bluuebunny/crossref_metadata_2025_split huggingface dataset:
In SilicoPredictive Modeling of CRISPR/Cas9 guide efficiency
Authors: Fusi Nicolo , Smith Ian , Doench John , Listgarten Jennifer 
Published: June 2015

ABSTRACTThe CRISPR/Cas9 system provides unprecedented genome editing capabilities; however, several facets of this system are under investigation for further characterization and optimization, including the choice of guide RNA that directs Cas9 to target DNA. In particular, given that one would like to target the protein-coding region of a gene, hundreds of guides satisfy the basic constraints of the CRISPR/Cas9 Protospacer Adjacent Motif sequence (PAM); however, not all of these guides actually generate gene knockouts with equal efficiency. Leveraging a broad set of experimental measurements of guide knockout efficiency, we introduce a state-of-the artin silicomodeling approach to identify guides that will lead to more effective gene knockout. We first investigated which guide and gene features are critical for prediction (e.g., single- and di-nucleotide identity of the gene target), which are helpful (e.g., thermodynamics), and which are predictive but redundant (e.g., microhomology). We also investigated evaluation measures for comparing predictive models in the present context, suggesting that Area Under the Receiver Operating Curve is not ideal. Finally, we explored a variety of different model classes and found that use of gradient-boosted regression trees produced the best predictive performance. Pointers to our open-source software, code, and prediction server will be available athttp://research.microsoft.com/en-us/projects/azimuth.
Floods and famine: climate‐induced collapse of a tropical predator‐prey community
Authors: Ujvari Beata , Brown Gregory , Shine Richard , Madsen Thomas 
Published: June 2015

Summary

Will climate change threaten wildlife populations by gradual shifts in mean conditions, or by increased frequency of extreme weather events?

Based on long‐term data (from 1991 to 2014), the aim of the present study was to analyse and compare the sensitivity of predator–prey demography to extreme climatic events versus normal, albeit highly variable, annual deviations in climatic conditions in the Australian wet–dry tropics.

From 1991 to 2005, predators (water pythons, Liasis fuscus) and their main prey (dusky rats, Rattus colletti) showed significant climate‐driven fluctuations in numbers.

These fluctuations were, however, trivial compared to the impact of two massive but brief deluges in 2007 and 2011, which virtually eliminated the dusky rats. The two floods resulted in the pythons experiencing an unprecedented famine in seven out of the last 8 years causing a massive shift in python demography, that is a significant reduction in feeding rates, reproductive output, growth rates, relative body mass, survival, mean body length and numbers (from 3173 in 1992 to 96 in 2013).

Our results demonstrate that attempts to predict faunal responses to climate change, even if based on long‐term studies, may be doomed to failure. Consequently, biologists may need to confront the uncomfortable truth that increased frequency of brief unpredictable bouts of extreme weather can influence populations far more than gradual deviations in mean climatic conditions.
Enhancing Clinical Content and Race/Ethnicity Data in Statewide Hospital Administrative Databases: Obstacles Encountered, Strategies Adopted, and Lessons Learned
Authors: Pine Michael , Kowlessar Niranjana M. , Salemi Jason L. , Miyamura Jill , Zingmond David S. , Katz Nicole E. , Schindler Joe 
Published: June 2015

ObjectivesEight grant teams used Agency for Healthcare Research and Quality infrastructure development research grants to enhance the clinical content of and improve race/ethnicity identifiers in statewide all‐payer hospital administrative databases.Principal FindingsGrantees faced common challenges, including recruiting data partners and ensuring their continued effective participation, acquiring and validating the accuracy and utility of new data elements, and linking data from multiple sources to create internally consistent enhanced administrative databases. Successful strategies to overcome these challenges included aggressively engaging with providers of critical sources of data, emphasizing potential benefits to participants, revising requirements to lessen burdens associated with participation, maintaining continuous communication with participants, being flexible when responding to participants' difficulties in meeting program requirements, and paying scrupulous attention to preparing data specifications and creating and implementing protocols for data auditing, validation, cleaning, editing, and linking. In addition to common challenges, grantees also had to contend with unique challenges from local environmental factors that shaped the strategies they adopted.ConclusionsThe creation of enhanced administrative databases to support comparative effectiveness research is difficult, particularly in the face of numerous challenges with recruiting data partners such as competing demands on information technology resources. Excellent communication, flexibility, and attention to detail are essential ingredients in accomplishing this task. Additional research is needed to develop strategies for maintaining these databases when initial funding is exhausted.
Availability of New Medicaid Patient Appointments and the Role of Rural Health Clinics
Authors: Richards Michael R. , Saloner Brendan , Kenney Genevieve M. , Rhodes Karin V. , Polsky Daniel 
Published: June 2015

