bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment and characterization of a canine soft tissue sarcoma patient‐derived xenograft model
Authors: Frazier J. P. , Beirne E. , Ditzler S. H. , Tretyak I. , Casalini J. R. , Thirstrup D. J. , Knoblaugh S. , Ward J. G. , Tripp C. D. , Klinghoffer R. A. 
Published: March 2016

AbstractSpontaneously occurring soft tissue sarcoma (STS) is relatively common in canine cancer patients. Because of the similarities to human disease, canine STSs are a valuable and readily available resource for the study of new therapeutics. In this study, a canine patient‐derived xenograft (PDX) model, CDX‐STS2, was established. The CDX‐STS2 model was engrafted and expanded for systemic administration studies with chemotherapeutic agents commonly used to treat STS, including doxorubicin, docetaxel and gemcitabine. Immunohistochemistry for drug‐specific biomarkers and tumour growth measurement revealed tumour sensitivity to doxorubicin and docetaxel, whereas gemcitabine had no effect on tumour growth. Although many human PDX tumour models have been established, relatively few canine PDX models have been reported to date. CDX‐STS2 represents a new STS PDX research model of canine origin that will be useful in bridging preclinical research with clinical studies of STS in pet dogs.
Treatment of advanced canine anal sac adenocarcinoma with hypofractionated radiation therapy: 77 cases (1999–2013)
Authors: McQuown B. , Keyerleber M. A. , Rosen K. , McEntee M. C. , Burgess K. E. 
Published: March 2016

AbstractCurrently no standard of care exists for advanced, inoperable or metastatic anal sac adenocarcinoma (ASAC). The objective of this retrospective study was to assess the role of hypofractionated radiation therapy (RT) in 77 dogs with measurable ASAC. A total of 38% of dogs experienced a partial response to RT. For dogs presenting with clinical signs related to the tumour, improvement or resolution of signs was noted in 63%. For dogs presenting with hypercalcemia of malignancy, resolution was noted in 31% with RT alone and an additional 46% with radiation, prednisone, and/or bisphosphonates. Median overall survival was 329 days (range: 252–448 days). Median progression free survival was 289 days (range: 224–469). There was no difference in survival based on radiation protocol, use of chemotherapy, previous surgery or advanced stage. Radiation toxicities were mild and infrequent. Hypofractionated RT is well tolerated and is applicable in the treatment of advanced primary, locoregional or metastatic ASAC.
Microbiological characterization of a newly established pig breed, Aachen Minipigs
Authors: Plotzki Elena , Heinrichs Gerd , Kubícková Barbara , Ulrich Rainer G. , Denner Joachim 
Published: March 2016

AbstractBackgroundTo alleviate the shortage of human donor organs or tissues for the treatment of organ and tissue failure including diabetes, pigs are considered suitable donor animals. As organs from conventional pigs are usually too large, those from minipigs may be better suited. We recently characterized the Göttingen Minipigs, a breed well characterized concerning the presence of zoonotic microorganisms and found hepatitis E virus (HEV) and porcine cytomegalovirus (PCMV) in some animals. Here, we characterize another minipig, the Aachen Minipig (AaMP), a pig breed recently established close to the town Aachen in Germany.MethodsThe animals were tested for the prevalence and expression of porcine endogenous retroviruses (PERVs) and the presence of some selected microorganisms, among them HEV, PCMV, and porcine lymphotropic herpesviruses (PLHVs) using highly sensitive and specific PCR and RT‐PCR methods. In addition, we screened for antibodies against HEV and PLHV.ResultsPERV‐A, PERV‐B, and PERV‐C sequences were found in the genome of all Aachen Minipigs. HEV RNA was found by real‐time RT‐PCR in most, and DNA of PCMV, PLHV‐2, and PLHV‐3 was found by PCR in some animals. The animals were free of eight other microorganisms tested, but some were seropositive for porcine circovirus 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine epidemic diarrhea virus (PEDV).ConclusionBased on medical examinations by veterinarians, the AaMP are in a good health status and seem to harbor only few microorganisms. To improve their status for use as donor pigs in xenotransplantation, the viruses detected might be eliminated by selection of negative animals, Cesarean section, and vaccination.
Uncertainty and variability in computational and mathematical models of cardiac physiology
Authors: Mirams Gary R. , Pathmanathan Pras , Gray Richard A. , Challenor Peter , Clayton Richard H. 
Published: March 2016

