bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulse‐Administered Toceranib Phosphate Plus Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs
Authors: Burton J.H. , Venable R.O. , Vail D.M. , Williams L.E. , Clifford C.A. , Axiak‐Bechtel S.M. , Avery A.C. , Thamm D.H. 
Published: June 2015

BackgroundNonresectable mast cell tumors (MCT) in dogs remain a therapeutic challenge, and investigation of novel combination therapies is warranted. Intermittent administration of tyrosine kinase inhibitors (TKI) combined with cytotoxic chemotherapy may effectively chemosensitize canineMCTwhile decreasing cost and adverse effects associated with either agent administered as monotherapy.Hypothesis/ObjectivesThe primary study objectives were to (1) identify the maximally tolerated dose (MTD), (2) determine the objective response rate (ORR) and (3) describe the adverse event profile of pulse‐administered toceranib phosphate (TOC) combined with lomustine.AnimalsForty‐seven client‐owned dogs with measurableMCT.MethodsToceranib phosphate was givenPOon days 1, 3 and 5 of a 21‐day cycle at a target dosage of 2.75 mg/kg. Lomustine was givenPOon day 3 of each cycle at a starting dosage of 50 mg/m2. All dogs were concurrently treated with diphenhydramine, omeprazole, and prednisone.ResultsTheMTDof lomustine was established at 50 mg/m2when combined with pulse‐administeredTOC; the dose‐limiting toxicity was neutropenia. Forty‐one dogs treated at theMTDwere evaluable for outcome assessment. TheORRwas 46% (4 complete response, 15 partial response) and the overall median progression‐free survival (PFS) was 53 days (1 to >752 days). On multivariate analysis, variables significantly associated with improvedPFSincluded response to treatment, absence of metastasis, and no previous chemotherapy.Conclusions and clinical importanceCombined treatment with pulse‐administeredTOCand lomustine generally is well tolerated and may be a reasonable treatment option for dogs with unresectable or metastaticMCT.
The formation of IIE iron meteorites investigated by the chondrule‐bearing Mont Dieu meteorite
Authors: Van Roosbroek N. , Debaille V. , Pittarello L. , Goderis S. , Humayun M. , Hecht L. , Jourdan F. , Spicuzza M. J. , Vanhaecke F. , Claeys Ph. 
Published: June 2015

AbstractA 435 kg piece of the Mont Dieu iron meteorite (MD) contains cm‐sized silicate inclusions. Based on the concentration of Ni, Ga, Ge, and Ir (8.59 ± 0.32 wt%, 25.4 ± 0.9 ppm, 61 ± 2 ppm, 7.1 ± 0.4 ppm, respectively) in the metal host, this piece can be classified as a IIE nonmagmatic iron. The silicate inclusions possess a chondritic mineralogy and relict chondrules occur throughout the inclusions. Major element analysis, oxygen isotopic analysis (Δ17O = 0.71 ± 0.02‰), and mean Fa and Fs molar contents (Fa15.7 ± 0.4 and Fs14.4 ± 0.5) indicate that MD originated as an H chondrite. Because of strong similarities with Netschaëvo IIE, MD can be classified in the most primitive subgroup of the IIE sequence. 40Ar/39Ar ages of 4536 ± 59 Ma and 4494 ± 95 Ma obtained on pyroxene and plagioclase inclusions show that MD belongs to the old (~4.5 Ga) group of IIE iron meteorites and that it has not been perturbed by any subsequent heating event following its formation. The primitive character of MD sheds light on the nature of its formation process, its thermal history, and the evolution of its parent body.
Plasma‐derived C1‐INH for managing hereditary angioedema in pediatric patients: A systematic review
Authors: Craig Timothy J. , Schneider Lynda C. , MacGinnitie Andrew J. 
Published: June 2015

