bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does modulation of the endocannabinoid system have potential therapeutic utility in cerebellar ataxia?
Authors: Stephens G. J. 
Published: March 2016

AbstractCerebellar ataxias represent a spectrum of disorders which are, however, linked by common symptoms of motor incoordination and typically associated with deficiency in Purkinje cell firing activity and, often, degeneration. Cerebellar ataxias currently lack a curative agent. The endocannabinoid (eCB) system includes eCB compounds and their associated metabolic enzymes, together with cannabinoid receptors, predominantly the cannabinoid CB1 receptor (CB1R) in the cerebellum; activation of this system in the cerebellar cortex is associated with deficits in motor coordination characteristic of ataxia, effects which can be prevented by CB1R antagonists. Of further interest are various findings that CB1R deficits may also induce a progressive ataxic phenotype. Together these studies suggest that motor coordination is reliant on maintaining the correct balance in eCB system signalling. Recent work also demonstrates deficient cannabinoid signalling in the mouse ‘ducky2J’ model of ataxia. In light of these points, the potential mechanisms whereby cannabinoids may modulate the eCB system to ameliorate dysfunction associated with cerebellar ataxias are considered.
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Programming of maternal and offspring disease: impact of growth restriction, fetal sex and transmission across generations
Authors: Cheong Jean N. , Wlodek Mary E. , Moritz Karen M. , Cuffe James S. M. 
Published: March 2016

AbstractBabies born small are at an increased risk of developing myriad adult diseases. While growth restriction increases disease risk in all individuals, often a second hit is required to unmask ‘programmed’ impairments in physiology. Programmed disease outcomes are demonstrated more commonly in male offspring compared with females, with these sex‐specific outcomes partly attributed to different placenta‐regulated growth strategies of the male and female fetus. Pregnancy is known to be a major risk factor for unmasking a number of conditions and can be considered a ‘second hit’ for women who were born small. As such, female offspring often develop impairments of physiology for the first time during pregnancy that present as pregnancy complications. Numerous maternal stressors can further increase the risk of developing a maternal complication during pregnancy. Importantly, these maternal complications can have long‐term consequences for both the mother after pregnancy and the developing fetus. Conditions such as preeclampsia, gestational diabetes and hypertension as well as thyroid, liver and kidney diseases are all conditions that can complicate pregnancy and have long‐term consequences for maternal and offspring health. Babies born to mothers who develop these conditions are often at a greater risk of developing disease in adulthood. This has implications as a mechanism for transmission of disease across generations. In this review, we discuss the evidence surrounding long‐term intergenerational implications of being born small and/or experiencing stress during pregnancy on programming outcomes.
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A quantitative metrology for performance characterization of five breast tomosynthesis systems based on an anthropomorphic phantom
Authors: Ikejimba Lynda , Lo Joseph Y. , Chen Yicheng , Oberhofer Nadia , Kiarashi Nooshin , Samei Ehsan 
Published: March 2016