ObjectiveTo examine the willingness to accept new Medicaid patients among certified rural health clinics (RHCs) and other nonsafety net rural providers.Data SourcesExperimental (audit) data from a 10‐state study of primary care practices, county‐level information from the Area Health Resource File, and RHC information from the Center for Medicare and Medicaid Services.Study DesignWe generate appointment rates for rural and nonrural areas by patient‐payer type (private, Medicaid, self‐pay) to then motivate our focus on within‐rural variation by clinic type (RHC vs. non‐RHC). Multivariate linear models test for statistical differences and assess the estimates’ sensitivity to the inclusion of control variables.Data CollectionThe primary data are from a large field study.Principal FindingsApproximately 80 percent of Medicaid callers receive an appointment in rural areas—a rate more than 20 percentage points greater than nonrural areas. Importantly, within rural areas, RHCs offer appointments to prospective Medicaid patients nearly 95 percent of the time, while the rural (nonsafety net) non‐RHC Medicaid rate is less than 75 percent. Measured differences are robust to covariate adjustment.ConclusionsOur study suggests that RHC status, with its alternative payment model, is strongly associated with new Medicaid patient acceptance. Altering RHC financial incentives may have consequences for rural Medicaid enrollees.
The Measurement of Stable Carbon Isotope Ratios of Eight Methamidophos Samples
Authors: Kawashima Hiroto 
Published: June 2015

AbstractBetween December 2007 and January 2008, people suffered from food poisoning in the Japanese prefectures of Chiba and Hyogo after eating frozen dumplings (gyoza) produced in China, which had very high concentrations (1490–19,290 ppm) of methamidophos (O,S‐dimethyl phosphoramidothioate). Thus, we measured the stable carbon isotope ratio of methamidophos using GC/C/IRMS to identify the source. We analyzed seven methamidophos reagents and one Chinese agricultural methamidophos chemical (MTD600) that contained many impurities. The δ13C values of the seven methamidophos reagents and MTD600 ranged from −49.23‰ to −31.90‰, with an average SD of 0.20‰, very high precision. This difference (17.33‰) was very large compared with that in previous reports and may be attributable to the material itself and the chemical processing of methamidophos. Criminals can easily obtain pesticides such as methamidophos; therefore, it is very important to identify the pesticide source and distribution route using stable isotopic science in the future.
Are overdoses treated by ambulance services an opportunity for additional interventions? A prospective cohort study
Authors: Gjersing Linn , Bretteville‐Jensen Anne Line 
Published: June 2015

AbstractAimsTo assess whether people who inject drugs (PWID) and who are treated for overdose by ambulance services have a greater mortality risk compared with other PWID, and to compare mortality risk within potentially critical time‐periods (1 week, 1 month, 3 months, 6 months, 1 year, 5 years) after an overdose attendance with the mortality risk within potentially non‐critical time‐periods (time before and/or after critical periods).DesignA prospective cohort study.SettingOslo, Norway.ParticipantsA total of 172 PWID street‐recruited in 1997 and followed‐up until the end of 2004.MeasurementsInterview data linked to data from ambulance records, Norwegian Correctional Services, Opioid Substitution Treatment records and National Cause of Death Registry. Separate Cox regression models (one for each critical time‐period) were estimated.FindingsAmbulance services treated 54% of the participants for an overdose during follow‐up. The mortality rate was 2.8 per 100 person‐years for those with an overdose and 3.3 for those without; the adjusted hazard ratio (HR) was 1.3 (95% CI = 0.6, 2.6, P = 0.482). Mortality risk was greater in all but the shortest critical time‐period following ambulance attendance than in the non‐critical periods. The mortality risk remained significantly elevated during critical periods, even when adjusted for total time spent in prison and substitution treatment. The HR ranged from 9.4 (95% CI = 3.5, 25.4) in the month after an overdose to 13.9 (95% CI = 6.4, 30.2) in the 5‐year period.ConclusionsMortality risk among people who inject drugs is significantly greater in time‐periods after an overdose attendance than outside these time‐periods.
Changes in the rate of nicotine metabolism across pregnancy: a longitudinal study
Authors: Bowker Katharine , Lewis Sarah , Coleman Tim , Cooper Sue 
Published: June 2015

