bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Use of Humoral Responses as a Marker of CMV Burden in HIV Patients on ART Requires Consideration of T-Cell Recovery and Persistent B-Cell Activation
Authors: Brunt Samantha J. , Lee Silvia , D’Orsogna Lloyd , Bundell Christine , Burrows Sally , Price Patricia 
Published: November 2014

Objectives.Elevated humoral responses to cytomegalovirus (CMV) associate with increased risk of cardiovascular disease (CVD) in HIV patients on antiretroviral therapy (ART). To better understand the persistence of CMV humoral responses in relation to CVD, we determined trends in CMV antibody levels over the first 10 years on ART.Design.We describe longitudinal analyses of plasma from 13 HIV patients commencing ART with <210 CD4 T-cells/µL and 27 controls. Antibodies reactive with CMV (fibroblast lysate, gB and IE-1 antigens), EBV-VCA, and HIVgp41 were quantitated. B-cell activation was assessed via total IgG and sBAFF. Inflammation was assessed via sTNF-RI and sCD14.Results.Amongst CMV seropositive HIV patients, levels of antibody reactive with CMV(P=0.03)and EBV-VCA(P=0.02)peaked after 1 year on ART. Levels of total IgG, sCD14, and sTNF-RI declined to approximate those in controls after 10 years, but sBAFF(P=0.0002), EBV-VCA(P=0.001), and CMV(P=0.0004)antibodies remained elevated. A strong correlation between sBAFF and CMVgB antibody was seen at 10 years(R=0.93,  P=0.0009)and verified in a second cohort.Conclusions.CMV antibody titres peak on ART and remain high. A correlation between CMV antibody and sBAFF suggests a role for HIV-induced B-cell pathology that may affect its use as a marker of CMV burden.
Imaging Intratumor Heterogeneity: Role in Therapy Response, Resistance, and Clinical Outcome
Authors: O'Connor James P.B. , Rose Chris J. , Waterton John C. , Carano Richard A.D. , Parker Geoff J.M. , Jackson Alan 
Published: November 2014

Abstract
Tumors exhibit genomic and phenotypic heterogeneity, which has prognostic significance and may influence response to therapy. Imaging can quantify the spatial variation in architecture and function of individual tumors through quantifying basic biophysical parameters such as CT density or MRI signal relaxation rate; through measurements of blood flow, hypoxia, metabolism, cell death, and other phenotypic features; and through mapping the spatial distribution of biochemical pathways and cell signaling networks using PET, MRI, and other emerging molecular imaging techniques. These methods can establish whether one tumor is more or less heterogeneous than another and can identify subregions with differing biology. In this article, we review the image analysis methods currently used to quantify spatial heterogeneity within tumors. We discuss how analysis of intratumor heterogeneity can provide benefit over more simple biomarkers such as tumor size and average function. We consider how imaging methods can be integrated with genomic and pathology data, instead of being developed in isolation. Finally, we identify the challenges that must be overcome before measurements of intratumoral heterogeneity can be used routinely to guide patient care. Clin Cancer Res; 21(2); 249–57. ©2014 AACR.
First-in-Human Dose Study of the Novel Transforming Growth Factor-β Receptor I Kinase Inhibitor LY2157299 Monohydrate in Patients with Advanced Cancer and Glioma
Authors: Rodon Jordi , Carducci Michael A. , Sepulveda-Sánchez Juan M , Azaro Analia , Calvo Emiliano , Seoane Joan , Braña Irene , Sicart Elisabet , Gueorguieva Ivelina , Cleverly Ann L. , Pillay N. Sokalingum , Desaiah Durisala , Estrem Shawn T. , Paz-Ares Luis , Holdhoff Matthias , Blakeley Jaishri , Lahn Michael M. , Baselga Jose 
Published: November 2014

