bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seniors' perceptions of prescription drug information sources
Authors: DeLorme Denise E. , Huh Jisu , Reid Leonard N. 
Published: June 2007

PurposeTo determine how seniors evaluate, compare, and use prescription drug information sources, provide insight on perceptions of the credibility, trustworthiness, and value of these sources, and capture verbatim comments for translation into scalar statements in future surveys.Design/methodology/approachA total of 25 in‐depth interviews were conducted with US seniors age 65 or older. The transcripts were analyzed using an interpretative approach.FindingsInformants distinguish between sources on the dimension of credibility; place the most trust in physicians but since they tend to experience a lack of time and attention from them, mass media seem to fill an information gap; and direct‐to‐physician promotions appear to have an indirect influence on patients' perceived credibility of and interaction with physicians.Research limitations/implicationsThe findings suggest that identification of key sources should consider two factors: frequency of access/utilization and trust in information provided by the source. The findings also provide empirically‐grounded statements for future scale development.Practical implicationsThe results suggest that for multi‐media campaign effectiveness: advertising for a new drug may be most effective on TV but as a brand enters growth or maturity, print may be a better option; marketers should emphasize print in the direct‐to‐consumer (DTC) advertising media mix; sampling strategies should be coordinated with product packaging literature and emphasized to promote trial; and marketers should attempt to increase internet usage among seniors and utilize the medium more actively but avoid online advertising.Originality/valueThe findings contribute to knowledge on the responsiveness of US seniors to DTC advertising and other prescription drug information sources.
Long‐range side‐chain–main‐chain interactions play crucial roles in stabilizing the (βα)8 barrel motif of the alpha subunit of tryptophan synthase
Authors: Yang Xiaoyan , Vadrevu Ramakrishna , Wu Ying , Matthews C. Robert 
Published: June 2007

AbstractThe role of hither‐to‐fore unrecognized long‐range hydrogen bonds between main‐chain amide hydrogens and polar side chains on the stability of a well‐studied (βα)8, TIM barrel protein, the alpha subunit of tryptophan synthase (αTS), was probed by mutational analysis. The F19–D46 and I97–D124 hydrogen bonds link the N terminus of a β‐strand with the C terminus of the succeeding antiparallel α‐helix, and the A103–D130 hydrogen bond links the N terminus of an α‐helix with the C terminus of the succeeding antiparallel β‐strand, forming clamps for the respective βα or αβ hairpins. The individual replacement of these aspartic acid side chains with alanine leads to what appear to be closely related partially folded structures with significantly reduced far‐UV CD ellipticity and thermodynamic stability. Comparisons with the effects of eliminating another main‐chain–side‐chain hydrogen bond, G26–S33, and two electrostatic side‐chain–side‐chain hydrogen bonds, D38–H92 and D112–H146, all in the same N‐terminal folding unit of αTS, demonstrated a unique role for the clamp interactions in stabilizing the native barrel conformation. Because neither the asparagine nor glutamic acid variant at position 46 can completely reproduce the spectroscopic, thermodynamic, or kinetic folding properties of aspartic acid, both size and charge are crucial to its unique role in the clamp hydrogen bond. Kinetic studies suggest that the three clamp hydrogen bonds act in concert to stabilize the transition state leading to the fully folded TIM barrel motif.
Influence of hPin1 WW N‐terminal domain boundaries on function, protein stability, and folding
Authors: Jäger Marcus , Nguyen Houbi , Dendle Maria , Gruebele Martin , Kelly Jeffery W. 
Published: June 2007

