bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing Prediction Performance of Neoadjuvant Chemotherapy Response in Bladder Cancer
Authors: Cremer Chris 
Published: September 2016

AbstractNeoadjuvant chemotherapy is a treatment routinely prescribed to patients diagnosed with muscle-invasive bladder cancer. Unfortunately, not all patients are responsive to this treatment and would greatly benefit from an accurate prediction of their expected response to chemotherapy. In this project, I attempt to develop a model that will predict response using tumour microarray data. I show that using my dataset, every method is insufficient at accurately classifying responders and non-responders.
Hazardous Alcohol Use Associated with Increased Sexual Risk Behaviors Among People Who Inject Drugs
Authors: Fairbairn Nadia , Hayashi Kanna , Milloy M‐J , Nolan Seonaid , Nguyen Paul , Wood Evan , Kerr Thomas 
Published: September 2016

BackgroundAlcohol is associated with a multitude of severe health consequences. While risk behaviors related to illicit drug use are commonly studied among people who inject drugs (PWID), the role of alcohol use has received substantially less attention in this population. We explored whether drug and sexual risk behaviors as well as experiences of violence were associated with hazardous alcohol use in a cohort of PWID.MethodsAnalyses were conducted using observational data from a prospective cohort of community‐recruited HIV‐negative PWID in Vancouver, Canada. We used the U.S. National Institute on Alcohol Abuse and Alcoholism definition of hazardous alcohol use (i.e., >14 drinks/wk or >4 drinks on 1 occasion for men, and >7 drinks/wk or >3 drinks on 1 occasion for women). We used multivariable generalized estimating equations (GEE) to identify the factors associated with hazardous alcohol use.ResultsBetween 2006 and 2012, 1,114 HIV‐negative individuals were recruited, and 186 (16.7%) reported hazardous alcohol use in the previous 6 months at baseline. In multivariable GEE analyses, having multiple sex partners (adjusted odds ratio [AOR] = 1.25), history of sexually transmitted infection (AOR = 1.50), experiencing violence (AOR = 1.36), and incarceration (AOR = 1.29) were each independently associated with hazardous alcohol use. Caucasian ethnicity (AOR = 0.56), ≥ daily heroin injection (AOR = 0.81), and engagement in addiction treatment (AOR = 0.84) were negatively associated with hazardous alcohol use (all p < 0.05).ConclusionsA considerable proportion of PWID reported hazardous alcohol use, which was independently associated with reporting sexual, but not drug‐related, HIV risk behaviors and experiencing recent violence. Findings suggest a need to integrate regular screening and evidence‐based alcohol interventions into treatment efforts for PWID.
Identifying women at risk for postpartum anxiety: a prospective population‐based study
Authors: Dennis C.‐L. , Falah‐Hassani K. , Brown H. K. , Vigod S. N. 
Published: September 2016

ObjectiveTo develop a multifactorial model to predict anxiety symptomatology at 8 weeks postpartum.MethodIn a population‐based study, 522 women in a health region near Vancouver, Canada, completed questionnaires at 1, 4, and 8 weeks postpartum. Questionnaires included risk factors measured at 1 week (sociodemographic, biological, pregnancy‐related, life stressors, social support, obstetric, and maternal adjustment). Sequential logistic regression was completed to develop a predictive model of anxiety symptomatology at 8 weeks (State‐Trait Anxiety Inventory score >40).ResultsThe prevalence of anxiety symptomatology at 1, 4, and 8 weeks postpartum was 22.6%, 17.2%, and 14.8% respectively. In multivariable models, anxiety symptomatology at 1 week (aOR 2.78, 95% CI: 1.04–7.43), multiparous parity (aOR 3.29, 95% CI: 1.28–8.48), history of psychiatric problems (aOR 3.07, 95% CI: 1.19–7.97), perceived stress (1 SD increase: aOR 4.92, 95% CI: 2.62–9.26), and childcare stress (1 SD increase: aOR 1.63, 95% CI: 1.01–2.64) were independent predictors of anxiety symptomatology at 8 weeks.ConclusionWhile a significant proportion of women experience anxiety symptomatology following childbirth, multiparous women with a psychiatric history who have high levels of diverse stress are at greatest risk. These key factors may be used to promote early identification and secondary preventive interventions.
Cervical length at 11–40 weeks: unconditional and conditional longitudinal reference ranges
Authors: Papastefanou Ioannis , Pilalis Athanasios , Kappou Dimitra , Souka Athena P. 
Published: September 2016

