bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward defining the autoimmune microbiome for type 1 diabetes
Authors: Giongo Adriana , Gano Kelsey A , Crabb David B , Mukherjee Nabanita , Novelo Luis L , Casella George , Drew Jennifer C , Ilonen Jorma , Knip Mikael , Hyöty Heikki , Veijola Riitta , Simell Tuula , Simell Olli , Neu Josef , Wasserfall Clive H , Schatz Desmond , Atkinson Mark A , Triplett Eric W 
Published: July 2010

Abstract
Several studies have shown that gut bacteria have a role in diabetes in murine models. Specific bacteria have been correlated with the onset of diabetes in a rat model. However, it is unknown whether human intestinal microbes have a role in the development of autoimmunity that often leads to type 1 diabetes (T1D), an autoimmune disorder in which insulin-secreting pancreatic islet cells are destroyed. High-throughput, culture-independent approaches identified bacteria that correlate with the development of T1D-associated autoimmunity in young children who are at high genetic risk for this disorder. The level of bacterial diversity diminishes overtime in these autoimmune subjects relative to that of age-matched, genotype-matched, nonautoimmune individuals. A single species, Bacteroides ovatus, comprised nearly 24% of the total increase in the phylum Bacteroidetes in cases compared with controls. Conversely, another species in controls, represented by the human firmicute strain CO19, represented nearly 20% of the increase in Firmicutes compared with cases overtime. Three lines of evidence are presented that support the notion that, as healthy infants approach the toddler stage, their microbiomes become healthier and more stable, whereas, children who are destined for autoimmunity develop a microbiome that is less diverse and stable. Hence, the autoimmune microbiome for T1D may be distinctly different from that found in healthy children. These data also suggest bacterial markers for the early diagnosis of T1D. In addition, bacteria that negatively correlated with the autoimmune state may prove to be useful in the prevention of autoimmunity development in high-risk children.
Mass Spectrometry Technologies
Authors: Fay Laurent B. , Kussmann Martin 
Published: July 2010

In modern nutrition research, mass spectrometry has developed into a tool to assess health, sensory as well as quality and safety aspects of food. Two strategies are followed for nutrient and metabolite analysis either in foodstuffs or in biological fluids sampled from the food consumer:
The “traditional” targeted conception, which measures only selected compounds with pre-determined properties such as a given mass or structure as described later.The more recent non-targeted conception, which includes fingerprinting of samples and evaluating the unidentified signals with statistical methods (e.g., principal component analysis, linear discriminant analysis, discriminant function analysis etc.).
For nutrients and metabolite identification purposes, in addition to NMR, two major techniques are currently applied, namely tandem mass spectrometry and accurate mass measurements. Tandem mass spectrometry enables elucidation and confirmation of metabolite structures, while accurate mass measurements in combination with isotope pattern analysis provide elemental composition of the metabolite. Furthermore, hydrogen/deuterium exchange experiments are combined with mass spectrometry 1 to distinguish between isomeric structures of analytes. On the other hand, quantification of nutrients and metabolites is mostly achieved using the selected-reaction monitoring technique on quadrupole-based platforms. Quadrupole analyzers provide the best linear and dynamic range for biological samples, but application of high-resolution with time-of-flight or Orbitrap analyzers can also separate the signal of interest from interferences thereby enhancing detection limits.
In this chapter, we will focus on a brief description of each mass spectrometric technique applied to nutrition research, with a short emphasis on the working principle of each ionization, mass separation and ion detection method. We will also describe some specific technologies like those enabling detection of stable-isotope labelled macro- and micro-nutrients.
Combination antibody treatment down-regulates epidermal growth factor receptor by inhibiting endosomal recycling
Authors: Spangler Jamie B. , Neil Jason R. , Abramovitch Sivan , Yarden Yosef , White Forest M. , Lauffenburger Douglas A. , Wittrup K. Dane 
Published: July 2010

