bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monitoring Primary Systemic Therapy of Large and Locally Advanced Breast Cancer by Using Sequential Positron Emission Tomography Imaging With [18F]Fluorodeoxyglucose
Authors: Schwarz-Dose Jörg , Untch Michael , Tiling Reinhold , Sassen Stefanie , Mahner Sven , Kahlert Steffen , Harbeck Nadia , Lebeau Annette , Brenner Winfried , Schwaiger Markus , Jaenicke Fritz , Avril Norbert 
Published: December 2008

Purpose To evaluate positron emission tomography (PET) using [18F]fluorodeoxyglucose (FDG) for prediction of histopathologic response early during primary systemic therapy of large or locally advanced breast cancer. Patients and Methods In a prospective multicenter trial, 272 FDG-PET scans were performed in 104 patients at baseline (n = 104) and after the first (n = 87) and second cycle (n = 81) of chemotherapy. The level and relative changes in standardized uptake value (SUV) of FDG uptake were assessed regarding their ability to predict histopathologic response. All patients underwent surgery after chemotherapy, and histopathologic response defined as minimal residual disease or gross residual disease served as the reference standard. Results Seventeen (16%) of 104 patients were histopathologic responders and 87 were (84%) nonresponders. All patients for whom baseline SUV was less than 3.0 (n = 24) did not achieve a histopathologic response. SUV decreased by 51% ± 18% after the first cycle of chemotherapy in histopathologic responders (n = 15), compared with 37% ± 21% in nonresponders (n = 54; P = .01). A threshold of 45% decrease in SUV correctly identified 11 of 15 responders, and histopathologic nonresponders were identified with a negative predictive value of 90%. Similar results were found after the second cycle when using a threshold of 55% relative decrease in SUV. Conclusion FDG-PET allows for prediction of treatment response by the level of FDG uptake in terms of SUV at baseline and after each cycle of chemotherapy. Moreover, relative changes in SUV after the first and second cycle are a strong predictor of response. Thus, FDG-PET may be helpful for individual treatment stratification in breast cancer patients.
Phase I Trial and Pharmacokinetic Study of Ixabepilone Administered Daily for 5 Days in Children and Adolescents With Refractory Solid Tumors
Authors: Widemann Brigitte C. , Goodspeed Wendy , Goodwin Anne , Fojo Tito , Balis Frank M. , Fox Elizabeth 
Published: December 2008

Purpose The objectives of this phase I trial were to determine the maximum-tolerated dose (MTD), toxicity profile, dose-limiting toxicities (DLTs), pharmacokinetics, and preliminary response rate for ixabepilone, a microtubule-stabilizing agent, administered intravenously daily for 5 days in children and adolescents. Patients and Methods Patients ≥ 2 and ≤ 18 years with relapsed or refractory solid tumors were enrolled onto sequential cohorts to the following five dose levels: 3.0 (n = 3), 4.5 (n = 4), 6.0 (n = 3), 8.0 (n = 6), and 10 (n = 3) mg/m2/d. Eligibility criteria, dose levels, definitions of DLT and MTD, and pharmacokinetic sampling times were designed to be as similar as possible to the adult phase I trial of ixabepilone on the same schedule. Results Nineteen children (median age, 10 years; range, 2 to 18 years) were enrolled, and 18 (12 with sarcomas) were assessable for toxicity. DLTs (grade 4 neutropenia for > 5 days and grade 3 fatigue) were observed in two of three patients receiving 10 mg/m2/d. The MTD of ixabepilone administered daily for 5 days every 21 days was 8 mg/m2/d. Myelosuppression, GI, and hepatic toxicities were common non-DLTs. Peripheral neuropathy was uncommon. Ixabepilone clearance was 475 ± 247 mL/min/m2, volume of distribution at steady-state was 12.2 ± 5.4 L/kg, and half-life was 14 hours. Conclusion The recommended dose of ixabepilone for phase II trials in solid tumors is 8 mg/m2/d daily for 5 days every 21 days. This dose is 33% higher than the MTD in adults receiving the same dosing schedule. Pharmacokinetic parameters in children and adolescents were highly variable but similar to adults.
Effective Treatment of Acute Promyelocytic Leukemia With All-Trans-Retinoic Acid, Arsenic Trioxide, and Gemtuzumab Ozogamicin
Authors: Ravandi Farhad , Estey Eli , Jones Dan , Faderl Stefan , O'Brien Susan , Fiorentino Jackie , Pierce Sherry , Blamble Deborah , Estrov Zeev , Wierda William , Ferrajoli Alessandra , Verstovsek Srdan , Garcia-Manero Guillermo , Cortes Jorge , Kantarjian Hagop 
Published: December 2008