AbstractAimsIncreased nicotine metabolism during pregnancy could explain why nicotine replacement therapy (NRT) appears to be less effective on smoking cessation in pregnancy than in non‐pregnant smokers, but little is known about nicotine metabolism across pregnancy. This study was conducted to determine when changes in nicotine metabolism occur during pregnancy and to describe the magnitude of these changes.DesignLongitudinal cohort study of pregnant smokers' nicotine metabolite ratio (NMR).Setting and Participants101 pregnant smokers recruited from hospital antenatal clinics in Nottingham, UK were asked to provide saliva samples at 8–14 weeks (n = 98), 18–22 weeks (n = 65), 32–36 weeks gestation (n = 47), 4 weeks postpartum (n = 44) and 12 weeks postpartum (n = 47).MeasurementsNicotine metabolite ratio (NMR) was measured using the ratio of cotinine to its primary metabolite trans‐3'‐hydroxycotinine. Multi‐level modelling was used to detect any overall difference in NMR between time points. The 12 week postpartum NMR was compared with the NMRs collected antenatally and 4 weeks postpartum.FindingsNMR changed over time (p = 0.0006). Compared with NMR at 12 weeks postpartum, NMR was significantly higher at 18–22 weeks (26% higher, 95% CI 12% to 38%) and 32–36 weeks (23% higher, 95% CI 9% to 35%). There was no significant difference between the 8‐14 weeks gestation or 4 weeks postpartum NMR and 12 weeks postpartum.ConclusionsNicotine metabolism appears to be faster during pregnancy; this faster metabolism is apparent from 18 to 22 weeks of pregnancy and appears to fall by 4 weeks after childbirth.
Submergence of black ash logs to control emerald ash borer and preserve wood forAmericanIndian basketmaking
Authors: Poland Therese M. , Ciaramitaro Tina M. , Emery Marla R. , Crook Damon J. , Pigeon Ed , Pigeon Angie 
Published: June 2015

AbstractIndigenous artisans in theGreatLakes region rely on the ring‐porous property of black ashFraxinus nigraMarshall (Oleaceae), which allows annual layers of xylem to be easily separated to make baskets that are important economic resources and vessels of culture.The emerald ash borerAgrilus planipennisFairmaire (Coleoptera:Buprestidae) is threateningNorthAmerica's ash resource, including black ash and this centuries‐old art form, resulting in grave concern about the availability of black ash trees for basketmaking and about movement of black ash (along withA. planipennis) from areas where it is cut to lands where it is pounded and split to make baskets.We evaluated the traditional practice of storing black ash logs submerged in water as a possible method for killing within‐tree life stages ofA. planipennisat the same time as preserving the wood's value for basketmaking.Black ash trees infested with overwinteringA. planipennislarvae were felled and cut into 60‐cm bolts in 2010 and in 2011. These were submerged in a river for different lengths of time and, after treatment, placed into rearing tubes to determine survival and adult emergence, or dissected within 24 h to determine larval mortality, and then pounded and peeled into splints to assess colour and pliability.In 2010, allA. planipennislarvae had died and no adults emerged from logs submerged in spring for 10 weeks or longer, whereas some larvae survived and adults emerged from logs submerged for up to 9 weeks.In 2011, submergence for 18 weeks during winter or 14 weeks in spring resulted in complete mortality ofA. planipennislarvae and no emergence of adults at the same time as still preserving wood quality for basketmaking.
Primary angle‐closure glaucoma: an update
Authors: Wright Carrie , Tawfik Mohammed A. , Waisbourd Michael , Katz Leslie J. 
Published: June 2015