Purpose:In medical imaging systems, proper rendition of anatomy is essential in discerning normal tissue from disease. Currently, digital breast tomosynthesis (DBT) systems are evaluated using subjective evaluation of lesion visibility in uniform phantoms. This study involved the development of a new methodology to objectively measure the rendition of a 3D breast model by an anthropomorphic breast phantom, and its implementation on five clinical DBT systems of different makes and models.Methods:A 3D, patient‐based breast phantom was fabricated based on XCAT breast models. This phantom was imaged on representative breast tomosynthesis systems. The ability of tomosynthesis systems to accurately reproduce the 3D structure of the breast was assessed by computational analysis of the resultant images in terms of three groups of indices: contrast index (CI), reflective of local difference between adipose and glandular material; adipose variability index (AVI), reflective of contributions of noise and artifacts within uniform adipose regions; and contrast detectability, which describes contrast against local background variability and is described by contrast variability index (CVI), coefficient of variation (COV), contrast to adipose variability index (CAVI), and contrast to noise ratio index (CNRI). The indices were obtained by comparing the image data to the gold standard 3D distribution of breast tissue in the model. Corresponding indices were measured within variable region of interest (ROI) sizes ranging from 10 to 37 mm. The characterization was performed on five tomosynthesis systems: Fuji Aspire Crystal, GE Essential, Hologic Dimension, IMS Giotto, and Siemens Inspiration, all evaluated at a fixed dose of 1.5 mGy average glandular dose, anonymized in random order from A to E.Results:Results are provided as a function of ROI size. The systems ranked orders in terms of CI with values of 7.4%, 7.0%, 6.9%, 6.4%, and 5.2% for systems A–E, respectively. This system ranking was identical for CNRI. Both CI and CNRI were constant over ROI size. The ranking was similar for CVI. The COV also changed little with ROI size and was similar across systems. For 10 mm ROIs, the average system COV was 0.7, which reduced to 0.5 with 37 mm ROIs. Two systems (A and B) exhibited highest AVI values when measured in 10 mm ROIs. This, however, was ROI‐size‐dependent with the three other systems (C–E) yielding higher AVI values when measured with 37 mm ROIs. Two systems (B and E) showed inferior CAVI compared to others.Conclusions:The quality of rendition tracked with differences in image appearance across systems. The findings illustrate that the anthropomorphic phantom can be used as a basis to extract quantitative values of image attributes in DBT.
Design and characterization of a new high‐dose‐rate brachytherapy Valencia applicator for larger skin lesions
Authors: Candela‐Juan C. , Niatsetski Y. , van der Laarse R. , Granero D. , Ballester F. , Perez‐Calatayud J. , Vijande J. 
Published: March 2016

Purpose:The aims of this study were (i) to design a new high‐dose‐rate (HDR) brachytherapy applicator for treating surface lesions with planning target volumes larger than 3 cm in diameter and up to 5 cm in size, using the microSelectron‐HDR or Flexitron afterloader (Elekta Brachytherapy) with a 192Ir source; (ii) to calculate by means of the Monte Carlo (MC) method the dose distribution for the new applicator when it is placed against a water phantom; and (iii) to validate experimentally the dose distributions in water.Methods:The penelope2008 MC code was used to optimize dwell positions and dwell times. Next, the dose distribution in a water phantom and the leakage dose distribution around the applicator were calculated. Finally, MC data were validated experimentally for a 192Ir mHDR‐v2 source by measuring (i) dose distributions with radiochromic EBT3 films (ISP); (ii) percentage depth–dose (PDD) curve with the parallel‐plate ionization chamber Advanced Markus (PTW); and (iii) absolute dose rate with EBT3 films and the PinPoint T31016 (PTW) ionization chamber.Results:The new applicator is made of tungsten alloy (Densimet) and consists of a set of interchangeable collimators. Three catheters are used to allocate the source at prefixed dwell positions with preset weights to produce a homogenous dose distribution at the typical prescription depth of 3 mm in water. The same plan is used for all available collimators. PDD, absolute dose rate per unit of air kerma strength, and off‐axis profiles in a cylindrical water phantom are reported. These data can be used for treatment planning. Leakage around the applicator was also scored. The dose distributions, PDD, and absolute dose rate calculated agree within experimental uncertainties with the doses measured: differences of MC data with chamber measurements are up to 0.8% and with radiochromic films are up to 3.5%.Conclusions:The new applicator and the dosimetric data provided here will be a valuable tool in clinical practice, making treatment of large skin lesions simpler, faster, and safer. Also the dose to surrounding healthy tissues is minimal.
Soybean Ferritin Expression in Saccharomyces cerevisiae Modulates Iron Accumulation and Resistance to Elevated Iron Concentrations
Authors: de Llanos Rosa , Martínez-Garay Carlos Andrés , Fita-Torró Josep , Romero Antonia María , Martínez-Pastor María Teresa , Puig Sergi 
Published: March 2016

ABSTRACT

Fungi, including the yeast
Saccharomyces cerevisiae
, lack ferritin and use vacuoles as iron storage organelles. This work explored how plant ferritin expression influenced baker's yeast iron metabolism. Soybean seed ferritin H1 (SFerH1) and SFerH2 genes were cloned and expressed in yeast cells. Both soybean ferritins assembled as multimeric complexes, which bound yeast intracellular iron
in vivo
and, consequently, induced the activation of the genes expressed during iron scarcity. Soybean ferritin protected yeast cells that lacked the Ccc1 vacuolar iron detoxification transporter from toxic iron levels by reducing cellular oxidation, thus allowing growth at high iron concentrations. Interestingly, when simultaneously expressed in
ccc1
Δ cells, SFerH1 and SFerH2 assembled as heteropolymers, which further increased iron resistance and reduced the oxidative stress produced by excess iron compared to ferritin homopolymer complexes. Finally, soybean ferritin expression led to increased iron accumulation in both wild-type and
ccc1
Δ yeast cells at certain environmental iron concentrations.