Due to its common dysregulation in epithelial-based cancers and extensive characterization of its role in tumor growth, epidermal growth factor receptor (EGFR) is a highly validated target for anticancer therapies. There has been particular interest in the development of monoclonal antibodies (mAbs) targeting EGFR, resulting in two approved mAb-based drugs and several others in clinical trials. It has recently been reported that treatment with combinations of noncompetitive mAbs can induce receptor clustering, leading to synergistic receptor down-regulation. We elucidate three key aspects of this phenomenon. First, we show that highly potent combinations consisting of two noncompetitive mAbs that target EGFR domain 3 reduce surface receptor levels by up to 80% with a halftime of 0.5–5 h in both normal and transformed human cell lines to an extent inversely proportional to receptor density. Second, we find the mechanism underlying down-regulation to be consistent with recycling inhibition. Third, in contrast to the agonism associated with ligand-induced down-regulation, we demonstrate that mAb-induced down-regulation does not activate EGFR or its downstream effectors and it leads to synergistic reduction in migration and proliferation of cells that secrete autocrine ligand. These new insights will aid in ongoing rational design of EGFR-targeted antibody therapeutics.
Impact of diuretic treatment and sodium intake on plasma volume in patients with compensated systolic heart failure
Authors: Bonfils Peter K. , Damgaard Morten , Taskiran Mustafa , Goetze Jens Peter , Norsk Peter , Gadsbøll Niels 
Published: July 2010

AimsIn patients with heart failure (HF), the use of diuretics may be a double‐edged sword that can alleviate symptoms of congestion, but also result in over‐diuresis and intravascular volume depletion. The purpose of the present study was to examine plasma volume (PV) in HF patients receiving from 0 to 160 mg of furosemide and to investigate whether determination of plasma N‐terminal fragment of pro‐brain natriuretic peptide (NT‐proBNP) concentrations can predict PV‐status.Methods and resultsPlasma volume, extracellular volume, glomerular filtration rate, NT‐proBNP, and daily renal sodium excretion were measured in 18 patients with medically treated, compensated HF and in 27 healthy volunteers. Cardiac function was examined by non‐invasive cardiac output determination and echocardiography. Exercise capacity was evaluated by 6 min walk test. There was a borderline significant difference in PV between patients with HF and control subjects (37.3 ± 6.0 and 40.2 ± 5.8 mL/kg, respectively, P = 0.092) with a significant tendency towards a contraction of PV with increasing use of diuretics (P = 0.031). There was no difference in extracellular volume between patients with HF and control subjects (P = 0.844). NT‐proBNP plasma concentrations had no correlation to either sodium excretion (P = 0.193) or PV (P = 0.471) in patients with HF.ConclusionPlasma volume in patients with HF was within normal limits, but patients treated with high doses of loop‐diuretics tended to have subnormal PV. Single measurement of NT‐proBNP plasma concentration could not be used to estimate intravascular volume status in patients with HF.
US state alcohol sales compared to survey data, 1993–2006
Authors: Nelson David E. , Naimi Timothy S. , Brewer Robert D. , Roeber James 
Published: July 2010

ABSTRACTAims Assess long‐term trends of the correlation between alcohol sales data and survey data.Design Analyses of state alcohol consumption data from the US Alcohol Epidemiologic Data System based on sales, tax receipts or alcohol shipments. Cross‐sectional, state annual estimates of alcohol‐related measures for adults from the US Behavioral Risk Factor Surveillance System using telephone surveys.Setting United States.Participants State alcohol tax authorities, alcohol vendors, alcohol industry (sales data) and randomly selected adults aged ≥ 18 years 1993–2006 (survey data).Measurements State‐level per capita annual alcohol consumption estimates from sales data. Self‐reported alcohol consumption, current drinking, heavy drinking, binge drinking and alcohol‐impaired driving from surveys. Correlation coefficients were calculated using linear regression models.Findings State survey estimates of consumption accounted for a median of 22% to 32% of state sales data across years. Nevertheless, state consumption estimates from both sources were strongly correlated with annual r‐values ranging from 0.55–0.71. State sales data had moderate‐to‐strong correlations with survey estimates of current drinking, heavy drinking and binge drinking (range of r‐values across years: 0.57–0.65; 0.33–0.70 and 0.45–0.61, respectively), but a weaker correlation with alcohol‐impaired driving (range of r‐values: 0.24–0.56). There were no trends in the magnitude of correlation coefficients.Conclusions Although state surveys substantially underestimated alcohol consumption, the consistency of the strength of the association between sales consumption and survey data for most alcohol measures suggest both data sources continue to provide valuable information. These findings support and extend the distribution of consumption model and single distribution theory, suggesting that both sales and survey data are useful for monitoring population changes in alcohol use.
Development of target‐specific treatments in multiple myeloma
Authors: Chanan‐Khan Asher A. , Borrello Ivan , Lee Kelvin P. , Reece Donna E. 
Published: July 2010