Purpose We examined the outcome of patients with newly diagnosed acute promyelocytic leukemia (APL) treated with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) with or without gemtuzumab ozogamicin (GO) but without traditional cytotoxic chemotherapy. Patients and Methods From February 2002 to March 2008, 82 patients with APL were treated with a combination of ATRA plus ATO. The first cohort of 65 patients received ATRA and ATO (beginning on day 10 of ATRA). High-risk patients (WBCs ≥ 10 × 109/L) received GO on the first day. From July 2007, the second cohort of 17 patients received ATRA and ATO concomitantly on day 1. They also received GO on day 1, if high risk, and if their WBC increased to more than 30 × 109/L during induction. Monitoring for PML-RARA fusion gene was conducted after induction and throughout consolidation and follow-up. Results Overall, 74 patients achieved complete remission (CR) and one achieved CR without full platelet recovery after the induction, for a response rate of 92%. Seven patients died at a median of 4 days (range, 1 to 24 days) after inclusion in the study from disease-related complications. The median follow-up is 99 weeks (range, 2 to 282 weeks). Among the responding patients, three experienced relapse at 39, 52, and 53 weeks. Three patients died after being in CR for 14, 21, and 71 weeks, all from a second malignancy. The estimated 3-year survival rate is 85%. Conclusion The combination of ATRA and ATO (with or without GO) as initial therapy for APL was effective and safe and can substitute chemotherapy-containing regimens.
Elevated Plasma YKL-40 Predicts Increased Risk of Gastrointestinal Cancer and Decreased Survival After Any Cancer Diagnosis in the General Population
Authors: Johansen Julia S. , Bojesen Stig E. , Mylin Anne K. , Frikke-Schmidt Ruth , Price Paul A. , Nordestgaard Børge G. 
Published: December 2008

Purpose Elevated plasma YKL-40 is a biomarker of poor prognosis in cancer patients. We tested the hypotheses that elevated plasma YKL-40 predicts risk of cancer as well as survival after a cancer diagnosis in the general population. Patients and Methods A prospective cohort study of 8,899 subjects (20 to 95 years) from the Danish general population, the Copenhagen City Heart Study, observed for 11 years for cancer incidence and 14 years for death: 1,432 participants had a first incident cancer, 968 of these died. Hazard ratios (HRs) for cancer events and death after events according to plasma YKL-40 in sex and 10 years age percentile categories: 0% to 33%, 34% to 66%, 67% to 90%, 91% to 95%, and 96% to 100%. Results The cumulative incidence of gastrointestinal cancer increased with increasing YKL-40 (trend P < .0001). Multifactorially adjusted HRs for gastrointestinal cancer were 1.0 (95% CI, 0.7 to 1.5) for YKL-40 in category 34% to 66%, 1.5 for 67% to 90% (95% CI, 1.0 to 2.3), 2.4 for 91% to 95%, (95% CI, 1.3 to 4.6), and 3.4 for 96% to 100% (95% CI, 1.9 to 6.1) versus YKL-40 category 0% to 33% (P < .0001). Participants with any cancer event and YKL-40 category 91% to 100% had a median survival time after the diagnosis of 1 year versus 4 years in participants with YKL-40 category 0% to 33% (P < .0001). Corresponding values for gastrointestinal cancer were 6 months versus 1 year (P = .007). Multifactorially adjusted HRs for early death were 1.8 (95% CI, 1.3 to 2.5; P < .0001) after any cancer and 2.4 (95% CI, 1.3 to 4.3; P = .005) after gastrointestinal cancer in participants with YKL-40 category 91% to 100% versus 0% to 33%. Conclusion In the general population, elevated plasma YKL-40 predicts increased risk of gastrointestinal cancer and decreased survival after any cancer diagnosis.
Powered ankle exoskeletons reveal the metabolic cost of plantar flexor mechanical work during walking with longer steps at constant step frequency
Authors: Sawicki Gregory S. , Ferris Daniel P. 
Published: December 2008

