP2, CO and FT expression was down‐regulated under long‐day conditions. LKP2 and ZTL physically interacted with FKF1, which was recruited from the nucleus into cytosolic speckles. LKP2 and ZTL inhibited the interaction of FKF1 with CYCLING DOF FACTOR 1, a ubiquitination substrate for FKF1 that is localized in the nucleus. The Kelch repeat regions of LKP2 and ZTL were sufficient for their physical interaction with FKF1 and translocation of FKF1 to the cytoplasm. Over‐expression of LKP2 Kelch repeats induced late flowering under long‐day conditions. lkp2 ztl double mutant plants flowered earlier than wild‐type plants under short‐day (non‐inductive) conditions, and both CO and FT expression levels were up‐regulated in the double mutant plants. The early flowering of lkp2 ztl was dependent on FKF1. LKP2, ZTL or both affected the accumulation of FKF1 protein during the early light period. These results indicate that an important role of LKP2 and ZTL in the photoperiodic pathway is repression of flowering under non‐inductive conditions, and this is dependent on FKF1.
Clinical features and prognosis of early colorectal cancer treated by endoscopic mucosal resection
Authors: Kim Mi Na , Kang Jung Mook , Yang Jong In , Kim Byoung Kwon , Im Jong Pil , Kim Sang Gyun , Jung Hyun Chae , Song In Sung , Kim Joo Sung 
Published: April 2011

AbstractBackground and Aims:  The incidence of early colorectal cancer (ECC) has been increasing. The aim of this study was to evaluate the clinical outcome and prognosis of ECC treated by endoscopic mucosal resection (EMR).Methods:  A total of 129 ECC patients who were initially treated by EMR between April 2005 and August 2007 were enrolled. Clinicopathological characteristics and prognoses were evaluated retrospectively.Results:  En bloc resection was performed in 85% of ECC patients, and piecemeal resection was performed in 15% of patients. Clear lateral and deep margins were achieved in 86% of cases. Of the 129 patients, 64 were found to have intramucosal cancer and 65 had submucosal cancer. Clinical characteristics were not different between patients with intramucosal cancer and submucosal cancer; however, poor differentiation and the absence of background adenoma showed significant association with submucosal cancer. Seven patients with submucosal cancer underwent subsequent surgical resection; five had lymphovascular invasion or a positive resection margin, one had perforation, and one patient requested surgical resection. Of these seven patients, one had residual cancer and two had lymph node metastasis. All patients with intramucosal cancer had no recurrence during the follow‐up period. Seven patients with submucosal cancer showed adverse outcomes within 3 years, such as residual/recurrence of primary cancer or lymph node metastasis; five showed lymphovascular invasion or a positive deep margin, and two had no histological risk factors.Conclusions:  Our results suggest that intramucosal cancer shows good prognosis, and a cure could be expected after EMR; however, adverse outcomes can occur in submucosal cancer. Therefore, meticulous endoscopic follow up is needed in patients with submucosal cancer for at least 3 years after EMR.
Prevalence of gastroesophageal reflux disease in a general population in Taiwan
Authors: Hung Li‐Ju , Hsu Ping‐I , Yang Chun‐Yuh , Wang E‐Ming , Lai Kwok‐Hung 
Published: April 2011

AbstractBackground and Aim:  To evaluate the prevalence and risk factors of gastroesophageal reflux disease (GERD) in a general population in Taiwan.Methods:  A validated symptom questionnaire, the Chinese GERD questionnaire, was utilized to determine the prevalence of GERD within a community in Taiwan. A cut‐off value for GERD diagnosis was a total score ≥12. Additionally, demographic data, including sex, age, body mass index, and consumption of tobacco and alcohol, were recorded, and a logistic regression analysis was conducted to search the independent risk factors for the development of GERD in a general population.Results:  In total, 1238 residents were recruited for this study. The monthly frequencies of heartburn, epigastric acidic discomfort, and acid regurgitation were 4.4%, 3.7%, and 2.9%, respectively. The GERD prevalence was 25% in the community. The multivariate analysis showed that female sex and age of 40–49 years and 50–59 years were independent risk factors related to the development of GERD, with odd ratios of 1.71, 3.65, and 2.41, respectively (95% confidence intervals: 1.26–2.34, 1.62–8.21, and 1.11–2.54, respectively).Conclusions:  GERD has become a common disorder in the general population in Taiwan. Female sex and age of 40–49 years and 50–59 years are risk factors for the development of GERD within a community.
Survival of patients with advanced hepatocellular carcinoma: Sorafenib versus other treatments
Authors: Kim Hwi Young , Park Joong‐Won , Nam Byung‐Ho , Kim Hyun Keun , Choi Joon‐Il , Kim Tae Hyun , Kim Hyun Beom , Kim Chang‐Min 
Published: April 2011