SummaryIn the last decade, the novel agents lenalidomide, bortezomib, and thalidomide have dramatically improved outcomes for patients with multiple myeloma (MM). A number of new therapies with precise targets involved in MM cell growth and replication are now in development and have the potential for further improvements. Second‐generation proteasome inhibitors and thalidomide derivatives may offer increased efficacy and safety. Investigational therapies with rationally selected targets in MM include inhibitors of histone deacetylase, heat shock protein 90, mammalian target of rapamycin, BCL2, Akt, mitogen‐activated protein kinase, and telomerase. In addition, monoclonal antibodies directed against several targets have been developed and many are showing promise in initial clinical trials in MM. Interest in the ancient remedy of arsenic trioxide has been revived because of its proapoptotic effects on mitochondria, despite its established toxicities. In general, combination regimens are proving the most efficacious, which is to be expected given the multiple overlapping pathways responsible for MM growth and progression.
Pulmonary adenocarcinoma with microcystic histology and intratumoral heterogeneity of EGFR gene polymorphism
Authors: Yeh Yi‐Chen , Chou Teh‐Ying 
Published: July 2010

Yeh Y‐C & Chou T‐Y (2010) Histopathology 57, 112–120 Pulmonary adenocarcinoma with microcystic histology and intratumoral heterogeneity of EGFR gene polymorphismAims:  To study the clinicopathological features of pulmonary adenocarcinomas with microcystic histology.Materials and results:  Two cases of pulmonary adenocarcinoma exhibiting a unique microcystic growth pattern were analysed. The 20‐mm tumour of a 59‐year‐old woman showed a predominantly complex microcystic architecture with a focal papillary configuration, whereas the 15‐mm tumour of another 46‐year‐old woman displayed a solely microcystic growth pattern. The first tumour was found to have metastasized to lymph nodes at surgery and, 4 years later, to the chest wall. The second tumour did not metastasize or recur over a follow‐up period of 12 years. The tumour cells were immunoreactive with thyroid transcription factor‐1 (TTF‐1), which helped to differentiate them from salivary gland‐type tumours. No mutations of epidermal growth factor receptor (EGFR) or K‐ras genes were detected. However, facilitated by laser microdissection, a Q787Q polymorphism was found in the microcystic component but not in the papillary component. To our knowledge, this is the first report to illustrate intratumoral heterogeneity of EGFR gene polymorphism among different growth patterns within the same tumour.Conclusions:  Pulmonary microcystic adenocarcinoma has a variable clinical outcome. The microcystic tumour cells are immunoreactive with TTF‐1 and may harbour polymorphisms of the EGFR gene.
Use of isogenic strains indicates CYP9M10 is linked to permethrin resistance in Culex pipiens quinquefasciatus
Authors: Hardstone M. C. , Komagata O. , Kasai S. , Tomita T. , Scott J. G. 
Published: July 2010

AbstractPrevious studies on a strain of Culex pipiens quinquefasciatus from Saudi Arabia indicated permethrin resistance was a result of cytochrome P450 mediated detoxification and kdr. The P450 detoxification was found to be larval specific and associated with a fitness cost in certain environments. The P450 responsible for resistance (and the fitness cost) has not been identified, but recently two candidate P450s (CYP4H34 and CYP9M10) have been found. We measured cytochrome P450 and cytochrome b5 content as well as the expression levels of CYP4H34 and CYP9M10 in a susceptible (SLAB) and two isogenic strains (isolated by repeated backcrossing and selection) of mosquito (ISOP450 and ISOJPAL) resistant to permethrin. Cytochrome P450 protein levels of the resistant strains were significantly higher (1.5‐fold) than SLAB, but were not significantly different from one another. Expression of CYP4H34 in the larvae and adults of the resistant (ISOP450 and ISOJPAL) and susceptible (SLAB) strains were not statistically different. CYP9M10 was found to be significantly over‐expressed in larvae of both permethrin‐resistant isogenic strains (1800‐fold in ISOP450 and 870‐fold in ISOJPAL) when compared to SLAB. Partial sequence analysis of CYP9M10 revealed eight polymorphic sites that distinguished the susceptible allele from the resistant allele. We conclude that CYP9M10 is linked to permethrin resistance in these strains of C. p. quinquefasciatus, and is likely to be the P450 gene responsible for resistance in these strains.
Community adjustment of mobile people with learning difficulties after total hospital closure: a preliminary report
Authors: Brook S. Lister , Bowler D. M. 
Published: July 2010