IMPORTANCE
Iron deficiency is a worldwide nutritional disorder to which women and children are especially vulnerable. A common strategy to combat iron deficiency consists of dietary supplementation with inorganic iron salts, whose bioavailability is very low. Iron-enriched yeasts and cereals are alternative strategies to diminish iron deficiency. Animals and plants possess large ferritin complexes that accumulate, detoxify, or buffer excess cellular iron. However, the yeast
Saccharomyces cerevisiae
lacks ferritin and uses vacuoles as iron storage organelles. Here, we explored how soybean ferritin expression influenced yeast iron metabolism, confirming that yeasts that express soybean seed ferritin could be explored as a novel strategy to increase dietary iron absorption.
Biofilms on Hospital Shower Hoses: Characterization and Implications for Nosocomial Infections
Authors: Soto-Giron Maria J. , Rodriguez-R Luis M. , Luo Chengwei , Elk Michael , Ryu Hodon , Hoelle Jill , Santo Domingo Jorge W. , Konstantinidis Konstantinos T. 
Published: March 2016

ABSTRACTAlthough the source of drinking water (DW) used in hospitals is commonly disinfected, biofilms forming on water pipelines are a refuge for bacteria, including possible pathogens that survive different disinfection strategies. These biofilm communities are only beginning to be explored by culture-independent techniques that circumvent the limitations of conventional monitoring efforts. Hence, theories regarding the frequency of opportunistic pathogens in DW biofilms and how biofilm members withstand high doses of disinfectants and/or chlorine residuals in the water supply remain speculative. The aim of this study was to characterize the composition of microbial communities growing on five hospital shower hoses using both 16S rRNA gene sequencing of bacterial isolates and whole-genome shotgun metagenome sequencing. The resulting data revealed aMycobacterium-like population, closely related toMycobacterium rhodesiaeandMycobacterium tusciae, to be the predominant taxon in all five samples, and its nearly complete draft genome sequence was recovered. In contrast, the fraction recovered by culture was mostly affiliated withProteobacteria, including members of the generaSphingomonas,Blastomonas, andPorphyrobacter.The biofilm community harbored genes related to disinfectant tolerance (2.34% of the total annotated proteins) and a lower abundance of virulence determinants related to colonization and evasion of the host immune system. Additionally, genes potentially conferring resistance to β-lactam, aminoglycoside, amphenicol, and quinolone antibiotics were detected. Collectively, our results underscore the need to understand the microbiome of DW biofilms using metagenomic approaches. This information might lead to more robust management practices that minimize the risks associated with exposure to opportunistic pathogens in hospitals.
Kinetics of Inactivation of Bacillus subtilis subsp.
niger
Spores and Staphylococcus albus on Paper by Chlorine Dioxide Gas in an Enclosed Space
Authors: Wang Tao , Wu Jinhui , Qi Jiancheng , Hao Limei , Yi Ying , Zhang Zongxing 
Published: March 2016

ABSTRACT

Bacillus subtilis
subsp.
niger
spore and
Staphylococcus albus
are typical biological indicators for the inactivation of airborne pathogens. The present study characterized and compared the behaviors of
B. subtilis
subsp.
niger
spores and
S. albus
in regard to inactivation by chlorine dioxide (ClO
2
) gas under different gas concentrations and relative humidity (RH) conditions. The inactivation kinetics under different ClO
2
gas concentrations (1 to 5 mg/liter) were determined by first-order and Weibull models. A new model (the Weibull-H model) was established to reveal the inactivation tendency and kinetics for ClO
2
gas under different RH conditions (30 to 90%). The results showed that both the gas concentration and RH were significantly (
P
< 0.05) and positively correlated with the inactivation of the two chosen indicators. There was a rapid improvement in the inactivation efficiency under high RH (>70%). Compared with the first-order model, the Weibull and Weibull-H models demonstrated a better fit for the experimental data, indicating nonlinear inactivation behaviors of the vegetative bacteria and spores following exposure to ClO
2
gas. The times to achieve a six-log reduction of
B. subtilis
subsp.
niger
spore and
S. albus
were calculated based on the established models. Clarifying the kinetics of inactivation of
B. subtilis
subsp.
niger
spores and
S. albus
by ClO
2
gas will allow the development of ClO
2
gas treatments that provide an effective disinfection method.

