bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Comparative Effectiveness of Angiotensin‐Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Patients With Diabetes
Authors: Padwal Raj , Lin Mu , Eurich Dean T. 
Published: August 2015

The evidence examining the effect of angiotensin‐converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) on mortality in high‐risk patients is conflicting. To further examine this controversy, the authors compared outcomes between ACE inhibitors and ARBs in a large clinical diabetes registry. A retrospective cohort of 87,472 incident users followed for 105,702 patient‐years was analyzed. Average age was 53.1±10.1 years, 54.2% were men, and 14.4% had cardiovascular disease. All‐cause hospitalization or all‐cause mortality, the composite primary endpoint, occurred in 10,943 (12.5%) patients. Compared with ACE inhibitors, the adjusted hazard for ARBs was 0.90 (95% confidence interval, 0.87–0.94) for all‐cause hospitalization or mortality; 0.95 (0.65–1.40) for mortality; 0.90 (0.87–0.94) for all‐cause hospitalization; and 0.81 (0.74–0.89) for cardiovascular admission. ARB use was associated with a reduced, not increased, risk of hospitalization/mortality relative to ACE inhibition. This was driven by lower hospitalization, with a null mortality result.
Up‐regulated TLR4 in cardiomyocytes exacerbates heart failure after long‐term myocardial infarction
Authors: Liu Li , Wang Yin , Cao Zhi‐Yong , Wang Meng‐Meng , Liu Xue‐Mei , Gao Ting , Hu Qi‐Kuan , Yuan Wen‐Jun , Lin Li 
Published: August 2015

AbstractIt remains unclear whether and how cardiomyocytes contribute to the inflammation in chronic heart failure (CHF). We recently reviewed the capacity of cardiomyocytes to initiate inflammation, by means of expressing certain immune receptors such as toll‐like receptors (TLRs) that respond to pathogen‐ and damage‐associated molecular patterns (PAMP and DAMP). Previous studies observed TLR4‐mediated inflammation within days of myocardial infarction (MI). This study examined TLR4 expression and function in cardiomyocytes of failing hearts after 4 weeks of MI in rats. The increases of TLR4 mRNA and proteins, as well as inflammatory cytokine production, were observed in both the infarct and remote myocardium. Enhanced immunostaining for TLR4 was observed in cardiomyocytes but not infiltrating leucocytes. The injection of lentivirus shRNA against TLR4 into the infarcted heart decreased inflammatory cytokine production and improved heart function in vivo. Accordingly, in cardiomyocytes isolated from CHF hearts, increases of TLR4 mRNA and proteins were detected. More robust binding of TLR4 with lipopolysaccharide (LPS), a PAMP ligand for TLR4, and heat shock protein 60 (HSP60), a DAMP ligand for TLR4, was observed in CHF cardiomyocytes under a confocal microscope. The maximum binding capacity (Bmax) of TLR4 was increased for LPS and HSP60, whereas the binding affinity (Kd) was not significantly changed. Furthermore, both LPS and HSP60 induced more robust production of inflammatory cytokines in CHF cardiomyocytes, which was reduced by TLR4‐blocking antibodies. We conclude that the expression, ligand‐binding capacity and pro‐inflammatory function of cardiomyocyte TLR4 are up‐regulated after long‐term MI, which promote inflammation and exacerbate heart failure.
High Serum Uric Acid Levels Are Associated with All‐Cause and Cardiovascular, but Not Cancer, Mortality in Elderly Adults
Authors: Wu Chen‐Yi , Hu Hsiao‐Yun , Chou Yiing‐Jenq , Huang Nicole , Chou Yi‐Chang , Lee Meng‐Sui , Li Chung‐Pin 
Published: August 2015