Abstract
Purpose: TGFβ signaling plays a key role in tumor progression, including malignant glioma. Small-molecule inhibitors such as LY2157299 monohydrate (LY2157299) block TGFβ signaling and reduce tumor progression in preclinical models. To use LY2157299 in the treatment of malignancies, we investigated its properties in a first-in-human dose (FHD) study in patients with cancer.
Experimental Design: Sixty-five patients (58 with glioma) with measurable and progressive malignancies were enrolled. Oral LY2157299 was given as a split dose morning and evening on an intermittent schedule of 14 days on and 14 days off (28-day cycle). LY2157299 monotherapy was studied in dose escalation (part A) first and then evaluated in combination with standard doses of lomustine (part B). Safety was assessed using Common Terminology Criteria for Adverse Events version 3.0, echocardiography/Doppler imaging, serum troponin I, and brain natriuretic peptide (BNP) levels. Antitumor activity was assessed by RECIST and Macdonald criteria.
Results: In part A, 16.6% (5/30) and in part B, 7.7% (2/26) of evaluable patients with glioma had either a complete (CR) or a partial response (PR). In both parts, 15 patients with glioma had stable disease (SD), 5 of whom had SD ≥6 cycles of treatment. Therefore, clinical benefit (CR+PR+SD ≥6 cycles) was observed in 12 of 56 patients with glioma (21.4%). LY2157299 was safe, with no cardiac adverse events.
Conclusions: On the basis of the safety, pharmacokinetics, and antitumor activity in patients with glioma, the intermittent administration of LY2157299 at 300 mg/day is safe for future clinical investigation. Clin Cancer Res; 21(3); 553–60. ©2014 AACR.
Sequential Intravesical Mitomycin plus Bacillus Calmette–Guérin for Non–Muscle-Invasive Urothelial Bladder Carcinoma: Translational and Phase I Clinical Trial
Authors: Svatek Robert S. , Zhao Xiang Ru. , Morales Edwin E. , Jha Mithilesh K. , Tseng Timothy Y. , Hugen Cory M. , Hurez Vincent , Hernandez Javier , Curiel Tyler J. 
Published: November 2014

Abstract
Purpose: To determine the safety and toxicities of sequential MMC (mitomycin C) + BCG (bacillus Calmette–Guérin) in patients with non–muscle-invasive bladder cancer (NMIBC) and explore evidence for potentiation of BCG activity by MMC.
Experimental Design: A 3 + 3 phase I dose-escalation trial of six weekly treatments was conducted in patients with NMIBC. MMC (10, 20, or 40 mg) was instilled intravesically for 30 minutes, followed by a 10-minute washout with gentle saline irrigation and then instillation of BCG (half or full strength) for 2 hours. Urine cytokines were monitored and compared with levels in a control cohort receiving BCG only. Murine experiments were carried out as described previously.
Results: Twelve patients completed therapy, including 3 patients receiving full doses. The regimen was well tolerated with no treatment-related dose-limiting toxicities. Urinary frequency and urgency, and fatigue were common. Eleven (91.7%) patients were free of disease at a mean (range) follow-up of 21.4 (8.4–27.0) months. Median posttreatment urine concentrations of IL2, IL8, IL10, and TNFα increased over the 6-week treatment period. A greater increase in posttreatment urinary IL8 during the 6-week period was observed in patients receiving MMC + BCG compared with patients receiving BCG monotherapy. In mice, intravesical MMC + BCG skewed tumor-associated macrophages (TAM) toward a beneficial M1 phenotype.
Conclusions: Instillation of sequential MMC + BCG is safe tolerable up to 40-mg MMC plus full-strength BCG. This approach could provide improved antitumor activity over BCG monotherapy by augmenting beneficial M1 TAMs. Clin Cancer Res; 21(2); 303–11. ©2014 AACR.
Initial Body Temperature in Ischemic Stroke
Authors: Kim Seo Hyun , Saver Jeffrey L. 
Published: November 2014

Background and Purpose—
Body temperature (BT) is an important physiological factor in acute ischemic stroke. However, the relationship of initial BT to stroke severity and degree of benefit from thrombolytic therapy has been delineated incompletely.

Methods—
We analyzed the public data set of the 2 National Institute of Neurological Disorders and Stroke Tissue-Type Plasminogen Activator (tPA) stroke trials, comparing patients with lower (<37.0°C) and higher (≥37.0°C) presenting BT.

Results—

Among 595 patients (297 placebo and 298 tPA treated) with documented initial BT, 77.1% had initial BT <37.0°C and 22.9% ≥37.0°C. Patients with higher initial BT had lower baseline stroke severity in both tPA-treated patients (the National Institute of Health Stroke Scale median, 11 versus 15;
P
=0.05) and placebo-treated patients (median, 13 versus 16;
P
<0.01). Patients with higher initial BT also had lower infarction volume on computed tomography at 3 months in both tPA-treated patients (median, 9.6 versus 16.7 cm
3
;
P
=0.08) and placebo-treated patients (median, 13.1 versus 28.1 cm
3
;
P
=0.02), but no clinical outcome differences. Analysis of lytic treatment effect found no heterogeneity in the degree of tPA benefit in both higher and lower BT groups (≥37.0°C: odds ratio for the modified Rankin Scale 0–1 outcome, 2.55; 95% confidence interval, 1.05–6.21 and <37.0°C: odds ratio, 2.30; 95% confidence interval, 1.38–3.84; heterogeneity
P
=0.83).