AbstractAn N‐terminally truncated and cooperatively folded version (residues 6–39) of the human Pin1 WW domain (hPin1 WW hereafter) has served as an excellent model system for understanding triple‐stranded β‐sheet folding energetics. Here we report that the negatively charged N‐terminal sequence (Met1‐Ala‐Asp‐Glu‐Glu5) previously deleted, and which is not conserved in highly homologous WW domain family members from yeast or certain fungi, significantly increases the stability of hPin1 WW (≈4 kJ mol−1 at 65°C), in the context of the 1–39 sequence based on equilibrium measurements. N‐terminal truncations and mutations in conjunction with a double mutant cycle analysis and a recently published high‐resolution X‐ray structure of the hPin1 cis/trans‐isomerase suggest that the increase in stability is due to an energetically favorable ionic interaction between the negatively charged side chains in the N terminus of full‐length hPin1 WW and the positively charged ε‐ammonium group of residue Lys13 in β‐strand 1. Our data therefore suggest that the ionic interaction between Lys13 and the charged N terminus is the optimal solution for enhanced stability without compromising function, as ascertained by ligand binding studies. Kinetic laser temperature‐jump relaxation studies reveal that this stabilizing interaction has not formed to a significant extent in the folding transition state at near physiological temperature, suggesting a differential contribution of the negatively charged N‐terminal sequence to protein stability and folding rate. As neither the N‐terminal sequence nor Lys13 are highly conserved among WW domains, our data further suggest that caution must be exercised when selecting domain boundaries for WW domains for structural, functional, or thermodynamic studies.
Crystal structures of TM0549 and NE1324—two orthologs of E. coli AHAS isozyme III small regulatory subunit
Authors: Petkowski Janusz J. , Chruszcz Maksymilian , Zimmerman Matthew D. , Zheng Heping , Skarina Tatiana , Onopriyenko Olena , Cymborowski Marcin T. , Koclega Katarzyna D. , Savchenko Alexei , Edwards Aled , Minor Wladek 
Published: June 2007

AbstractCrystal structures of two orthologs of the regulatory subunit of acetohydroxyacid synthase III (AHAS, EC 2.2.1.6) from Thermotoga maritima (TM0549) and Nitrosomonas europea (NE1324) were determined by single‐wavelength anomalous diffraction methods with the use of selenomethionine derivatives at 2.3 Å and 2.5 Å, respectively. TM0549 and NE1324 share the same fold, and in both proteins the polypeptide chain contains two separate domains of a similar size. Each protein contains a C‐terminal domain with ferredoxin‐type fold and an N‐terminal ACT domain, of which the latter is characteristic for several proteins involved in amino acid metabolism. The ferredoxin domain is stabilized by a calcium ion in the crystal structure of NE1324 and by a Mg(H2O)62+ ion in TM0549. Both TM0549 and NE1324 form dimeric assemblies in the crystal lattice.
Enhanced biocontrol activity of Trichoderma virens transformants constitutively coexpressing β‐1,3‐ and β‐1,6‐glucanase genes
Authors: DJONOVIĆ SLAVICA , VITTONE GLORIA , MENDOZA‐HERRERA AZUCENA , KENERLEY CHARLES M. 
Published: June 2007

SUMMARYEvidence for the role of chitinases, proteases and β‐1,3‐ and β‐1,6‐glucanases in mycoparasitism by Trichoderma species has been well documented. Moreover, constitutive over‐expression of genes encoding individual cell‐wall‐degrading enzymes (CWDEs) has been shown to improve the potential of biological agents. In this study, we generated transformants of T. virens in which β‐1,3‐ and β‐1,6‐glucanase genes, TvBgn2 and TvBgn3, respectively, were constitutively coexpressed in the same genetic T. virens Gv29.8 wild‐type background. The double over‐expression transformants (dOEs) grow and sporulate slower than the wild‐type (WT). However, the reduction in growth did not seem to affect their mycoparasitic and biocontrol capabilities, as dOEs displayed much higher levels of total β‐1,3‐ and β‐1,6‐glucanase activity than the WT. This higher enzymatic activity of dOEs positively correlated with observed in vitro inhibition of Pythium ultimum and Rhizoctonia solani mycelia, and with enhanced bioprotection of cotton seedlings against P. ultimum, R. solani and Rhizopus oryzae. Besides effective biocontrol of all pathogens at an original inoculum level, the performance of dOEs was highly enhanced (up to 312% of WT performance) when pathogen pressure was greater (i.e. concentration of inoculum was higher or pathogens applied in combination). These results demonstrate that the strategy of introducing multiple lytic enzyme‐encoding genes through transformation of a given biocontrol strain can be successfully used to achieve better biocontrol.
A LuxR homologue of Xanthomonas oryzae pv. oryzae is required for optimal rice virulence
Authors: FERLUGA SARA , BIGIRIMANA JOSEPH , HÖFTE MONICA , VENTURI VITTORIO 
Published: June 2007