IMPORTANCE
Chlorine dioxide (ClO
2
) gas is a novel and effective fumigation agent with strong oxidization ability and a broad biocidal spectrum. The antimicrobial efficacy of ClO
2
gas has been evaluated in many previous studies. However, there are presently no published models that can be used to describe the kinetics of inactivation of airborne pathogens by ClO
2
gas under different gas concentrations and RH conditions. The first-order and Weibull (Weibull-H) models established in this study can characterize and compare the behaviors of
Bacillus subtilis
subsp.
niger
spores and
Staphylococcus
albus
in regard to inactivation by ClO
2
gas, determine the kinetics of inactivation of two chosen strains under different conditions of gas concentration and RH, and provide the calculated time to achieve a six-log reduction. These results will be useful to determine effective conditions for ClO
2
gas to inactivate airborne pathogens in contaminated air and other environments and thus prevent outbreaks of airborne illness.
Effectiveness of footwear and foot orthoses for calcaneal apophysitis: a 12-month factorial randomised trial
Authors: James Alicia M , Williams Cylie M , Haines Terry P 
Published: March 2016

ObjectiveCalcaneal apophysitis, is a relatively common cause of heel pain in children. Very few randomised studies have evaluated treatment options. This trial compared the effectiveness of currently employed treatment options for the relief of pain and disability associated with calcaneal apophysitis.DesignFactorial 2×2 randomised comparative effectiveness trial with 1, 2, 6 and 12-month follow-up.SettingParticipants were recruited from the caseload of podiatrists at Monash health and Peninsula Health.ParticipantsChildren aged 8–14 years with clinically diagnosed calcaneal apophysitis.InterventionsTreatment factor 1: two different types of in-shoe orthoses: a heel raise or prefabricated orthoses. Treatment factor 2: footwear replacement or no footwear replacement.OutcomesOur primary outcome was functional disability, the secondary outcomes were pain and ankle dorsiflexion range.ResultsA total of 133 children and their parents responded to the recruitment advertisement, 124 participated in the trial.At the 1 and 2-month follow-up points, there was a main effect of the shoe insert (heel raise) in only the physical domain for the Oxford ankle foot questionnaire (p=0.04). At the 6 and 12-month follow-up points, there was no main effect or interaction effect for any outcome measure.ConclusionThis trial indicates at the 2-month time point there is a relative advantage in the use of heel raises over prefabricated orthoses for the treatment for calcaneal apophysitis. At 12 months there was no relative advantage to any one of the investigated treatment choices over another. Therefore, if a physical impact is experienced for greater than 2 months, the selection of treatment choice may defer to clinical judgement, cost-minimisation and or patient preference.Trial registration numberACTRN12609000696291.
Distribution of lifespan gain from primary prevention intervention
Authors: Finegold Judith A , Shun-Shin Matthew J , Cole Graham D , Zaman Saman , Maznyczka Annette , Zaman Sameer , Al-Lamee Rasha , Ye Siqin , Francis Darrel P 
Published: March 2016

