bluuebunny/crossref_metadata_2025_split huggingface dataset:
Birthweight and Childhood Cancer: Preliminary Findings from the International Childhood Cancer Cohort Consortium (I4C)
Authors: Paltiel Ora , Tikellis Gabriella , Linet Martha , Golding Jean , Lemeshow Stanley , Phillips Gary , Lamb Karen , Stoltenberg Camilla , Håberg Siri E. , Strøm Marin , Granstrøm Charlotta , Northstone Kate , Klebanoff Mark , Ponsonby Anne‐Louise , Milne Elizabeth , Pedersen Marie , Kogevinas Manolis , Ha Eunhee , Dwyer Terence ,   International Childhood Cancer Cohort Consortium
Published: May 2015

AbstractBackgroundEvidence relating childhood cancer to high birthweight is derived primarily from registry and case–control studies. We aimed to investigate this association, exploring the potential modifying roles of age at diagnosis and maternal anthropometrics, using prospectively collected data from the International Childhood Cancer Cohort Consortium.MethodsWe pooled data on infant and parental characteristics and cancer incidence from six geographically and temporally diverse member cohorts [the Avon Longitudinal Study of Parents and Children (UK), the Collaborative Perinatal Project (USA), the Danish National Birth Cohort (Denmark), the Jerusalem Perinatal Study (Israel), the Norwegian Mother and Child Cohort Study (Norway), and the Tasmanian Infant Health Survey (Australia)]. Birthweight metrics included a continuous measure, deciles, and categories (≥4.0 vs. <4.0 kilogram). Childhood cancer (377 cases diagnosed prior to age 15 years) risk was analysed by type (all sites, leukaemia, acute lymphoblastic leukaemia, and non‐leukaemia) and age at diagnosis. We estimated hazard ratios (HR) and 95% confidence intervals (CI) from Cox proportional hazards models stratified by cohort.ResultsA linear relationship was noted for each kilogram increment in birthweight adjusted for gender and gestational age for all cancers [HR = 1.26; 95% CI 1.02, 1.54]. Similar trends were observed for leukaemia. There were no significant interactions with maternal pre‐pregnancy overweight or pregnancy weight gain. Birthweight ≥4.0 kg was associated with non‐leukaemia cancer among children diagnosed at age ≥3 years [HR = 1.62; 95% CI 1.06, 2.46], but not at younger ages [HR = 0.7; 95% CI 0.45, 1.24, P for difference = 0.02].ConclusionChildhood cancer incidence rises with increasing birthweight. In older children, cancers other than leukaemia are particularly related to high birthweight. Maternal adiposity, currently widespread, was not demonstrated to substantially modify these associations. Common factors underlying foetal growth and carcinogenesis need to be further explored.
Contribution ofClostridium difficileinfection to the development of lower gastrointestinal adverse events during autologous stem cell transplantation
Authors: Apewokin S. , Goodwin J.A. , Lee J.Y. , Erickson S.W. , Sanathkumar N. , Raj V.R. , Zhou D. , McKelvey K.D. , Stephens O. , Coleman E.A. 
Published: May 2015