SUMMARYWe examined the metabolic cost of plantar flexor muscle–tendon mechanical work during human walking. Nine healthy subjects walked at constant step frequency on a motorized treadmill at speeds corresponding to 80% (1.00 m s–1), 100% (1.25 m s–1), 120% (1.50 m s–1) and 140% (1.75 m s–1) of their preferred step length (L*) at 1.25 m s–1. In each condition subjects donned robotic ankle exoskeletons on both legs. The exoskeletons were powered by artificial pneumatic muscles and controlled using soleus electromyography (i.e. proportional myoelectric control). We measured subjects' metabolic energy expenditure and exoskeleton mechanics during both unpowered and powered walking to test the hypothesis that ankle plantarflexion requires more net metabolic power (W kg–1) at longer step lengths for a constant step frequency (i.e. preferred at 1.25 m s–1). As step length increased from 0.8 L* to 1.4 L*, exoskeletons delivered ∼25% more average positive mechanical power (P=0.01; +0.20±0.02 W kg–1to +0.25±0.02 W kg–1, respectively). The exoskeletons reduced net metabolic power by more at longer step lengths (P=0.002;–0.21±0.06 W kg–1 at 0.8 L* and–0.70±0.12 W kg–1 at 1.4 L*). For every 1 J of exoskeleton positive mechanical work subjects saved 0.72 J of metabolic energy (`apparent efficiency'=1.39) at 0.8 L* and 2.6 J of metabolic energy (`apparent efficiency'=0.38) at 1.4 L*. Declining ankle muscle–tendon `apparent efficiency' suggests an increase in ankle plantar flexor muscle work relative to Achilles' tendon elastic energy recoil during walking with longer steps. However, previously stored elastic energy in Achilles' tendon still probably contributes up to 34% of ankle muscle–tendon positive work even at the longest step lengths we tested. Across the range of step lengths we studied, the human ankle muscle–tendon system performed 34–40% of the total lower-limb positive mechanical work but accounted for only 7–26% of the net metabolic cost of walking.
Swimming for your life: locomotor effort and oxygen consumption during the green turtle (Chelonia mydas) hatchling frenzy
Authors: Booth David T. 
Published: December 2008

SUMMARYSwimming effort and oxygen consumption of newly emerged green turtle Chelonia mydas hatchlings was measured simultaneously and continuously for the first 18 h of swimming after hatchlings entered the water. Oxygen consumption was tightly correlated to swimming effort during the first 12 h of swimming indicating that swimming is powered predominantly by aerobic metabolism. The patterns of swimming effort and oxygen consumption could be divided into three distinct phases: (1) the rapid fatigue phase from 0 to 2 h when the mean swim thrust decreased from 45 to 30 mN and oxygen consumption decreased from 33 to 18 ml h–1; (2) the slow fatigue phase from 2 to 12 h when the mean swim thrust decreased from 30 to 22 mN and oxygen consumption decreased from 18 to 10 ml h–1; and(3) the sustained effort phase from 12 to 18 h when mean swim thrust averaged 22 mN and oxygen consumption averaged 10 ml h–1. The decrease in mean swim thrust was caused by a combination of a decrease in front flipper stroke rate during a power stroking bout, a decrease in mean maximum thrust during a power stroking bout and a decrease in the proportion of time spent power stroking. Hence hatchlings maximise their swimming thrust as soon as they enter the water, a time when a fast swimming speed will maximise the chance of surviving the gauntlet of predators inhabiting the shallow fringing reef before reaching the relative safety of deeper water.
Source, topography and excitatory effects of GABAergic innervation in cockroach salivary glands
Authors: Rotte Cathleen , Witte Jeannine , Blenau Wolfgang , Baumann Otto , Walz Bernd 
Published: December 2008

SUMMARYCockroach salivary glands are innervated by dopaminergic and serotonergic neurons. Both transmitters elicit saliva secretion. We studied the distribution pattern of neurons containing γ-aminobutyric acid (GABA)and their physiological role. Immunofluorescence revealed a GABA-immunoreactive axon that originates within the subesophageal ganglion at the salivary neuron 2 (SN2) and this extends within the salivary duct nerve towards the salivary gland. GABA-positive fibers form a network on most acinar lobules and a dense plexus in the interior of a minor fraction of acinar lobules. Co-staining with anti-synapsin revealed that some putative GABAergic terminals seem to make pre-synaptic contacts with GABA-negative release sites. Many putative GABAergic release sites are at some distance from other synapses and at distance from the acinar tissue. Intracellular recordings from isolated salivary glands have revealed that GABA does not affect the basolateral membrane potential of the acinar cells directly. When applied during salivary duct nerve stimulation, GABA enhances the electrical response of the acinar cells and increases the rates of fluid and protein secretion. The effect on electrical cell responses is mimicked by the GABAB receptor agonists baclofen and SKF97541, and blocked by the GABAB receptor antagonists CGP52432 and CGP54626. These findings indicate that GABA has a modulatory role in the control of salivation, acting presynaptically on serotonergic and/or dopaminergic neurotransmission.
Habitat temperature is an important determinant of cholesterol contents in copepods
Authors: Hassett R. Patrick , Crockett Elizabeth L. 
Published: December 2008