Conclusions—
In patients with hyperacute stroke, higher presenting temperatures are associated with less severe neurological deficits and reduced final infarct volumes. Presenting temperature does not modify the benefit of tPA on 3-month favorable outcome.
Gender influences headache characteristics with increasing age in migraine patients
Authors: Bolay Hayrunnisa , Ozge Aynur , Saginc Petek , Orekici Gulhan , Uludüz Derya , Yalın Osman , Siva Aksel , Bıçakçı Şebnem , Karakurum Başak , Öztürk Musa 
Published: November 2014

Background and aims Migraine headache is one of the most common primary headache disorders and is three times more prevalent in women than in men, especially during the reproductive ages. The neurobiological basis of the female dominance has been partly established. The present study aimed to investigate the effect of gender on the headache manifestations in migraine patients. Methods The study group consisted of 2082 adult patients from five different hospitals’ tertiary care-based headache clinics. The relationship between headache characteristics and gender was evaluated in migraine with aura (MwA) and migraine without aura (MwoA). The duration, severity, frequency of headache and associated symptoms were evaluated in both genders and age-dependent variations and analyzed in two subgroups. Results Women with migraine were prone to significantly longer duration and intensity of headache attacks. Nausea, phonophobia and photophobia were more prevalent in women. Median headache duration was also longer in women than in men in MwA ( p = 0.013) and MwoA ( p < 0.001). Median headache intensity was higher in women than in men in MwA ( p = 0.010) and MwoA ( p = 0.009). The frequency of nausea was significantly higher in women than in men in MwA ( p = 0.049). Throbbing headache quality and associated features (nausea, photophobia, and phonophobia) were significantly more frequent in women than in men in MwoA. The gender impact varied across age groups and significant changes were seen in female migraineurs after age 30. No age-dependent variation was observed in male migraineurs. Conclusion Gender has an influence on the characteristics of the headache as well as on the associated symptoms in migraine patients, and this impact varies across the age groups, particularly in women.
Is the Use of Oral Contraceptives Associated With Operatively Treated Anterior Cruciate Ligament Injury?
Authors: Rahr-Wagner Lene , Thillemann Theis Muncholm , Mehnert Frank , Pedersen Alma Becic , Lind Martin 
Published: November 2014

Background: The incidence of anterior cruciate ligament (ACL) injuries is 2 to 9 times higher in women than in men. In addition, in vitro studies have demonstrated that ACL is an estrogen target tissue, and some studies have therefore suggested a protective association between oral contraceptives (OC) and the likelihood of sustaining ACL injury. Hypothesis: There is a protective association between OC use and the likelihood of operatively treated ACL injury. Study Design: Case-control study; Level of evidence, 3. Methods: The study population included 4497 women with an operatively treated ACL injury registered in the Danish Knee Ligament Reconstruction Registry for the 2005 to 2011 period and 8858 age-matched controls with no ACL injury. The study evaluated exposure to OC use at the time of ACL injury (index date) and in the 5 previous years (“ever user”) or no OC use (“never user”). Ever users were further classified as either new users (patients who redeemed their first prescription within the first year before the index date), long-term users (redeemed additional prescriptions 1 to 5 years before the index date), or recent users (redeemed their most recent prescription >1 year before the index date). Finally, a dose-response analysis of OC use was performed. Conditional logistic regression was used to calculate the relative risk (RR) with a 95% CI of sustaining an operatively treated ACL injury according to OC use. Results: The adjusted RR associating OC with ACL injury was 0.82 (95% CI, 0.75-0.90) between ever users and never users. Furthermore, there was a decreased RR of sustaining ACL injury of 0.80 (95% CI, 0.74-0.91) in long-term users and 0.81 (95% CI, 0.72-0.89) in recent users. Using OC for more than 4 years did not seem to alter the likelihood of sustaining an operatively treated ACL injury. Conclusion: This population-based pharmacoepidemiological study including 13,355 women indicates that a protective association exists between OC use and the likelihood of sustaining an operatively treated ACL injury. Although this study does indicate a protective association of OC use, OC should not be used as a prophylactic measure before additional clinical studies have further clarified the biological and causal association between OC use and the likelihood of sustaining operatively treated ACL injury.
Effects of T-2 mycotoxin on in vitro development and chromatin status of mouse embryos in preimplantation stages
Authors: Somoskői Bence , Kovács Melinda , Cseh Sándor 
Published: November 2014

