bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss-of-Function Mutation of REDUCED WALL ACETYLATION2 in Arabidopsis Leads to Reduced Cell Wall Acetylation and Increased Resistance to Botrytis cinerea
Authors: Manabe Yuzuki , Nafisi Majse , Verhertbruggen Yves , Orfila Caroline , Gille Sascha , Rautengarten Carsten , Cherk Candice , Marcus Susan E. , Somerville Shauna , Pauly Markus , Knox J. Paul , Sakuragi Yumiko , Scheller Henrik Vibe 
Published: January 2011

Abstract
Nearly all polysaccharides in plant cell walls are O-acetylated, including the various pectic polysaccharides and the hemicelluloses xylan, mannan, and xyloglucan. However, the enzymes involved in the polysaccharide acetylation have not been identified. While the role of polysaccharide acetylation in vivo is unclear, it is known to reduce biofuel yield from lignocellulosic biomass by the inhibition of microorganisms used for fermentation. We have analyzed four Arabidopsis (Arabidopsis thaliana) homologs of the protein Cas1p known to be involved in polysaccharide O-acetylation in Cryptococcus neoformans. Loss-of-function mutants in one of the genes, designated REDUCED WALL ACETYLATION2 (RWA2), had decreased levels of acetylated cell wall polymers. Cell wall material isolated from mutant leaves and treated with alkali released about 20% lower amounts of acetic acid when compared with the wild type. The same level of acetate deficiency was found in several pectic polymers and in xyloglucan. Thus, the rwa2 mutations affect different polymers to the same extent. There were no obvious morphological or growth differences observed between the wild type and rwa2 mutants. However, both alleles of rwa2 displayed increased tolerance toward the necrotrophic fungal pathogen Botrytis cinerea.
Clinical presentation, evolution, and prognosis of precursor B‐cell lymphoblastic lymphoma in trials LMT96, EORTC 58881, and EORTC 58951
Authors: Ducassou Stéphane , Ferlay Céline , Bergeron Christophe , Girard Sandrine , Laureys Geneviève , Pacquement Hélène , Plantaz Dominique , Lutz Patrick , Vannier Jean‐Pierre , Uyttebroeck Anna , Bertrand Yves 
Published: January 2011

SummaryIn children, lymphoblastic lymphomas represent 30% of Non‐Hodgkin lymphomas (NHL), and approximately 15% are precursor B‐cell lymphomas (PBLL). Our study evaluated their main clinical characteristics, evolution, and prognosis in three trials. From 1989 to 2008, 53 children with PBLL (median age 7·75 years) were included in three protocols: Malignant Lymphoma Therapy (LMT) 96, European Organization for Research and Treatment of Cancer (EORTC) 58881, and EORTC 58951 using Berlin‐Frankfürt‐Münster‐derived acute lymphoblastic leukaemia (ALL) therapy. There were 10 stage I disease, 9 stage II, 9 stage III and 25 stage IV. Clinical presentation was heterogeneous with a majority of bone lesions and cutaneous or subcutaneous manifestations. At diagnosis 23 patients had bone marrow involvement, and only three had central nervous system involvement. The median follow‐up was 74 months. At last follow‐up, 45 patients were in continuous complete remission, whereas eight had progressed or had relapsed (7 Stages IV and 1 Stage III) and died. Two patients had a secondary neoplasia, and are still alive. Disease stage was a major prognostic factor, with better overall survival (OS) and event‐free survival (EFS) (P < 0·05) rates observed in patients with Stage I to III as compared to those with Stage IV. Treatment with protocols derived from ALL therapy are efficient with an 82% EFS and an 85% OS at 5 years.
Improving the quality of general surgical operation notes in accordance with the Royal College of Surgeons guidelines: a prospective completed audit loop study
Authors: Singh Rahul , Chauhan Robert , Anwar Suhail 
Published: January 2011