AbstractA study is described in which 50 residents of a hospital for people with leaming difficulties were assessed immediately before and i year after moving into two types of community provision; purpose‐built campuses or small homes in residential streets. Measures were taken of residents’ adaptive and unwanted behaviours and of aspects of their lifestyles. The results report the changes in these measures that were found for both campus and small home residents.
Assessing clinicians’ consultation with people with profound learning disability: producing a rating scale
Authors: Kerr M. P. , Evans S. , Nolan M. , Fraser W. I. 
Published: July 2010

AbstractThis paper describes the development of a scale for assessing clitiicians’ communication with people with profound learning disability. Four psychiatrists and four nurses were assessed completing three simple non‐invasive clinical procedures—blood pressure, pulse and axillary temperature—with people with profound learning disability. Videotaped assessmetit of consultations was performed by three experienced speech and language therapists using a previously designed scale for analysing encounters with people with mild learning disability. This led to the production of a new scale specifically for people with profound learning disability. A significant inter‐rater reliability was found between the three speech therapists for total scores (rater a‐b, corr = 0·654, P= 0·006; rater a–c, corr = 0·795, P= 0·0001: rater b–c, corr = 0·673, P = 0·004). Significant reliability between raters was also found for the subsections of verbal behaviour and non‐verbal behaviour.
The effect of age on language in people with Down's syndrome
Authors: Cooper S.‐A. , Collacott R. A. 
Published: July 2010

AbstractIt has been previously suggested, in a small‐sized study of 60 people with Down's syndrome, that receptive language skills were lower, the older the individual, whereas expressive language skills did not correlate with age (Carter‐Young & Kramer 1991), By assessing language skills on 345 Down's syndrome adults living in Leicestershire (91% of the total population), the present authors have been able to confirm this finding, using the AAMD Adaptive Behaviour Scale. This may have clinical relevance with regard to communication with older people with Down's syndrome, and also for estimation of an individual's skill level when he or she was younger.
Intra‐individual factors influencing efficacy of interventions for stereotyped behaviours: a meta‐analysis
Authors: Wehmeyer M. L. 
Published: July 2010

AbstractThe efficacy of treatments targeting stereotyped behaviours has been the focal point of several reviews. This study examined efficacy as a function of intra‐individual characteristics, including age, gender, level of disability and topography of the behaviour. A meta‐analysis of studies reporting treatments of stereotyped behaviours appearing in 23 journals over 20 years was conducted. Efficacy was determined using two metrics. Percentage Non‐overlapping Data and Percentage Zero Data, which indicate treatment success as a function of the degree to which the behaviour fell below baseline levels, and once reaching zero, remained there. Non‐parametric analyses indicated differences in treatment efficacy according to age and the form of the stereotypy. Implications for the design of treatments to address stereotypies are discussed.
Exercise effects on night‐to‐night fluctuations in self‐rated sleep among older adults with sleep complaints
Authors: BUMAN MATTHEW P. , HEKLER ERIC B. , BLIWISE DONALD L. , KING ABBY C. 
Published: July 2010