AbstractIntroductionOur aim was to establish unconditional and conditional longitudinal reference ranges for cervical length throughout pregnancy.Material and methodsProspective longitudinal study. In singleton pregnancies repeated cervical length measurements were carried out by transvaginal ultrasound throughout gestation. Multilevel modeling was applied to establish cervical length reference ranges from 11 to 40 weeks.ResultsIn all, 4397 women contributed to 13 765 cervical length measurements. A linear mixed effects random intercept–random slope model was fitted to the data. Mean cervical length had a negative non‐linear polynomial association with gestational age. Unconditional ranges were developed. Terms that allow the construction of personalized cervical length charts conditional to a previous measurement were calculated.ConclusionsWe constructed longitudinal reference charts for cervical length in singleton pregnancies. Cervical length should be adjusted according to specific gestational‐age‐dependent ranges. Individualization of cervical assessment is feasible by the application of charts conditional to previous measurements.
Reporting on data monitoring committees in neonatal randomised controlled trials is inconsistent
Authors: Perrem LM , Gosling S , Ravikumar I , Khashan AS , Miletin J , Ryan CA , Dempsey E 
Published: September 2016

AbstractAimTo evaluate the reported use of data monitoring committees (DMCs), the frequency of interim analysis, prespecified stopping rules and early trial termination in neonatal randomised controlled trials (RCTs).MethodsWe reviewed neonatal RCTs published in four high‐impact general medical journals, specifically looking at safety issues including documented involvement of a DMC, stated interim analysis, stopping rules and early trial termination. We searched all journal issues over an 11‐year period (2003–2013) and recorded predefined parameters on each item for RCTs meeting inclusion criteria.ResultsSeventy neonatal trials were identified in four general medical journals: Lancet, New England Journal of Medicine (NEJM), British Medical Journal and Journal of American Medical Association. A total of 43 (61.4%) studies reported the presence of a DMC, 36 (51.4%) explicitly mentioned interim analysis, stopping rules were reported in 15 (21.4%) RCTs and seven (10%) trials were terminated early. The NEJM most frequently reported these parameters compared to the other three journals reviewed.ConclusionWhile the majority of neonatal RCTs report on DMC involvement and interim analysis, there is still scope for improvement. Clear documentation of safety‐related issues should be a central component of reporting in neonatal trials involving newborn infants.
Population‐based study shows that Hirschsprung disease does not have a negative impact on education and income
Authors: Granström Anna Löf , Svenningsson Anna , Nordenskjöld Agneta , Wester Tomas 
Published: September 2016

AbstractAimHirschsprung disease is a multifactorial disease, which is mainly treated during childhood. There is a risk of impaired bowel function for a long time after surgery, and its impact on adult life has not been well studied. This study assessed whether having Hirschsprung disease affected social parameters such as educational level and income.MethodsThis nationwide, population‐based cohort study included all patients with Hirschsprung disease, registered in the Swedish National Patient Register from 1964 and 2013, who were each matched by age and sex to ten individuals randomly selected from the Swedish Population Register. The study outcomes were the highest educational level and individual disposable income in 2013 registered by Statistics Sweden.ResultsThe study comprised 389 patients and 3847 controls, both 76% male, with a median age of 25 years. There were no statistically significant differences in highest educational level between the groups (p = 0.327). The median individual disposable income was 142 200 (0–817 200) Swedish Krona in the patient group and 159 000 (0–3 418 900) in the control group (p = 0.615).ConclusionThe highest educational level and the individual disposable income did not differ between patients with Hirschsprung disease and controls, indicating that the disease had a low impact on these parameters.
Proliferative Properties of 17β‐aminoestrogens in MCF‐7 Human Breast Cancer Cells
Authors: Lemini Cristina , Estela Avila María , Medina Martha , Sánchez Carlos , Figueroa Alejandra , García‐Mondragón Maria Juana , Vargas‐Vázquez Arsenio , Jiménez‐Orozco Alejandro 
Published: September 2016

