bluuebunny/crossref_metadata_2025_split huggingface dataset:
More satisfied, but why? A pooled patient‐level analysis of treatment satisfaction following the initiation of insulin glargine vs. comparators in insulin‐naïve patients with type 2 diabetes mellitus
Authors: Polonsky W. , Traylor L. , Wei W. , Shi R. , Ameer B. , Vlajnic A. , Nicolucci A. 
Published: September 2013

AimTo assess patient‐reported outcomes associated with initiating insulin glargine among insulin‐naïve patients with type 2 diabetes mellitus (T2DM).MethodsThis was a pooled analysis of patient‐level data from Phase 3, randomized controlled trials evaluating once‐daily insulin glargine vs. comparator treatment for ≥24 weeks in previously insulin‐naïve adult patients with T2DM and poor glycaemic control. Eligible studies utilized strict, predefined insulin titration algorithms with weekly dose‐adjustment to achieve fasting plasma glucose (FPG) levels of ≤5.6 mmol/l. Treatment satisfaction was measured using the Diabetes Treatment Satisfaction Questionnaire (DTSQ) change (c) and status (s) versions.ResultsA total of 1577 patients from four studies were included; 830 patients treated with insulin glargine and 747 with comparators. At week 24, DTSQc scores improved in both groups with a significantly higher increase in treatment satisfaction for insulin glargine vs. comparators (13.5 vs. 12.1; p < 0.0001). Multivariate regression analysis revealed that significant predictors of DTSQc improvement at week 24 were insulin glargine treatment (p < 0.0001), higher baseline DTSQs (p < 0.0001), and lower baseline body weight (p = 0.0103). Greater improvement in DTSQc at week 24 was significantly associated with decrease from baseline in glycosylated haemoglobin (p < 0.001) and FPG (p = 0.0001); a numerically more positive change in weight from baseline approached significance (p = 0.07).ConclusionInitiation of insulin glargine in insulin‐naïve patients with T2DM is associated with greater improvements in treatment satisfaction than alternative interventions, with perceived improvements in glycaemic control and baseline weight likely to be important factors.
Reducing capacity of water extracts of biochars and their solubilization of soilMn andFe
Authors: Graber E. R. , Tsechansky L. , Lew B. , Cohen E. 
Published: September 2013

SummaryBiochar, being produced in an oxygen‐restricted environment, is chemically more reduced than the original feedstock. Consequently, it was hypothesized that reduced biochar components could participate in redox‐mediated reactions in the soil. This hypothesis was tested by measuring the reducing capacities of aqueous extracts of biochars and the reduction and solubilization of soilMn andFe oxides by the extracts. The reduction capacity of extracts from biochars produced from three feedstocks (eucalyptus wood,EUC; olive pomace,OP; and greenhouse waste,GHW) at different highest pyrolysis treatment temperatures (HTT; 350, 450, 600 and 800°C) was less for theEUCfeedstock than the others, and was greater for biochars produced at lowerHTTs. The organic fraction of the extracts apparently was responsible for the major part of the reducing capacity. Extracts of smaller‐HTTbiochars, having greater dissolved organic carbon (DOC) contents, had greater reducing capacities than extracts of larger‐HTTbiochars from the same feedstock. Extracts of twoGHWbiochars (GHW‐450 andGHW‐600) solubilizedMn andFe from soils atpHvalues below 8. The extract with the greater reducing capacity (GHW‐450) solubilized both metals to a significantly greater extent. Smaller‐HTTbiochars produced from agricultural wastes, having a greater variety and concentration of soluble reducing agents, are expected to have more impact on soil redox reactions than larger‐HTTbiochars. By participating in chemical and biological redox‐mediated reactions in the soil, biochar could influence microbial electron shuttling, nutrient cycling, pollutant degradation, contaminant mobilization and abiotic formation of humic structures.
The spatial patterns of directional phenotypic selection
Authors: Siepielski Adam M. , Gotanda Kiyoko M. , Morrissey Michael B. , Diamond Sarah E. , DiBattista Joseph D. , Carlson Stephanie M. 
Published: September 2013