Key points
Mathematical and computational models of cardiac physiology have been an integral component of cardiac electrophysiology since its inception, and are collectively known as the Cardiac Physiome.
We identify and classify the numerous sources of variability and uncertainty in model formulation, parameters and other inputs that arise from both natural variation in experimental data and lack of knowledge.
The impact of uncertainty on the outputs of Cardiac Physiome models is not well understood, and this limits their utility as clinical tools.
We argue that incorporating variability and uncertainty should be a high priority for the future of the Cardiac Physiome.
We suggest investigating the adoption of approaches developed in other areas of science and engineering while recognising unique challenges for the Cardiac Physiome; it is likely that novel methods will be necessary that require engagement with the mathematics and statistics community.
AbstractThe Cardiac Physiome effort is one of the most mature and successful applications of mathematical and computational modelling for describing and advancing the understanding of physiology. After five decades of development, physiological cardiac models are poised to realise the promise of translational research via clinical applications such as drug development and patient‐specific approaches as well as ablation, cardiac resynchronisation and contractility modulation therapies. For models to be included as a vital component of the decision process in safety‐critical applications, rigorous assessment of model credibility will be required. This White Paper describes one aspect of this process by identifying and classifying sources of variability and uncertainty in models as well as their implications for the application and development of cardiac models. We stress the need to understand and quantify the sources of variability and uncertainty in model inputs, and the impact of model structure and complexity and their consequences for predictive model outputs. We propose that the future of the Cardiac Physiome should include a probabilistic approach to quantify the relationship of variability and uncertainty of model inputs and outputs.
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Wolbachia Modulates Lipid Metabolism in Aedes albopictus Mosquito Cells
Authors: Molloy Jennifer C. , Sommer Ulf , Viant Mark R. , Sinkins Steven P. 
Published: March 2016

ABSTRACTCertain strains of the intracellular endosymbiontWolbachiacan strongly inhibit or block the transmission of viruses such as dengue virus (DENV) byAedesmosquitoes, and the mechanisms responsible are still not well understood. Direct infusion and liquid chromatography-Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry-based lipidomics analyses were conducted usingAedes albopictusAa23 cells that were infected with thewMel andwMelPop strains ofWolbachiain comparison to uninfected Aa23-T cells. Substantial shifts in the cellular lipid profile were apparent in the presence ofWolbachia. Most significantly, almost all sphingolipid classes were depleted, and some reductions in diacylglycerols and phosphatidylcholines were also observed. These lipid classes have previously been shown to be selectively enriched in DENV-infected mosquito cells, suggesting thatWolbachiamay produce a cellular lipid environment that is antagonistic to viral replication. The data improve our understanding of the intracellular interactions betweenWolbachiaand mosquitoes.IMPORTANCEMosquitoes transmit a variety of important viruses to humans, such as dengue virus and Zika virus. Certain strains of the intracellular bacterial genus calledWolbachiafound in or introduced into mosquitoes can block the transmission of viruses, including dengue virus, but the mechanisms responsible are not well understood. We found substantial shifts in the cellular lipid profiles in the presence of these bacteria. Some lipid classes previously shown to be enriched in dengue virus-infected mosquito cells were depleted in the presence ofWolbachia, suggesting thatWolbachiamay produce a cellular lipid environment that inhibits mosquito-borne viruses.
Two Bacterial Genera, Sodalis and Rickettsia, Associated with the Seal Louse Proechinophthirus fluctus (Phthiraptera: Anoplura)
Authors: Boyd Bret M. , Allen Julie M. , Koga Ryuichi , Fukatsu Takema , Sweet Andrew D. , Johnson Kevin P. , Reed David L. 
Published: March 2016