ObjectivesTo estimate the all‐cause, cardiovascular, and cancer mortality risks associated with serum uric acid levels in elderly adults.DesignCohort study.SettingThe Annual Geriatric Health Examination Program database from 2006 to 2010.PaticipantsCommunity‐dwelling Taipei citizens aged 65 and older (N = 77,541).MeasurementsStratified according to sex, serum uric acid levels were analyzed in quartiles and as normal versus high categories. Mortality was determined by matching cohort identifications with national death files.ResultsMen had significantly higher uric acid levels than women (P < .001), and mean levels increased with age (P < .001). Serum uric acid levels (normal vs high) were an independent risk factor for all‐cause and cardiovascular mortality in men and women, with the strongest association found for cardiovascular mortality. The association between serum uric acid levels and cardiovascular mortality was independent of other cardiovascular risk factors such as hypertension, diabetes mellitus, hyperlipidemia, and glomerular filtration rate levels. When levels were analyzed as quartiles, men with levels in the second quartile had the lowest hazard ratios for all‐cause and cardiovascular mortality.ConclusionHigh serum uric acid levels are associated with greater risk of all‐cause and cardiovascular mortality but not cancer mortality in elderly adults. Further studies are warranted to investigate the prognostic implications and potential utility in the monitoring of therapy.
Delivery of a Vitamin D Intervention in Homebound Older Adults Using a Meals‐on‐Wheels Program: A Pilot Study
Authors: Houston Denise K. , Tooze Janet A. , Demons Jamehl L. , Davis Brooke L. , Shertzer‐Skinner Rachel , Kearsley Linda B. , Kritchevsky Stephen B. , Williamson Jeff D. 
Published: August 2015

ObjectivesTo assess the feasibility of a vitamin D intervention delivered through a Meals‐on‐Wheels (MOW) program to improve 25‐hydroxyvitamin D (25(OH)D) concentrations and reduce falls in homebound older adults.DesignSingle‐blind, cluster randomized trial.SettingMOW, Forsyth County, North Carolina.ParticipantsCommunity‐dwelling homebound adults aged 65 to 102 (N = 68).InterventionMOW clients were randomized to vitamin D3 (100,000 IU/month; n = 38) or active placebo (400 IU vitamin E/month; n = 30) according to MOW delivery route.MeasurementsSerum 25(OH)D was assessed at baseline and 5‐month follow‐up; proportions of participants in 25(OH)D categories were compared using Fisher exact test. Falls were assessed using monthly fall calendars, and rate of falls was estimated using negative binomial generalized estimating equation models.ResultsMean ± standard deviation 25(OH)D concentrations were 20.9 ± 11.5 ng/mL at baseline, with 57% having 25(OH)D concentrations less than 20 ng/mL. Retention and adherence were high (>90%). After the 5‐month intervention, only one of 34 participants randomized to vitamin D3 had 25(OH)D concentrations less than 20 ng/mL, compared with 18 of 25 participants randomized to placebo (P < .001). In unadjusted analyses, the rate of falls over 5 months was not significantly different according to intervention group (risk ratio (RR) = 0.48, 95% confidence interval (CI) = 0.19–1.19), but after adjustment for sex, race, season of year, baseline 25(OH)D status, and history of falls, participants randomized to vitamin D3 had a lower rate of falling than those randomized to placebo (RR = 0.42, 95% CI = 0.21–0.87).ConclusionA vitamin D intervention delivered through MOW was feasible, resulting in improvements in 25(OH)D concentrations and a lower rate of falls in adjusted analyses. Further research is needed to validate the reduction in falls from this type of intervention.
Recent developments in the diagnosis and treatment of pulmonary embolism
Authors: van der Hulle T. , Dronkers C. E. A. , Klok F. A. , Huisman M. V. 
Published: August 2015