AbstractAims and objectives  Accurate documentation of surgical operation notes is crucial as it facilitates the post‐operative management of the patients. It also serves as an important medico‐legal document for any discrepancies or disputes. The objectives of this study were twofold: to compare operation note documentation against guidelines published in Good Surgical Practice by the Royal College of Surgeons of England (RCS Eng), 2008, and to improve adherence to these guidelines, through educating surgeons and the introduction of theatre aide‐memoires.Method  We prospectively identified 100 general surgical patients operated between February 2010 and July 2010. Equal numbers of upper gastroenterology, colorectal and vascular patients were selected. We audited operation note documentation against the RCS Eng guidelines. Our findings were presented at the trust clinical governance meeting. Areas with deficient documentation were highlighted. In addition to educating surgeons, aide‐memoires were subsequently introduced in the operating theatres and our practice was re‐audited.Results  A total of 18 RCS Eng guidelines were identified and audited. The first audit cycle revealed poor areas in documentation of ‘emergency/elective procedure’ (36%), ‘time of operation’ (36%), ‘date of operation’ (87%), ‘assistant’ (87%) and ‘post‐operative management’ (88%). After educating surgeons and introducing aide‐memoires in theatres, the results were re‐audited with an equal number of patients. The re‐audit demonstrated a clear improvement in four out of five deficient areas with compliance reaching almost up to 100%.Conclusion  Operation note documentation is of paramount importance, it has medical and legal implications. Educating surgeons and providing aide‐memoires in theatres clearly improved documentation of operation notes in compliance with the RCS Eng guidelines.
How to improve specific databases for clinical data in rare diseases? The example of hereditary haemorrhagic telangiectasia
Authors: Decullier Evelyne , Dupuis‐Girod Sophie , Plauchu Henri , Perret Jacques , Chapuis François 
Published: January 2011

AbstractIntroduction  The objectives of reference centres for rare diseases are multiple and mainly concern disease management and coordination between specialties, but they also have to improve knowledge through epidemiological studies and biomedical research. A first database was created by the hereditary haemorrhagic telangiectasia network to achieve these objectives, but facing a lack of data entered in the first database, we established a new database, named CIROCO (Clinical Investigation for the Rendu‐Osler Cohort). This new database was constructed after the first database assessment.Methods  We listed all difficulties encountered in the first database. We focused on three themes: database technical characteristics, database design (the number and characteristics of variables and the overall structure) and data entry. Based on this expertise, we defined the characteristics that should lead to an optimization of the database. We then compared the performance of these databases in terms of available data.Results  The first database had 1273 fields spread out on 14 forms. A total of 838 patients was entered from 2001 to 2005 and among the 1273 fields, 205 (16%) had no data at all. The new database gathered 362 fields from the first database and 173 new fields. These fields were rearranged into 443 variables. A total of 1410 patients directly seen by the clinicians were entered. For patients seen by clinicians each variable used for defining the disease was available for at least 93% of patients.Conclusion  Items to be included in a specific database should be carefully selected in order to achieve good results and an epidemiological utility.
Behavioural and emotional problems in people with severe and profound intellectual disability
Authors: Forster S. , Gray K. M. , Taffe J. , Einfeld S. L. , Tonge B. J. 
Published: January 2011

AbstractBackground  People with severe and profound levels of intellectual disability (ID) are frequently examined as a single group in research. However, these two groups may be significantly different, particularly in the area of emotional and behavioural difficulties.Method  The Developmental Behaviour Checklist (DBC) was completed by parents and caregivers of 107 people with severe ID and 22 people with profound ID at four time periods across 12 years. Regression analyses were used to examine trends in sub‐scale scores across time and groups.Results  Significant differences between the groups of people with severe and profound ID were found. People with profound ID had significantly lower scores across all sub‐scales except Social Relating. This was usually related to fewer items being selected as present for people with profound ID, as opposed to the scores being attributable to lower item severity scores.Conclusions  There are significant differences between groups of people with severe and profound ID in scores on the DBC, indicating differences in behavioural and emotional problems. Caution should be exercised by researchers treating these two disparate groups as a single group, and by practitioners translating such findings into practice.
Increase of weakly acidic gas esophagopharyngeal reflux (EPR) and swallowing‐induced acidic/weakly acidic EPR in patients with chronic cough responding to proton pump inhibitors
Authors: Kawamura O. , Shimoyama Y. , Hosaka H. , Kuribayashi S. , Maeda M. , Nagoshi A. , Zai H. , Kusano M. 
Published: January 2011

