bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phylogenetics of a Fungal Invasion: Origins and Widespread Dispersal of White-Nose Syndrome
Authors: Drees Kevin P. , Lorch Jeffrey M. , Puechmaille Sebastien J. , Parise Katy L. , Wibbelt Gudrun , Hoyt Joseph R. , Sun Keping , Jargalsaikhan Ariunbold , Dalannast Munkhnast , Palmer Jonathan M. , Lindner Daniel L. , Marm Kilpatrick A. , Pearson Talima , Keim Paul S. , Blehert David S. , Foster Jeffrey T. 
Published: December 2017

ABSTRACT

Globalization has facilitated the worldwide movement and introduction of pathogens, but epizoological reconstructions of these invasions are often hindered by limited sampling and insufficient genetic resolution among isolates.
Pseudogymnoascus destructans
, a fungal pathogen causing the epizootic of white-nose syndrome in North American bats, has exhibited few genetic polymorphisms in previous studies, presenting challenges for both epizoological tracking of the spread of this fungus and for determining its evolutionary history. We used single nucleotide polymorphisms (SNPs) from whole-genome sequencing and microsatellites to construct high-resolution phylogenies of
P. destructans
. Shallow genetic diversity and the lack of geographic structuring among North American isolates support a recent introduction followed by expansion via clonal reproduction across the epizootic zone. Moreover, the genetic relationships of isolates within North America suggest widespread mixing and long-distance movement of the fungus. Genetic diversity among isolates of
P. destructans
from Europe was substantially higher than in those from North America. However, genetic distance between the North American isolates and any given European isolate was similar to the distance between the individual European isolates. In contrast, the isolates we examined from Asia were highly divergent from both European and North American isolates. Although the definitive source for introduction of the North American population has not been conclusively identified, our data support the origin of the North American invasion by
P. destructans
from Europe rather than Asia.

IMPORTANCE
This phylogenetic study of the bat white-nose syndrome agent,
P. destructans
, uses genomics to elucidate evolutionary relationships among populations of the fungal pathogen to understand the epizoology of this biological invasion. We analyze hypervariable and abundant genetic characters (microsatellites and genomic SNPs, respectively) to reveal previously uncharacterized diversity among populations of the pathogen from North America and Eurasia. We present new evidence supporting recent introduction of the fungus to North America from a diverse Eurasian population, with limited increase in genetic variation in North America since that introduction.
T Cell Production of GM-CSF Protects the Host during Experimental Tuberculosis
Authors: Robinson Richard T. 
Published: December 2017

ABSTRACTAlthough classically associated with myelopoiesis, granulocyte-macrophage colony-stimulating factor (GM-CSF) is increasingly recognized as being important for tuberculosis (TB) resistance. GM-CSF is expressed by nonhematopoietic and hematopoietic lineages following infection withMycobacterium tuberculosisand is necessary to restrictM. tuberculosisgrowth in experimental models. Until the recent study by Rothchild et al. (mBio 8:e01514-17, 2017,https://doi.org/10.1128/mBio.01514-17), it was unknown whether GM-CSF-producing T cells contribute to TB resistance. Rothchild et al. identify which conventional and nonconventional T cell subsets produce GM-CSF during experimental TB, establish their protective nature using a variety of approaches, and provide a mechanistic basis for their ability to restrictM. tuberculosisgrowth. This commentary discusses the significance of these findings to basic and applied TB research. As translated to human disease, these findings suggest vaccine-mediated expansion of GM-CSF-producing T cells could be an effective prophylactic or therapeutic TB strategy.
Use of PRO Measures to Inform Tolerability in Oncology Trials: Implications for Clinical Review, IND Safety Reporting, and Clinical Site Inspections
Authors: Kim Janice , Singh Harpreet , Ayalew Kassa , Borror Kristina , Campbell Michelle , Johnson Laura Lee , Karesh Alyson , Khin Ni A. , Less Joanne R. , Menikoff Jerry , Minasian Lori , Mitchell Sandra A. , Papadopoulos Elektra J. , Piekarz Richard L. , Prohaska Kevin A. , Thompson Susan , Sridhara Rajeshwari , Pazdur Richard , Kluetz Paul G. 
Published: December 2017