AbstractBackgroundLower gastrointestinal (GI) adverse events (LGAE) are common afflictions of patients undergoing stem cell transplantation (SCT). Unfortunately, the pathophysiology remains poorly characterized. Emerging data suggest a prominent role of intestinal microbiota; however, contributions of pathogenic gut microbiota such asClostridium difficileare not well defined. We performed a genome‐wide association study (GWAS) to investigate clinical and genetic factors associated with development ofLGAE.MethodsA total of 972 patients undergoing autologousSCTwere graded forLGAEbased on Common Terminology Criteria for Adverse Events (v 4.0). GermlineDNAmaterial was obtained from leukapharesis products and genotyped using Illumina®Whole Genome Genotyping Infinium chemistry and HumanOmni1‐Quad Bead chips containing over 1.1 million single nucleotide polymorphisms (SNPs) (Illumina, San Diego, California,USA). Statistical models incorporating clinical factors, genetic factors, and a combination of clinical plus genetic factors were utilized to compare patients who developed severeLGAE(grade 2 or above) and others.ResultsAmong 972 patients, 459 (47.2%) developed severeLGAE. Baseline hemoglobin and hematocrit, estimated glomerular filtration rate, β2‐microglobulin, protocol type, andC. difficileinfection (CDI) were associated with severeLGAEon univariate analysis, Genomic comparisons between groups did not reveal anySNPs associated with severeLGAEand neither did incorporation of genetic factors into the clinical model. In addition, 11 candidateSNPs associated with upperGImucositis were evaluated, alongside clinical factors in a multivariate model. OnlyCDIwas found to be associated with severeLGAEin all models.ConclusionCDIis a prominent factor in the development ofLGAEin patients undergoing autologousSCT.
Sorting of Clathrin‐Independent Cargo Proteins Depends on Rab35 Delivered by Clathrin‐Mediated Endocytosis
Authors: Dutta Dipannita , Donaldson Julie G. 
Published: May 2015

AbstractClathrin‐mediated endocytosis (CME) and clathrin‐independent endocytosis (CIE) co‐exist in most cells but little is known about their communication and coordination. Here we show that when CME was inhibited, endocytosis by CIE continued but endosomal trafficking of CIE cargo proteins was altered. CIE cargo proteins that normally traffic directly into Arf6‐associated tubules after internalization and avoid degradation (CD44, CD98 and CD147) now trafficked to lysosomes and were degraded. The endosomal tubules were also absent and Arf6‐GTP levels were elevated. The altered trafficking, loss of the tubular endosomal network and elevated Arf6‐GTP levels caused by inhibition of CME were rescued by expression of Rab35, a Rab associated with clathrin‐coated vesicles, or its effector ACAPs, Arf6 GTPase activating proteins (GAP) that inactivate Arf6. Furthermore, siRNA knockdown of Rab35 recreated the phenotype of CME ablation on CIE cargo trafficking without altering endocytosis of transferrin. These observations suggest that Rab35 serves as a CME detector and that loss of CME, or Rab35 input, leads to elevated Arf6‐GTP and shifts the sorting of CIE cargo proteins to lysosomes and degradation.
Dermoscopic features in 12 cats with dermatophytosis and in 12 cats with self‐induced alopecia due to other causes: an observational descriptive study
Authors: Scarampella Fabia , Zanna Giordana , Peano Andrea , Fabbri Elisabetta , Tosti Antonella 
Published: May 2015

BackgroundDermoscopy is a noninvasive technique allowing rapid magnified in vivo observation of the skin and structures that lie beneath the skin surface. Various congenital and acquired hair shaft abnormalities may also be evaluated by dermoscopy. Additionally, characteristic features of Microsporum canis‐induced tinea capitis and trichotillomania in humans have been reported.ObjectivesTo describe the dermoscopic findings observed in cats with patchy alopecia due to M. canis infection and in cats with self‐inflicted hair loss.AnimalsTwenty‐four client‐owned cats presented at a veterinary referral practice.MethodsDermoscopy was performed with a hand‐held nonpolarized light dermoscope at 10‐fold magnification. The glass plate of the dermoscope was applied gently to the lesions and no sedation was required.ResultsTwelve cats were diagnosed with dermatophytosis and 12 with self‐induced alopecia due to other causes. At 10‐fold magnification, the most characteristic findings observed in circumscribed lesions of cats with dermatophytosis were opaque, slightly curved, broken hairs of a homogeneous thickness (comma‐like structures) and a variable amount of brown‐to‐yellow greasy scales. In cats with self‐induced alopecia, multiple hairs with a normal shaft cleanly broken at different lengths, short tufts of hairs broken at an equal level and hook‐like and coiled hairs were observed.Conclusions and clinical importanceThis observational descriptive study suggests that dermoscopy may represent a helpful noninvasive in vivo technique in the differential diagnosis of patchy alopecia in cats.
Mountainous genus Anterastes (Orthoptera, Tettigoniidae): autochthonous survival across several glacial ages via vertical range shifts
Authors: Çıplak Battal , Kaya Sarp , Boztepe Zehra , Gündüz İslam 
Published: May 2015