AbstractBackground  Gastro‐esophageal reflux disease (GERD)‐related chronic cough (CC) may have multifactorial causes. To clarify the characteristics of esophagopharyngeal reflux (EPR) events in CC patients whose cough was apparently influenced by gastro‐esophageal reflux (GER), we studied patients with CC clearly responding to full‐dose proton pump inhibitor (PPI) therapy (CC patients).Methods  Ten CC patients, 10 GERD patients, and 10 healthy controls underwent 24‐h ambulatory pharyngo‐esophageal impedance and pH monitoring. Weakly acidic reflux was defined as a decrease of pH by >1 unit with a nadir pH >4. In six CC patients, monitoring was repeated after 8 weeks of PPI therapy. The number of each EPR event and the symptom association probability (SAP) were calculated. Symptoms were evaluated by a validated GERD symptom questionnaire.Key Results  Weakly acidic gas EPR and swallowing‐induced acidic/weakly acidic EPR only occurred in CC patients, and the numbers of such events was significantly higher in the CC group than in the other two groups (P < 0.05, respectively). Symptom association probability analysis revealed a positive association between GER and cough in three CC patients. Proton pump inhibitor therapy abolished swallowing‐induced acidic/weakly acidic EPR, reduced weakly acidic gas EPR, and improved symptoms (all P < 0.05).Conclusions & Inferences  Most patients with CC responding to PPI therapy had weakly acidic gas EPR and swallowing‐induced acidic/weakly acidic EPR. A direct effect of acidic mist or liquid refluxing into the pharynx may contribute to chronic cough, while cough may also arise indirectly from reflux via a vago‐vagal reflex in some patients.
Intimate Adherence by Enteropathogenic Escherichia coli Modulates TLR5 Localization and Proinflammatory Host Response in Intestinal Epithelial Cells
Authors: Salazar‐Gonzalez H. , Navarro‐Garcia F. 
Published: January 2011

AbstractEnteropathogenic Escherichia coli (EPEC) causes diarrhoeal disease by altering enterocyte physiology and producing mucosal inflammation. Many details concerning the host response against EPEC remain unknown. We evaluated the role of EPEC virulence factors on the inflammatory response through an analysis of bacterial recognition, cell signalling, and cytokine production using an in vitro epithelial cell infection model. Interestingly, we found that EPEC infection recruits Toll‐like receptor 5 (TLR5) to the cell surface. We confirmed that type 3 secretion system (T3SS) and flagellin (FliC) are necessary for efficient extracellular regulated kinases 1 and 2 (ERK1/2) activation and found that intimin could down‐regulate this pathway. Besides flagellin, intimin was required to keep nuclear factor kappa B (NF‐κB) activated during infection. EPEC infection activated tumour necrosis factor alpha (TNF‐α) production and induced interleukin (IL)‐1β and IL‐8 release. Virulence factors such as intimin, T3SS, EspA and fliC were required for IL‐1β secretion, whereas intimin and T3SS participated in IL‐8 release. Flagellin was essential for late secretion of TNF‐α and IL‐8 and intimin stimulated cytokine secretion. Initial adherence limited TNF‐α release, whereas late attachment sustained TNF‐α secretion. We conclude that intimin modulates TLR5 activation and intimate adherence alters the proinflammatory response.
Exposure to Mycobacterium avium Decreases the Protective Effect of the DNA Vaccine pVAXhsp65 Against Mycobacterium tuberculosis‐Induced Inflammation of the Pulmonary Parenchyma
Authors: Martins D. R. , Pelizon A. C. , Zorzella‐Pezavento S. F. G. , Seger J. , Santos Junior R. R. , Fonseca D. M. , Justulin Jr L. A. , Silva C. L. , Sartori A. 
Published: January 2011

AbstractThis work investigated the effect of previous Mycobacterium avium exposure on the protective ability of the DNA vaccine pVAXhsp65 against inflammation in the pulmonary parenchyma. BALB/c mice were presensitized with heat‐killed M. avium and then immunized with three doses of pVAXhsp65 prior to challenge with Mycobacterium tuberculosis. M. avium sensitization induced high levels of spontaneous IL‐5 production that were concomitant with a positive delayed‐type hypersensitivity reaction; antigen‐specific IFN‐γ production was also observed upon splenocyte stimulation. Prior exposure to M. avium resulted in altered cytokine and antibody production induced by immunization with pVAXhsp65; instead of a Th1 response, vaccinated mice previously exposed to M. avium developed a strong Th2 response. This switch to a Th2 response coincided with the loss of the anti‐inflammatory effect of pVAXhsp65 vaccination previously observed in the pulmonary parenchyma of mice infected with M. tuberculosis. These results suggest that exposure to environmental mycobacteria can modulate immune responses induced by mycobacterial vaccines other than bacillus Calmette–Guérin.
Influences of increased levels of biotin, zinc or mannan‐oligosaccharides in the diet on foot pad dermatitis in growing turkeys housed on dry and wet litter
Authors: Youssef I. M. I. , Beineke A. , Rohn K. , Kamphues J. 
Published: January 2011

