bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Three Times a Week Glatiramer Acetate on Cerebral T1 Hypointense Lesions in Relapsing‐Remitting Multiple Sclerosis
Authors: Zivadinov Robert , Dwyer Michael G. , Ramasamy Deepa P. , Davis Mat D. , Steinerman Joshua R. , Khan Omar 
Published: September 2015

ABSTRACTBACKGROUND AND PURPOSETwo definitions of T1 hypointense (T1H) lesions can be derived from pre‐contrast images: those that may or may not have a corresponding gadolinium‐enhancing correlate on post‐contrast images (T1H total), and those that are simultaneously non‐gadolinium‐enhancing on post‐contrast scans (T1H non‐enhancing). To determine the differences in lesion evolution between these two T1H definitions, we examined the effect of glatiramer acetate 40 mg/mL three times weekly subcutaneous injection (GA40) on the number of new or enlarging T1H total and T1H non‐enhancing lesions in patients with relapsing‐remitting multiple sclerosis (RRMS).METHODSThe Phase III GALA study randomized 1404 RRMS subjects 2:1 to receive GA40 or placebo for 12 months. MRI scans were obtained at baseline and at months 6 and 12. Cumulative numbers of T1H total and of T1H non‐enhancing lesions were analyzed using an adjusted negative binomial regression model. A total of 1,357 patients had MRI data collected at either the month 6 or month 12 visit.RESULTSAmong the 1,357 patients with MRI scans performed at either the month 6 or month 12 visit, 883 treated with GA40 developed an adjusted cumulative mean of 1.72 T1H total lesions versus 2.62 in 440 placebo controls (risk ratio, .66; 95% CI, .54‐.80; P < .0001). On T1H non‐enhanced scans, GA40‐treated patients developed an adjusted cumulative mean of 1.35 T1H non‐enhancing lesions versus 1.91 in placebo controls (risk ratio, .71; CI, .58‐.87; P = .0009).CONCLUSIONSGA40 significantly reduced the number of new or enlarging T1H total lesions and T1H non‐enhancing lesions compared with placebo. Although the treatment effect magnitude was comparable with both definitions, the use of T1H non‐enhancing lesions may be more relevant for more uniform standardization in future clinical trials.
Determination of the status of stakeholder participation in the management of the Lake Malawi basin through application of Integrated Lake Basin Management
Authors: Chidammodzi C. L. , Muhandiki V. S. 
Published: September 2015

AbstractLake Malawi is the southernmost of the Great Rift Valley Lakes of Africa and boasts the world's greatest freshwater fish biodiversity. Along with its basin, the lake provides many benefits to the country of Malawi. Settlements, agriculture and fishing are some of the major uses of the lake basin, making community involvement a necessary component of its management. With the use of key informant interviews, questionnaire survey, document review and site observations, this study demonstrates the applicability of the Integrated Lake Basin Management framework in the Lake Malawi Basin in regard to stakeholder participation. The main objective was to assess the participation of stakeholders, especially local communities, in the management of the lake basin. The framework applied in this study is discussed. The study findings indicate strong to very strong stakeholder participation, with notably high levels of awareness and women's involvement. Enhancing the understanding of the complex nature of lake basin issues, especially those related to the linkages between the water body and the basin, is a topic requiring further attention.
Self‐Healing Extranodal Cutaneous Rosai‐Dorfman in a Child
Authors: Toledo del Castillo Blanca , Mata‐Fernández Cristina , Rodríguez Soria Virna J. , Parra Blanco Verónica , Loughlin Gerard , Campos‐Domínguez Minia 
Published: September 2015

AbstractSinus histiocytosis with massive lymphadenopathy, or Rosai‐Dorfman disease (RDD), is commonly characterized by painless cervical lymphadenopathy. Exclusively cutaneous Rosai‐Dorfman disease is rare. In the absence of massive lymphadenopathy, the nonspecific skin lesions may complicate the diagnosis. To our knowledge, the case reported herein is the youngest case of extranodal cutaneous RDD.
Neonatal Hairy Ear Pinnae and Gestational Diabetes: Just a Coincidence?
Authors: Valerio Enrico , Riello Laura , Chirico Michela , Semenzato Rossella , Cutrone Mario 
Published: September 2015