AbstractPresently, medications approved for children with Hereditary Angioedema (HAE) are extremely limited. This is especially the case for children under 12 years of age. For this reason we reviewed and summarized the data on treatment of children with HAE. Available data indicate that plasma derived C1‐inhibitor is a safe, effective treatment option for HAE in pediatric patients, including those below 12 years of age. Other therapies are also appear safe for the under 12 year of age, but less data are available. Importantly, home‐based treatment of HAE in this age group appears to be safe and effective and can improve quality of life. These findings support current HAE consensus guidelines which strongly recommend the use of plasma derived C1‐inhibitor as a first‐line treatment in children and encourage home and self‐treatment.
Exhaled breath temperature in elite swimmers: The effects of a training session in adolescents with or without asthma
Authors: Couto Mariana , Santos Paulo , Silva Diana , Delgado Luís , Moreira André 
Published: June 2015

AbstractBackgroundCooling of the airways and inflammation have been pointed as possible mechanisms for exercise‐induced asthma (EIA). We aimed to investigate the effect of training and asthma on exhaled breath temperature (EBT) of elite swimmers.MethodsElite swimmers annually screened (skin prick tests, spirometry before and after salbutamol inhalation, induced sputum cell counts, and methacholine bronchial challenge) at our department (n = 27) were invited to this prospective study. Swimmers who agreed to participate in the present study (n = 22, 10 with asthma) had axillary temperature and EBT measured (X‐halo®) before and after a swimming training session (aerobic/non‐aerobic). Linear regression models were used to assess the effect of asthma and other possible explanatory variables (demographics, PD20, baseline EBT, training intensity, axillary temperature, and the number of hours trained in that week) on EBT change.ResultsEBT significantly increased after training independently of lung function, airway responsiveness, and inflammation in all swimmers (mean ± SD: 0.32 ± 0.57; p = 0.016). No differences were observed between asthmatic swimmers and others. A significant correlation was observed between baseline and post‐exercise EBTs (r = 0.827, p < 0.001). Asthma was not a predictor of ΔEBT after adjusting for confounders; baseline EBT was the variable most strongly associated with ΔEBT, explaining by itself alone 46% of the outcome (r2 = 0.464).ConclusionAlthough these are preliminary data, a relationship between airway's inflammation and respiratory heat loss during exercise could not be confirmed, suggesting that the increase in exhaled breath temperature is a physiologic rather than a pathological response to exercise.
Progesterone 5β‐reductase genes of theBrassicaceae family as function‐associated molecular markers
Authors: Munkert J. , Costa C. , Budeanu O. , Petersen J. , Bertolucci S. , Fischer G. , Müller‐Uri F. , Kreis W. 
Published: June 2015

AbstractThis study aimed to define progesterone 5β‐reductases (P5βR,EC1.3.99.6, enone 1,4‐reductases) as function‐associated molecular markers at the plant family level. ThereforecDNAs were isolated from 25 Brassicaceae species, including two species,Erysimum crepidifoliumandDraba aizoides, known to produce cardiac glycosides. The sequences were used in a molecular phylogeny study. The cladogram created is congruent to the existing molecular analyses. Recombinant His‐tagged forms of theP5βRcDNAs fromAethionema grandiflorum, Draba aizoides, Nasturtium officinale, Raphanus sativusandSisymbrium officinalewere expressed inE. coli. Enone 1,4‐reductase activity was demonstratedin vitrousing progesterone and 2‐cyclohexen‐1‐one as substrates. Evidence is provided that functional P5βRs are ubiquitous in the Brassicaceae. The recombinant P5βR enzymes showed different substrate preferences towards progesterone and 2‐cyclohexen‐1‐one. Sequence comparison of the catalytic pocket of the P5βR enzymes and homology modelling usingDigitalis lanataP5βR (PDB ID: 2V6G) as template highlighted the importance of the hydrophobicity of the binding pocket for substrate discrimination. It is concluded thatP5βRgenes or P5βR proteins can be used as valuable function‐associated molecular markers to infer taxonomic relationship and evolutionary diversification from a metabolic/catalytic perspective.
Is There Such a Thing as Relative Analyticity?
Authors: Büttner Kai Michael 
Published: June 2015