AbstractThe 17β‐aminoestrogens (AEs) prolame, butolame and pentolame are weakly oestrogenic in rodents and display anticoagulant properties in contrast to oestradiol (E2) which presents pro‐coagulant effects, potentially thrombogenic. They possess anti‐anxiety and antidepressive properties, being good candidates for menopausal hormone therapy (MHT). Their capability to induce proliferation of MCF‐7 human breast cancer cells, in which proliferative rate depends on oestrogens, has not been explored; thus, the aim of this work was to characterize it. AEs’ proliferation properties were evaluated compared with E2 in MCF‐7 carcinoma cell line cultures using established methods. Receptor mediation on cell proliferation was studied by co‐incubating them with the oestrogen receptor antagonists tamoxifen, ICI 182,780 and the selective antagonists MPP (ERα) and PHTPP (ERβ). E2 and AEs increased MCF‐7 cell proliferation; their proliferative effect was between 1.5‐2 and E2 = 3.6 compared with controls (0); their relative proliferative effect was 18–38% (E2 = 100%) with a relative proliferative potency of 4.5–8.9 (E2 = 100). The ERα antagonist MPP inhibited the MCF‐7 cell proliferation induced by E2 and AEs; on the contrary, the ERβ antagonist PHTPP exacerbated the proliferative response, showing that the AEs’ proliferative activity was mainly ERα‐mediated and apparently controlled by ERβ. Preliminary cytometric DNA flow analysis showed that AEs’ cell cycle S phase inducer property was lower than E2 following the proliferative order: E2 > butolame > prolame > pentolame, indicating pentolame with the weakest proliferative properties and being the safest of this series as a candidate for MHT.
Use of a Target‐Mediated Drug Disposition Model to Predict the Human Pharmacokinetics and Target Occupancy of GC1118, an Anti‐epidermal Growth Factor Receptor Antibody
Authors: Park Wan‐Su , Han Seunghoon , Lee Jongtae , Hong Taegon , Won Jonghwa , Lim Yangmi , Lee Kyuhyun , Byun Han Yeul , Yim Dong‐Seok 
Published: September 2016

AbstractGC1118 is an anti‐epidermal growth factor receptor (EGFR) monoclonal antibody that is currently under clinical development. In this study, the pharmacokinetics (PK) of GC1118 were modelled in monkeys to predict human PK and receptor occupancy (RO) profiles. The serum concentrations of GC1118 and its comparator (cetuximab) were assessed in monkeys with a non‐compartmental analysis and a target‐mediated drug disposition (TMDD) model after intravenous infusion (3–25 mg/kg) of these drugs. The scaling exponent of the EGFR synthesis rate was determined using a sensitivity analysis. The human cetuximab exposures were simulated by applying different exponents (0.7–1.0) for the EGFR synthesis rate in the allometric monkey PK model. Simulated Cmax and area under the curve values therein were compared with those previously reported in the literature to find the best exponent for the EGFR synthesis rate in human beings. The TMDD model appropriately described the monkey PK profile, which showed a decrease in clearance (CL; 1.2–0.4 ml/hr/kg) as the dose increased. The exponents for CL (0.75) and volume of distribution (Vd; 1.0) were used for the allometric scaling to predict human PK. The allometric coefficient for the EGFR synthesis rate chosen by the sensitivity analysis was 0.85, and the RO profiles that could not be measured experimentally were estimated based on the predicted concentrations of the total target and the drug–target complex. Our monkey TMDD model successfully predicts human PK and RO profiles of GC1118 and can be used to determine the appropriate dose for a first‐in‐human study investigating this drug.
Students and Doctors are Unaware of the Cost of Drugs they Frequently Prescribe
Authors: Schutte Tim , Tichelaar Jelle , Nanayakkara Prabath , Richir Milan , van Agtmael Michiel 
Published: September 2016

AbstractGiven the increasing healthcare costs of an ageing population, there is growing interest in rational prescribing, which takes costs of medication into account. We aimed to gain insight into the attitude to and knowledge of medication costs of medical students and doctors in daily practice. This was a cross‐sectional electronic survey among medical students (bachelor/master) and doctors (consultants/registrars). Attitude to costs was evaluated using a cost‐consciousness scale. In open questions, the participants estimated the cost of commonly prescribed (generic/non‐generic) drugs (including separate pharmacy dispensing costs). They were asked where they could find information about drug costs. Overall, a reasonable cost‐consciousness was found. Students were less conscious of the cost than were doctors (15.56 SD 3.25 versus 17.81 SD 2.25; scale 0–24; p = 0.001). In contrast to this consciousness, actual estimated drug costs were within a 25% margin for only 5.4% of generic and 13.7% of proprietary drugs (Wilcoxon signed‐rank, p < 0.001). The price of generic drugs was frequently overestimated (77.5%) and that of proprietary drugs was underestimated (51.4%). The dispensing costs were estimated correctly for 30% of the drugs. Most doctors (84%) and a minority of students (40%) were able to identify at least one source of information about drug costs. While doctors and students considered it important to be aware of the cost of drugs, this attitude is not reflected in their ability to estimate the cost of frequently prescribed drugs. Cost awareness is important in therapeutic reasoning and cost‐effective prescribing. Both should be better addressed in (undergraduate) pharmacotherapy education.
Smooth muscle contraction and growth of stromal cells in the human prostate are both inhibited by the Src family kinase inhibitors, AZM475271 and PP2
Authors: Wang Yiming , Gratzke Christian , Tamalunas Alexander , Rutz Beata , Ciotkowska Anna , Strittmatter Frank , Herlemann Annika , Janich Sophie , Waidelich Raphaela , Liu Chunxiao , Stief Christian G , Hennenberg Martin 
Published: September 2016