AbstractA newborn girl of 36 weeks gestation was noted to have several anomalies, including bilateral low ear attachment with ear pinnae hypertrichosis, left preauricular pit, micrognathia, short lingual frenulum, and short neck. Pregnancy history revealed poorly controlled maternal gestational diabetes (GD). Localized hypertrichosis of the ear pinnae may represent a potential marker of GD and thereby alert physicians to suspect other potentially GD‐associated conditions such as macrosomia, asphyxia, respiratory distress, hypoglycemia, hypocalcemia, hyperbilirubinemia, polycythemia, hypertrophic cardiomyopathy, and congenital anomalies, particularly those involving the central nervous system.
The U.S. Pediatric Dermatology Workforce: An Assessment of Productivity and Practice Patterns
Authors: Fogel Alexander L. , Teng Joyce M. C. 
Published: September 2015

AbstractBackgroundPediatric dermatology has always played an important role in children's healthcare, but there has been a shortage of pediatric dermatologists nationwide for more than a decade, and few metrics of productivity and practice patterns exist. This study sought to provide insight into these and other factors of the pediatric dermatology workforce.MethodsElectronic surveys were distributed to all 226 U.S. board‐certified pediatric dermatologists.ResultsA total of 108/226 (48%) of the electronic surveys were returned. Sixty percent of respondents were employed full‐ or part‐time in academic environments and 81% were salaried. Respondents reported that children constituted 79.5% of their practice, and the average respondent spent 3.8 days/week treating 92.6 patients, considerably lower than the 136.3 patients/week that the average general dermatologist sees. The academic practice environment was associated with children constituting a larger proportion of the practice (p < 0.001), fewer patients seen per week (85.9, p < 0.001), and longer median new patient wait times (60 vs 15 days) than in other practice environments. Private practitioners saw significantly more patients per week than those in academic environments (112.7, p = 0.005). Male and female practitioners reported approximately equal patient care days per week, similar wait times, and similar proportions of children in their practices.ConclusionsThis assessment revealed productivity and practice pattern differences between the various pediatric dermatology practice environments and between pediatric and general dermatology. This study provides important information for workforce planning and care availability assessments and baseline information for future studies.
A first insight into the scanning behaviour of the presocial blow fly larvae
Authors: Boulay Julien , Betremieux Cécile , Hédouin Valéry , Charabidzé Damien 
Published: September 2015

AbstractAggregation of necrophagous larvae has several benefits: the sharing of salivary enzymes (exodigestion), temperature regulation, protection from predators and parasites, etc., and is well developed in blow flies (Diptera:Calliphoridae). The present study focuses on the aggregation mechanism used by the necrophagous larvae ofLucilia sericataMeigen, the common green bottle fly. The ability of single larva to detect and follow a signal (trail) created by conspecifics is investigated initially. A circular ring is drawn in aPetri dish where 20 starved larvae have crawled for a period of 30 min. A naïve (test) larva is then placed in the dish and video‐tracked. Naïve larvae are able to detect the boundaries of the larvae‐crawled area and stay preferentially within this conspecific‐marked zone. In a second step, the orientation of larvae by scanning, a dedicated, ground‐signal detection behaviour of dipteran larvae, is analyzed. Four experimental conditions are tested: control, presence of food, conspecifics, and food + conspecifics. When conspecifics have been previously present in a given area, the scanning behaviour by naïve larvae in this area decreases (both in number and frequency of scans). Accordingly, scanning by necrophagous larvae ofL. sericatashould be considered not only as locomotion behaviour, but also as a potential way to detect signals from conspecifics for the purpose of aggregation. The chemical composition of the attractant(s), the behavioural effects (attraction or retention) and the implication of larval signalling in the aggregation process are new fields to explore.
Gene Expression and Localization of NGF and Its Cognate Receptors NTRK1 and NGFR in the Sex Organs of Male Rabbits
Authors: Maranesi M , Zerani M , Leonardi L , Pistilli A , Arruda‐Alencar J , Stabile AM , Rende M , Castellini C , Petrucci L , Parillo F , Moura A , Boiti C 
Published: September 2015