AbstractFine bases his influential conception of essence on a particular account of definitions. And he complements it with a specific account of analyticity. I will argue that Fine's conception of relative analyticity confuses the idea of a sentence's being true in virtue of a term's definition with the idea of a sentence's being true in virtue of a term's meaning. His idea that correct definitions specify essential properties of meanings is mistaken. The correctness of definitions can only be assessed by reference to the actual usage of the terms involved. The resulting conception of definitions leads to a deflationary interpretation of claims about essences.
Validation of a questionnaire for asthma case identification in pre‐schools in Latin America
Authors: Busi Luciano E. , Sly Peter D. , Llancaman Lidia 
Published: June 2015

AbstractBackground and objectiveWe recently developed and validated a screening questionnaire for determining which school‐aged children may need further investigation to diagnose and manage asthma. In the present study we sought to extend this to pre‐school aged children.MethodsQuestions from the school‐aged questionnaire and literature on pre‐school asthma were used to inform a focus group of parents with pre‐school‐aged children with asthma to develop a screening questionnaire. Parents of children attending 6 randomly selected kindergartens in Trelew, Argentina (n = 639) were invited to respond to the questionnaire. A reliability test–retest was undertaken in 187 randomly selected parents who completed the same questionnaire twice within 2–5 weeks. Clinical assessment included a standardized history and physical examination, spirometry before and after a β‐agonist inhaler, and chest X‐ray. Asthma was diagnosed by the pulmonologist.ResultsCompleted surveys were returned for 620 children, 607 of whom underwent clinical evaluation. The mean age was 4.21 years (range of 3.01–5.50) and included 82.5% white and 49.4% male children. Asthma was diagnosed in 103 (17.0%) children); 72 (69.9%) of these children did not have a previous diagnosis of asthma. The specificity, sensitivity, positive predictive value and negative predictive value of the questionnaire were 93.2%, 86.1%, 57.8% and 98.4%, respectively.ConclusionsWe have demonstrated the utility of a screening questionnaire for identifying pre‐school‐aged children who may benefit from further assessment for asthma.
Targets for Ibrutinib Beyond B Cell Malignancies
Authors: Berglöf A. , Hamasy A. , Meinke S. , Palma M. , Krstic A. , Månsson R. , Kimby E. , Österborg A. , Smith C. I. E. 
Published: June 2015

AbstractIbrutinib (Imbruvica™) is an irreversible, potent inhibitor of Bruton's tyrosine kinase (BTK). Over the last few years, ibrutinib has developed from a promising drug candidate to being approved by FDA for the treatment of three B cell malignancies, a truly remarkable feat. Few, if any medicines are monospecific and ibrutinib is no exception; already during ibrutinib's initial characterization, it was found that it could bind also to other kinases. In this review, we discuss the implications of such interactions, which go beyond the selective effect on BTK in B cell malignancies. In certain cases, the outcome of ibrutinib treatment likely results from the combined inhibition of BTK and other kinases, causing additive or synergistic, effects. Conversely, there are also examples when the clinical outcome seems unrelated to inhibition of BTK. Thus, more specifically, adverse effects such as enhanced bleeding or arrhythmias could potentially be explained by different interactions. We also predict that during long‐term treatment bone homoeostasis might be affected due to the inhibition of osteoclasts. Moreover, the binding of ibrutinib to molecular targets other than BTK or effects on cells other than B cell‐derived malignancies could be beneficial and result in new indications for clinical applications.
Nucleated erythrocytes in blood smears of dogs undergoing chemotherapy
Authors: Moretti P. , Giordano A. , Stefanello D. , Ferrari R. , Castellano S. , Paltrinieri S. 
Published: June 2015