AbstractPrimary angle‐closure glaucoma is potentially a devastating disease, responsible for half of glaucoma‐related blindness worldwide. Angle closure is characterized by appositional approximation or contact between the iris and trabecular meshwork. It tends to develop in eyes with shallow anterior chambers, anteriorly positioned or pushed lenses, and angle crowding. Risk of primary angle‐closure glaucoma is high among women, the elderly and the hyperopic, and it is most prevalent in Asia. Investigation into genetic mechanisms of glaucoma inheritance is underway. Diagnosis relies on gonioscopy and may be aided by anterior segment optical coherence tomography and ultrasound biomicroscopy. Treatment is designed to control intraocular pressure while monitoring changes to the angle and optic nerve head. Treatment typically begins with medical management through pressure‐reducing topical medications. Peripheral iridotomy is often performed to alleviate pupillary block, while laser iridoplasty has been found effective for mechanisms of closure other than pupillary block, such as plateau iris syndrome. Phacoemulsification, with or without goniosynechialysis, both in eyes with existing cataracts and in those with clear lenses, is thus far a viable treatment alternative. Long‐term research currently underway will examine its efficacy in cases of angle closure in early stages of the disease. Endoscopic cyclophotocoagulation is another treatment option, which can be combined with cataract surgery. Trabeculectomy remains effective therapy for more advanced cases.
Paediatricians require more information before they routinely co‐administer the meningococcal B vaccine with routine infant vaccines
Authors: Wagner Angelika , Kundi Michael , Zwiauer Karl , Wiedermann Ursula 
Published: June 2015

AbstractAimThe four‐component meningococcal serogroup B (4CMenB) vaccine was licensed by the European Medicines Agency in 2013. We evaluated current practice regarding multiple vaccines and the attitudes of paediatricians towards the 4CMenB before it became available in Austria in 2014.MethodsWe sent 1624 Austrian paediatricians an email invitation to participate in our nationwide web‐based survey and 231 responded.ResultsMost participants regarded the 4CMenB vaccine as a long‐needed and necessary tool against meningococcal B disease. However, most participants would not co‐administer this vaccine with other routine infant vaccines. The survey showed that 58.9% of paediatricians already co‐administered the hexavalent vaccine with the pneumococcal conjugate vaccine, but most of them would not add a third vaccine at the same visit. This was mainly due to lack of experience with the vaccine and also because they assumed that parents would not consent. Importantly, paediatricians said they wanted an explicit recommendation in the Austrian Immunisation Plan on the timing of the 4CMenB vaccine before they would confidently and routinely use it for infants.ConclusionPaediatricians required more information for themselves and for parents before routinely co‐administering the 4CMenB vaccine. They also requested a national recommendation on its timing.
Suspected intramedullary bone infarct subsequent to tibial plateau levelling osteotomy in a dog
Authors: Newman ME , Johnson KA 
Published: June 2015

BackgroundBone infarction is a syndrome associated with disruption to the medullary blood supply of a long bone and may present as either a cause of lameness or, more commonly, an incidental finding. Bone infarction is a known complication of total hip replacement in the dog and may be associated with several other systemic diseases.Case ReportA 3‐year‐old female desexed Labrador Retriever presented for acute lameness 4 weeks following tibial plateau levelling osteotomy (TPLO). Subsequent radiographs revealed an increase in medullary bone opacity, radiographically consistent with a medullary bone infarction. The lesion was followed with serial radiographs and appeared to spontaneously resolve.ConclusionThis is the first reported case of bone infarction following TPLO in the dog. Bone infarction should be considered as an unlikely but potential complication of TPLO.
Concurrent idiopathic vestibular syndrome and facial nerve paralysis in a cat
Authors: Fraser AR , Long SN , le Chevoir MA 
Published: June 2015

Case reportA 4‐year‐old male neutered Domestic Medium‐hair cat was referred for right head tilt and ataxia of 2 weeks duration. On examination it was determined that the cat had right facial nerve paralysis and peripheral vestibular signs. Haematology and serum biochemical testing were performed in addition to magnetic resonance imaging of the brain and ears, and cerebrospinal fluid analysis. An underlying condition was not identified. A diagnosis of idiopathic vestibular syndrome and concurrent idiopathic right facial nerve paralysis was consequently made. The cat was re‐evaluated over the following weeks and was determined to have complete resolution of clinical signs within 7 weeks.ConclusionVestibular dysfunction and concurrent facial nerve paralysis have previously been reported in the cat, but not of an idiopathic nature.
Susceptibility to antimicrobials of mastitis‐causing Staphylococcus aureus, Streptococcus uberis and Str. dysgalactiae from New Zealand and the USA as assessed by the disk diffusion test
Authors: Petrovski KR , Grinberg A , Williamson NB , Abdalla ME , Lopez‐Villalobos N , Parkinson TJ , Tucker IG , Rapnicki P 
Published: June 2015