Abstract
Cancer therapeutics frequently lead to symptomatic adverse events (AE) that can affect treatment tolerability. The NCI has developed the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) to assess symptomatic AEs by direct patient self-report. Although longitudinal assessment of patient-reported symptomatic AEs holds promise to better inform treatment tolerability, using patient-reported outcome (PRO) measures to assess symptomatic AEs has raised several regulatory and good clinical practice issues among those who conduct cancer clinical trials. These include concerns regarding trial monitoring, clinical review of PRO results by investigators and delegated clinical staff, whether PRO data on symptomatic AEs require investigational new drug (IND) safety reporting, and how the trial conduct and resultant PRO data will be assessed during clinical investigator site inspections. This article addresses current thinking regarding these issues in cancer clinical trials from the FDA, the NCI, and the Office for Human Research Protections. PRO measures, such as PRO-CTCAE, that assess symptomatic AEs in cancer trials are considered similar to other PRO assessments of symptoms, function, and health-related quality of life and can generate complementary data that may inform tolerability. Clarity on operational concerns related to incorporating PRO measures to inform tolerability is critical to continue the advancement of rigorous PRO assessment in cancer clinical trials. Clin Cancer Res; 24(8); 1780–4. ©2017 AACR.
See related commentary by Nipp and Temel, p. 1777
Repeated Combined Chemotherapy with Cisplatin Lowers Carnitine Levels in Gastric Cancer Patients
Authors: Kawai Akimasa , Matsumoto Hideo  , Endou Youko , Honda Yui , Kubota Hisako , Higashida Masaharu , Hirai Toshihiro 
Published: December 2017

<b><i>Background/Aims:</i></b> Carnitine plays an important role in the metabolism of fatty acids. It has also been reported that the administration of anticancer drugs may lead to reductions in serum carnitine levels due to decreased activity of organic cation transporter novel 2, which plays a role in the reabsorption of carnitine in the tubules of the kidney. We therefore studied the change in carnitine levels when chemotherapy was administered repeatedly to patients with gastric cancer. <b><i>Methods:</i></b> Ten patients with upper gastrointestinal cancer were enrolled in this study between December 2014 and August 2015. All patients were administered chemotherapy consisting of TS-1 and cisplatin every 3 weeks: 3 received it as adjuvant therapy post resection, the remaining 7 received it as treatment for unresectable tumors. Before the start of each chemotherapy cycle, serum was collected. <b><i>Results:</i></b> The mean total carnitine level was 54.5 ± 13.7 μmol/L prior to commencing chemotherapy; it was 46.7 ± 13.5 and 41.4 ± 14.8 μmol/L at the second and third cycles respectively. The total carnitine level was decreased in a statistically significant manner (<i>p</i> = 0.0039). The serum level of total protein and cholinesterase was also decreased significantly (<i>p</i> = 0.0218 and <i>p</i> = 0.0418). <b><i>Conclusion:</i></b> Carnitine levels decreased during repeated chemotherapy in patients with gastric cancer, and they are associated with the nutritional status.
Right Atrial Deformation in Predicting Outcomes in Pediatric Pulmonary Hypertension
Authors: Jone Pei-Ni , Schäfer Michal , Li Ling , Craft Mary , Ivy D. Dunbar , Kutty Shelby 
Published: December 2017

Background—
Elevated right atrial (RA) pressure is a risk factor for mortality, and RA size is prognostic of adverse outcomes in pulmonary hypertension (PH). There is limited data on phasic RA function (reservoir, conduit, and pump) in pediatric PH. We sought to evaluate (1) the RA function in pediatric PH patients compared with controls, (2) compare the RA deformation indices with Doppler indices of diastolic dysfunction, functional capacity, biomarkers, invasive hemodynamics, and right ventricular functional indices, and (3) evaluate the potential of RA deformation indices to predict clinical outcomes.