Background and PurposeIn benign prostatic hyperplasia, increased prostate smooth muscle tone and prostate volume may contribute alone or together to urethral obstruction and voiding symptoms. Consequently, it is assumed there is a connection between smooth muscle tone and growth in the prostate, but any molecular basis for this is poorly understood. Here, we examined effects of Src family kinase (SFK) inhibitors on prostate contraction and growth of stromal cells.Experimental ApproachSFK inhibitors, AZM475271 and PP2, were applied to human prostate tissues to assess effects on smooth muscle contraction, and to cultured stromal (WPMY‐1) and c‐Src‐deficient cells to examine effects on proliferation, actin organization and viability.Key ResultsSFKs were detected by real time PCR, western blot and immunofluorescence in human prostate tissues, some being located to smooth muscle cells. AZM475271 (10 μM) and PP2 (10 μM) inhibited SFK in prostate tissues and WPMY‐1 cells. Both inhibitors reduced α1‐adrenoceptor‐mediated and neurogenic contraction of prostate strips. This may result from cytoskeletal deorganization, which was observed in response to AZM475271 and PP2 in WPMY‐1 cells by staining of actin filaments with phalloidin. This was paralleled by reduced proliferation of wildtype but not of c‐Src‐deficient cells; cytotoxicity was mainly observed at higher concentrations (>50 μM).Conclusions and ImplicationsIn human prostate, smooth muscle tone and growth are both controlled by an SFK‐dependent process, which may explain their common role in bladder outlet obstruction. Targeting prostate smooth muscle tone and prostate growth simultaneously by a single compound may, in principal, be possible.
Continuous administration of the mTORC1 inhibitor everolimus induces tolerance and decreases autophagy in mice
Authors: Kurdi Ammar , De Doncker Mireille , Leloup Arthur , Neels Hugo , Timmermans Jean‐Pierre , Lemmens Katrien , Apers Sandra , De Meyer Guido R Y , Martinet Wim 
Published: September 2016

Background and PurposeEverolimus is an allosteric inhibitor of the mechanistic target of rapamycin complex 1 (mTORC1) widely known for its potent autophagy stimulating properties. Because everolimus shows poor solubility and stability in aqueous solutions, long‐term in vivo administration in preclinical models is challenging. The aim of the present study was to evaluate the effects of short‐term and long‐term everolimus administration on mTORC1 inhibition and autophagy induction in mice.Experimental ApproachWe developed a vehicle in which everolimus was solubilized and stable at 37°C for at least 1 month. Using osmotic minipumps, GFP microtubule‐associated protein light chain 3 transgenic mice were treated continuously either with vehicle or everolimus (1.5 mg·kg−1 per day) for 3 or 28 days. Alternatively, a regimen consisting of intermittent everolimus administration (every other day) for 56 days by oral gavage was used. Autophagy markers and mTORC1 activation status were investigated in the liver.Key ResultsAs expected, everolimus inhibited mTORC1 and stimulated autophagy in the liver after 3 days of treatment. However, continuous administration for 28 days resulted in hyperactivation of the Akt1‐mTORC1 pathway accompanied by a remarkable decrease in autophagy markers. Everolimus given intermittently for 56 days partially rescued mTORC1 sensitivity to the drug but without inducing autophagy. The failure to induce autophagy following long‐term everolimus administration was due to uncoupling of the mTORC1 substrate unc‐51 like autophagy activating kinase 1.Conclusions and ImplicationsOur data encourage the use of intermittent everolimus regimens to prevent tolerance and to extend its activity.
Preparation, characterization, and in vitro evaluation of bleomycin‐containing nanoliposomes
Authors: Chiani Mohsen , Shokrgozar Mohammad Ali , Azadmanesh Kayhan , Norouzian Dariush , Mehrabi Mohammad Reza , Najmafshar Aazam , Akbarzadeh Azim 
Published: September 2016