T-2 toxin is a mycotoxin produced by phytopathogenic fungi of the Fusarium genus and has many well-studied deleterious effects on mammalian cells and reproductive tract. Despite the wide scale studies, the effects on preimplantation stage embryos are lacking. The aim of our study was to investigate the impact of T-2 on the cleavage stage of mouse embryos with regard to development to blastocysts and nuclear chromatin status. Six-weeks-old BDF1 female mice were superovulated and placed together overnight with mature males. Zygotes were flushed 20 h after human chorionic gonadotropin injection and divided randomly into treated (supplemented with 0.5, 0.75, and 1 ng/ml T-2) and nontreated (control) groups. Embryos were cultured in vitro for 96 h. Developmental stage was evaluated in the 72nd- and 96th-h for assessment of development dynamics. At the end of culture period, blastocysts from treated and control groups with normal morphology were selected for nuclear chromatin analysis. Blastocysts were categorized (grade A, B, and C) depending on the proportion of blasomeres with micronuclei and/or lobulated nuclei. Our data show significant decrease in the proportions of blastocysts in the 0.75 and 1 ng/ml toxin-supplemented groups compared with the control group. Blastocyst rate did not differ in embryos treated with 0.5 ng/ml T-2 but 24 h delay was found in blastocoel formation in all the treated groups. Only grade A (21.1%) and B (78.9%) blastocysts were found in low-toxin-contaminated group similar to the control ones (50–50%). Grade C embryos appeared in the 0.75 ng/ml (10%) treated group and the rate increased significantly (33.3%) in the highest contaminated group. T-2 mycotoxin has a harmful effect on early embryo development which results in decreased blastocyst proportion, delayed blastulation, and increased rate of chromatin damage.
Assessing Infant Feeding Attitudes of Expectant Women in a Provincial Population in Canada
Authors: Twells Laurie K. , Midodzi William K. , Ludlow Valerie , Murphy-Goodridge Janet , Burrage Lorraine , Gill Nicole , Halfyard Beth , Schiff Rebecca , Newhook Leigh Anne 
Published: November 2014

Background: Maternal attitudes to infant feeding are predictive of intent and initiation of breastfeeding. Objectives: The Iowa Infant Feeding Attitude Scale (IIFAS) has not been validated in the Canadian population. This study was conducted in Newfoundland and Labrador, a Canadian province with low breastfeeding rates. Objectives were to assess the reliability and validity of the IIFAS in expectant mothers; to compare attitudes to infant feeding in urban and rural areas; and to examine whether attitudes are associated with intent to breastfeed. Methods: The IIFAS assessment tool was administered to 793 pregnant women. Differences in the total IIFAS scores were compared between urban and rural areas. Reliability and validity analysis was conducted on the IIFAS. The receiver operating characteristic (ROC) of the IIFAS was assessed against mother’s intent to breastfeed. Results: The mean ± SD of the total IIFAS score of the overall sample was 64.0 ± 10.4. There were no significant differences in attitudes between urban (63.9 ± 10.5) and rural (64.4 ± 9.9) populations. There were significant differences in total IIFAS scores between women who intend to breastfeed (67.3 ± 8.3) and those who do not (51.6 ± 7.7), regardless of population region. The high value of the area under the curve (AUC) of the ROC (AUC = 0.92) demonstrates excellent ability of the IIFAS to predict intent to breastfeed. The internal consistency of the IIFAS was strong, with a Cronbach’s alpha greater than .80 in the overall sample. Conclusion: The IIFAS examined in this provincial population provides a valid and reliable assessment of maternal attitudes toward infant feeding. This tool could be used to identify mothers less likely to breastfeed and to inform health promotion programs.
Yucca-derived synthesis of gold nanomaterial and their catalytic potential
Authors: Krishnamurthy Sneha , Esterle Andrea , Sharma Nilesh C , Sahi Shivendra V 
Published: November 2014