AbstractBackground and Aim:  Although sorafenib is recommended for patients with advanced hepatocellular carcinoma (HCC), a substantial portion of HCC patients in Asia are still treated with other treatments, mainly due to the prohibitive cost of sorafenib. We aimed to evaluate the clinical outcome of patients treated with sorafenib and those treated with other modalities in a single‐center cohort.Methods:  We reviewed the medical records of two groups of consecutive patients with advanced HCC, according to applied treatment modalities, between January 2007 and September 2009 as follows: patients who received sorafenib for 6 weeks or more (n = 123) and patients who were treated with one or more of other treatments, including transarterial chemoembolization, radiation, and cytotoxic chemotherapy (n = 253).Results:  Overall survival did not differ significantly between these two groups (8.4 vs 8.2 months; P = 0.601). Significant prognostic factors were high α‐fetoprotein (≥ 200 ng/mL), massive/infiltrative intrahepatic tumors, macrovascular invasion, extrahepatic spread, and higher tumor‐node‐metastasis stage. Subgroup analysis, according to these factors, showed that sorafenib resulted in superior survival in patients with extrahepatic spread (hazard ratio [HR] = 0.539; P = 0.003) and massive/infiltrative tumors (HR = 0.680; P = 0.036). In the absence of each prognostic factor, other treatments were better than sorafenib.Conclusions:  Considering the survival benefit for sorafenib over other treatments in patients with extrahepatic spread and massive/infiltrative intrahepatic tumors, these characteristics might be regarded as compelling indications for sorafenib.
Clinical significance of normal chest radiographs among HIV‐seropositive patients with suspected tuberculosis in Uganda
Authors: YOO SAMUEL D. , CATTAMANCHI ADITHYA , DEN BOON SASKIA , WORODRIA WILLIAM , KISEMBO HARRIET , HUANG LAURENCE , DAVIS J. LUCIAN 
Published: April 2011

ABSTRACTBackground and objective:  The frequency, aetiologies and outcomes of normal chest radiographs (CXRs) among HIV‐seropositive patients with suspected pulmonary tuberculosis (TB) have been infrequently described.Methods:  Consecutive HIV‐seropositive adults hospitalized for cough of ≥2 weeks duration at Mulago Hospital (Kampala, Uganda), between September 2007 and July 2008, were enrolled. Baseline CXRs were obtained on admission. Patients with sputum smears that were negative for acid‐fast bacilli (AFB) were referred for bronchoscopy with bronchoalveolar lavage (BAL). BAL fluid was examined for mycobacteria, Pneumocystis jirovecii and other fungi. Patients were followed for 2 months after enrolment.Results:  Of the 334 patients, 54 (16%) had normal CXRs. These patients were younger (median age 30 vs 34 years, P = 0.002), had lower counts of CD4+ T lymphocytes (median 13 vs 57 cells/µL, P < 0.001), and were less likely to be smear positive for AFB (17% vs 39%, P = 0.002) than those with abnormal CXRs. Pulmonary TB was the most frequent diagnosis (44%) among those with normal CXRs, followed by unknown diagnoses, pulmonary aspergillosis and pulmonary cryptococcosis. The frequency of normal CXRs was 12% among pulmonary TB patients. There was a trend towards increased 2‐month mortality among patients with normal CXRs compared to those with abnormal CXRs (40% vs 29%, P = 0.15).Conclusions:  Normal CXR findings were common among HIV‐seropositive patients with suspected TB, especially those who were young, those with low CD4+ T cell counts and those with sputum smears that were negative for AFB. Mortality was high among those with normal CXRs. Normal CXR findings should not preclude further diagnostic evaluation in this population.
Prevalence of Type 1 diabetes autoantibodies (GAD and IA2) in Sardinian children and adolescents with autoimmune thyroiditis
Authors: Pilia S. , Casini M. R. , Cambuli V. M. , Ibba A. , Civolani P. , Zavattari P. , Incani M. , Mossa P. , Baroni M. G. , Mariotti S. , Loche S. 
Published: April 2011