ABSTRACT

Roughly 10% to 15% of insect species host heritable symbiotic bacteria known as endosymbionts. The lice parasitizing mammals rely on endosymbionts to provide essential vitamins absent in their blood meals. Here, we describe two bacterial associates from a louse,
Proechinophthirus fluctus
, which is an obligate ectoparasite of a marine mammal. One of these is a heritable endosymbiont that is not closely related to endosymbionts of other mammalian lice. Rather, it is more closely related to endosymbionts of the genus
Sodalis
associated with spittlebugs and feather-chewing bird lice. Localization and vertical transmission of this endosymbiont are also more similar to those of bird lice than to those of other mammalian lice. The endosymbiont genome appears to be degrading in symbiosis; however, it is considerably larger than the genomes of other mammalian louse endosymbionts. These patterns suggest the possibility that this
Sodalis
endosymbiont might be recently acquired, replacing a now-extinct, ancient endosymbiont. From the same lice, we also identified an abundant bacterium belonging to the genus
Rickettsia
that is closely related to
Rickettsia ricketsii
, a human pathogen vectored by ticks. No obvious masses of the
Rickettsia
bacterium were observed in louse tissues, nor did we find any evidence of vertical transmission, so the nature of its association remains unclear.

IMPORTANCE
Many insects are host to heritable symbiotic bacteria. These heritable bacteria have been identified from numerous species of parasitic lice. It appears that novel symbioses have formed between lice and bacteria many times, with new bacterial symbionts potentially replacing existing ones. However, little was known about the symbionts of lice parasitizing marine mammals. Here, we identified a heritable bacterial symbiont in lice parasitizing northern fur seals. This bacterial symbiont appears to have been recently acquired by the lice. The findings reported here provide insights into how new symbioses form and how this lifestyle is shaping the symbiont genome.
Vacuolar H+-ATPase Protects Saccharomyces cerevisiae Cells against Ethanol-Induced Oxidative and Cell Wall Stresses
Authors: Charoenbhakdi Sirikarn , Dokpikul Thanittra , Burphan Thanawat , Techo Todsapol , Auesukaree Choowong 
Published: March 2016

ABSTRACTDuring fermentation, increased ethanol concentration is a major stress for yeast cells. Vacuolar H+-ATPase (V-ATPase), which plays an important role in the maintenance of intracellular pH homeostasis through vacuolar acidification, has been shown to be required for tolerance to straight-chain alcohols, including ethanol. Since ethanol is known to increase membrane permeability to protons, which then promotes intracellular acidification, it is possible that the V-ATPase is required for recovery from alcohol-induced intracellular acidification. In this study, we show that the effects of straight-chain alcohols on membrane permeabilization and acidification of the cytosol and vacuole are strongly dependent on their lipophilicity. These findings suggest that the membrane-permeabilizing effect of straight-chain alcohols induces cytosolic and vacuolar acidification in a lipophilicity-dependent manner. Surprisingly, after ethanol challenge, the cytosolic pH in Δvma2and Δvma3mutants lacking V-ATPase activity was similar to that of the wild-type strain. It is therefore unlikely that the ethanol-sensitive phenotype ofvmamutants resulted from severe cytosolic acidification. Interestingly, thevmamutants exposed to ethanol exhibited a delay in cell wall remodeling and a significant increase in intracellular reactive oxygen species (ROS). These findings suggest a role for V-ATPase in the regulation of the cell wall stress response and the prevention of endogenous oxidative stress in response to ethanol.IMPORTANCEThe yeastSaccharomyces cerevisiaehas been widely used in the alcoholic fermentation industry. Among the environmental stresses that yeast cells encounter during the process of alcoholic fermentation, ethanol is a major stress factor that inhibits yeast growth and viability, eventually leading to fermentation arrest. This study provides evidence for the molecular mechanisms of ethanol tolerance, which is a desirable characteristic for yeast strains used in alcoholic fermentation. The results revealed that straight-chain alcohols induced cytosolic and vacuolar acidification through their membrane-permeabilizing effects. Contrary to expectations, a role for V-ATPase in the regulation of the cell wall stress response and the prevention of endogenous oxidative stress, but not in the maintenance of intracellular pH, seems to be important for protecting yeast cells against ethanol stress. These findings will expand our understanding of the mechanisms of ethanol tolerance and provide promising clues for the development of ethanol-tolerant yeast strains.
Environmental Metabolomics of the Tomato Plant Surface Provides Insights on Salmonella enterica Colonization
Authors: Han Sanghyun , Micallef Shirley A. 
Published: March 2016

