bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional profiling in Streptococcus mutans: construction and examination of a genomic collection of gene deletion mutants
Authors: Quivey R.G. , Grayhack E.J. , Faustoferri R.C. , Hubbard C.J. , Baldeck J.D. , Wolf A.S. , MacGilvray M.E. , Rosalen P.L. , Scott‐Anne K. , Santiago B. , Gopal S. , Payne J. , Marquis R.E. 
Published: May 2015

SummaryA collection of tagged deletion mutant strains was created in Streptococcus mutans UA159 to facilitate investigation of the aciduric capability of this oral pathogen. Gene‐specific barcoded deletions were attempted in 1432 open reading frames (representing 73% of the genome), and resulted in the isolation of 1112 strains (56% coverage) carrying deletions in distinct non‐essential genes. As S. mutans virulence is predicated upon the ability of the organism to survive an acidic pH environment, form biofilms on tooth surfaces, and out‐compete other oral microflora, we assayed individual mutant strains for the relative fitness of the deletion strain, compared with the parent strain, under acidic and oxidative stress conditions, as well as for their ability to form biofilms in glucose‐ or sucrose‐containing medium. Our studies revealed a total of 51 deletion strains with defects in both aciduricity and biofilm formation. We have also identified 49 strains whose gene deletion confers sensitivity to oxidative damage and deficiencies in biofilm formation. We demonstrate the ability to examine competitive fitness of mutant organisms using the barcode tags incorporated into each deletion strain to examine the representation of a particular strain in a population. Co‐cultures of deletion strains were grown either in vitro in a chemostat to steady‐state values of pH 7 and pH 5 or in vivo in an animal model for oral infection. Taken together, these data represent a mechanism for assessing the virulence capacity of this pathogenic microorganism and a resource for identifying future targets for drug intervention to promote healthy oral microflora.
Neurologic outcome of urea cycle disorder liver transplant recipients may be predicted by pretransplant neurological imaging
Authors: Bolton Scott M. , Campbell Kathleen M. , Kukreja Marcia , Kohli Rohit 
Published: May 2015

AbstractLiver transplantation treats the hepatic affectation of UCDs; however, irreversible neurologic damage pretransplant is difficult to assess providing transplant teams with ethical dilemmas for liver transplantation. The purpose of our study was to determine whether pretransplant neuroimaging can predict developmental outcomes post‐liver‐transplant in children with UCDs. Methods: Patients undergoing liver transplantation for UCDs at Cincinnati Children's Hospital Medical Center between 2002 and 2012 were identified. Neurologic assessments prior to and after transplantation were categorized into mild, moderate, or severe disability. Neuroimaging data were categorized into mild, moderate, or severe by a single pediatric neuroradiologist. Results: Fifteen patients were identified of whom eight had neuroimaging prior to transplantation. Of the eight patients that had neuroimaging, four were categorized as severe, one moderate, and three no‐to‐mild delay. All four patients whose imaging was severe were found to have moderate‐to‐severe neurologic delay. Of the three patients with no‐to‐mild changes on neuroimaging two of three were found to have no‐to‐mild delay on developmental assessments after transplantation. Conclusion: Neuroimaging may be a helpful tool in determining developmental prognosis and outcomes post‐liver‐transplantation for UCDs. Further studies maybe needed to validate our preliminary findings.
The Ruthven manuscript of Gavin Douglas's Eneados and a new manuscript witness of Julius Caesar Scaliger's Epidorpides
Authors: Wingfield Emily 
Published: May 2015

AbstractThis article takes as its focus a set of Latin verses (copied in a late sixteenth‐ or early seventeenth‐century Scots hand) on fol. 1v of the so‐called Ruthven manuscript (Edinburgh, University Library, MS Dc.1.43) of Gavin Douglas's Eneados. These were not recorded in the seminal Scottish Text Society edition of the poem by Coldwell and have not, to the best of my knowledge, been previously discussed elsewhere. They can, however, now be identified as extracts from Books 3 (‘mane accinge’) and 2 (‘humiles nobilitat virtus’ and ‘te cura nunc’) of Julius Caesar Scaliger's Epidorpides (first published posthumously in 1573 in Geneva as De sapientia et beatitudine libri octo, quos Epidorpides inscripsit and again in 1574 as part of Poemata in duos partes divisa (Heidelberg)). In this article, I transcribe and identify the verses, document those connections between the elder and younger Scaliger and three Scottish writers (Buchanan, Melville and Rollock) that might account for the appearance of the verses in the Ruthven manuscript, and consider what correspondences one might draw between the three extracts from Scaliger's Epidorpides on fol. 1v of the Ruthven manuscript and the subsequent translation of Virgil's Aeneid by Gavin Douglas.
Prevalence of auditory hallucinations in Norwegian adolescents: Results from a population‐based study
Authors: Kompus Kristiina , Løberg Else‐Marie , Posserud Maj‐Britt , Lundervold Astri Johansen 
Published: May 2015