ContentsExperiments were devised to characterize the expression of nerve growth factor, beta polypeptide (NGF), and its cognate receptors neurotrophic tyrosine kinase receptor type 1 (NTRK1) and nerve growth factor receptor (NGFR) in rabbit male sex organs, as well as the concentrations of NGF in both seminal and blood plasma of sexually mature male rabbits. Immunoreactivity and gene expression for NGF and cognate receptors were detected in testis, prostate gland and seminal vesicle. The highest levels of NGF and NTRK1 transcripts were found in the prostate, while intermediate expressions were found in the testis. NGFR transcripts were expressed at the same levels in both testis and prostate and were more abundant than in seminal vesicles. The widespread distribution of NGF in all prostate glandular cells, together with its relative high mRNA abundance, confirms that the prostate of rabbits is the main source of this neurotrophin. In conclusion, the present data suggest that the NGF system is involved in the testicular development and spermatogenesis of rabbits and that NGF may act as a potential ovulation‐inducing factor being abundantly present in the seminal plasma.
Services Productivity, Trade Policy and Manufacturing Exports
Authors: Hoekman Bernard , Shepherd Ben 
Published: September 2015

AbstractThis paper analyses the linkage between services and manufacturing productivity performance, using firm‐level data for over 100 developing countries. We find strong evidence for such a linkage, although the effect is small: at the average rate of services input intensity, a 10 per cent improvement in services productivity is associated with an increase in manufacturing productivity of 0.3 per cent. Services trade restrictiveness indices are found to be a statistically significant determinant of manufactured exports performance, a finding that is robust to the inclusion of the overall level of trade restrictiveness that is applied against manufactured exports directly. The main channel through which services trade restrictions negatively affect manufactured exports is through FDI, a finding that is consistent with the stylised fact in the literature that FDI is a key channel for trade in services and an important vehicle through which services technology and know‐how is transferred across countries. At the sectoral level, restrictions on transport and retail distribution services have the largest negative impact on exports of manufactures.
Spatial fractionation of the dose using neon and heavier ions: A Monte Carlo study
Authors: Peucelle C. , Martínez‐Rovira I. , Prezado Y. 
Published: September 2015

Purpose:This work explores a new radiation therapy approach which might trigger a renewed use of neon and heavier ions to treat cancers. These ions were shown to be extremely efficient in radioresistant tumor killing. Unfortunately, the efficient region also extends into the normal tissue in front of the tumor. The strategy the authors propose is to profit from the well‐established sparing effect of thin spatially fractionated beams, so that the impact on normal tissues might be minimized while a high tumor control is achieved. The main goal of this work is to provide a proof of concept of this new approach. With that aim, a dosimetric study was carried out as a first step to evaluate the interest of further explorations of this avenue.Methods:The gate/geant4 v.6.1 Monte Carlo simulation platform was employed to simulate arrays of rectangular minibeams (700 μm × 2 cm) of four ions (Ne, Si, Ar, and Fe). The irradiations were performed with a 2 cm‐long spread‐out Bragg peak centered at 7 cm‐depth. Dose distributions in a water phantom were scored considering two minibeams center‐to‐center distances: 1400 and 3500 μm. Peak and valley doses, peak‐to‐valley dose ratios (PVDRs), beam penumbras, and relative contribution of nuclear fragments and electromagnetic processes were assessed as figures of merit. In addition, the type and proportion of the secondary nuclear fragments were evaluated in both peak and valley regions.Results:Extremely high PVDR values (>100) and low valley doses were obtained. The higher the atomic number (Z) of the primary ion is, the lower the valleys and the narrower the penumbras. Although the yield of secondary nuclear products increases with Z, the actual dose being deposited by the secondary nuclear fragments in the valleys starts to be the dominant contribution at deeper points, helping in the sparing of proximal normal tissues. Additionally, a wider center‐to‐center distance leads to a minimized contribution of heavier secondary fragments in valleys.Conclusions:The computed dose distributions suggest that a spatial fractionation of the dose combined to the use of submillimetric field sizes might allow profiting from the high efficiency of neon and heavier ions for the treatment of radioresistant tumors, while preserving normal tissues. The authors’ results support the further exploration of this avenue. Next steps include the realization of biological experiment to confirm the shifting of normal tissue complication probability curves.
Microbiological Assessment of Polymyxin B Components Tested Alone and in Combination
Authors: Kassamali Zahra , Prince Randall A. , Danziger Larry H. , Rotschafer John C. , Rhomberg Paul R. , Jones Ronald N. 
Published: September 2015

ABSTRACT

We investigated the antimicrobial activity of four polymyxin B components, B1, B2, B3, and isoleucine (Ile)-B1, individually and in combination. B3 was the most active agent against all organisms tested except
Acinetobacter baumannii
, for which Ile-B1 was most active. One combination met the criteria for synergy, B3 plus Ile-B1. No combinations exhibited antagonism. The dominant components of polymyxin B products (B1 and B2) were associated with the lowest probability of improved antibacterial activity when combined.
Role of Semen on Vaginal HIV-1 Transmission and Maraviroc Protection
Authors: Council Olivia D. , Swanson Michael D. , Spagnuolo Rae Ann , Wahl Angela , Garcia J. Victor 
Published: September 2015