ABSTRACT

Foodborne illness-causing enteric bacteria are able to colonize plant surfaces without causing infection. We lack an understanding of how epiphytic persistence of enteric bacteria occurs on plants, possibly as an adaptive transit strategy to maximize chances of reentering herbivorous hosts. We used tomato (
Solanum lycopersicum
) cultivars that have exhibited differential susceptibilities to
Salmonella enterica
colonization to investigate the influence of plant surface compounds and exudates on enteric bacterial populations. Tomato fruit, shoot, and root exudates collected at different developmental stages supported growth of
S. enterica
to various degrees in a cultivar- and plant organ-dependent manner.
S. enterica
growth in fruit exudates of various cultivars correlated with epiphytic growth data (
R
2
= 0.504;
P
= 0.006), providing evidence that plant surface compounds drive bacterial colonization success. Chemical profiling of tomato surface compounds with gas chromatography-time of flight mass spectrometry (GC-TOF-MS) provided valuable information about the metabolic environment on fruit, shoot, and root surfaces. Hierarchical cluster analysis of the data revealed quantitative differences in phytocompounds among cultivars and changes over a developmental course and by plant organ (
P
< 0.002). Sugars, sugar alcohols, and organic acids were associated with increased
S. enterica
growth, while fatty acids, including palmitic and oleic acids, were negatively correlated. We demonstrate that the plant surface metabolite landscape has a significant impact on
S. enterica
growth and colonization efficiency. This environmental metabolomics approach provides an avenue to understand interactions between human pathogens and plants that could lead to strategies to identify or breed crop cultivars for microbiologically safer produce.

IMPORTANCE
In recent years, fresh produce has emerged as a leading food vehicle for enteric pathogens.
Salmonella
-contaminated tomatoes represent a recurrent human pathogen-plant commodity pair. We demonstrate that
Salmonella
can utilize tomato surface compounds and exudates for growth. Surface metabolite profiling revealed that the types and amounts of compounds released to the plant surface differ by cultivar, plant developmental stage, and plant organ. Differences in exudate profiles explain some of the variability in
Salmonella
colonization susceptibility seen among tomato cultivars. Certain medium- and long-chain fatty acids were associated with restricted
Salmonella
growth, while sugars, sugar alcohols, and organic acids correlated with larger
Salmonella
populations. These findings uncover the possibility of selecting crop varieties based on characteristics that impair foodborne pathogen growth for enhanced safety of fresh produce.
Recording and treatment of premenstrual syndrome in UK general practice: a retrospective cohort study
Authors: Sammon Cormac J , Nazareth Irwin , Petersen Irene 
Published: March 2016