Knowing the prevalence and characteristics of auditory verbal hallucinations (AVH) in adolescents is important for estimations of need for mental health care and assessment of psychosis risk. In this report we assess the prevalence of AVH in a population‐based sample of 16–19 years old Norwegian adolescents (n = 9,646, 46.4% male) using two items assessing AVH (from the extended Launay‐Slade Hallucination Scale). The prevalence of hearing a voice speaking thoughts aloud was 10.6%. The prevalence of being troubled by voices was 5.3%, showing that negative emotionality about AVH is less frequent than the experience of hearing voices. Female respondents had slightly increased risk for being troubled by voices than males (odds ratio = 1.3), while age did not modulate prevalence. This AVH prevalence is in line with earlier reports in smaller samples of adolescents and indicates that AVH are not uncommon in this period of life. Further longitudinal studies are needed to investigate the value of AVH in predicting psychiatric disorder.
The role of point‐of‐care tests in antibiotic stewardship for urinary tract infections in a resource‐limited setting on the Thailand–Myanmar border
Authors: Chalmers Lauren , Cross Jessica , Chu Cindy S. , Phyo Aung Pyae , Trip Margreet , Ling Clare , Carrara Verena , Watthanaworawit Wanitda , Keereecharoen Lily , Hanboonkunupakarn Borimas , Nosten François , McGready Rose 
Published: May 2015

AbstractObjectivePublished literature from resource‐limited settings is infrequent, although urinary tract infections (UTI) are a common cause of outpatient presentation and antibiotic use. Point‐of‐care test (POCT) interpretation relates to antibiotic use and antibiotic resistance. We aimed to assess the diagnostic accuracy of POCT and their role in UTI antibiotic stewardship.MethodsOne‐year retrospective analysis in three clinics on the Thailand–Myanmar border of non‐pregnant adults presenting with urinary symptoms. POCT (urine dipstick and microscopy) were compared to culture with significant growth classified as pure growth of a single organism >105 CFU/ml.ResultsIn 247 patients, 82.6% female, the most common symptoms were dysuria (81.2%), suprapubic pain (67.8%) and urinary frequency (53.7%). After excluding contaminated samples, UTI was diagnosed in 52.4% (97/185); 71.1% (69/97) had a significant growth on culture, and >80% of these were Escherichia coli (20.9% produced extended‐spectrum β‐lactamase (ESBL)). Positive urine dipstick (leucocyte esterase ≥1 and/or nitrate positive) compared against positive microscopy (white blood cell >10/HPF, bacteria ≥1/HPF, epithelial cells <5/HPF) had a higher sensitivity (99% vs. 57%) but a lower specificity (47% vs. 89%), respectively. Combined POCT resulted in the best sensitivity (98%) and specificity (81%). Nearly one in ten patients received an antimicrobial to which the organism was not fully sensitive.ConclusionOne rapid, cost‐effective POCT was too inaccurate to be used alone by healthcare workers, impeding antibiotic stewardship in a high ESBL setting. Appropriate prescribing is improved with concurrent use and concordant results of urine dipstick and microscopy.
Canine cutaneous melanocytic tumours: significance of β‐catenin and survivin immunohistochemical expression
Authors: Bongiovanni Laura , D'Andrea Alessandra , Porcellato Ilaria , Ciccarelli Andrea , Malatesta Daniela , Romanucci Mariarita , Della Salda Leonardo , Mechelli Luca , Brachelente Chiara 
Published: May 2015