SUMMARYIn Gram‐negative bacteria a typical quorum sensing (QS) system usually involves the production and response to acylated homoserine lactones (AHLs). An AHL QS system is most commonly mediated by a LuxI family AHL synthase and a LuxR family AHL response regulator. This study reports for the first time the presence of a LuxR family‐type regulator in Xanthomonas oryzae pv. oryzae (Xoo), which has been designated as OryR. The primary structure of OryR contains the typical signature domains of AHL QS LuxR family response regulators: an AHL‐binding and a HTH DNA binding motif. The oryR gene is conserved among 26 Xoo strains and is also present in the genomes of close relatives X. campestris pv. campestris and X. axonopodis pv. citri. Disrupting oryR in three Xoo strains resulted in a significant reduction of rice virulence. The wild‐type Xoo strains do not seem to produce AHLs and analysis of the Xoo sequenced genomes did not reveal the presence of a LuxI‐family AHL synthase. The OryR protein was shown to be induced by macerated rice and affected the production of two secreted proteins: a cell‐wall‐degrading cellobiosidase and a 20‐kDa protein of unknown function. By expressing and purifying OryR it was then observed that it was solubilized when grown in the presence of rice extract indicating that there could be a molecule(s) in rice which binds OryR. The role of OryR as a possible in planta induced LuxR family regulator is discussed.
Familial risks for asthma among twins and other siblings based on hospitalizations in Sweden
Authors: Hemminki K. , Li X. , Sundquist K. , Sundquist J. 
Published: June 2007

SummaryBackground
Asthma is a common disabling condition, with known environmental and familial risk factors and with their assumed interactions. We wanted to carry out a family study on asthma to address gene–environment interactions at a population level.Methods
We conducted a nation‐wide study on familial risks for asthma. An asthma database was constructed by linking the Multigeneration Register on 0–72‐year‐old subjects to the Hospital Discharge Register for diagnosed asthma cases in Sweden from years 1987 to 2004. Standardized incidence ratios (SIRs) were calculated for affected singleton siblings, twins and spouses by comparing with those whose siblings or spouses had no asthma.Results
A total of 67 370 hospitalized cases and 5638 affected siblings were identified with a familial SIR of 3.70, which was independent of sex, diagnostic age and age differences between the siblings. The SIR for different‐sex twins was 5.17 and for same‐sex twins it was 13.38. There was a low correlation between spouses for asthma.Conclusions
Asthma shows a higher familial risk than many common diseases. The higher difference in familial excess risk between singleton siblings and different‐sex twins provides strong genetic epidemiological evidence for gene–environment interactions in asthma. The concept of gene–environment interactions needs to be accommodated in future aetiological studies on asthma. Data on environmental factors and family history are important for clinical risk estimation.
Optimizing fat oxidation through exercise in severely obese Caucasian adolescents
Authors: Lazzer Stefano , Busti Carlo , Agosti Fiorenza , De Col Alessandra , Pozzo Renzo , Sartorio Alessandro 
Published: June 2007

SummaryObjective  To measure the contribution of substrate oxidation to energy expenditure during cycling at different workloads and to identify the exercise intensity that elicits the maximum fat oxidation rate in groups of severely obese or nonobese Caucasian adolescents.Design  A total of 30 severely obese subjects (mean body mass index, BMI = 34·7 kg/m2; fat‐mass = 39·9%) and 30 nonobese sedentary adolescents (mean BMI = 22·7 kg/m2; fat‐mass = 21·8%) aged 14–16 years, participated in this study. Body composition was assessed by bioelectrical impedance. Peak oxygen uptake (V̇O2peak) and maximal fat oxidation rate were determined with indirect calorimetry by using a graded exercise test on an electromagnetically braked cycle ergometer.Results  Predicted V̇O2max were expressed in absolute (l/min) and relative (ml/kg FFM/min) values, and maximal work rates were not significantly different between obese and nonobese adolescents, but were significantly higher in boys than in girls. No significant differences in fat oxidation rates were found in obese and nonobese sedentary adolescents during the graded exercise test. Maximal fat oxidation was observed at an exercise intensity corresponding to (mean ± SD) 41 ± 3%V̇O2max or 58 ± 3% HRmax. At this exercise intensity, fat oxidation rates were higher in boys than in girls (0·32 ± 0·02 g/min vs. 0·25 ± 0·02 g/min, P < 0·001).Conclusions  Severely obese and sedentary nonobese adolescents reached maximal fat oxidation rates at 41%V̇O2max, which corresponds to 58% HRmax. At this exercise intensity, fat oxidation rates were higher in boys than in girls probably due to higher V̇O2max and absolute workload during the exercise steps for boys compared with those for girls.
Growth hormone (GH) secretion and response to GH therapy after total body irradiation and haematopoietic stem cell transplantation during childhood
Authors: Bakker B. , Oostdijk W. , Geskus R. B. , Stokvis‐Brantsma W. H. , Vossen J. M. , Wit J. M. 
Published: June 2007