Diabet. Med. 28, 896–899 (2011)AbstractAims  Type 1 diabetes and autoimmune thyroiditis are common autoimmune diseases characterized by the presence of autoantibodies against tissue‐specific components. Non‐thyroid‐specific autoantibodies are frequent in patients with autoimmune thyroiditis. The prevalence of Type 1 diabetes autoantibodies in patients with autoimmune thyroiditis is unknown.Methods  The prevalence of Type 1 diabetes autoantibodies (GAD and IA2) was analysed in 236 Sardinian children and adolescents with autoimmune thyroiditis. GAD and IA2 antibodies were measured at the time of the diagnosis of autoimmune thyroiditis and re‐evaluated after 1 year in the children who were shown to be positive. Autoantibody prevalence was evaluated in 949 healthy age‐matched controls.Results  The prevalence of GAD and/or IA2 antibodies was 8% in the children and adolescents with autoimmune thyroiditis and 4.1% in control subjects (P = 0.017). When Type 1 diabetes autoantibodies were separately analysed, the difference remained significant for IA2 (3.39% in autoimmune thyroiditis vs. 1.16% in control subjects, P = 0.012), but not for GAD (5.1% in autoimmune thyroiditis vs. 3.79% in control subjects, P = 0.367). Seven of 10 children with autoimmune thyroiditis and detectable Type 1 diabetes autoantibodies at the diagnosis remained positive after 1 year. In the course of 2 years of follow‐up, two patients who were positive for Type 1 diabetes autoantibodies at the time of diagnosis of autoimmune thyroiditis developed diabetes.Conclusions  This is the first study reporting the prevalence of Type 1 diabetes autoantibodies in a selected cohort of genetically homogeneous children and adolescents with autoimmune thyroiditis. The main finding was that the prevalence of Type 1 diabetes autoantibodies and of newly diagnosed Type 1 diabetes in patients with autoimmune thyroiditis was significantly higher than that observed in the general paediatric population, suggesting that children with autoimmune thyroiditis are at increased risk of developing Type 1 diabetes.
The Finnish Diabetes Risk Score is associated with insulin resistance but not reduced β‐cell function, by classical and model‐based estimates
Authors: Brodovicz K. G. , Dekker J. M. , Rijkelijkhuizen J.M. , Rhodes T. , Mari A. , Alssema M. , Nijpels G. , Williams‐Herman D.E. , Girman C. J. 
Published: April 2011

Diabet. Med. 28, 1078–1081 (2011)AbstractAims  The Finnish Diabetes Risk Score (FINDRISC) is widely used for risk stratification in Type 2 diabetes prevention programmes. Estimates of β‐cell function vary widely in people without diabetes and reduced insulin secretion has been described in people at risk for diabetes. The aim of this analysis was to evaluate FINDRISC as a tool to characterize reduced β‐cell function in individuals without known diabetes.Methods  In this population‐based cohort from the Hoorn municipal registry, subjects received an oral glucose tolerance test and a meal tolerance test on separate days, in random order, within 2 weeks. One hundred and eighty‐six subjects, age 41–66 years, with no known Type 2 diabetes were included. Of those, 163 (87.6%) had normal glucose metabolism and 23 (12.4%) had abnormal glucose metabolism (19 with impaired glucose metabolism; four with newly diagnosed Type 2 diabetes based on study results). Insulin sensitivity and β‐cell function (classical: insulinogenic index; ratio of areas under insulin/glucose curves; model‐based: glucose sensitivity; rate sensitivity; potentiation) estimates were calculated from oral glucose tolerance test and meal tolerance test data.Results  FINDRISC was associated with insulin sensitivity (r = −0.41, P < 0.0001), insulin/glucose areas under the curve (meal tolerance test: r = 0.29, P < 0.0001; oral glucose tolerance test: r = 0.21, P = 0.01) and potentiation factor (meal tolerance test: r = 0.21, P = 0.01). After adjusting for insulin sensitivity, these associations with β‐cell function were no longer significant.Conclusions  After adjustment for insulin sensitivity, FINDRISC was not associated with reduced β‐cell function in subjects without known Type 2 diabetes. While insulin secretion and insulin sensitivity are both components in Type 2 diabetes development, insulin sensitivity appears to be the dominant component behind the association between FINDRISC and diabetes risk.
HbA1c in adults without known diabetes from southern Europe. Impact of the new diagnostic criteria in clinical practice
Authors: Bernal‐Lopez M. R. , Santamaría‐Fernandez S. , Lopez‐Carmona D. , Tinahones F. J. , Mancera‐Romero J. , Peña‐Jimenez D. , Jansen‐Chaparro S. , Baca‐Osorio A. J. , Cuesta‐Muñoz A. L. , Serrano‐Rios M. , Gomez‐Huelgas R. 
Published: April 2011