SUMMARYEffects of habitat and acclimation temperature on cholesterol contents were examined in oceanic and inshore species of copepods. The cholesterol content of five species of thermally acclimated copepods was determined, and nine species (representing six families) were sampled to assess the role of habitat temperature. The species selected have maximum habitat temperatures (and temperature tolerances) that vary at least twofold. Levels of dietary cholesterol required to achieve maximum growth were also studied at different acclimation temperatures in a eurythermal copepod. Both eggs and copepodites of Calanus finmarchicus had higher cholesterol levels at the warm acclimation temperature (16°C) than at the cooler temperature (6°C). Neither Acartia tonsa, Acartia hudsonica, Temora longicornis nor Eurytemora affinis altered cholesterol contents with acclimation temperature. Maximum growth rates were achieved at fourfold higher concentrations of dietary cholesterol in warm-acclimated Eurytemora affinis than in cold-acclimated animals. The most consistent trend is the positive relationship between cholesterol content and habitat temperature. Species residing in warmer habitats (e.g. Centropages typicus, Eurytemora affinis) had approximately twice the cholesterol of species living in colder waters (e.g. Calanus glacialis, Euchaeta norvegica). A similar pattern was observed for comparisons of species within genera (Calanus,Acartia and Centropages), with the species abundant at lower latitudes having more cholesterol than the northern congener. These data indicate that habitat temperature is an important determinant of cholesterol content, and cholesterol endows membranes with the stability required for a range of body temperatures.
Intense echolocation calls from two `whispering' bats,Artibeus jamaicensisandMacrophyllum macrophyllum(Phyllostomidae)
Authors: Brinkløv Signe , Kalko Elisabeth K. V. , Surlykke Annemarie 
Published: December 2008

SUMMARYBats use echolocation to exploit a variety of habitats and food types. Much research has documented how frequency–time features of echolocation calls are adapted to acoustic constraints imposed by habitat and prey but emitted sound intensities have received little attention. Bats from the family of Phyllostomidae have been categorised as low intensity (whispering)gleaners, assumed to emit echolocation calls with low source levels(approximately 70 dB SPL measured 10 cm from the bat's mouth). We used a multi-microphone array to determine intensities emitted from two phyllostomid bats from Panamá with entirely different foraging strategies. Macrophyllum macrophyllum hunts insects on the wing and gaffs them with its tail membrane and feet from or above water surfaces whereas Artibeus jamaicensis picks fruit from vegetation with its mouth. Recordings were made from bats foraging on the wing in a flight room. Both species emitted surprisingly intense signals with maximum source levels of 105 dB SPL r.m.s. for M. macrophyllum and 110 dB SPL r.m.s. for A. jamaicensis, hence much louder than a `whisper'. M. macrophyllumwas consistently loud (mean source level 101 dB SPL) whereas A. jamaicensis showed a much more variable output, including many faint calls and a mean source level of 96 dB SPL. Our results support increasing evidence that echolocating bats in general are much louder than previously thought. We discuss the importance of loud calls and large output flexibility for both species in an ecological context.
Kinematics of benthic suction feeding in Callichthyidae and Mochokidae,with functional implications for the evolution of food scraping in catfishes
Authors: Van Wassenbergh Sam , Lieben Tim , Herrel Anthony , Huysentruyt Frank , Geerinckx Tom , Adriaens Dominique , Aerts Peter 
Published: December 2008

SUMMARY
Food scraping has independently evolved twice from suction feeding in the evolution of catfishes: within neotropical Loricarioidea and paleotropical Mochokidae. To gain insight in the evolutionary transitions associated with the evolution towards scraping, we analyzed prey capture kinematics in two species of benthic suction feeders which belong to taxa that are closely related to the scraper lineages (respectively, Corydoras splendensand Synodontis multipunctatus), and compared it to prey capture in a more distantly related, generalist suction feeder (Clarias gariepinus). Simultaneous ventral and lateral view high-speed videos were recorded to quantify the movements of the lower jaw, hyoid, pectoral girdle and neurocranium. Additionally, ellipse modeling was applied to relate head shape differences to buccal expansion kinematics. Similarly to what has been observed in scrapers, rotations of the neurocranium are minimal in the benthic suction feeders, and may consequently have facilitated the evolution of a scraping feeding mechanism. The hypothesis that fish with a more laterally compressed head rely more heavily on lateral expansion of the buccal cavity to generate suction, was confirmed in our sample of catfish species. Since an important contribution of lateral expansion of the head to suction may avoid the need for a strong, ventral depression of the mouth floor during feeding,we hypothesized that this may have allowed a closer association with the substrate in the ancestors of scrapers. However, our hypothesis was not supported by an ancestral state reconstruction, which suggests that scraping probably evolved from sub-terminal mouthed ancestors with dorsoventrally flattened heads.
The unequal influences of the left and right vagi on the control of the heart and pulmonary artery in the rattlesnake,Crotalus durissus
Authors: Taylor E. W. , Andrade Denis V. , Abe Augusto S. , Leite Cleo A. C. , Wang Tobias 
Published: December 2008