SummaryObjective  In January 1997 we introduced a protocol for the treatment with GH of children with impaired growth after unfractionated total body irradiation (TBI). This study is an evaluation of that protocol.Patients and methods  Between January 1997 and July 2005, 66 patients (48 male) treated for haematological malignancies had at least two years of disease‐free survival after TBI‐based conditioning for stem cell transplantation (SCT). Stimulated and/or spontaneous GH secretion was decreased in 8 of the 29 patients tested because of impaired growth. Treatment with GH (daily dose 1·3 mg/m2 body surface area) was offered to all 29 patients and initiated in 23 of them (17 male). The main outcome measure was the effect of GH therapy on height standard deviation scores (SDS) after onset of GH therapy, estimated by random‐effect modelling with corrections for sex, age at time of SCT and puberty (data analysed on intention‐to‐treat basis).Results  At time of analysis, median duration of therapy was 3·2 years; median follow‐up after start of GH therapy was 4·2 years. The estimated effect of GH therapy, modelled as nonlinear (logit) curve, was +1·1 SD after 5 years. Response to GH therapy did not correlate to GH secretion status.Conclusion  GH therapy has a positive effect on height SDS after TBI, irrespective of GH secretion status.
Age‐related penetrance of endocrine tumours in multiple endocrine neoplasia type 1 (MEN1): a multicentre study of 258 gene carriers
Authors: Machens Andreas , Schaaf Ludwig , Karges Wolfram , Frank‐Raue Karin , Bartsch Detlef K. , Rothmund Matthias , Schneyer Ulrich , Goretzki Peter , Raue Friedhelm , Dralle Henning 
Published: June 2007

SummaryObjective  In multiple endocrine neoplasia type 1 (MEN1), age‐related tumour penetrance according to the type of MEN1 germline mutation has not been investigated in‐depth. This study was conducted to examine whether carriers of out‐of‐frame/truncating and in‐frame MEN1 mutations differ in age‐related tumour penetrance.Design  A multicentre study with biochemical, hormonal and radiological screening for MEN1‐associated tumours.Patients  A total of 258 MEN1 carriers from six major German tertiary referral centres averaging 43 years of age at last follow‐up.Measurements  Main outcome measure was time to first diagnosis of MEN1‐associated tumours.Results  Independent of the year of birth and observation period, time to first tumour diagnosis did not vary much by the type of MEN1 germline mutation or endocrine organ system, and perhaps not even by the type of endocrine tumour when the amount of time was considered by which the diagnosis probably has been advanced through the manifestation of hormonal symptoms. Parathyroid hyperplasia and adenomas developed almost twice as often as enteropancreatic and pituitary tumours (77%vs. 49–32%), and more than five to sevenfold as often as adrenal cortical tumours and carcinoids (77%vs. 15–10%), reaching penetrance rates of up to 90%, 60%, 40%, 26% and 17%, respectively. The heterogeneity of tumour penetrance was marked, ranging from 9 years to 25 years for the earliest, and from 68 years to 77 years for the latest tumour manifestation.Conclusions  Because of our inability of predicting tumour penetrance and malignant transformation individually, life‐long follow‐up of MEN1 carriers is warranted to prevent tumour morbidity.
The molecular causes of low ATM protein expression in breast carcinoma; promoter methylation and levels of the catalytic subunit of DNA‐dependent protein kinase
Authors: Treilleux I , Chapot B , Goddard S , Pisani P , Angèle S , Hall J 
Published: June 2007

Aims:  To investigate whether aberrant methylation of the ATM promoter or loss of the catalytic subunit of DNA‐dependent protein kinase (DNA‐PKcs) may be the underlying causes of reduced ATM protein levels often seen in breast tumours.Methods and results:  Methylation‐specific polymerase chain reaction was used to determine the ATM promoter status and DNA‐PKcs levels were measured by immunohistochemistry. None of the 74 invasive carcinomas (ICs) studied showed ATM promoter hypermethylation, whereas promoter methylation of CDKN2A/p16 (1.8%) and GSTP1 (15.8%) was detected. Of 92 ICs examined, 68 had reduced DNA‐PKcs levels, supporting previous findings that alterations in double‐strand break repair are associated with breast cancer pathogenesis. Although no association was found between the DNA‐PKcs and ATM scores for the series of 92 tissues and 22/24 tissues with normal DNA‐PKcs had reduced ATM, 29 tumours showed low expression of both DNA‐PKcs and ATM compared with normal tissues.Conclusions:  No evidence was found that the reduction in ATM protein levels seen in breast carcinoma is the result of epigenetic silencing. However, cross‐regulation between DNA‐PKcs and ATM may be a possible cause in a subset of tumours and warrants further investigation.
CK7+/CK20– immunoexpression profile is typical of salivary gland neoplasia
Authors: Meer S , Altini M 
Published: June 2007