Diabet. Med. 28, 1319–1322 (2011)AbstractAims  To analyse the differences in the prevalence of diabetes and dysglycaemia using fasting plasma glucose and HbA1c criteria.Methods  Analytical cross‐sectional study undertaken in a random sample of 2144 individuals (age 18–80 years) without known diabetes from the primary care setting in Malaga (Spain). Dysglycaemia was defined as fasting plasma glucose 5.6–6.9 mmol/l or HbA1c 39–46 mmol/mol (5.7–6.4%) and diabetes as fasting plasma glucose ≥ 7.0 mmol/l or HbA1c≥ 48 mmol/mol (≥ 6.5%).Results  The proportion of subjects who were normoglycaemic was significantly higher using fasting plasma glucose than HbA1c (83.5 vs. 65%) (P < 0.0001). Compared with fasting plasma glucose, HbA1c detects more cases of dysglycaemia (32 vs. 14.8%) (P < 0.0001) and diabetes (3 vs. 1.7%) (P < 0.0001).Conclusions  In our environment, using HbA1c for the diagnosis of pre‐diabetes and diabetes could increase the target population for preventive and therapeutic measures. Further cost‐effectiveness studies are needed before the widespread diagnostic use of HbA1c can be recommended.
Circulating LL‐37 is a biomarker for eczema severity in children
Authors: Leung T.F. , Ching K.W. , Kong A.P.S. , Wong G.W.K. , Chan J.C.N. , Hon K.L. 
Published: April 2011

AbstractBackground  Eczema lesions are characterized by impaired expression of antimicrobial peptides such as cathelicidin, which play crucial roles in the innate immune defence against cutaneous infections. LL‐37 corresponds to amino acids 134–170 of human cathelicidin and is a multifunctional host defence molecule essential for normal immune responses to infection and tissue injury.Objectives  The aim of this study was to investigate the relationship between childhood eczema and circulating LL‐37 levels.Methods  One hundred and forty‐four eczema children and 36 controls were recruited. Eczema severity was assessed by SCORing Atopic Dermatitis (SCORAD) and serum LL‐37 concentration measured using enzyme immunoassay. Patients’ skin hydration and transepidermal water loss at forearms were measured using Corneometer and Tewameter.Results  Patients’ mean SCORAD was 49.2 and their disease was classified as mild (n = 28; 12.8%), moderate (n = 95; 43.6%) and severe (n = 95; 43.6%). Serum LL‐37 concentrations did not differ between eczema patients and controls (mean: 832 pg/mL vs. 952 pg/mL, P = 0.471). However, serum LL‐37 concentrations increased with increasing eczema severity among the patients (P = 0.005 for trend). This biomarker shows weakly positive correlation with patients’ objective SCORAD (r = 0.207, P = 0.013) and age (r = 0.170, P = 0.041), but not skin hydration or transepidermal water loss (P > 0.09). Linear regression confirmed significant association between objective SCORAD and serum LL‐37 when adjusted for age and gender as covariates (β = 0.171, P = 0.038). On the other hand, serum LL‐37 did not differ between patients with and without heavy growth of staphylococci (P = 0.151).Conclusions  Circulating LL‐37 may be a biomarker for severity of childhood eczema, which supports the importance of innate immunity in eczema pathogenesis.
HNA‐3a–specific antibodies recognize choline transporter–like protein‐2 peptides containing arginine, but not glutamine at Position 154
Authors: Curtis Brian R. , Sullivan Mia J. , Holyst M. Trudy , Szabo Aniko , Bougie Daniel W. , Aster Richard H. 
Published: April 2011

BACKGROUND: Antibodies specific for the neutrophil antigen HNA‐3a cause severe, sometimes fatal transfusion‐related acute lung disease (TRALI) when transfused, but it has not been possible to screen blood donors for anti‐HNA‐3a because using neutrophils as targets was impractical and molecular properties of the antigen were unknown. Recently it was shown that HNA‐3a is carried on choline transporter–like protein‐2 (CTL2) and that the HNA‐3a/b phenotype is closely correlated with an R154Q amino acid polymorphism in CTL2. However, it has not been shown by direct experiment that R154 is essential for the HNA‐3a epitope.STUDY DESIGN AND METHODS: Preliminary attempts to express recombinant full‐length CTL2 (R154) recognized by anti‐HNA‐3a were unsuccessful. We therefore tested HNA‐3a–specific antibodies from donors implicated in TRALI reactions for reactivity against chemically synthesized linear and cyclic CTL2 peptides containing R154 or Q154.RESULTS: Nine of 20 HNA‐3a antibodies recognized the R154, but not the Q154 version of a cyclic 36‐residue CTL2 peptide (D131‐K166). However, 11 others failed to distinguish between the two versions of this peptide.CONCLUSION: The findings provide direct evidence that R154 in the context of CTL2 D131‐K166 is necessary to create the HNA‐3a epitope but, in the context of cyclic CTL2 peptide D131‐K166, is sufficient to detect only about one‐half of the HNA‐3a–specific antibodies implicated in TRALI. It is likely that fragments of CTL2 longer than can be made on a large scale with an automated synthesizer will be needed to produce a target capable of detecting all examples of anti‐HNA‐3a in donated blood.