Although the high‐latitude range margins in Europe and North America are intensively studied, attention is gradually turned towards the taxa/populations inhabiting glacial refugia. Here, we evaluate the genealogical history of the cold‐adapted Anatolio‐Balkan genus Anterastes especially to test the possible effects of intrarefugial vertical range shifts during climatic oscillations of the Quaternary. Using concatenated data from sequences of COI+16S and ITS1–5.8S–ITS2, intrageneric relationships and the time of speciation events were estimated. Thirteen different demographic analyses were performed using a data set produced from sequences of 16S. Different phylogenetic analyses recovered similar lineages with high resolution. The molecular chronogram estimated speciation events in a period ranging from 5.60 to 1.22 Myr. Demographic analyses applied to 13 populations and five lineages suggested constant population size. Genetic diversity is significantly reduced in a few populations, while not in others. Fixation indices suggested extremely diverged populations. In the light of these data, the following main conclusions were raised: (i) although glacial refugia are the biodiversity hotspots, species level radiation of the cold‐adapted lineages is mainly prior to the Mid‐Pleistocene transition; (ii) heterogeneous topography provides refugial habitats and allows populations to survive through vertical range shifts during climatic fluctuations; (iii) prolonged isolation of refugial populations do not always result in reduced intrapopulation diversity, but in high level of genetic differentiation; (iv) the cold‐adapted lineages with low dispersal ability might have not colonised the area out of Anatolian refugium during interglacial periods; and (v) populations of invertebrates may have restricted ranges, but this does not mean that they have small effective population size.
Nationwide Surveillance of Azole Resistance in Aspergillus Diseases
Authors: Vermeulen Edith , Maertens Johan , De Bel Annelies , Nulens Eric , Boelens Jerina , Surmont Ignace , Mertens Anna , Boel An , Lagrou Katrien 
Published: May 2015

ABSTRACT

Aspergillus
disease affects a broad patient population, from patients with asthma to immunocompromised patients. Azole resistance has been increasingly reported in both clinical and environmental
Aspergillus
strains. The prevalence and clinical impact of azole resistance in different patient populations are currently unclear. This 1-year prospective multicenter cohort study aimed to provide detailed epidemiological data on
Aspergillus
resistance among patients with
Aspergillus
disease in Belgium. Isolates were prospectively collected in 18 hospitals (April 2011 to April 2012) for susceptibility testing. Clinical and treatment data were collected with a questionnaire. The outcome was evaluated to 1 year after a patient's inclusion. A total of 220
Aspergillus
isolates from 182 patients were included. The underlying conditions included invasive aspergillosis (
n
= 122 patients), allergic bronchopulmonary aspergillosis (APBA) (
n
= 39 patients), chronic pulmonary aspergillosis (
n
= 10 patients),
Aspergillus
bronchitis (
n
= 7 patients), and aspergilloma (
n
= 5 patients). The overall azole resistance prevalence was 5.5% (95% confidence interval [CI] 2.8 to 10.2%) and was 7.0% (4/57; 95% CI, 2.3 to 17.2%) in patients with APBA, bronchitis, aspergilloma, or chronic aspergillosis and 4.6% in patients with invasive aspergillosis (5/108; 95% CI, 1.7 to 10.7%). The 6-week survival in invasive aspergillosis was 52.5%, while susceptibility testing revealed azole resistance in only 2/58 of the deceased patients. The clinical impact of
Aspergillus fumigatus
resistance was limited in our patient population with
Aspergillus
diseases.
Pharmacokinetics of Second-Line Antituberculosis Drugs after Multiple Administrations in Healthy Volunteers
Authors: Park Sang-In , Oh Jaeseong , Jang Kyungho , Yoon Jangsoo , Moon Seol Ju , Park Jong Sun , Lee Jae Ho , Song Junghan , Jang In-Jin , Yu Kyung-Sang , Chung Jae-Yong 
Published: May 2015