BackgroundRecent investigations have highlighted the controversial role of Wnt/β‐catenin pathway activation in human cutaneous melanoma. Survivin has been proposed as a valid prognostic marker for invasive and metastatic melanomas and lymph node melanoma metastasis in human cutaneous melanoma and is a promising therapeutic target.Hypothesis/ObjectivesOur aim was to investigate the immunohistochemical expression of survivin and β‐catenin in canine cutaneous melanocytic tumours, in order to understand their prognostic significance.MethodsTwenty‐one melanocytic tumours (10 melanocytomas and 11 melanomas) were investigated by immunohistochemistry using specific anti‐survivin and anti‐β‐catenin antibodies. A semi‐quantitative method was used to analyse the results; β‐catenin immunolabelling in neoplastic cells was evaluated as cytoplasmic, membranous or nuclear. The number of survivin‐positive cells was counted within ~1000 neoplastic cells. Results were related to histopathological features, evaluated in haematoxylin‐ and eosin‐stained slides, and to the clinical data obtained through a telephone survey with referring veterinarians.ResultsDespite a low level of expression in the majority of cases, β‐catenin was found to be correlated strongly with malignant behaviour (P < 0.01). An overexpression of nuclear survivin was statistically related to histological features of malignancy, presence of metastasis and death related to melanoma spread (P < 0.01).Conclusions and clinical importanceThe low nuclear β‐catenin expression, mainly found in metastatic cases, would indicate that β‐catenin activation may have only limited importance in the development or progression of canine cutaneous melanoma. The correlation of nuclear survivin expression with malignancy would indicate that survivin is possibly a useful prognostic marker and therapeutic target in canine melanoma patients.
Nematode dermatitis due to Angiostrongylus vasorum infection in a dog
Authors: Cavana Paola , Bensignor Emmanuel , Blot Stéphane , Carlus Marine , Chermette René , Crosaz Odile , Grimm Felix , Hurion Murielle , Jeandel Aurélien , Polack Bruno 
Published: May 2015

BackgroundAngiostrongylus vasorum is a nematode that primarily infects Canidae. The adult parasites are found in the pulmonary arterial circulation and the right side of the heart. The most common clinical sign is respiratory dysfunction. Bleeding, neurological, ocular, cardiovascular and gastrointestinal disorders are also reported. Skin lesions are very unusual.Hypothesis/ObjectivesThis report describes a nematode dermatitis due to A. vasorum infection. To the best of the authors' knowledge, this is the first case of a dog infected with this parasite that initially presented with skin lesions only.AnimalA 3‐year‐old female Weimaraner dog presented with a crusted papular dermatitis on the bridge of the nose and on the pinnae, and an erythematous pododermatitis with erosions and perionyxis of one digit of 1 week's duration. Two weeks later the dog developed respiratory distress.Methods and resultsSkin scrapings and fungal culture were negative for parasites and dermatophytes. Histopathological examination showed dermal granulomas and pyogranulomas with eosinophils centred around parasitic elements compatible with nematode larvae. Angiostrongylus vasorum DNA was demonstrated in skin biopsies. Chest radiographs were compatible with verminous pneumonia and a Baermann test revealed A. vasorum larvae. The dog was treated orally with fenbendazole, with rapid improvement and complete cure after 3 months.Conclusions and clinical importanceAngiostrongylus vasorum should be considered in dogs presented with skin lesions and respiratory signs. Skin biopsy, chest radiographs and Baermann test should be included in the diagnostic investigation.
Barcroft's bold assertion: All dwellers at high altitudes are persons of impaired physical and mental powers
Authors: West John B. 
Published: May 2015

AbstractBarcroft's bold assertion that everyone at high altitude has physical and mental impairment compared with sea level was very provocative. It was a result of the expedition that he led to Cerro de Pasco in Peru, altitude 4300 m. Although it is clear that newcomers to high altitude have reduced physical powers, some people believe that this does not apply to permanent residents who have been at high altitude for generations. The best evidence supports Barcroft's contention, although permanent residents often perform better than acclimatized lowlanders. Turning to neuropsychological function, newcomers to high altitude certainly have some impairment, and there is evidence that the same applies to highlanders. However the notion that permanent residents are impaired is anathema to many people. For example the eminent Peruvian physician Carlos Monge took great exception to Barcroft's remark and even attributed it to the fact that Barcroft was suffering from acute mountain sickness when he made it! Monge referred to ‘climatic aggression’, by which he meant the negative consequences of the inevitable hypoxia of high altitude. Recent technological advances such as oxygen enrichment of room air can overcome this ‘aggression’. This might be useful in some settings at high altitude such as a nursery where newborn babies are cared for, and possibly operating rooms where the surgeon's dexterity may be enhanced. Other situations might be dormitories, conference rooms, and perhaps some school rooms. These constitute possible ways by which the effects of Barcroft's assertion might be countered.
Single-Crystalline, Nanoporous Gallium Nitride Films With Fine Tuning of Pore Size for Stem Cell Engineering
Authors: Han Lin , Zhou Jing , Schimert Kristin I. , Sun Yubing , Zhang Yu , Han Jung , Fu Jianping , Fan Rong 
Published: May 2015