AbstractLocal adaptation, adaptive population divergence and speciation are often expected to result from populations evolving in response to spatial variation in selection. Yet, we lack a comprehensive understanding of the major features that characterise the spatial patterns of selection, namely the extent of variation among populations in the strength and direction of selection. Here, we analyse a data set of spatially replicated studies of directional phenotypic selection from natural populations. The data set includes 60 studies, consisting of 3937 estimates of selection across an average of five populations. We performed meta‐analyses to explore features characterising spatial variation in directional selection. We found that selection tends to vary mainly in strength and less in direction among populations. Although differences in the direction of selection occur among populations they do so where selection is often weakest, which may limit the potential for ongoing adaptive population divergence. Overall, we also found that spatial variation in selection appears comparable to temporal (annual) variation in selection within populations; however, several deficiencies in available data currently complicate this comparison. We discuss future research needs to further advance our understanding of spatial variation in selection.
Analysis of mitochondrial COI sequences of the Diachasmimorpha longicaudata (Hymenoptera: Braconidae) species complex in Thailand
Authors: Julsirikul Duangta , Worapong Jeerapun , Kitthawee Sangvorn 
Published: September 2013

AbstractDiachasmimorpha longicaudata is an Opiinae parasitoid used to control tephritid fruit flies, which cause tremendous economic losses of fruits worldwide. In Thailand, D. longicaudata is classified as three sibling species, DLA, DLB and DLBB, based on the morphological and biological species concepts but their genetic variation has not been studied. Therefore, we investigated the genetic differentiation of the mitochondrial COI gene to clarify the ambiguous taxonomy of this species complex. The 603‐bp COI region was sequenced from laboratory‐bred colonies and field‐collected specimens from seven locations representing five geographical regions in Thailand. DLA was associated with the host Bactrocera correcta while DLB and DLBB were associated with Bactrocera dorsalis. The interspecific nucleotide differences of COI sequences among the three groups ranged from 6.70% to 7.62% (Kimura 2‐parameter distance), which adequately separates species complexes within the order Hymenoptera and supports the current sibling species classification. The neighbor joining, maximum likelihood and consensus Bayesian phylogenetic trees constructed from COI sequences revealed that the three sibling species of laboratory and field‐collected D. longicaudata are monophyletic with 100% support. The high genetic variation and molecular phylogeny of the COI sequences were shown to discriminate between the D. longicaudata species examined in this study.
Functional and structural brain networks in epilepsy: What have we learned?
Authors: van Diessen Eric , Diederen Sander J. H. , Braun Kees P. J. , Jansen Floor E. , Stam Cornelis J. 
Published: September 2013

SummaryBrain functioning is increasingly seen as a complex interplay of dynamic neural systems that rely on the integrity of structural and functional networks. Recent studies that have investigated functional and structural networks in epilepsy have revealed specific disruptions in connectivity and network topology and, consequently, have led to a shift from “focus” to “networks” in modern epilepsy research. Disruptions in these networks may be associated with cognitive and behavioral impairments often seen in patients with chronic epilepsy. In this review, we aim to provide an overview that would introduce the clinical neurologist and epileptologist to this new theoretical paradigm. We focus on the application of a theory, called “network analysis,” to characterize resting‐state functional and structural networks and discuss current and future clinical applications of network analysis in patients with epilepsy.
Microstructural integrity of early‐ versus late‐myelinating white matter tracts in medial temporal lobe epilepsy
Authors: Lee Chu‐Yu , Tabesh Ali , Benitez Andreana , Helpern Joseph A. , Jensen Jens H. , Bonilha Leonardo 
Published: September 2013

SummaryPurposePatients with medial temporal lobe epilepsy (MTLE) exhibit structural brain damage involving gray matter (GM) and white matter (WM). The mechanisms underlying tissue loss in MTLE are unclear and may be associated with a combination of seizure excitotoxicity and WM vulnerability. The goal of this study was to investigate whether late‐myelinating WM tracts are more vulnerable to injury in MTLE compared with early myelinating tracts.MethodsDiffusional kurtosis imaging scans were obtained from 25 patients with MTLE and from 36 matched healthy controls. Diffusion measures from regions of interest (ROIs) for both late‐ and early myelinating WM tracts were analyzed. Regional Z‐scores were computed with respect to normal controls to compare WM in early myelinating tracts versus late‐myelinating tracts.Key FindingsWe observed that late‐myelinating tracts exhibited a larger decrease in mean, axial, and radial kurtosis compared with early myelinating tracts. We also observed that the change in radial kurtosis was more pronounced in late‐myelinating tracts ipsilateral to the side of seizure onset.SignificanceThese results suggest a developmentally based preferential susceptibility of late‐myelinating WM tracts to damage in MTLE. Brain injury in epilepsy may be due to the pathologic effects of seizures in combination with regional WM vulnerability.
Distal limb desensitisation following analgesia of the digital flexor tendon sheath in horses using four different techniques
Authors: Jordana M. , Martens A. , Duchateau L. , Vanderperren K. , Saunders J. , Oosterlinck M. , Pille F. 
Published: September 2013