ABSTRACT

Therapeutic drug monitoring (TDM) of second-line antituberculosis drugs would allow for optimal individualized dosage adjustments and improve drug safety and therapeutic outcomes. To evaluate the pharmacokinetic (PK) characteristics of clinically relevant, multidrug treatment regimens and to improve the feasibility of TDM, we conducted an open-label, multiple-dosing study with 16 healthy subjects who were divided into two groups. Cycloserine (250 mg),
p
-aminosalicylic acid (PAS) (5.28 g), and prothionamide (250 mg) twice daily and pyrazinamide (1,500 mg) once daily were administered to both groups. Additionally, levofloxacin (750 mg) and streptomycin (1 g) once daily were administered to group 1 and moxifloxacin (400 mg) and kanamycin (1 g) once daily were administered to group 2. Blood samples for PK analysis were collected up to 24 h following the 5 days of drug administration. The PK parameters, including the maximum plasma concentration (
C
max
) and the area under the plasma concentration-time curve during a dosing interval at steady state (AUC
τ
), were evaluated. The correlations between the PK parameters and the concentrations at each time point were analyzed. The mean
C
max
and AUC
τ
, respectively, for each drug were as follows: cycloserine, 24.9 mg/liter and 242.3 mg · h/liter; PAS, 65.9 mg/liter and 326.5 mg · h/liter; prothionamide, 5.3 mg/liter and 22.1 mg · h/liter; levofloxacin, 6.6 mg/liter and 64.4 mg · h/liter; moxifloxacin, 4.7 mg/liter and 54.2 mg · h/liter; streptomycin, 42.0 mg/liter and 196.7 mg · h/liter; kanamycin, 34.5 mg/liter and 153.5 mg · h/liter. The results indicated that sampling at 1, 2.5, and 6 h postdosing is needed for TDM when all seven drugs are administered concomitantly. This study indicates that PK characteristics must be considered when prescribing optimal treatments for patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT02128308.)
Evaluation of Ceftaroline Alone and in Combination against Biofilm-Producing Methicillin-Resistant Staphylococcus aureus with Reduced Susceptibility to Daptomycin and Vancomycin in an
In Vitro
Pharmacokinetic/Pharmacodynamic Model
Authors: Barber Katie E. , Smith Jordan R. , Ireland Cortney E. , Boles Blaise R. , Rose Warren E. , Rybak Michael J. 
Published: May 2015

ABSTRACT

Annually, medical device infections are associated with >250,000 catheter-associated bloodstream infections (CLABSI), with up to 25% mortality.
Staphylococcus aureus
, a primary pathogen in these infections, is capable of biofilm production, allowing organism persistence in harsh environments, offering antimicrobial protection. With increases in
S. aureus
isolates with reduced susceptibility to current agents, ceftaroline (CPT) offers a therapeutic alternative. Therefore, we evaluated whether CPT would have a role against biofilm-producing methicillin-resistant
S. aureus
(MRSA), including those with decreased susceptibilities to alternative agents. In this study, we investigated CPT activity alone or combined with daptomycin (DAP) or rifampin (RIF) against 3 clinical biofilm-producing MRSA strains in an
in vitro
biofilm pharmacokinetic/pharmacodynamic (PK/PD) model. Simulated antimicrobial regimens were as follows: 600 mg of CPT every 8 h (q8h) (free maximum concentration of drug [
fC
max
], 17.04 mg/liter; elimination half-life [
t
1/2
], 2.66 h), 12 mg/kg of body weight/day of DAP (
fC
max
, 14.7 mg/liter;
t
1/2
, 8 h), and 450 mg of RIF q12h (
fC
max
, 3.5 mg/liter;
t
1/2
, 3.4 h), CPT plus DAP, and CPT plus RIF. Samples were obtained and plated to determine colony counts. Differences in log
10
CFU/cm
2
were evaluated by analysis of variance with Tukey's
post hoc
test. The strains were CPT and vancomycin susceptible and DAP nonsusceptible (DNS). CPT displayed activity throughout the experiment. DAP demonstrated initial activity with regrowth at 24 h in all strains. RIF was comparable to the drug-free control, and little benefit was observed when combined with CPT. CPT plus DAP displayed potent activity, with an average log
10
CFU/cm
2
reduction of 3.33 ± 1.01 from baseline. CPT demonstrated activity against biofilm-producing DNS MRSA. CPT plus DAP displayed therapeutic enhancement over monotherapy, providing a potential option for difficult-to-treat medical device infections.
Mode of Action of Clofazimine and Combination Therapy with Benzothiazinones against Mycobacterium tuberculosis
Authors: Lechartier Benoit , Cole Stewart T. 
Published: May 2015