ObjectiveWhen advising patients about possible initiation of primary prevention treatment, clinicians currently do not have information on expected impact on lifespan, nor how much this increment differs between individuals.MethodsFirst, UK cardiovascular and non-cardiovascular mortality data were used to calculate the mean lifespan gain from an intervention (such as a statin) that reduces cardiovascular mortality by 30%. Second, a new method was developed to calculate the probabilitydistributionof lifespan gain. Third, we performed a survey in three UK cities on 11 days between May–June 2014 involving 396 participants (mean age 40 years, 55% male) to assess how individuals evaluate potential benefit from primary prevention therapies.ResultsAmong numerous identical patients, the lifespan gain, from an intervention that reduces cardiovascular mortality by 30%, is concentrated within an unpredictable minority. For example, men aged 50 years with national average cardiovascular risk have mean lifespan gain of 7 months. However, 93% of these identical individuals gain no lifespan, while the remaining 7% gain a mean of 99 months. Many survey respondents preferred achanceof large lifespan gain to the equivalent life expectancy gain given as certainty. Indeed, 33% preferred a 2% probability of 10 years to fivefold more gain, expressed as certainty of 1 year.ConclusionsPeople who gain lifespan from preventative therapy gain far more than the average for their risk stratum, even if perfectly defined. This may be important in patient decision-making. Looking beyond mortality reduction alone from preventative therapy, the benefits are likely to be even larger.
Therapeutic and diagnostic outcomes of a standardised, comprehensive care pathway for patients with systemic sclerosis
Authors: Meijs Jessica , Schouffoer Anne A , Ajmone Marsan Nina , Kroft Lucia J M , Stijnen Theo , Ninaber Maarten K , Huizinga Tom W J , Vliet Vlieland Theodora P M , de Vries-Bouwstra Jeska K 
Published: March 2016

ObjectivesTo determine the outcomes, including number of medical interventions and initiation of immunosuppressive treatment of a standardised, comprehensive, diagnostic care pathway for patients with systemic sclerosis (SSc). Patient characteristics associated with need for medical interventions and with need for immunosuppressive treatment were determined.MethodsData were routinely gathered in connection with a 2-day care pathway combining multidisciplinary care and complete diagnostic work-up of organ involvement in SSc. The number of patients in whom the pathway resulted in medical interventions, and/or initiation of immunosuppressives was recorded. Patient characteristics and diagnostic tests results were compared between patients with and without medical interventions, and patients with and without initiation of immunosuppressives by means of multivariable logistic regression analyses.ResultsDuring a period of 44 months, 226 patients with SSc were referred to the care pathway. They included 186 (82%) women with mean age of 54 (SD 14.5) years, and median disease duration of 4 years (range 1–11); 73 (32%) of them had diffuse cutaneous SSc. Medical interventions were initiated in 191 (85%) patients, including initiation of immunosuppressive treatment in n=49 (22%). Presence of telangiectasias and higher erythrocyte sedimentation rate were associated with any medical intervention. Of commonly available variables, lower age, higher skin score and absence of anticentromere antibody were associated with initiation of immunosuppressives.ConclusionsA standardised comprehensive 2-day care pathway for patients with SSc resulted in additional diagnostic or therapeutic interventions in 85% of the patients, regardless of SSc subtype and disease duration. In 22% of the patients, immunosuppressive treatment was initiated.
Association of the different types of radiographic damage with physical function in patients with rheumatoid arthritis: analysis of the RAPID trials
Authors: Gherghe Ana Maria , Ramiro Sofia , Landewé Robert , Mihai Carina , van der Heijde Désirée 
Published: March 2016

ObjectivesTo evaluate the separate effects of erosions (E) (bone damage), joint space narrowing (JSN) (cartilage loss) and (sub)luxation (SLUX) (soft tissue damage) in four different joint groups on physical disability in rheumatoid arthritis (RA).Methods3-year follow-up data from the Rheumatoid Arthritis PreventIon of structural Damage (RAPID) 1 and 2 trials were used. These randomised controlled trials compared certolizumab plus methotrexate (MTX) versus MTX in patients with RA. Physical function was measured by Health Assessment Questionnaire (HAQ). Radiographic damage was measured by the van der Heijde-modified Sharp score; separate scores for E, JSN and SLUX were available. Generalised estimating equations were performed to assess the relationship between HAQ and E, JSN and SLUX scores, separately and in all joint groups.ResultsIn separate models for each type of damage and after adjusting for age, gender, baseline disease activity and treatment group, E and JSN were more strongly associated with HAQ than with SLUX. In combined models, JSN was the only type of lesion associated with HAQ when all joints were included together. When separate joint groups were analysed, E in the wrist and JSN in the metacarpophalangeal joints (MCPs) were most strongly associated with function.ConclusionsAmong RA-related joint damage, cartilage loss quantified by JSN is an important determinant of physical function. However, when analysing joint groups separately, erosive damage in the wrist and JSN in the MCPs had the most important influence on disability. These data indicate that the comprehensive assessment of joint damage is needed to reliably reflect disease-related damage.