AbstractThe frequency of normoblastemia in dogs receiving chemotherapy is unknown. To provide this information, we calculated the percentage and number of nucleated erythrocytes (nRBCs) in blood of dogs treated for lymphoma (n = 284), mast cell tumour (n = 40) or carcinoma (n = 46). Relative normoblastemia (>1 or >5%) and absolute normoblastemia (>0.1 or >0.4 × 103 µL−1) were found after administration of vincristine (49.3, 20.5, 42.5, 19.2%, respectively), carboplatin (37.0, 2.2, 34.8, 13.0%), cyclophosphamide (30.8, 7.7, 23.1, 7.7%), doxorubicin (25.0, 8.3, 21.7, 6.7%), vinblastine and prednisone (25.0; 5.0; 22.5; 7.5%). Absolute normoblastemia was very severe (>1.0 × 103 nRBC µL−1) after administration of vincristine (9.6%), doxorubicin (3.3%), vinblastine and prednisone (2.5%). Absolute normoblastemia negatively correlated with RBC counts (P < 0.001) and positively (P < 0.001) with reticulocyte and WBC counts, but correlation coefficients were low (−0.19, 0.37, 0.15). Vincristine, doxorubicin or vinblastine and prednisone may induce severe normoblastemia. This may increase WBC counts and mask neutropenia associated with chemotherapy.
Acute flavanol consumption improves the cerebral vasodilatory capacity in college‐aged African Americans
Authors: Hurr Chansol , Harrison Michelle L. , Brothers R. Matthew 
Published: June 2015

New Findings

What is the central question of this study?
The purpose was to determine whether acute flavanol consumption improves cerebral vasodilatory capacity during rebreathing‐induced hypercapnia in African Americans.

What is the main finding and its importance?
The reduced cerebral vasodilatory response to hypercapnia in young healthy African Americans was improved acutely following consumption of a flavanol‐rich beverage. This may have important clinical implications regarding racial differences in cerebrovascular disease risk and possible interventional approaches to offset this risk.

African Americans (AAs) have increased risk for cardiovascular and cerebrovascular disease. African Americans have attenuated cerebral vasodilator capacity during hypercapnia relative to Caucasian Americans (CAs). This study tested the hypothesis, using a placebo‐controlled crossover design, that acute flavanol consumption improves the range of change in cerebral vascular conductance [CVCI, (a)] and the maximal CVCI (y0) achieved during rebreathing‐induced increases in end‐tidal carbon dioxide tension. Fourteen college‐aged AAs and 14 CAs participated. Both a and y0 were lower in AAs prior to flavanols (for a, AAs, 46 ± 16 versus CAs, 74 ± 18% CVCI, P < 0.001; and for y0, AAs, 151 ± 18 versus CAs, 176 ± 20% CVCI, P = 0.002); however, these variables were increased after flavanols such that there were no differences between groups (for a, AAs, 64 ± 19 versus CAs, 72 ± 22% CVCI, P = 0.35; and for y0, AAs, 166 ± 22 versus CAs, 176 ± 22% CVCI, P = 0.26). Both a and y0 were also lower in AAs prior to placebo (for a, AAs, 52 ± 19 versus CAs, 76 ± 15% CVCI, P = 0.002; and for y0, AAs, 156 ± 20 versus CAs, 177 ± 21% CVCI, P = 0.015), and these differences remained following placebo (for a, AAs, 52 ± 17 versus CAs, 80 ± 20% CVCI, P < 0.001; and for y0, AAs, 152 ± 18 versus CAs, 181 ± 25% CVCI, P = 0.003). These data suggest that acute flavanol consumption improves cerebral vasodilatory capacity during hypercapnia in AAs.
IP-10 Is a Sensitive Biomarker of Antigen Recognition in Whole-Blood Stimulation Assays Used for the Diagnosis of Mycobacterium bovis Infection in African Buffaloes (Syncerus caffer)
Authors: Goosen Wynand J. , Cooper David , Miller Michele A. , van Helden Paul D. , Parsons Sven D. C. 
Published: June 2015