ABSTRACT

Clofazimine (CZM) is an antileprosy drug that was recently repurposed for treatment of multidrug-resistant tuberculosis. In
Mycobacterium tuberculosis
, CZM appears to act as a prodrug, which is reduced by NADH dehydrogenase (NDH-2), to release reactive oxygen species upon reoxidation by O
2
. CZM presumably competes with menaquinone (MK-4), a key cofactor in the mycobacterial electron transfer chain, for its reduction by NDH-2. We studied the effect of MK-4 supplementation on the activity of CZM against
M. tuberculosis
and found direct competition between CZM and MK-4 for the cidal effect of CZM, against nonreplicating and actively growing bacteria, as MK-4 supplementation blocked the drug's activity against nonreplicating bacteria. We demonstrated that CZM, like bedaquiline, is synergistic
in vitro
with benzothiazinones such as 2-piperazino-benzothiazinone 169 (PBTZ169), and this synergy also occurs against nonreplicating bacteria. The synergy between CZM and PBTZ169 was lost in an MK-4-rich medium, indicating that MK-4 is the probable link between their activities. The efficacy of the dual combination of CZM and PBTZ169 was tested
in vivo
, where a great reduction in bacterial load was obtained in a murine model of chronic tuberculosis. Taken together, these data confirm the potential of CZM in association with PBTZ169 as the basis for a new regimen against drug-resistant strains of
M. tuberculosis
.
Effect of Resistance Mechanisms on the Inoculum Effect of Carbapenem in Klebsiella pneumoniae Isolates with Borderline Carbapenem Resistance
Authors: Adler Amos , Ben-Dalak Ma'ayan , Chmelnitsky Ina , Carmeli Yehuda 
Published: May 2015

ABSTRACT

We aimed to examine the effects of resistance mechanisms on several resistance phenotypes among carbapenem-resistant
Klebsiella pneumoniae
isolates with borderline carbapenem MICs. We compared carbapenemase-negative
K. pneumoniae
with carbapenemase-producing
K. pneumoniae
(CPKP) isolates with similar MICs. CPKP isolates exhibited a marked inoculum effect and were more resistant to the bactericidal effect of meropenem. This suggests that MIC measurements alone may not be sufficient in predicting the therapeutic efficacy of carbapenems against CPKP.
Superior Serum Concentrations with Posaconazole Delayed-Release Tablets Compared to Suspension Formulation in Hematological Malignancies
Authors: Cumpston Aaron , Caddell Ryan , Shillingburg Alexandra , Lu Xiaoxiao , Wen Sijin , Hamadani Mehdi , Craig Michael , Kanate Abraham S. 
Published: May 2015