Methods and Results—

Sixty-six PH patients (mean age 7.9±4.7 years) were compared with 36 controls (7.7±4.4 years). RA and right ventricular deformation indices were obtained using 2-dimensional speckle tracking (2DCPA; TomTec, Germany). RA strain, strain rates, emptying fraction, and right ventricular longitudinal strain were measured. RA function was impaired in PH patients versus controls (
P
<0.001). There were significant associations between RA function with invasive hemodynamics (
P
<0.01). RA reservoir, pump function, the rate of RA filling, and atrial minimum volume predicted adverse clinical outcomes (hazard ratio [HR], 0.15; confidence interval [CI], 0.03–0.73;
P
<0.01; HR, 0.05; CI, 0.003–0.43;
P
<0.004; HR, 0.04; CI, 0.006–0.56;
P
<0.01; and HR, 8.6; CI, 1.6–37.2;
P
<0.01, respectively).

Conclusions—
RA deformation properties are significantly altered in pediatric PH patients. Progressive worsening of RA reservoir and conduit functions is related to changes in right ventricular diastolic dysfunction. RA reservoir function, pump function, the rate of atrial filling, and atrial minimum volume emerged as outcome predictors in pediatric PH.
The Influence of Investor-Centered Values in the Operation of Political Risk Insurance
Authors: Karagöz Tuğba 
Published: December 2017

Abstract
This article analyses the investor-centeredness in the regulatory and operative framework of political risk insurance arrangements. The dominant approach to the concept of political risk is profoundly market oriented and the operation of political risk arrangements, based on this approach, involves mechanisms of investment climate surveillance and supervision that further foster investor-centered values. This article argues that the authority of the agents that provide political risk insurance is dependent on the continued promotion of such values. In order to maintain their underwriting business, investment insurers are responsive to investors’ demand for a favorable investment climate in the host country and financial securities in the event of loss or damage – even when these demands are not legitimate. This is illustrated with reference to the operation of a major political risk insurance provider, the US government agency Overseas Private Investment Corporation.
Variational Computation of Sensible and Latent Heat Flux over Lake Superior
Authors: Cao Zuohao , Mackay Murray D. , Spence Christopher , Fortin Vincent 
Published: December 2017

Abstract
Sensible and latent heat fluxes over Lake Superior are computed using a variational approach with a Bowen ratio constraint and inputs of 7 years of half-hourly temporal resolution observations of hydrometeorological variables over the lake. In an advancement from previous work focusing on the sensible heat flux, in this work computations of the latent heat flux are required so that a new physical constraint of the Bowen ratio is introduced. Verifications are made possible for fluxes predicted by a Canadian operational coupled atmosphere–ocean model due to recent availabilities of observed and model-predicted fluxes over Lake Superior. The observed flux data with longer time periods and higher temporal resolution than those used in previous studies allows for the examination of detailed performances in computing these fluxes. Evaluations utilizing eddy-covariance measurements over Lake Superior show that the variational method yields higher correlations between computed and measured sensible and latent heat fluxes than a flux-gradient method. The variational method is more accurate than the flux-gradient method in computing these fluxes at annual, monthly, daily, and hourly time scales. Under both unstable and stable conditions, the variational method considerably reduces mean absolute errors produced by the flux-gradient approach in computing the fluxes. It is demonstrated with 2 months of data that the variational method obtains higher correlation coefficients between the observed and the computed sensible and latent heat fluxes than the coupled model predicted, and yields lower mean absolute errors than the coupled model. Furthermore, comparisons are made between the coupled-model-predicted fluxes and the fluxes computed based on three buoy observations over Lake Superior.
Turbulence-Induced Anti-Stokes Flow and the Resulting Limitations of Large-Eddy Simulation
Authors: Pearson Brodie 
Published: December 2017

AbstractThis study shows that the presence of Stokes drift us in the turbulent upper ocean induces a near-surface Eulerian current that opposes the Stokes drift. This current is distinct from previously studied anti-Stokes currents because it does not rely on the presence of planetary rotation or mean lateral gradients. Instead, the anti-Stokes flow arises from an interaction between the Stokes drift and turbulence. The new anti-Stokes flow is antiparallel to us near the ocean surface, is parallel to us at depth, and integrates to zero over the depth of the boundary layer. The presence of Stokes drift in large-eddy simulations (LES) is shown to induce artificial energy production caused by a combination of the new anti-Stokes flow and LES numerics. As a result, care must be taken when designing and interpreting simulations of realistic wave forcing, particularly as rotation becomes weak and/or us becomes perpendicular to the surface wind stress. The mechanism of the artificial energy production is demonstrated for a generalized LES subgrid scheme.
NIH Funding within Otolaryngology: 2005‐2014
Authors: Lennon Christen J. , Hunter Jacob B. , Mistry Akshitkumar M. , Espahbodi Mana , Deasey Matthew , Niesner K. J. , Labadie Robert F. 
Published: December 2017