SummaryFoot pad dermatitis (FPD) is very common in turkeys and it is an animal health and welfare issue affecting not only performance and walking ability but also the carcass quality. Thus, there is a great need to find out the preventive measures against this problem. The potential roles of extra dietary biotin, Zn and mannan‐oligosaccharides (MOS) in preventing the development of FPD were assessed in this study which was conducted on 2‐week‐old female turkeys over a period of 4 weeks. The birds were allotted to four groups, with 29 each, and housed on dry wood shavings in floor pens. The turkeys were fed a control (300 μg biotin and 50 mg Zn/kg), high biotin (2000 μg/kg), high Zn (150 mg/kg) or MOS (1%) diet. Half of the turkeys in each group were additionally exposed to wet litter (27% DM) for 8 h daily in adjacent separate boxes. Foot pads of the birds were examined on days 0, 7, 14, 21 and 28 and assessed macroscopically and histopathologically for foot pad lesions. High dietary levels of biotin or Zn significantly reduced the severity of FPD on dry litter (score 1 vs. 2 in control) but not on wet litter. However, MOS did not affect the severity of foot pad lesions either on dry or wet litter. In addition, the severity was overall substantially higher on wet (approximately three times) than on dry litter. The present results suggest that adding high levels of biotin or Zn to the diet could reduce the development and severity of FPD on dry litter but without having any preventive effects on wet litter. Finally, the high litter moisture appears to be the major factor resulting in FPD. Therefore, the litter should be maintained dry to minimize the prevalence and severity of FPD in turkeys.
The clinical implications of hepatitis B virus genotype: Recent advances
Authors: Lin Chih‐Lin , Kao Jia‐Horng 
Published: January 2011

AbstractOutcomes of chronic hepatitis B virus (HBV) infection are heterogeneous. Estimates of annual incidence of cirrhosis and hepatocellular carcinoma (HCC) are 2–10% and 1–3%, respectively. Several viral factors, including HBV genotype, viral load and specific viral mutations, have been associated with disease progression. Among these, HBV genotype is not only predictive of clinical outcomes but has also been associated with response to interferon treatment. Currently, at least 10 HBV genotypes and several subtypes have been identified; they have distinct geographic distribution. Acute infection with genotypes A and D results in higher rates of chronicity than genotypes B and C. Compared to genotype A and B cases, patients with genotypes C and D have lower rates of spontaneous hepatitis B e antigen (HBeAg) seroconversion; when this occurs, it tends to be delayed. HBV genotype C has a higher frequency of basal core promoter (BCP) A1762T/G1764A mutation, pre‐S deletion and is associated with higher viral load than genotype B. Similarly, genotype D has a higher prevalence of BCP A1762T/G1764A mutation than genotype A. These observations suggest important pathogenic differences between HBV genotypes. These may contribute to more severe liver disease, including cirrhosis and HCC with genotypes C and D HBV infection. In addition, genotype A and B patients have better responses to interferon‐based therapy than genotypes C and D, but there are few consistent differences for direct HBV antivirals. In conclusion, genotyping of chronic HBV infections can help practicing physicians identify those at risk of disease progression and determine optimal anti‐viral therapy.
Treatment of chronic hepatitis B: Evolution over two decades
Authors: Yuen Man‐Fung , Lai Ching‐Lung 
Published: January 2011