SUMMARYAutonomic control of the cardiovascular system in reptiles includes sympathetic components but heart rate (fH), pulmonary blood flow (Q̇pul) and cardiac shunt patterns are primarily controlled by the parasympathetic nervous system. The vagus innervates both the heart and a sphincter on the pulmonary artery. The present study reveals that whereas both the left and right vagi influence fH, it is only the left vagus that influences pulmonary vascular resistance. This is associated with the fact that rattlesnakes, in common with some other species of snakes, have a single functional lung, as the other lung regresses during development. Stimulation of the left cervical vagus in anaesthetised snakes slowed the heart and markedly reduced blood flow in the pulmonary artery whereas stimulation of the right cervical vagus slowed the heart and caused a small increase in stroke volume (VS) in both the systemic and pulmonary circulations. Central stimulation of either vagus caused small (5–10%)reductions in systemic blood pressure but did not affect blood flows or fH. A bilateral differentiation between the vagi was confirmed by progressive vagotomy in recovered snakes. Transection of the left vagus caused a slight increase in fH (10%) but a 70%increase in Q̇pul, largely due to an increase in pulmonary stroke volume (VS,pul). Subsequent complete vagotomy caused a 60% increase in fHaccompanied by a slight rise in Q̇pul, with no further change in VS,pul. By contrast, transection of the right vagus elicited a slight tachycardia but no change in VS,pul. Subsequent complete vagotomy was accompanied by marked increases in fH, Q̇puland VS,pul. These data show that although the heart receives bilateral vagal innervation, the sphincter on the pulmonary artery is innervated solely by the left vagus. This paves the way for an investigation of the role of the cardiac shunt in regulating metabolic rate, as chronic left vagotomy will cause a pronounced left–right shunt in recovered animals,whilst leaving intact control of the heart, via the right vagus.
Molecular Population Genetics of theSRKandSCRSelf-Incompatibility Genes in the Wild Plant SpeciesBrassica cretica(Brassicaceae)
Authors: Edh Kristina , Widén Björn , Ceplitis Alf 
Published: December 2008

AbstractSelf-incompatibility (SI) in plants is a classic example of a trait evolving under strong frequency-dependent selection. As a consequence, population genetic theory predicts that the S locus, which controls SI, should maintain numerous alleles, display a high level of nucleotide diversity, and, in structured populations, show a lower level of among-population differentiation compared to neutral loci. Population-level investigations of DNA sequence variation at the S locus have recently been carried out in the genus Arabidopsis, largely confirming results from theoretical models of S-locus evolutionary dynamics, but no comparable studies have been done in wild Brassica species. In this study, we sequenced parts of the S-locus genes SRK and SCR, two tightly linked genes that are directly involved in the determination of SI specificity in samples from four natural populations of the wild species Brassica cretica. The amount and distribution of nucleotide diversity, as well as the frequency spectrum of putative functional haplotypes, observed at the S locus in B. cretica fit very well with expectations from theoretical models, providing strong evidence for frequency-dependent selection acting on the S locus in a wild Brassica species.
Correcting Estimators of θ and Tajima's D for Ascertainment Biases Caused by the Single-Nucleotide Polymorphism Discovery Process
Authors: Ramírez-Soriano Anna , Nielsen Rasmus 
Published: December 2008

Abstract
Most single-nucleotide polymorphism (SNP) data suffer from an ascertainment bias caused by the process of SNP discovery followed by SNP genotyping. The final genotyped data are biased toward an excess of common alleles compared to directly sequenced data, making standard genetic methods of analysis inapplicable to this type of data. We here derive corrected estimators of the fundamental population genetic parameter θ = 4Neμ (Ne, effective population size; μ, mutation rate) on the basis of the average number of pairwise differences and on the basis of the number of segregating sites. We also derive the variances and covariances of these estimators and provide a corrected version of Tajima's D statistic. We reanalyze a human genomewide SNP data set and find substantial differences in the results with or without ascertainment bias correction.