AbstractDue to the nonspecific symptoms of the condition, a diagnosis of acute pulmonary embolism (PE) is frequently considered. However, PE will only be confirmed in 10–20% of patients. Because the imaging test of choice, computed tomography pulmonary angiography (CTPA), is costly and associated with radiation exposure and other complications, a validated diagnostic algorithm consisting of a clinical decision rule and D‐dimer test should be used to safely exclude PE in 20–30% of patients without the need for CTPA. Recently, the age‐adjusted D‐dimer threshold has been validated, and this has increased the proportion of patients at older age in whom PE can be excluded without CTPA. Initial therapeutic management of PE depends on the risk of short‐term PE‐related mortality. Haemodynamically unstable patients should be closely monitored and receive thrombolytic therapy unless contraindicated because of an unacceptably high bleeding risk, whereas patients with low‐risk PE may be safely discharged early from hospital or receive only outpatient treatment. The PESI score and Hestia decision rule are available to select patients in whom early discharge or outpatient treatment will be safe, although the safety of these strategies should be confirmed in additional studies. Standard PE therapy consists of low molecular weight heparin (LMWH) followed by vitamin K antagonists (VKAs). Recently, several nonvitamin K‐dependent oral anticoagulants have been shown to be as effective as LMWH/VKAs, and maybe safer. Determining the optimal duration of treatment for a first unprovoked PE remains a challenge, although clinical prediction rules for estimating the risk of recurrence of venous thromboembolism and anticoagulation‐associated haemorrhage are under investigation. Using these prediction rules may lead to both more standardized and more individualized long‐term treatment of PE.
Sensory Profile of Portuguese White Wines Using Long‐Term Memory: A Novel Nationwide Approach
Authors: Jose‐Coutinho Anibal , Avila Patricia , Ricardo‐Da‐Silva Jorge M. 
Published: August 2015

AbstractWhite wine sensory profiling of all 12 Protected Geographical Indications (PGIs) of mainland Portugal was achieved through completion of extended sensory questionnaires by 20 professional wine experts. No samples were assessed; the experiment was based on memory alone. Three macro‐zonings were found and typicality differences were statistically validated and sensory described. PGI MINHO was found the most typical of all PGIs, with several extreme rates on Color, Aroma and Taste. SOUTHERN cluster of the four meridional PGIs presented several extreme, therefore typical, sensory assessments, mostly opposite to the profile of PGI Minho. Color tonality, alcohol and acidity were mutually related and respective variations were correlated with published findings and expressed as key factors for regional macro‐zoning differentiation. Moreover, with the proposed methodology it was possible to achieve a novel nationwide sensory characterization of PGIs, overcoming ongoing macroscaling and sample representativeness limitations and envisaging new nation‐sized sensory studies.Practical ApplicationsThis innovative nationwide study on white wine typicality, namely on sensory profiles of PGI (and PDO) certified wines, may contribute to the debate of scale factors that result in significant gains in areas such as wine certification (3–5 certification boards instead of existent 12), admission of transregional wine certification for high volume brands and a better and clearer communication and marketing that would reach a larger group of consumers with condensed information on typicality. Moreover, to develop a method that bypass the sampling problem of wines that would be representative of a given PGI or, in general, a nation‐sized area may be considered useful and widely applicable to sensory studies.
Initial dissolution kinetics of cocrystal of carbamazepine with nicotinamide
Authors: Hattori Yusuke , Sato Maiko , Otsuka Makoto 
Published: August 2015

Abstract

Objectives
Objectives of this study are investigating the initial dissolution kinetics of the cocrystal of carbamazepine (CBZ) with nicotinamide (NIC) and understanding its initial dissolution process.

Methods
Cocrystal solids of CBZ with NIC were prepared by co-milling and solvent evaporation methods. The formation of cocrystal solid was verified via X-ray diffraction measurement. Dissolution tests of the solids were performed using an original flow cell and ultraviolet–visible spectroscopic detector. The spectra monitored in situ were analyzed to determine the dissolved compounds separately using the classical least squares regression method. The initial dissolution profiles were interpreted using simultaneous model of dissolution and phase changes.

Key findings
In the initial dissolution, CBZ in the cocrystal structure dissolved in water and it was suggested that CBZ reached a metastable intermediate state simultaneously with dissolution. The cocrystal solid prepared by solvent evaporation provided a higher rate constant of the phase change than that prepared by co-milling. Our results thus support the use of evaporation as the method of choice to produce ordered cocrystal structures.