ABSTRACT

Posaconazole (PCZ), approved for prophylaxis against invasive fungal disease in high-risk patients, is commercially available orally as a suspension formulation (PCZ-susp) and as a delayed-release tablet (PCZ-tab). We evaluated the serum steady-state concentrations (
C
ss
) of PCZ stratified by the administered formulation for antifungal prophylaxis in patients with myeloid malignancies (
n
= 150). The primary outcome was the attainment rate of the target
C
ss
of ≥700 ng/ml. Secondary outcomes included toxicity assessment (hepatotoxicity and corrected QT [QTc] interval prolongation) and breakthrough fungal infections. Patients who received the PCZ-susp (
n
= 118) or PCZ-tab (
n
= 32) and had PCZ
C
ss
assessment after at least 7 days of therapy were eligible. The median
C
ss
in the PCZ-susp group was 390 ng/ml (range, 51 to 1,870 ng/ml; mean, 436 ng/ml) compared to 1,740 ng/ml (range, 662 to 3,350 ng/ml; mean, 1,781 ng/ml) in the PCZ-tab group (
P
< 0.0001). The percentages of patients achieving the target goal of ≥700 ng/ml were 17% versus 97%, respectively (
P
< 0.0001). Hepatotoxicity (grade 2 or higher) occurred in 1 patient in each group. QTc interval measurements were available for 32 patients in the PCZ-susp group and for 12 patients in the PCZ-tab group, and prolonged intervals of grade 2 or higher were noted in 9% (
n
= 3) and 17% (
n
= 2), respectively (
P
= 0.6). Breakthrough fungal infections in the PCZ-susp and PCZ-tab groups were 7% (
n
= 8) and 3% (
n
= 1), respectively (
P
= 0.68). We conclude that the use of PCZ-tab was associated with higher
C
ss
and with the probability of achieving therapeutic goals without worsening of adverse effects.
Risk Factors for Acquisition and Loss of Clostridium difficile Colonization in Hospitalized Patients
Authors: Dubberke Erik R. , Reske Kimberly A. , Seiler Sondra , Hink Tiffany , Kwon Jennie H. , Burnham Carey-Ann D. 
Published: May 2015

ABSTRACT

Asymptomatic colonization may contribute to
Clostridium difficile
transmission. Few data identify which patients are at risk for colonization. We performed a prospective cohort study of
C. difficile
colonization and risk factors for
C. difficile
acquisition and loss in hospitalized patients. Patients admitted to medical or surgical wards at a tertiary care hospital were enrolled; interviews and chart review were performed to determine patient demographics,
C. difficile
infection (CDI) history, medications, and health care exposures. Stool samples/rectal swabs were collected at enrollment and discharge; stool samples from clinical laboratory tests were also included. Samples were cultured for
C. difficile
, and the isolates were tested for toxins A and B and ribotyped. Chi-square tests and univariate logistic regression were used for the analyses. Two hundred thirty-five patients were enrolled. Of the patients, 21% were colonized with
C. difficile
(toxigenic and nontoxigenic) at admission and 24% at discharge. Ribotype 027 accounted for 6% of the strains at admission and 12% at discharge. Of the patients colonized at admission, 78% were also colonized at discharge. Cephalosporin use was associated with
C. difficile
acquisition (47% of patients who acquired
C. difficile
versus 25% of patients who did not;
P
= 0.03). β-lactam–β-lactamase inhibitor combinations were associated with a loss of
C. difficile
colonization (36% of patients who lost
C. difficile
colonization versus 8% of patients colonized at both admission and discharge;
P
= 0.04), as was metronidazole (27% versus 3%;
P
= 0.03). Antibiotic use affects the epidemiology of asymptomatic
C. difficile
colonization, including acquisition and loss, and it requires additional study.
Response to Switch from Intermittent Therapy to Daily Therapy for Refractory Nodular Bronchiectatic Mycobacterium avium Complex Lung Disease
Authors: Koh Won-Jung , Jeong Byeong-Ho , Jeon Kyeongman , Park Hye Yun , Kim Su-Young , Huh Hee Jae , Ki Chang-Seok , Lee Nam Yong , Shin Sung Jae , Daley Charles L. 
Published: May 2015

ABSTRACT

Intermittent three-times-weekly antibiotic therapy is recommended for the initial treatment of patients with noncavitary nodular bronchiectatic
Mycobacterium avium
complex lung disease. Although some experts recommend switching from intermittent to daily therapy for patients whose sputum has persistent positive cultures after intermittent therapy, the clinical efficacy of these modifications is unknown. Of 20 patients whose sputum had persistent positive cultures after 12 months of intermittent antibiotic therapy, specimens from 6 patients (30%) achieved a negative culture after a change to daily therapy.