Abstract
Single-crystalline nanoporous gallium nitride (GaN) thin films were fabricated with the pore size readily tunable in 20–100 nm. Uniform adhesion and spreading of human mesenchymal stem cells (hMSCs) seeded on these thin films peak on the surface with pore size of 30 nm. Substantial cell elongation emerges as pore size increases to ∼80 nm. The osteogenic differentiation of hMSCs occurs preferentially on the films with 30 nm sized nanopores, which is correlated with the optimum condition for cell spreading, which suggests that adhesion, spreading, and stem cell differentiation are interlinked and might be coregulated by nanotopography.
Association of Longitudinal Changes of Physical Activity on Smoking Cessation Among Young Daily Smokers
Authors: Loprinzi Paul D. , Walker Jerome F. 
Published: May 2015

Objective:To our knowledge, no longitudinal epidemiological study among daily smokers has examined the effects of physical activity change/trajectory on smoking cessation. The purpose of this study was to examine the longitudinal effects of changes in physical activity on smoking cessation among a national sample of young (16–24 y) daily smokers.Methods:Data from the 2003–2005 National Youth Smoking Cessation Survey were used (N = 1178). Using hierarchical agglomerative cluster analysis, 5 distinct self-reported physical activity trajectories over 3 time periods (baseline, 12-month, and 24-month follow-up) were observed, including stable low physical activity, decreasing physical activity, curvilinear physical activity, stable high physical activity, and increasing physical activity. Nicotine dependence (Heaviness of Smoking Index) and demographic parameters were assessed via survey.Results:With stable low physical activity (16.2% quit smoking) serving as the referent group, those in the stable high physical activity (24.8% quit smoking) group had 1.8 greater odds of not smoking at the 24-month follow-up period (odds ratio = 1.81; 95% confidence interval, 1.12–2.91) after adjusting for nicotine dependence, age, gender, race-ethnicity, and education.Conclusions:Maintenance of regular physical activity among young daily smokers may help to facilitate smoking cessation.
Staphylococcus aureus Metabolic Adaptations during the Transition from a Daptomycin Susceptibility Phenotype to a Daptomycin Nonsusceptibility Phenotype
Authors: Gaupp Rosmarie , Lei Shulei , Reed Joseph M. , Peisker Henrik , Boyle-Vavra Susan , Bayer Arnold S. , Bischoff Markus , Herrmann Mathias , Daum Robert S. , Powers Robert , Somerville Greg A. 
Published: May 2015

ABSTRACT

Staphylococcus aureus
is a major cause of nosocomial and community-acquired infections. The success of
S. aureus
as a pathogen is due in part to its many virulence determinants and resistance to antimicrobials. In particular, methicillin-resistant
S. aureus
has emerged as a major cause of infections and led to increased use of the antibiotics vancomycin and daptomycin, which has increased the isolation of vancomycin-intermediate
S. aureus
and daptomycin-nonsusceptible
S. aureus
strains. The most common mechanism by which
S. aureus
acquires intermediate resistance to antibiotics is by adapting its physiology and metabolism to permit growth in the presence of these antibiotics, a process known as adaptive resistance. To better understand the physiological and metabolic changes associated with adaptive resistance, six daptomycin-susceptible and -nonsusceptible isogenic strain pairs were examined for changes in growth, competitive fitness, and metabolic alterations. Interestingly, daptomycin nonsusceptibility coincides with a slightly delayed transition to the postexponential growth phase and alterations in metabolism. Specifically, daptomycin-nonsusceptible strains have decreased tricarboxylic acid cycle activity, which correlates with increased synthesis of pyrimidines and purines and increased carbon flow to pathways associated with wall teichoic acid and peptidoglycan biosynthesis. Importantly, these data provided an opportunity to alter the daptomycin nonsusceptibility phenotype by manipulating bacterial metabolism, a first step in developing compounds that target metabolic pathways that can be used in combination with daptomycin to reduce treatment failures.
Population Pharmacokinetics, Tolerability, and Safety of Dihydroartemisinin-Piperaquine and Sulfadoxine-Pyrimethamine-Piperaquine in Pregnant and Nonpregnant Papua New Guinean Women
Authors: Benjamin John M. , Moore Brioni R. , Salman Sam , Page-Sharp Madhu , Tawat Somoyang , Yadi Gumal , Lorry Lina , Siba Peter M. , Batty Kevin T. , Robinson Leanne J. , Mueller Ivo , Davis Timothy M. E. 
Published: May 2015