SummaryReasons for performing studyControversy exists about the desensitisation obtained after diagnostic analgesia of the digital flexor tendon sheath (DFTS) during lameness examinations.ObjectivesTo determine whether DFTS analgesia results in inadvertent desensitisation of the palmar/plantar digital nerves and whether this depends on the injection technique used.Study designCrossover experimental study.MethodsThe DFTS of 9 horses were injected with local anaesthetic solution and radiodense contrast medium using one of the following techniques: Proximal (at lateral proximal recess of the DFTS), Axial (axial to the lateral proximal sesamoid bone), Base (at base of the lateral proximal sesamoid bone), and Distal (at palmar/plantar mid‐pastern). In total, 72 injections were performed. Skin desensitisation at the heel bulbs was tested with a dynamometer before and at 15, 30, 90 and 120 min after injection.ResultsOverall, complete desensitisation of a heel bulb at one or more time points after injection occurred in 22 limbs (30.6%). An additional 7 limbs were partially desensitised. Complete skin desensitisation occurred in 10, 3, 4 and 5 limbs using the Proximal, Axial, Base and Distal techniques respectively. Significant differences between techniques were only found at T30. The probability of skin desensitisation at the heel bulbs was 4 times higher when using the Proximal compared with the Axial and Base techniques in the forelimbs, and 3 times higher compared with the Axial and Distal techniques in the hindlimbs. Skin desensitisation nearly always occurred exclusively on the lateral heel bulb. Bilateral desensitisation only occurred in 5 limbs.ConclusionsAnaesthesia of the palmar/plantar digital nerves with distal limb desensitisation often occurs after DFTS analgesia. A higher chance of desensitisation exists when injecting the proximal DFTS recess. It is advisable to verify skin sensitivity at the heel bulbs after DFTS analgesia to avoid false interpretations about the origin of pain causing lameness.
Syndromic surveillance for evaluating the occurrence of healthcare‐associated infections in equine hospitals
Authors: Ruple‐Czerniak A. A. , Aceto H. W. , Bender J. B. , Paradis M. R. , Shaw S. P. , Van Metre D. C. , Weese J. S. , Wilson D. A. , Wilson J. , Morley P. S. 
Published: September 2013

SummaryReasons for performing studyMethods that can be used to estimate rates of healthcare‐associated infections and other nosocomial events have not been well established for use in equine hospitals. Traditional laboratory‐based surveillance is expensive and cannot be applied in all of these settings.ObjectivesTo evaluate the use of a syndromic surveillance system for estimating rates of occurrence of healthcare‐associated infections among hospitalised equine cases.Study designMulticentre, prospective longitudinal study.MethodsThis study included weaned equids (n = 297) that were admitted for gastrointestinal disorders at one of 5 participating veterinary referral hospitals during a 12‐week period in 2006. A survey form was completed by the primary clinician to summarise basic case information, procedures and treatments the horse received, and whether one or more of 7 predefined nosocomial syndromes were recognised at any point during hospitalisation. Adjusted rates of nosocomial events were estimated using Poisson regression. Risk factors associated with the risk of developing a nosocomial event were analysed using multivariable logistic regression.ResultsAmong the study population, 95 nosocomial events were reported to have occurred in 65 horses. Controlling for differences among hospitals, 19.7% (95% confidence interval, 14.5–26.7) of the study population was reported to have had at least one nosocomial event recognised during hospitalisation. The most commonly reported nosocomial syndromes that were unrelated to the reason for hospitalisation were surgical site inflammation and i.v. catheter site inflammation.ConclusionsSyndromic surveillance systems can be standardised successfully for use across multiple hospitals without interfering with established organisational structures, in order to provide useful estimates of rates related to healthcare‐associated infections.
Serum levels of leptin receptor in patients with malignant melanoma as a new tumor marker
Authors: Mizutani Hironori , Fukushima Satoshi , Masuguchi Shinichi , Yamashita Junji , Miyashita Azusa , Nakahara Satoshi , Aoi Jun , Inoue Yuji , Jinnin Masatoshi , Ihn Hironobu 
Published: September 2013