Aims:  To evaluate cytokeratin (CK) 7/20 expression patterns in salivary gland neoplasia.Methods and results:  Formalin‐fixed paraffin embedded tissue from 153 salivary gland tumours were evaluated for CK7/20 immunoreactivity. The tumours included pleomorphic adenoma (n = 24), myoepithelioma (n = 9), papillary cystadenoma (n = 3), oncocytoma (n = 2), adenoid cystic carcinoma (n = 22), mucoepidermoid carcinoma (n = 21), polymorphous low‐grade adenocarcinoma (n = 21), carcinoma ex‐pleomorphic adenoma (n = 11), acinic cell carcinoma (n = 17), epimyoepithelial carcinoma (n = 7), oncocytic carcinoma (n = 3), hyalinizing clear cell carcinoma (n = 1), papillary cystadenocarcinoma (n = 1), salivary duct carcinoma (n = 3), adenocarcinoma (not otherwise specified) (n = 4) and squamous carcinoma (n = 4). Immunohistochemical procedures were performed using monoclonal antibodies CK7 (OV‐TL 12/30), CK20 (Ks 20.8) and M3515 cytokeratin (AE1/AE3) in the presence of appropriate controls. The results were expressed semiquantitatively, according to the estimated percentage of positive tumour cells: 1+, 5–25%; 2+, 26–75%; and 3+, 76–100%. All salivary gland neoplasms showed a CK7+/CK20– immunoprofile ranging from 5 to 100%. Squamous carcinoma showed negative CK7/20 immunoexpression.Conclusions:  Although the CK7/20 immunoprofile is not useful in distinguishing the various types of salivary gland neoplasms or between benign and malignant salivary gland tumours, it may facilitate differentiation of primary salivary gland neoplasia from metastatic tumours and squamous carcinoma, and the diagnosis of metastatic salivary gland tumours.
Cyclin A expression and its diagnostic value in pleomorphic adenoma and carcinoma expleomorphic adenoma of the parotid gland
Authors: Patel R S , Hughes C W , Fredericks S , Lee C S , Rose B , Gao K , Smith G , Hong A , O'Brien C J 
Published: June 2007

Aims:  To investigate cyclin A expression in pleomorphic adenoma (PA) and carcinoma expleomorphic adenoma (CXPA) of the parotid gland with a view to assessing its potential value as a diagnostic marker for CXPA.Methods and results:  Cyclin A expression in PA and CXPA was studied using semiquantitiative immunohistochemistry. The epithelial component of the tumours expressed cyclin A in a statistically significantly (P < 0.005) higher number of CXPA cases (86%) compared with the PA cases (39%). Cyclin A was not expressed in normal salivary tissues of PA and CXPA.Conclusions:  High cyclin A expression is a useful marker for the pathological diagnosis of CXPA.
How people with advanced cancer manage changing eating habits
Authors: Hopkinson Jane B 
Published: June 2007

AbstractTitle.  How people with advanced cancer manage changing eating habits Aim.  This paper is a report of a study to explore the management of changing eating habits in people with advanced cancer.Background.  Internationally there is interest in supporting self‐management as a way of helping people to live with illness. It is unknown if promoting self‐management in people with cancer can lead to beneficial health outcomes. In order to develop and test interventions that promote self‐management in cancer patients, it is first important to understand ways in which they can help themselves.Method.  A mixed‐methods exploratory case study of the meaning, management and manifestations of weight loss and change in eating habits was conducted with 30 patients receiving palliative home care in England in 2003. Semi‐structured interview data were analysed using both content and thematic approaches.Findings.  Participants described a total of 141 different self‐actions, each of which formed a component of up to four self‐action strategies that were used to aid life with advanced cancer. The strategies were ‘Taking control’, ‘Promoting self‐worth’, ‘Relationship work’, and ‘Distraction’. Employing these strategies led to changes in thinking and behaviour that were motivated by a desire to sustain or enhance well‐being. The pattern of self‐action strategies adopted by each individual is theorized to be dependent on the personal and contextual resources available.Conclusion.  Patients can and do find their own solutions to eating problems and nurses should support this self‐action. The proposed theory of self‐management of eating change provides an understanding that can inform the provision of this support.