ABSTRACT

African buffaloes (
Syncerus caffer
) are maintenance hosts of
Mycobacterium bovis
, the causative agent of bovine tuberculosis. They act as reservoirs of this infection for a wide range of wildlife and domestic species, and the detection of infected animals is important to control the geographic spread and transmission of the disease. Interferon gamma (IFN-γ) release assays (IGRAs) utilizing pathogen-derived peptide antigens are highly specific tests of
M. bovis
infection; however, the diagnostic sensitivities of these assays are suboptimal. We evaluated the diagnostic utility of measuring antigen-dependent interferon gamma-induced protein 10 (IP-10) release as an alternative to measuring IFN-γ levels.
M. bovis
-exposed buffaloes were tested using the Bovigam PC-EC and Bovigam PC-HP assays and a modified QuantiFERON TB-Gold (mQFT) assay. IP-10 was measured in the harvested plasma and was produced in significantly greater abundance in response to
M. bovis
antigens in Bovigam-positive than in Bovigam-negative animals. For each assay, using the Bovigam results as a reference, receiver operating characteristic curve analysis was done to determine diagnostically relevant cutoff values for IP-10. Thereafter, mQFT test results derived from measurement of IP-10 and IFN-γ were compared and a larger number of Bovigam-positive animals were detected using IP-10 as a diagnostic marker. Moreover, using IP-10, agreement between the mQFT assay and the Bovigam assays was increased, while the excellent agreement between the Bovigam assays was retained. We conclude that IP-10 is a sensitive marker of antigen recognition and that measurement of this cytokine in antigen-stimulated whole blood might increase the sensitivity of conventional IGRAs in African buffaloes.
Genomic Epidemiology of Clostridium botulinum Isolates from Temporally Related Cases of Infant Botulism in New South Wales, Australia
Authors: McCallum Nadine , Gray Timothy J. , Wang Qinning , Ng Jimmy , Hicks Leanne , Nguyen Trang , Yuen Marion , Hill-Cawthorne Grant A. , Sintchenko Vitali 
Published: June 2015

ABSTRACT

Infant botulism is a potentially life-threatening paralytic disease that can be associated with prolonged morbidity if not rapidly diagnosed and treated. Four infants were diagnosed and treated for infant botulism in NSW, Australia, between May 2011 and August 2013. Despite the temporal relationship between the cases, there was no close geographical clustering or other epidemiological links.
Clostridium botulinum
isolates, three of which produced botulism neurotoxin serotype A (BoNT/A) and one BoNT serotype B (BoNT/B), were characterized using whole-genome sequencing (WGS).
In silico
multilocus sequence typing (MLST) found that two of the BoNT/A-producing isolates shared an identical novel sequence type, ST84. The other two isolates were single-locus variants of this sequence type (ST85 and ST86). All BoNT/A-producing isolates contained the same chromosomally integrated BoNT/A2 neurotoxin gene cluster. The BoNT/B-producing isolate carried a single plasmid-borne
bont
/B gene cluster, encoding BoNT subtype B6. Single nucleotide polymorphism (SNP)-based typing results corresponded well with MLST; however, the extra resolution provided by the whole-genome SNP comparisons showed that the isolates differed from each other by >3,500 SNPs. WGS analyses indicated that the four infant botulism cases were caused by genomically distinct strains of
C. botulinum
that were unlikely to have originated from a common environmental source. The isolates did, however, cluster together, compared with international isolates, suggesting that
C. botulinum
from environmental reservoirs throughout NSW have descended from a common ancestor. Analyses showed that the high resolution of WGS provided important phylogenetic information that would not be captured by standard seven-loci MLST.
First Human Case of Fungal Keratitis Caused by a Putatively Novel Species of Lophotrichus
Authors: Eghrari Allen O. , Gibas Connie , Watkins Tonya , Vahedi Sina , Lee Rick , Houle Elizabeth , Suarez Maria Jose , Eberhart Charles , Sutton Deanna A. , Wiederhold Nathan P. , Sikder Shameema , Zhang Sean X. 
Published: June 2015