SummarySleep interventions have rarely explored reductions in night‐to‐night fluctuations [i.e. intra‐individual variability (IIV)] in sleep, despite the negative impacts of such fluctuations on affective states and cognitive and physical symptoms. In a community‐based randomized controlled trial we evaluated whether physical exercise reduced IIV in self‐rated sleep outcomes among middle‐aged and older adults with sleep complaints. Under‐active adults 55 years and older (n = 66, 67% women) with mild to moderate sleep complaints were randomized to 12 months of a moderate‐intensity endurance exercise (n = 36) or a health education control group (n = 30). Daily sleep logs, Pittsburgh Sleep Quality Index (PSQI) and in‐home polysomnographic sleep recordings (PSG) were collected at baseline, 6 months and 12 months. Sleep log‐derived means and IIV were computed for sleep‐onset latency (SOL), time in bed, feeling rested in the morning, number of nighttime awakenings, and wake after final awakening (WAFA). Using intent‐to‐treat methods, at 6 months no differences in IIV were observed by group. At 12 months, SOL‐based IIV was reduced in the exercise group compared with the control (difference = 23.11, 95% CI: 3.04–47.18, P = 0.025, Cohen’s d = 0.57). This change occurred without mean‐level or IIV changes in sleep–wake schedules. For all sleep variables, except SOL and WAFA, IIV changes and mean‐level changes in each variable were negatively correlated (r = −0.312 to −0.691, P < 0.05). Sleep log‐derived IIV changes were modestly correlated with mean‐level PSQI and PSG‐based changes at 12 months. Twelve months of moderate‐intensity exercise reduced night‐to‐night fluctuations in self‐rated time to fall asleep, and this relationship was independent of mean‐level time to fall asleep.
Pharmacokinetics of cefpodoxime in plasma and subcutaneous fluid following oral administration of cefpodoxime proxetil in male beagle dogs
Authors: KUMAR V. , MADABUSHI R. , LUCCHESI M. B. B. , DERENDORF H. 
Published: July 2010

Kumar, V., Madabushi, R., Lucchesi, M. B. B., Derendorf, H. Pharmacokinetics of cefpodoxime in plasma and subcutaneous fluid following oral administration of cefpodoxime proxetil in male beagle dogs. J. vet. Pharmacol. Therap.34, 130–135.Pharmacokinetics of cefpodoxime in plasma (total concentration) and subcutaneous fluid (free concentration using microdialysis) was investigated in dogs following single oral administration of prodrug cefpodoxime proxetil (equivalent to 5 and 10 mg/kg of cefpodoxime). In a cross over study design, six dogs per dose were utilized after a 1 week washout period. Plasma, microdialysate, and urine samples were collected upto 24 h and analyzed using high performance liquid chromatography. The average maximum concentration (Cmax) of cefpodoxime in plasma was 13.66 (±6.30) and 27.14 (±4.56) μg/mL with elimination half‐life (t1/2) of 3.01 (±0.49) and 4.72 (±1.46) h following 5 and 10 mg/kg dose, respectively. The respective average area under the curve (AUC0–∞) was 82.94 (±30.17) and 107.71 (±30.79) μg·h/mL. Cefpodoxime was readily distributed to skin and average free Cmax in subcutaneous fluid was 1.70 (±0.55) and 3.06 (±0.93) μg/mL at the two doses. Urinary excretion (unchanged cefpodoxime) was the major elimination route. Comparison of subcutaneous fluid concentrations using pharmacokinetic/pharmacodynamic indices of fT>MIC indicated that at 10 mg/kg dose; cefpodoxime would yield good therapeutic outcome in skin infections for bacteria with MIC50 upto 0.5 μg/mL while higher doses (or more frequent dosing) may be needed for bacteria with higher MICs. High urine concentrations suggested cefpodoxime use for urinary infections in dogs.
The Rad4 homologue YDR314C is essential for strand‐specific repair of RNA polymerase I‐transcribed rDNA in Saccharomyces cerevisiae
Authors: den Dulk Ben , Brandsma Jourica A. , Brouwer Jaap 
Published: July 2010

SummaryThe Saccharomyces cerevisiae protein Rad4 is involved in damage recognition in nucleotide excision repair (NER). In RNA polymerase II‐transcribed regions Rad4 is essential for both NER subpathways global genome repair (GGR) and transcription coupled repair (TCR). In ribosomal DNA (rDNA), however, the RNA polymerase I‐transcribed strand can be repaired in the absence of Rad4. In Saccharomyces cerevisiae the YDR314C protein shows homology to Rad4. The possible involvement of YDR314C in NER was studied by analysing strand‐specific cyclobutane pyrimidine dimer (CPD) removal in both RNA pol I‐ and RNA pol II‐transcribed genes. Here we show that the Rad4‐independent repair of rDNA is dependent on YDR314C. Moreover, in Rad4 proficient cells preferential repair of the transcribed strand of RNA pol I‐transcribed genes was lost after deletion of YDR314C, demonstrating that Rad4 cannot replace YDR314C. CPD removal from the RNA pol II‐transcribed RPB2 gene was unaffected in ydr314c mutants. We conclude that the two homologous proteins Rad4 and YDR314C are both involved in NER and probably have a similar function, but operate at different loci in the genome and are unable to replace each other.