AbstractLeptin is known to be abnormally expressed in a variety of cancers, and leptin receptors have been reported to be expressed on human melanoma cells. In this study, we evaluated the possibility that the serum levels of leptin receptor could be a tumor marker of malignant melanoma (MM). Serum samples were obtained from 71 patients with MM, and the serum levels of leptin receptor were measured by double‐determinant ELISA. Interestingly, serum levels of leptin receptor decreased gradually with the stages of MM, being highest at in situ and lowest at stage IV. There was also a trend of reverse correlation between tumor thickness and serum levels of leptin receptor. To our knowledge, this is the first report investigating the serum levels of leptin receptor in MM, and serum leptin receptor levels may be used as a useful tumor marker of MM.
Full‐length dysferlin expression driven by engineered human dystrophic blood derived CD133+ stem cells
Authors: Meregalli Mirella , Navarro Claire , Sitzia Clementina , Farini Andrea , Montani Erica , Wein Nicolas , Razini Paola , Beley Cyriaque , Cassinelli Letizia , Parolini Daniele , Belicchi Marzia , Parazzoli Dario , Garcia Luis , Torrente Yvan 
Published: September 2013

The protein dysferlin is abundantly expressed in skeletal and cardiac muscles, where its main function is membrane repair. Mutations in the dysferlin gene are involved in two autosomal recessive muscular dystrophies: Miyoshi myopathy and limb‐girdle muscular dystrophy type 2B. Development of effective therapies remains a great challenge. Strategies to repair the dysferlin gene by skipping mutated exons, using antisense oligonucleotides (AONs), may be suitable only for a subset of mutations, while cell and gene therapy can be extended to all mutations. AON‐treated blood‐derived CD133+ stem cells isolated from patients with Miyoshi myopathy led to partial dysferlin reconstitution in vitro but failed to express dysferlin after intramuscular transplantation into scid/blAJ dysferlin null mice. We thus extended these experiments producing the full‐length dysferlin mediated by a lentiviral vector in blood‐derived CD133+ stem cells isolated from the same patients. Transplantation of engineered blood‐derived CD133+ stem cells into scid/blAJ mice resulted in sufficient dysferlin expression to correct functional deficits in skeletal muscle membrane repair. Our data suggest for the first time that lentivirus‐mediated delivery of full‐length dysferlin in stem cells isolated from Miyoshi myopathy patients could represent an alternative therapeutic approach for treatment of dysferlinopathies.
Modulation of ligand–heme reactivity by binding pocket residues demonstrated in cytochrome c' over the femtosecond–second temporal range
Authors: Russell Henry J. , Hardman Samantha J. O. , Heyes Derren J. , Hough Michael A. , Greetham Gregory M. , Towrie Michael , Hay Sam , Scrutton Nigel S. 
Published: September 2013

The ability of hemoproteins to discriminate between diatomic molecules, and the subsequent affinity for their chosen ligand, is fundamental to the existence of life. These processes are often controlled by precise structural arrangements in proteins, with heme pocket residues driving reactivity and specificity. One such protein is cytochrome c', which has the ability to bind nitric oxide (NO) and carbon monoxide (CO) on opposite faces of the heme, a property that is shared with soluble guanylate cycle. Like soluble guanylate cyclase, cytochrome c' also excludes O2 completely from the binding pocket. Previous studies have shown that the NO binding mechanism is regulated by a proximal arginine residue (R124) and a distal leucine residue (L16). Here, we have investigated the roles of these residues in maintaining the affinity for NO in the heme binding environment by using various time‐resolved spectroscopy techniques that span the entire femtosecond–second temporal range in the UV‐vis spectrum, and the femtosecond–nanosecond range by IR spectroscopy. Our findings indicate that the tightly regulated NO rebinding events following excitation in wild‐type cytochrome c' are affected in the R124A variant. In the R124A variant, vibrational and electronic changes extend continuously across all time scales (from fs–s), in contrast to wild‐type cytochrome c' and the L16A variant. Based on these findings, we propose a NO (re)binding mechanism for the R124A variant of cytochrome c' that is distinct from that in wild‐type cytochrome c'. In the wider context, these findings emphasize the importance of heme pocket architecture in maintaining the reactivity of hemoproteins towards their chosen ligand, and demonstrate the power of spectroscopic probes spanning a wide temporal range.
The oxygen‐tolerant and NAD+‐dependent formate dehydrogenase from Rhodobacter capsulatus is able to catalyze the reduction of CO2 to formate
Authors: Hartmann Tobias , Leimkühler Silke 
Published: September 2013