Conclusion
We suggest that CBZ forms dihydrate during the dissolution process; however, during the initial phase of dissolution, CBZ changes to a metastable intermediate phase.
Does dispersal influence the strength of intraspecific competition in a stream salamander?
Authors: Davenport J. M. , Lowe W. H. 
Published: August 2015

AbstractMetacommunity ecology emphasizes the role of dispersal in linking local processes across space. Competition is one such local process that can be affected by dispersal. Dispersal can influence intraspecific trait variation, thereby affecting the strength of intraspecific competition and, consequently, the relative importance of intra‐ versus interspecific interactions. Prior research has shown that spring salamanders, Gyrinophilus porphyriticus, self‐organize within streams by a common trait (body condition) and that dispersal and gene flow along streams vary with slope. Building on this prior work, we tested how dispersal influences the strength of intraspecific competition via one of two spatial mechanisms: (1) spatial sorting of individuals by traits that affect competitive performance or (2) variation in gene flow resulting in evolutionary divergence of traits affecting competitive performance. To test these alternative mechanisms, we conducted a mesocosm experiment with spring salamanders from downstream and upstream sites of streams with low and high rates of dispersal and gene flow. Spatial patterns of intraspecific competitive performance differed significantly in the low‐ and high‐dispersal streams. In the low‐dispersal stream, downstream individuals were better intraspecific competitors than upstream individuals, whereas the opposite was true in the high‐dispersal stream. These differences support the spatial sorting mechanism, reinforcing direct dispersal data showing that high‐performance individuals are more likely to move upstream in the high‐dispersal stream and to remain downstream in the low‐dispersal stream. To our knowledge, this is the first time that spatial sorting has been explicitly identified as contributing to the strength of intraspecific interactions. Our study underscores the importance of integrating natural rates of dispersal into mechanistic experiments to understand spatial variability in the strength of intra‐ and interspecific species interactions.
Detecting recent selective sweeps while controlling for mutation rate and background selection
Authors: Huber Christian D. , DeGiorgio Michael , Hellmann Ines , Nielsen Rasmus 
Published: August 2015

AbstractA composite likelihood ratio test implemented in the program sweepfinder is a commonly used method for scanning a genome for recent selective sweeps. sweepfinder uses information on the spatial pattern (along the chromosome) of the site frequency spectrum around the selected locus. To avoid confounding effects of background selection and variation in the mutation process along the genome, the method is typically applied only to sites that are variable within species. However, the power to detect and localize selective sweeps can be greatly improved if invariable sites are also included in the analysis. In the spirit of a Hudson–Kreitman–Aguadé test, we suggest adding fixed differences relative to an out‐group to account for variation in mutation rate, thereby facilitating more robust and powerful analyses. We also develop a method for including background selection, modelled as a local reduction in the effective population size. Using simulations, we show that these advances lead to a gain in power while maintaining robustness to mutation rate variation. Furthermore, the new method also provides more precise localization of the causative mutation than methods using the spatial pattern of segregating sites alone.
Understanding the 7‐Cys module amplification of C. neoformans metallothioneins: how high capacity Cu‐binding polypeptides are built to neutralize host nutritional immunity
Authors: Espart Anna , Gil‐Moreno Selene , Palacios Òscar , Capdevila Mercè , Atrian Sílvia 
Published: August 2015

SummaryCryptococcus neoformans metallothioneins (MTs), CnMT1 and CnMT2, have been identified as essential infectivity and virulence factors of this pathogen. Both MTs are unusually long Cu‐thioneins, exhibiting protein architecture and metal‐binding abilities compatible with the hypothesis of resulting from three and five tandem repetitions of 7‐Cys motives, respectively, each of them folding into Cu5‐clusters. Through the study of the Zn(II)‐ and Cu(I)‐binding capabilities of several CnMT1 truncated mutants, we show that a 7‐Cys segment of CnMT1 folds into Cu5‐species, of additive capacity when joined in tandem. All the obtained Cu‐complexes share practically similar architectural features, if judging by their almost equivalent CD fingerprints, and they also share their capacity to restore copper tolerance in MT‐devoid yeast cells. Besides the analysis of the modular composition of these long fungal MTs, we evaluate the features of the Cys‐rich stretch spacer and flanking sequences that allow the construction of stable metal clusters by adjacent union of binding modules. Overall, our data support a mechanism by which some microbial MTs may have evolved to enlarge their original metal co‐ordination capacity under the specific selective pressure of counteracting the Cu‐based immunity mechanisms evolved by the infected hosts.
Modification of starch metabolism in transgenic Arabidopsis thaliana increases plant biomass and triples oilseed production
Authors: Liu Fushan , Zhao Qianru , Mano Noel , Ahmed Zaheer , Nitschke Felix , Cai Yinqqi , Chapman Kent D. , Steup Martin , Tetlow Ian J. , Emes Michael J. 
Published: August 2015