ObjectivesTo investigate the rate of recording of premenstrual syndrome diagnoses in UK primary care and describe pharmacological treatments initiated following a premenstrual syndrome (PMS) diagnosis.DesignRetrospective cohort study.SettingUK primary care.ParticipantsWomen registered with a practice contributing to The Health Improvement Network primary care database between 1995 and 2013.Primary and secondary outcome measuresThe primary outcome was the rate of first premenstrual syndrome records per 1000 person years, stratified by calendar year and age. The secondary outcome was the proportions of women with a premenstrual syndrome record prescribed a selective serotonin reuptake inhibitor, progestogen, oestrogen, combined oral contraceptive, progestin only contraceptive, gonadotrophin-releasing hormone, danazol and vitamin B6.ResultsThe rate of recording of premenstrual syndrome diagnoses decreased over calendar time from 8.43 in 1995 to 1.72 in 2013. Of the 38 614 women without treatment in the 6 months prior to diagnosis, 54% received a potentially premenstrual syndrome-related prescription on the day of their first PMS record while 77% received a prescription in the 24 months after. Between 1995 and 1999, the majority of women were prescribed progestogens (23%) or vitamin B6(20%) on the day of their first PMS record; after 1999, these figures fell to 3% for progestogen and vitamin B6with the majority of women instead being prescribed a selective serotonin reuptake inhibitor (28%) or combined oral contraceptive (17%).ConclusionsRecording of premenstrual syndrome diagnoses in UK primary care has declined substantially over time and preferred prescription treatment has changed from progestogen to selective serotonin reuptake inhibitor and combined oral contraceptives.
A cross-sectional observational study of high override rates of drug allergy alerts in inpatient and outpatient settings, and opportunities for improvement
Authors: Slight Sarah Patricia , Beeler Patrick E , Seger Diane L , Amato Mary G , Her Qoua L , Swerdloff Michael , Dalleur Olivia , Nanji Karen C , Cho InSook , Maniam Nivethietha , Eguale Tewodros , Fiskio Julie M , Dykes Patricia C , Bates David W 
Published: March 2016

ObjectivesTo evaluate how often and why providers overrode drug allergy alerts in both the inpatient and outpatient settings.DesignA cross-sectional observational study of drug allergy alerts generated over a 3-year period between 1 January 2009 and 31 December 2011.SettingA 793-bed tertiary care teaching affiliate of Harvard Medical School and 36 primary care practices.ParticipantsDrug allergy alerts were displayed for a total of 29 420 patients across both settings.Main outcome measuresProportion of drug allergy alerts displayed and overridden, proportion of appropriate overrides, proportion of overrides in each medication class, different reasons for overriding and types of reactions overridden.ResultsA total of 158 023 drug allergy alerts were displayed, 131 615 (83%) in the inpatient setting and 26 408 (17%) in the outpatient setting; 128 157 (81%) of which were overridden. A random sample of inpatient (n=200, 0.19%) and outpatient (n=50, 0.25%) alert overrides were screened for appropriateness, with >96% considered appropriate. Alerts for some drug classes, such as ‘non-antibiotic sulfonamides’, were overridden for >81% of prescriptions in both settings. The most common override reason waspatient has taken previously without allergic reaction. In the inpatient setting alone, 70.9% of alerts that warned against the risk ofanaphylaxiswere overridden.ConclusionsThe information contained in patients’ drug allergy lists needs to be regularly updated. Most of the drug allergy alerts were overridden, with the majority of alert overrides in the subsample considered appropriate. Some of the rules for these alerts should be carefully reviewed and modified, or removed. Further research is needed to understand providers’ overriding of alerts that warned against the risk of ‘anaphylaxis’, which are more concerning with respect to patient safety.
Factors associated with perpetration of intimate partner violence among college students in China
Authors: Kamimura A , Nourian M M , Assasnik N , Franchek-Roa K 
Published: March 2016

ObjectivesIntimate partner violence (IPV) is a significant public health threat that contributes to a wide range of physical and mental health issues for victims. However, critical information on IPV in China is still lacking. The purpose of this study was to examine factors affecting IPV perpetration as well as victimisation in mainland China.MethodsThe data were from the International Dating Violence Study 2001–2006 (N=731). The lifetime prevalence of victimisation and perpetration of IPV (ie, physical, psychological and/or sexual) was used for analysis. The following individual characteristics and exposures were included in the analysis based on previous studies which showed an association between these characteristics and IPV: childhood sexual abuse history, substance abuse, violence socialisation, dominance, anger management and communication problems.ResultsPerpetrators of physical IPV have a higher prevalence of being victims of IPV than non-perpetrators. Female perpetrators have a higher prevalence of anger management issues than male perpetrators. Levels of anger management and violence socialisation are predictors of physical IPV perpetration only for female perpetrators.ConclusionsIPV interventions for victims should include interventions for perpetration given that many Chinese victims of IPV also perpetrate IPV. Practice and research on professional education and services for treating individuals who have IPV experience need to be developed in China.