AbstractThere has been a recent paradigm shift in the indications and endpoints of treatment for chronic hepatitis B (CHB). Hepatitis B e antigen (HBeAg)‐negative disease is being increasingly recognized. Antiviral treatment for both HBeAg‐positive and HBeAg‐negative patients should aim at long‐term suppression of HBV DNA, with the ultimate ideal endpoint of hepatitis B surface antigen (HBsAg) seroconversion. Conventional interferon alpha (IFN‐α), the only agent licensed in 1991, has been superseded by pegylated IFN‐α. HBeAg seroconversion using pegylated IFN‐α is 33%, with only 25% of HBeAg‐positive patients achieving undetectable HBV DNA by polymerase chain reaction (PCR) assay. Five nucleoside/nucleotide analogues have been licensed since 1998. Lamivudine, an L‐nucleoside, is limited by the development of resistance in 76% of patients after 5 years of therapy. Telbivudine, another L‐nucleoside, is more potent than lamivudine but resistance still develops in 25% of HBeAg‐positive and 11% HBeAg‐negative patients after 2 years. Adefovir, an acyclic phosphonate, is relatively weak, but is effective against lamivudine‐ and telbivudine‐ resistant mutations, for which it should be used in combination (add‐on therapy) rather than substituted. Resistance to adefovir develops slowly, rising to 29% for HBeAg‐negative patients by year 5, but more rapidly when used alone for lamivudine‐resistant HBV. Currently the two first line nucleoside/nucleotides are entecavir and tenofovir. Entecavir, a cyclopentane (D‐nucleoside), is very potent, with 94% of patients having undetectable HBV DNA after 5 years. Resistance develops in only 1.2% of treatment‐naïve patients. Tenofovir, another acyclic nucleotide, is more potent with less renal toxicity compared to adefovir. It is effective against lamivudine‐resistant mutations when used alone. No resistance to tenofovir has been described after its use for 3 years or longer, often for patients with human immunodeficiency virus/HBV co‐infection. With these current, potent antiviral agents associated with very low rates of resistance, long‐term HBV DNA suppression and possibly even reversal of cirrhosis can now be achieved in a proportion of patients. In addition, long‐term treatment with these antiviral agents is associated with a reduced risk of development of hepatocellular carcinoma.
Nonalcoholic fatty liver in Asia: Firmly entrenched and rapidly gaining ground
Authors: Chitturi Shivakumar , Wong Vincent Wai‐Sun , Farrell Geoff 
Published: January 2011

AbstractNonalcoholic fatty liver disease (NAFLD) is becoming an important chronic liver disorder in Asia. Prevalence figures show regional variations but at least 10% of the general population in Asia have fatty liver. Fatty liver can develop with relatively small changes in weight (2–3 kg), often with increasing central adiposity. The metabolic syndrome may precede or follow NAFLD. Overt diabetes is present in one‐third of cases but when oral glucose tolerance tests are performed, a further third of individuals have impaired glucose tolerance or diabetes. Natural history data are still scarce but cases of advanced hepatic fibrosis and hepatocellular carcinoma are now regularly reported. Many cases of cryptogenic cirrhosis are also attributable to NAFLD. Histological progression has been demonstrated for patients with NASH as well as for those with hepatic steatosis alone. Genetic factors may in part contribute to the rise in NAFLD. Polymorphisms within apolipoprotein C3 (APOC3) gene have been linked to NAFLD in lean Indian men. Although a number of other polymorphisms involving genes controlling adipose distribution, insulin signalling, adipokine responses and hepatic fibrosis have been reported, these studies have been underpowered. Transient elastography could help in detecting and monitoring hepatic fibrosis but further refinements in technique are necessary for obese individuals. Of the biomarkers, hyaluronic acid and cytokeratin‐18 fragment testing show promise as markers of hepatic fibrosis and NASH, respectively. Lifestyle alterations including dietary changes and increased physical activity remain the cornerstone of management. Attention should be paid to prevention through public education of campaigns addressing the increase in both adult and childhood obesity.
Diabetic gastroparesis—Backwards and forwards
Authors: Chang Jessica , Rayner Christopher K , Jones Karen L , Horowitz Michael 
Published: January 2011

AbstractDiabetic gastroparesis was once thought to be rare, associated with a poor prognosis, and to affect only patients with type 1 diabetes and irreversible autonomic neuropathy. A landmark study conducted by Horowitz et al. and published in JGH in 1986 paved the way for further studies to examine the pathophysiology, natural history and prognosis of diabetic gastroparesis, as well as its optimal management. This review summarizes the developments in knowledge gained over the last ∼25 years that have led to understanding about normal and disordered gastric emptying in diabetes, with a particular emphasis on the inter‐relationship between the rate of gastric emptying and the regulation of blood glucose.