Bleomycin is an anticancer drug used against various types of cancers. The aim of this study was to prepare a new PEGylated and non‐PEGylated nanoliposomal formulation of bleomycin (PEG‐nLip‐BLM and nLip‐BLM) and evaluate their anticancer activity in different tumor cell lines. The liposomes were prepared by thin‐film hydration method, and then, bleomycin (BLM) was loaded to the prepared vesicles. The size, zeta potential, entrapment efficiency, loading rate, release profile, and cytotoxicity of liposomal formulations in TC‐1, LLC1, and HFLF‐PI5 cell lines were investigated. Mean particle size and zeta potential of the PEG‐nLip‐BLM and nLip‐BLM were found to be 99.4 ± 4.6 nm and −34.83 ± 4.7 mV; and 112.2 ± 7.2 nm and −27.5 ± 3.2 mV, respectively, which were stable for at least 2 months. Encapsulation and loading efficiency of BLM for PEG‐nLip‐BLM and nLip‐BLM were obtained about 83.1 ± 4.2% and 14.3 ± 2.5%; and 78.3 ± 8.6% and 11.1 ± 3.3%, respectively. Drug release study showed a slow release pattern without considerable burst effect. The liposomal formulations indicated lower toxicity compared to free drug in case of TC‐1 and HFLF‐PI5 cells, but their cytotoxicity against LLC1 cells was significantly higher than free drug. The results of this study indicated that PEG‐nLip‐BLM can be a suitable candidate for drug delivery to solid tumors.
Language Brokering and Depressive Symptoms in Mexican‐American Adolescents: Parent–Child Alienation and Resilience as Moderators
Authors: Kim Su Yeong , Hou Yang , Gonzalez Yolanda 
Published: September 2016

This study aimed to untangle the mixed effects of language brokering by examining a contextual factor (i.e., parent–child alienation) and a personal attribute (i.e., resilience) that may relate to adolescents’ feelings during translating (i.e., sense of burden and efficacy) and that may moderate the association between such feelings and adolescent depressive symptoms. Participants included 557 adolescent language brokers (Mage = 12.96) in Mexican‐American families. Results showed that adolescents with a strong sense of alienation from parents or low resilience (a) experienced more burden or less efficacy in translating and (b) were more susceptible to the detrimental effects of feeling a sense of burden and the beneficial effects of experiencing a sense of efficacy, as measured by depressive symptoms.
The influence of titanium surface characteristics on macrophage phenotype polarization during osseous healing in type I diabetic rats: a pilot study
Authors: Lee Ryan S. B. , Hamlet Stephen M. , Ivanovski Saso 
Published: September 2016

AbstractObjectivesThis study assessed the effect of titanium surface modification on macrophage phenotype polarization and osseous healing under diabetic conditions.Materials and methodsCritical‐sized calvarial defects were created in healthy and streptozotocin‐induced type I diabetic Sprague‐Dawley rats. Titanium (Ti) discs with either large‐grit sandblasted and acid‐etched micro‐rough (SLA) or hydrophilic‐modified SLA (modSLA) surfaces were used to cover the healing defect for a period of up to 28 days. Samples of the exudate within the calvarial defect and beneath the titanium discs were collected 1, 4 and 7 days post‐surgery for inflammatory cytokine analysis using an ELISA. The macrophage phenotype(s) on the Ti disc surfaces were determined by CD11c+ (M1) and CD163+ (M2) immunofluorescent staining. Samples of the healing defects at days 14 and 28 were also prepared for histomorphometric analysis.ResultsCytokine levels in the diabetic animals were higher than those of the healthy group throughout the observation period. The modSLA surface significantly reduced MIP‐2 levels at day 1 in both diabetic and healthy animals, and MCP‐1 levels at day 4 in the diabetic animals. Immuno‐fluorescent staining showed that an M2‐like macrophage phenotype was more frequently found on the modSLA surface at day 1 in healthy and day 4 in both healthy and diabetic animals. Histomorphometric analysis showed more new bone formation on the modSLA surface at days 14 and 28 in both groups, although statistically significant differences were only found in the healthy group.ConclusionDiabetic conditions greatly increased the expression of proinflammatory cytokines during osseous healing. The modSLA surface was shown to promote an M2‐like macrophage phenotypic response in titanium adherent macrophages despite the significantly elevated inflammatory environment induced by uncontrolled type I diabetes. Modulation of the macrophage phenotype by the modSLA surface in the early healing period was associated with osseous healing under both healthy and uncontrolled diabetic conditions.