The formate dehydrogenase from Rhodobacter capsulatus (RcFDH) is an oxygen‐tolerant protein with an (αβγ)2 subunit composition that is localized in the cytoplasm. It belongs to the group of metal and NAD+‐dependent FDHs with the coordination of a molybdenum cofactor, four [Fe4S4] clusters and one [Fe2S2] cluster associated with the α‐subunit, one [Fe4S4] cluster and one FMN bound to the β‐subunit, and one [Fe2S2] cluster bound to the γ‐subunit. RcFDH was heterologously expressed in Escherichia coli and characterized. Cofactor analysis showed that the bis‐molybdopterin guanine dinucleotide cofactor is bound to the FdsA subunit containing a cysteine ligand at the active site. A turnover rate of 2189 min−1 with formate as substrate was determined. The back reaction for the reduction of CO2 was catalyzed with a kcat of 89 min−1. The preference for formate oxidation shows an energy barrier for CO2 reduction of the enzyme. Furthermore, the FMN‐containing and [Fe4S4]‐containing β‐subunit together with the [Fe2S2]‐containing γ‐subunit forms a diaphorase unit with activities for both NAD+ reduction and NADH oxidation. In addition to the structural genes fdsG, fdsB, and fdsA, the fds operon in R. capsulatus contains the fdsC and fdsD genes. Expression studies showed that RcFDH is only active when both FdsC and FdsD are present. Both proteins are proposed to be involved in bis‐molybdopterin guanine dinucleotide modification and insertion into RcFDH.
Sharp evaluation of the Oore–Burns integral for cracks subjected to arbitrary normal stress field
Authors: Livieri P. , Segala F. 
Published: September 2013

ABSTRACTThis paper presents a new approximation formula for the Oore–Burns integral related to three‐dimensional weight functions. The approach drastically reduces the computational time of the Oore–Burns integral with respect to previous formulations because the mesh over the integration domain can be very coarse without loss of accuracy. This is made possible by analytic evaluation of the coefficient of δ1/2 of the deviation between the integral and its Riemann sum (δ is the size of the mesh over the crack). In the case of a penny‐shaped crack, the new equation can be considered as an explicit formulation of the exact weight function of Galin.In order to confirm the accuracy of our new formulation, we consider the case of penny‐shaped cracks under different types of mode I loading. Predictions of the stress intensity factor are compared with analytical predictions along the crack, and the new equation appears to be stable with respect to the refinement of the mesh. Furthermore, it is accurate even when the stress field is represented with high‐order polynomial terms.Finally, we apply our approximation of the Oore–Burns integral to an elliptical crack with small eccentricity under uniform pressure. Agreement with the Irwin solution is excellent.
Probabilistic risk analysis of fracture of aircraft structures using a Bayesian approach to update the distribution of the equivalent initial flaw sizes
Authors: Torregosa R. F. , Hu W. 
Published: September 2013

ABSTRACTA new method has been proposed to improve the accuracy of the probabilistic risk analysis of aircraft structures by progressively updating the distribution of the initial flaw sizes based on subsequent observations. The current flight hours of an aircraft are used to update the initial assumption of the distribution of the initial flaw sizes, based on the Bayes' theorem. Two Bayesian updating methods are presented: the first using the successful flight hours of the aircraft being analysed and the second using flight histories of similar aircraft in the fleet. In the first method, it is demonstrated that the Bayesian updating method can improve the risk analysis results of a single aircraft by utilising its own flight history. In the second method, it is demonstrated that the risk analysis result can be improved by utilising the collective flight histories of all aircraft in a fleet.