ObjectiveTo compare the antimicrobial susceptibility patterns of three common mastitis pathogens (Staphylococcus aureus, Streptococcus uberis and Str. dysgalactiae) isolated from milk samples from New Zealand and the USA.MethodsA total of 182 S. aureus, 126 Str. uberis and 89 Str. dysgalactiae isolates from New Zealand (107, 106 and 41, respectively) and the USA (75, 20 and 48, respectively) were assessed using the disk diffusion test.ResultsSusceptibility varied among the bacterial species. All isolates were susceptible to the amoxicillin–clavulanic acid combination. Resistance to lincomycin was most frequent (susceptibility of 8.6%) across all species. Non‐susceptible (i.e. resistant or intermediate) isolates of S. aureus were identified for the three non‐isoxazolyl penicillins (amoxicillin, ampicillin and penicillin: 20.6% and 36.0%) and lincomycin (99.9% and 94.6%) for NZ and the USA, respectively. Resistance to erythromycin (5.3%) and tetracyclines (6.7%) was detected only in isolates from the USA. There were differences in susceptibility between Str. uberis and Str. dysgalactiae; all streptococcal isolates demonstrated resistance to aminoglycosides (neomycin 52.4% and streptomycin 27.9%) and enrofloxacin (28%). Resistance of Str. dysgalactiae to tetracycline was almost 100.0% and to oxytetracycline 89.9%.Conclusion and clinical relevanceMost of the isolates tested were susceptible to most of the antimicrobials commonly used for treatment of bovine mastitis, with the exception of the lincosamides. Susceptibility to a selected class‐representative antimicrobial and at the genus level should be interpreted with caution. Differences between NZ and the USA confirm the value of national surveys to determine the susceptibility patterns of mastitis pathogens.
Cutaneous and systemic mycoses from infection with Lecanicillium spp. in captive Guthega skinks (Liopholis guthega)
Authors: Scheelings TF , Dobson EC , Hooper C , Eden P 
Published: June 2015

BackgroundGuthega skinks have been listed as critically endangered and are considered particularly vulnerable to extinction because of their isolation and restricted distribution. There is no information on their captive husbandry, or the diseases that affect them.Case reportCutaneous and systemic mycosis from infection with Lecanicillium spp. was diagnosed in a captive colony of Guthega skinks (Liopholis guthega). Infection resulted in the death of five lizards. Diagnosis of infection was confirmed using a combination of histopathology, fungal culture and DNA sequencing from all affected animals. An additional four similarly affected individuals were successfully treated with a combination of voriconazole (10 mg/kg PO once daily) and shallow baths of benzalkonium chloride and polyhexamethylene biguanide hydrochloride (F10) (1 : 250, 20 min once daily). This is the first report of Lecanicillium spp. infection in reptiles.
In vivo characterisation of two Australian isolates of Marek's disease virus including pathology, viral load and neuropathotyping based on clinical signs
Authors: Wajid SJ , Walkden‐Brown SW , Vanselow BA , Islam AFMF , Renz KG 
Published: June 2015

ObjectiveTo evaluate the pathogenicity of Australian Marek's disease virus (MDV) isolate MPF23 (1985) against the reference strain MPF57 based on pathology, viral load and neuropathotyping on the basis of clinical signs.ProcedureTwo MDV challenge isolates (MPF57 or MPF23) were administered to unvaccinated specific‐pathogen free (SPF) layer chicks on day 5 after hatch at three challenge doses (500, 2000 or 8000 plaque‐forming units (pfu)/chick). Mortality, body weight, immune organ weights, MDV load in peripheral blood lymphocytes (PBL) and clinical signs were measured to 56 days post challenge (dpc).ResultsMPF23 was the more pathogenic of the two viruses, inducing higher mortality (81% vs 62%) and incidence of MD lesions (100% vs 76%). MPF23 induced earlier, more sustained and more severe neurological signs in the period 26–56 dpc. However, there were few differences during the 0–23 dpc used in the neuropathotyping classification under test. The observed pattern during this earlier period classified both viruses as neuropathotype B, consistent with a very virulent pathotype. MDV load in PBL at 7 and 44 dpc did not differ between virus isolates, but the load at 7 dpc was significantly and negatively associated with time to euthanasia or death.ConclusionMPF23 appears to be as, or more, virulent than the MDV strains isolated over the subsequent two decades. The neuropathotyping system developed in the USA did not clearly differentiate between the two isolates under test; however, extension of the period of assessment of clinical signs beyond 26 dpc did reveal clear differences.