Abstract
AuNPs ranging in 20 to 300 nm size were synthesized at a room temperature using Yucca filamentosa leaf extract. Diverse nanomaterial morphologies were obtained by varying the extract concentration, reaction pH, and temperature. While low volumes of extract (0.25 and 0.5 mL) induced the formation of microscale Au sheets with edge length greater than 1 μm, high volumes yielded spherical particles ranging from 20 to 200 nm. Varying pH of the solution significantly influenced the particle shape with the production of largely spherical particles at pH 5 to 6 and truncated triangles at pH 2. Separation of multidimensional nanostructures was achieved using a novel method of sucrose density gradient centrifugation. The catalytic function of Yucca-derived AuNPs was demonstrated by degradation of a wastewater dye: methylene blue using spectrophotometric measurements over time. Treatment with Au nanosheets and spheres demonstrated methylene blue degradation approximately 100% greater than the activity in control at 60 min.
Neuromorphic crossbar circuit with nanoscale filamentary-switching binary memristors for speech recognition
Authors: Truong Son Ngoc , Ham Seok-Jin , Min Kyeong-Sik 
Published: November 2014

Abstract
In this paper, a neuromorphic crossbar circuit with binary memristors is proposed for speech recognition. The binary memristors which are based on filamentary-switching mechanism can be found more popularly and are easy to be fabricated than analog memristors that are rare in materials and need a more complicated fabrication process. Thus, we develop a neuromorphic crossbar circuit using filamentary-switching binary memristors not using interface-switching analog memristors. The proposed binary memristor crossbar can recognize five vowels with 4-bit 64 input channels. The proposed crossbar is tested by 2,500 speech samples and verified to be able to recognize 89.2% of the tested samples. From the statistical simulation, the recognition rate of the binary memristor crossbar is estimated to be degraded very little from 89.2% to 80%, though the percentage variation in memristance is increased very much from 0% to 15%. In contrast, the analog memristor crossbar loses its recognition rate significantly from 96% to 9% for the same percentage variation in memristance.
Age and ultra-marathon performance - 50 to 1,000 km distances from 1969 – 2012
Authors: Romer Tobias , Rüst Christoph Alexander , Zingg Matthias Alexander , Rosemann Thomas , Knechtle Beat 
Published: November 2014

Abstract
We investigated age and performance in distance-limited ultra-marathons held from 50 km to 1,000 km. Age of peak running speed and running speed of the fastest competitors from 1969 to 2012 in 50 km, 100 km, 200 km and 1,000 km ultra-marathons were analyzed using analysis of variance and multi-level regression analyses. The ages of the ten fastest women ever were 40 ± 4 yrs (50 km), 34 ± 7 yrs (100 km), 42 ± 6 yrs (200 km), and 41 ± 5 yrs (1,000 km). The ages were significantly different between 100 km and 200 km and between 100 km and 1,000 km. For men, the ages of the ten fastest ever were 34 ± 6 yrs (50 km), 32 ± 4 yrs (100 km), 44 ± 4 yrs (200 km), and 47 ± 9 yrs (1,000 km). The ages were significantly younger in 50 km compared to 100 km and 200 km and also significantly younger in 100 km compared to 200 km and 1,000 km. The age of the annual ten fastest women decreased in 50 km from 39 ± 8 yrs (1988) to 32 ± 4 yrs (2012) and in men from 35 ± 5 yrs (1977) to 33 ± 5 yrs (2012). In 100 km events, the age of peak running speed of the annual ten fastest women and men remained stable at 34.9 ± 3.2 and 34.5 ± 2.5 yrs, respectively. Peak running speed of top ten runners increased in 50 km and 100 km in women (10.6 ± 1.0 to 15.3 ± 0.7 km/h and 7.3 ± 1.5 to 13.0 ± 0.2 km/h, respectively) and men (14.3 ± 1.2 to 17.5 ± 0.6 km/h and 10.2 ± 1.2 to 15.1 ± 0.2 km/h, respectively). In 200 km and 1,000 km, running speed remained unchanged. In summary, the best male 1,000 km ultra-marathoners were ~15 yrs older than the best male 100 km ultra-marathoners and the best female 1,000 km ultra-marathoners were ~7 yrs older than the best female 100 km ultra-marathoners. The age of the fastest 50 km ultra-marathoners decreased across years whereas it remained unchanged in 100 km ultra-marathoners. These findings may help athletes and coaches to plan an ultra-marathoner’s career. Future studies are needed on the mechanisms by which the fastest runners in the long ultra-marathons tend to be older than those in shorter ultra-marathons.