ABSTRACT
We used bone marrow/liver/thymus (BLT) humanized mice to establish the effect of semen on vaginal HIV infection and on the efficacy of topically applied maraviroc. Our results demonstrate that vaginal transmission of cell-free HIV occurs efficiently in the presence of semen and that topically applied maraviroc efficiently prevents HIV transmission in the presence of semen. We also show that semen has no significant effect on the transmission of transmitted/founder viruses or cell-associated viruses.
Bactericidal Effect of Tomatidine-Tobramycin Combination against Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa Is Enhanced by Interspecific Small-Molecule Interactions
Authors: Boulanger Simon , Mitchell Gabriel , Bouarab Kamal , Marsault Éric , Cantin André , Frost Eric H. , Déziel Eric , Malouin François 
Published: September 2015

ABSTRACT

This study investigated the antibacterial activity of the plant alkaloid tomatidine (TO) against
Staphylococcus aureus
grown in the presence of
Pseudomonas aeruginosa
. Since the
P. aeruginosa
exoproduct 4-hydroxy-2-heptylquinoline-
N
-oxide (HQNO) is known to cause a respiratory deficiency in
S. aureus
and respiratory-deficient
S. aureus
are known to be hypersensitive to TO, we assessed kill kinetics of TO (8 μg/ml) against
S. aureus
in coculture with
P. aeruginosa
. Kill kinetics were also assessed using
P. aeruginosa
mutants deficient in the production of different exoproducts and quorum sensing-related compounds. After 24 h in coculture, TO increased the killing of
S. aureus
by 3.4 log
10
CFU/ml in comparison to that observed in a coculture without TO. The effect of TO was abolished when
S. aureus
was in coculture with the
lasR
rhlR
,
pqsA
,
pqsL
, or
lasA
mutant of
P. aeruginosa
. The bactericidal effect of TO against
S. aureus
in coculture with the
pqsL
mutant was restored by supplemental HQNO. In an
S. aureus
monoculture, the combination of HQNO and TO was bacteriostatic, indicating that the
pqsL
mutant produced an additional factor required for the bactericidal effect. The bactericidal activity of TO was also observed against a tobramycin-resistant methicillin-resistant
S. aureus
(MRSA) in coculture with
P. aeruginosa
, and the addition of tobramycin significantly suppressed the growth of both microorganisms. TO shows a strong bactericidal effect against
S. aureus
when cocultured with
P. aeruginosa
. The combination of TO and tobramycin may represent a new treatment approach for cystic fibrosis patients frequently cocolonized by MRSA and
P. aeruginosa
.
In Vivo
Evolution of CMY-2 to CMY-33 β-Lactamase in Escherichia coli Sequence Type 131: Characterization of an Acquired Extended-Spectrum AmpC Conferring Resistance to Cefepime
Authors: Pires João , Taracila Magdalena , Bethel Christopher R. , Doi Yohei , Kasraian Sara , Tinguely Regula , Sendi Parham , Bonomo Robert A. , Endimiani Andrea 
Published: September 2015

ABSTRACT

Cefepime is frequently prescribed to treat infections caused by AmpC-producing Gram-negative bacteria. CMY-2 is the most common plasmid-mediated AmpC (pAmpC) β-lactamase. Unfortunately, CMY variants conferring enhanced cefepime resistance have been reported. Here, we describe the evolution of CMY-2 to an extended-spectrum AmpC (ESAC) in clonally identical
Escherichia coli
isolates obtained from a patient. The CMY-2-producing
E. coli
isolate (CMY-2-
Ec
) was isolated from a wound. Thirty days later, one CMY-33-producing
E. coli
isolate (CMY-33-
Ec
) was detected in a bronchoalveolar lavage fluid sample. Two weeks before the isolation of CMY-33-
Ec
, the patient received cefepime. CMY-33-
Ec
and CMY-2-
Ec
were identical by repetitive extragenic palindromic-PCR (rep-PCR), being of hyperepidemic sequence type 131 (ST131) but showing different β-lactam MICs (e.g., cefepime MIC, 16 and ≤0.5 μg/ml for CMY-33-
Ec
and CMY-2-
Ec
, respectively). Identical CMY-2-
Ec
isolates were also found in a rectal swab. CMY-33 differs from CMY-2 by a Leu293-Ala294 deletion. Expressed in
E. coli
strain DH10B, both CMYs conferred resistance to ceftazidime (≥256 μg/ml), but the cefepime MICs were higher for CMY-33 than CMY-2 (8 versus 0.25 μg/ml, respectively). The
k
cat
/