ObjectiveAnalyze grants awarded between 2005 and 2014 to otolaryngology departments that appear in the National Institutes of Health (NIH) RePORTER database, summarize characteristics of grant recipients associated with otolaryngology departments as listed in the RePORTER between 2005 and 2014, and identify trends in otolaryngology NIH funding between 2005 and 2014 by topic.Study DesignCase series.SettingNIH database inquiry.SubjectsGrant recipients.MethodsThe RePORTER was queried for all grants awarded to otolaryngology departments between 2005 and 2014. All grants classified as new, renewal, or revision were included while duplicates were excluded.ResultsIn total, 475 grants to 51 institutions were categorized by topic and subtopic. Internet searches were conducted for characteristics of 352 principal investigators. Sixty‐seven percent of awardees had a PhD, 22% had an MD, and 11% had an MD/PhD. Sex ratios varied by degrees held. Although 31% of all grant recipients were women, this ratio was not seen when recipients were classified by degree type, with 78% of women holding a PhD compared with 55% of men (P =. 0013). Of the award types, 39% were R01s, 15% were R21s, and 10% were R03s. The top 3 represented topics were otology/neurotology (52%), audiology (25%), and head and neck surgery (14%). The mean annual award amount, after adjusting for inflation to 2014 dollars, was $226,495.76, with 72.8% awarded by the National Institute of Deafness and Communication Disorders. Twenty percent of awardees received multiple grants.ConclusionNIH funding in otolaryngology tends to be awarded to those with PhDs studying the hearing sciences, with 1 in 5 having multiple awards. As in other areas of NIH funding, women are underrepresented overall.
Correct Site Surgery
Authors: Beesley John 
Published: December 2017

Dear AfPP I am an anaesthetic practitioner working within a busy surgical day unit. In recent months, while undertaking presurgical checks with the patient and ward nurse, I have reported a number of incidents where patients have not had their site of surgery marked. On one particular occasion the wrong site had been marked. There is confusion among medical staff as to how the intended surgical site should be marked. Please could you clarify whether there are any national standards for correct site surgery. Concerned from Cambridge
Acupressure and Acupuncture in Preventing and Managing Postoperative Nausea and Vomiting in Adults
Authors: Abraham Jenny 
Published: December 2017

This literature review sets out to investigate the effectiveness of acupressure and acupuncture in preventing and managing postoperative nausea and vomiting (PONV) in adult patients. PONV is problematic, affecting patient satisfaction, delayed discharge and even patient re-admission. Current treatment of PONV constitutes a variety of drug therapies, which are only partially effective. With the integration of complementary and alternative medicines in healthcare, this review examined 10 research studies investigating the use of acupressure and acupuncture in treating PONV. Three studies found acupressure to be effective in preventing PONV. However, population samples were small and the research designs had numerous anomalies. Overall the article suggests that acupuncture and acupressure are ineffective in preventing and managing PONV in adult patients. Further investigation of the effectiveness of acupressure and acupuncture, combined with current drug therapies, using well designed and adequately powered studies is needed. Published studies predominantly examined the use of P6 as the pressure point. Further studies should examine other ‘acupoint’ sites, to ascertain whether these are effective dependent upon the operative site.
Surgery for tennis elbow: a systematic review
Authors: Bateman Marcus , Littlewood Chris , Rawson Beth , Tambe Amol A. 
Published: December 2017