ABSTRACT

We report an aggressive fungal keratitis caused by a putatively novel species of
Lophotrichus
in a patient with traumatic injury to the cornea from a dog paw. The organism was isolated from the patient's necrotic cornea, which perforated despite coverage with hourly fortified broad-spectrum topical antibiotic therapy. This report represents the first case of human infection caused by this species.
Comparison of Established Diagnostic Methodologies and a Novel Bacterial
smpB
Real-Time PCR Assay for Specific Detection of Haemophilus influenzae Isolates Associated with Respiratory Tract Infections
Authors: Reddington Kate , Schwenk Stefan , Tuite Nina , Platt Gareth , Davar Danesh , Coughlan Helena , Personne Yoann , Gant Vanya , Enne Virve I. , Zumla Alimuddin , Barry Thomas 
Published: June 2015

ABSTRACT

Haemophilus influenzae
is a significant causative agent of respiratory tract infections (RTI) worldwide. The development of a rapid
H. influenzae
diagnostic assay that would allow for the implementation of infection control measures and also improve antimicrobial stewardship for patients is required. A number of nucleic acid diagnostics approaches that detect
H. influenzae
in RTIs have been described in the literature; however, there are reported specificity and sensitivity limitations for these assays. In this study, a novel real-time PCR diagnostic assay targeting the
smpB
gene was designed to detect all serogroups of
H. influenzae
. The assay was validated using a panel of well-characterized
Haemophilus
spp. Subsequently, 44
Haemophilus
clinical isolates were collected, and 36 isolates were identified as
H. influenzae
using a gold standard methodology that combined the results of matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and a
fucK
diagnostic assay. Using the novel
smpB
diagnostic assay, 100% concordance was observed with the gold standard, demonstrating a sensitivity of 100% (95% confidence interval [CI], 90.26% to 100.00%) and a specificity of 100% (95% CI, 63.06% to 100.00%) when used on clinical isolates. To demonstrate the clinical utility of the diagnostic assay presented, a panel of lower RTI samples (
n
= 98) were blindly tested with the gold standard and
smpB
diagnostic assays. The results generated were concordant for 94/98 samples tested, demonstrating a sensitivity of 90.91% (95% CI, 78.33% to 97.47%) and a specificity of 100% (95% CI, 93.40% to 100.00%) for the novel
smpB
assay when used directly on respiratory specimens.
Vertebral Osteomyelitis Caused by Helicobacter cinaedi
Authors: Yoshizaki Aisa , Takegawa Hiroshi , Doi Asako , Mizuno Yasushi , Nishioka Hiroaki 
Published: June 2015

ABSTRACT

Helicobacter cinaedi
causes bacteremia, cellulitis, and gastroenteritis. We report the first case of vertebral osteomyelitis caused by
H. cinaedi
in an elderly man with low back pain and fever. The pathogen was detected in blood and lumbar disc, and the infection was successfully treated with oral doxycycline for 11 weeks.
Prospective Two-Center Comparison of Three Chromogenic Agars for Methicillin-Resistant Staphylococcus aureus Screening in Hospitalized Patients
Authors: Dodémont Magali , Verhulst Carlo , Nonhoff Claire , Nagant Carole , Denis Olivier , Kluytmans Jan 
Published: June 2015

ABSTRACT

Three chromogenic media, chromID MRSA SMART (SMART), chromID MRSA first generation (chromID), and
Brilliance
MRSA (OX2), were evaluated for methicillin-resistant
Staphylococcus aureus
(MRSA) screening using 1,220 samples. The sensitivity at 24 h was significantly better with the SMART agar (66.4%) than that with chromID agar (50.5%). Enrichment and incubation until 48 h are still needed for an optimal yield.