K
m

or inhibitor complex inactivation (
k
inact
)/

K
i

app
(μM
−1
s
−1
) indicated that CMY-33 possesses an extended-spectrum β-lactamase (ESBL)-like spectrum compared to that of CMY-2 (e.g., cefoxitin, 0.2 versus 0.4; ceftazidime, 0.2 versus not measurable; cefepime, 0.2 versus not measurable; and tazobactam, 0.0018 versus 0.0009, respectively). Using molecular modeling, we show that a widened active site (∼4-Å shift) may play a significant role in enhancing cefepime hydrolysis. This is the first
in vivo
demonstration of a pAmpC that under cephalosporin treatment expands its substrate spectrum, resembling an ESBL. The prevalence of CMY-2-
Ec
isolates is rapidly increasing worldwide; therefore, awareness that cefepime treatment may select for resistant isolates is critical.
In Vitro
and
In Vivo
Investigation of the Inhibition of Trypanosoma brucei Cell Growth by Lipophilic Bisphosphonates
Authors: Yang Gyongseon , Zhu Wei , Kim Kuglae , Byun Soo Young , Choi Gahee , Wang Ke , Cha Jeong Seok , Cho Hyun-Soo , Oldfield Eric , No Joo Hwan 
Published: September 2015

ABSTRACT

We report the results of a screen of a library of 925 potential prenyl synthase inhibitors against
Trypanosoma brucei
farnesyl diphosphate synthase (TbFPPS) and against
T. brucei
, the causative agent of human African trypanosomiasis. The most potent compounds were lipophilic analogs of the bone resorption drug zoledronate, some of which had submicromolar to low micromolar activity against bloodstream form
T. brucei
and selectivity indices of up to ∼300. We evaluated the effects of two such inhibitors on survival and parasitemia in a
T. brucei
mouse model of infection and found that survival increased by up to 16 days. We also investigated the binding of three lipophilic bisphosphonates to an expressed TbFPPS using crystallography and investigated the thermodynamics of binding using isothermal titration calorimetry.
Rate ofFKSMutations among Consecutive Candida Isolates Causing Bloodstream Infection
Authors: Shields Ryan K. , Nguyen M. Hong , Press Ellen G. , Cumbie Richard , Driscoll Eileen , Pasculle A. William , Clancy Cornelius J. 
Published: September 2015

ABSTRACTPreciseFKSmutation rates amongCandidaspecies are undefined because studies have not systematically screened consecutive, disease-causing isolates. The Sensititre YeastOne (SYO) assay measures echinocandin MICs againstCandidawith less variability than reference broth microdilution methods. However, clinical breakpoint MICs may overstate caspofungin nonsusceptibility compared to other agents. Our objectives were to determineCandidaFKSmutation rates by studying consecutive bloodstream isolates and to determine if discrepant susceptibility results were associated withFKSmutations.FKShot spots were sequenced in echinocandin-intermediate and -resistant isolates and those from patients with breakthrough candidemia or ≥3 days of prior echinocandin exposure. Overall, 453 isolates from 384 patients underwent susceptibility testing; 16% were echinocandin intermediate or resistant. Intermediate susceptibility rates were higher forCandida glabratathan for other species (P< 0.0001) and higher for caspofungin than for other agents (P< 0.0001). Resistance rates were similar between agents.FKSmutations were detected in 5% of sequenced isolates and 2% of isolates overall. Corresponding rates amongC. glabrataisolates were 8% and 4%, respectively. AmongCandida albicansisolates, rates were 5% and <1%, respectively. Mutations occurred exclusively with prior echinocandin exposure and were not detected in other species. Isolates with discrepant susceptibility results did not harborFKSmutations. Mutation rates among isolates resistant to ≥2, 1, and 0 agents were 75%, 13%, and 0%, respectively. In conclusion,FKSmutations were uncommon among non-C. glabrataspecies, even with prior echinocandin exposure. Discrepancies in echinocandin susceptibility by SYO testing were not driven by mutations and likely reflect imprecise caspofungin clinical breakpoints.