Background There is no consensus on the most suitable treatment for tennis elbow but, in the USA, surgical intervention is increasing despite a lack of supportive research evidence. The aim of this systematic review was to provide a balanced update based on all relevant published randomized controlled trials conducted to date. Methods An electronic search of MEDLINE, EMBASE, CINAHL, BNI, AMED, PsycINFO, HBE, HMIC, PubMed, TRIP, Dynamed Plus and The Cochrane Library was complemented by hand searching. Risk of bias was assessed using the Cochrane Risk of Bias Tool and data were synthesized narratively, based on levels of evidence, as a result of heterogeneity. Results Twelve studies of poor methodological quality were included. The available data suggest that surgical interventions for tennis elbow are no more effective than nonsurgical and sham interventions. Surgical technique modifications may enhance effectiveness compared to traditional methods but have not been tested against a placebo. Conclusions Current research evidence suggests that surgery for tennis elbow is no more effective than nonsurgical treatment based on evidence with significant methodological limitations. Given the recalcitrant nature of tennis elbow for some patients, further research in the form of a high-quality placebo-controlled surgical trial with an additional conservative arm is required to usefully inform clinical practice.
The complete genome sequence of Ensifer meliloti strain CCMM B554 (FSM-MA), a highly effective nitrogen-fixing microsymbiont of Medicago truncatula Gaertn
Authors: Nagymihály Marianna , Vásarhelyi Bálint M. , Barrière Quentin , Chong Teik-Min , Bálint Balázs , Bihari Péter , Hong Kar-Wai , Horváth Balázs , Ibijbijen Jamal , Amar Mohammed , Farkas Attila , Kondorosi Éva , Chan Kok-Gan , Gruber Véronique , Ratet Pascal , Mergaert Peter , Kereszt Attila 
Published: December 2017

AbstractStrain CCMM B554, also known as FSM-MA, is a soil dwelling and nodule forming, nitrogen-fixing bacterium isolated from the nodules of the legume Medicago arborea L. in the Maamora Forest, Morocco. The strain forms effective nitrogen fixing nodules on species of the Medicago, Melilotus and Trigonella genera and is exceptional because it is a highly effective symbiotic partner of the two most widely used accessions, A17 and R108, of the model legume Medicago truncatula Gaertn. Based on 16S rRNA gene sequence, multilocus sequence and average nucleotide identity analyses, FSM-MA is identified as a new Ensifer meliloti strain. The genome is 6,70 Mbp and is comprised of the chromosome (3,64 Mbp) harboring 3574 predicted genes and two megaplasmids, pSymA (1,42 Mbp) and pSymB (1,64 Mbp) with respectively 1481 and 1595 predicted genes. The average GC content of the genome is 61.93%. The FSM-MA genome structure is highly similar and co-linear to other E. meliloti strains in the chromosome and the pSymB megaplasmid while, in contrast, it shows high variability in the pSymA plasmid. The large number of strain-specific sequences in pSymA as well as strain-specific genes on pSymB involved in the biosynthesis of the lipopolysaccharide and capsular polysaccharide surface polysaccharides may encode novel symbiotic functions explaining the high symbiotic performance of FSM-MA.
A Retrospective Analysis of Clinical Research Misconduct Using FDA-Issued Warning Letters and Clinical Investigator Inspection List From 2010 to 2014
Authors: Romano Christopher A. , Nair Singh , Delphin Ellise S. 
Published: December 2017

BACKGROUND:
The US Food and Drug Administration (FDA) conducts inspections of clinical investigation sites as a component of clinical trial regulation. The FDA describes the results of these inspections in the Clinical Investigator Inspection List (CLIIL). More serious violations are followed up in FDA warning letters issued to investigators. The primary objective of the current study is to qualitatively and quantitatively describe the CLIIL data and contents of FDA-issued warning letters from 2010 to 2014.

METHODS:
We retrospectively analyzed the CLIIL and FDA warning letters. For the CLIIL, we quantified the frequency of each violation among other data points. We compared recent data (2010–2014) to the previous 5 years (2005–2009). To analyze FDA warning letters, we developed a coding system to quantify the frequency of violations found.

RESULTS:
We analyzed 3637 inspections in the CLIIL database and 60 warning letters. Overall, there was a decrease or no change in all violations in the CLIIL database. The largest violation code reported was “failure to follow investigational plan” in both the 2005–2009 and 2010–2014 timeframes. Coding of FDA warning letters shows that the most common violations reported were failing to maintain accurate case histories (10.82%), enrolling ineligible subjects (8.85%), and failing to perform required tests (8.52%).

CONCLUSIONS:
The overall decrease in violations is encouraging. But, the high proportion of violations related to failure to follow the investigational plan is concerning as the complexity of trials increases. We conclude that more detailed information is necessary to accurately evaluate these violations. The current study provides a model for creating more granular data of violations to better inform clinical investigators and improve clinical trials.