SummaryWe have identified a novel means to achieve substantially increased vegetative biomass and oilseed production in the model plant Arabidopsis thaliana. Endogenous isoforms of starch branching enzyme (SBE) were substituted by either one of the endosperm‐expressed maize (Zea mays L.) branching isozymes, ZmSBEI or ZmSBEIIb. Transformants were compared with the starch‐free background and with the wild‐type plants. Each of the maize‐derived SBEs restored starch biosynthesis but both morphology and structure of starch particles were altered. Altered starch metabolism in the transformants is associated with enhanced biomass formation and more‐than‐trebled oilseed production while maintaining seed oil quality. Enhanced oilseed production is primarily due to an increased number of siliques per plant whereas oil content and seed number per silique are essentially unchanged or even modestly decreased. Introduction of cereal starch branching isozymes into oilseed plants represents a potentially useful strategy to increase biomass and oilseed production in related crops and manipulate the structure and properties of leaf starch.
The mechanism of Rubisco‐catalysed oxygenation
Authors: Tcherkez Guillaume 
Published: August 2015

AbstractRibulose‐1,5‐bisphosphate carboxylase/oxygenase (Rubisco) is the cornerstone of photosynthetic carbon assimilation because it catalyses the fixation of CO2 onto ribulose‐1,5‐bisphosphate (RuBP). The enzyme also catalyses RuBP oxygenation, thereby evolving phosphoglycolate which is recycled along the photorespiratory pathway. Oxygenation is quantitatively important, because under ordinary gaseous conditions, more than one third of RuBP molecules are oxygenated rather than carboxylated. However, contrary to carboxylation, the chemical mechanism of oxygenation is not well known, and little progress has been made since the early 80s. Here, I review recent experimental data that provide some new insights into the reaction mechanism, and carry out simple calculations of kinetic parameters. Isotope effects suggest that oxygenation is less likely initiated by a redox phenomenon (such as superoxide production) and more likely involves concerted chemical events that imply interactions with protons. A possible energy profile of the reaction is drawn which suggests that the generation of the oxygenated reaction intermediate (peroxide) is irreversible. Possible changes in oxygenation‐associated rate constants between Rubisco forms are discussed.
Is there a relationship between low vitamin D and rotaviral diarrhea?
Authors: Bucak Ibrahim Hakan , Ozturk Agah Bahadır , Almis Habip , Cevik Muhammer Özgür , Tekin Mehmet , Konca Çapan , Turgut Mehmet , Bulbul Mehmet 
Published: August 2015

AbstractBackgroundFor children under 5 years of age, 1700 000 000 episodes of diarrhea are seen worldwide, and death occurs in 700 000 of these cases due to diarrhea. Rotavirus is an important cause of diarrhea in this age group, and many studies have shown that vitamin D plays a pivotal role in the immune system, as well as in antimicrobial peptide gene expression. In addition, lower vitamin D has been correlated with higher rates of infectious diseases such as respiratory tract infection, tuberculosis, and viral infection.MethodsSeventy patients with rotaviral diarrhea and 67 healthy patients were enrolled in this study. Serum 25‐hydroxy vitamin D3 (25(OH)D3), parathormone, calcium, phosphate, alkaline phosphatase, complete blood count parameters, and C‐reactive protein were compared between pre‐school children hospitalized due to rotaviral diarrhea and healthy children. Additionally, birthweight, feeding habits in the first 6 months of life, vitamin D and multivitamin supplements, and rotaviral vaccinations were also evaluated in each group.ResultsThere were no differences between the groups with regard to gender and age, but 25(OH)D3 was significantly different: 14.6 ± 8.7 ng/mL in the rotaviral diarrhea patients versus 29.06 ± 6.51 ng/mL in the health controls (P < 0.001), and serum 25(OH)D3 <20 ng/mL (OR, 6.3; 95%CI: 3.638–10.909; P < 0.001) was associated with rotaviral diarrhea.ConclusionsLow vitamin D is associated with rotaviral diarrhea. This is the first study in the literature to show this, and this result needs to be repeated in larger controlled clinical studies.