ABSTRACT

The tolerability, safety, and disposition of dihydroartemisinin (DHA) and piperaquine (PQ) were assessed in 32 pregnant (second/third trimester) and 33 nonpregnant Papua New Guinean women randomized to adult treatment courses of DHA-PQ (three daily doses) or sulfadoxine-pyrimethamine (SP)-PQ (three daily PQ doses, single dose of SP). All dose adminstrations were observed, and subjects fasted for 2 h postdose. Plasma PQ was assayed by using high-performance liquid chromatography, and DHA was assessed by using liquid chromatography-mass spectrometry. Compartmental pharmacokinetic models were developed using a population-based approach. Both regimens were well tolerated. There was an expected increase in the rate-corrected electrocardiographic QT interval which was independent of pregnancy and treatment. Two pregnant and two nonpregnant women had
Plasmodium falciparum
parasitemia which cleared within 48 h, and no other subject became slide positive for malaria during 42 days of follow-up. Of 30 pregnant women followed to delivery, 27 (90%) delivered healthy babies and 3 (10%) had stillbirths; these obstetric outcomes are consistent with those in the general population. The area under the plasma PQ concentration-time curve (AUC
0–∞
) was lower in the pregnant patients (median [interquartile range], 23,721 μg · h/liter [21,481 to 27,951 μg · h/liter] versus 35,644 μg · h/liter [29,546 to 39,541 μg · h/liter];
P
< 0.001) in association with a greater clearance relative to bioavailability (73.5 liters/h [69.4 to 78.4] versus 53.8 liters/h [49.7 to 58.2];
P
< 0.001), but pregnancy did not influence the pharmacokinetics of DHA. The apparent pharmacokinetic differences between the present study and results from other studies of women with uncomplicated malaria that showed no effect of pregnancy on the AUC
0–∞
of PQ and greater bioavailability may reflect differences in postdose fat intake, proportions of women with malaria, and/or racial differences in drug disposition.
Pharmacokinetics of Piperaquine Transfer into the Breast Milk of Melanesian Mothers
Authors: Moore Brioni R. , Salman Sam , Benjamin John , Page-Sharp Madhu , Yadi Gumal , Batty Kevin T. , Siba Peter M. , Mueller Ivo , Davis Timothy M. E. 
Published: May 2015

ABSTRACT

Transfer of piperaquine (PQ) into breast milk was examined in 27 Papua New Guinean women given a 3-day course of dihydroartemisinin-PQ or sulfadoxine-pyrimethamine-PQ during the second/third trimester. Breast milk was sampled on days 1, 2, 3 to 5, 7 to 11, and 14 to 17 postdelivery, a median of 70 days postdose (range, 6 to 145 days). A blood sample was taken at delivery, and additional serial samples were available from 9 women who delivered within 42 days of dosing. Milk and plasma PQ were assayed by high-performance liquid chromatography. A population-based approach was used to model the log
e
(plasma) and milk concentration-time data. A sigmoid
E
max
model best described PQ breast milk transfer. The population average milk:plasma PQ ratio was 0.58, with a peak of 2.5 at delivery. The model-derived maximum milk intake (148 ml/kg of body weight/day) was similar to the accepted value of 150 ml/kg/day. The median estimated absolute and relative cumulative infant PQ doses were 22 μg and 0.07%, respectively, corresponding to absolute and relative daily doses of 0.41 μg/kg and 0.004%. Model-based simulations for PQ treatment regimens given at birth, 1 week postdelivery, and 6 weeks postdelivery showed that the highest median estimated relative total infant dose (0.36%; median absolute total dose of 101 μg/kg) was seen after maternal PQ treatment 6 weeks postpartum. The maximum simulated relative total and daily doses from any scenario were 4.3% and 2.5%, respectively, which were lower than the recommended 10% upper limit. Piperaquine is transferred into breast milk after maternal treatment doses, but PQ exposure for suckling infants appears safe.