bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics, exposure, efficacy and safety of obinutuzumab in rituximab‐refractory follicular lymphoma patients in the GADOLIN phase III study
Authors: Gibiansky Ekaterina , Gibiansky Leonid , Buchheit Vincent , Frey Nicolas , Brewster Michael , Fingerle‐Rowson Günter , Jamois Candice 
Published: May 2019

AimsRituximab is standard care in a number of lymphoma subtypes, including follicular lymphoma (FL), although many patients are resistant to rituximab, or develop resistance with repeated treatment, and a high proportion relapse. Obinutuzumab is a novel anti‐CD20 monoclonal antibody with improved efficacy over rituximab. It is approved for previously untreated chronic lymphocytic leukaemia (CLL), and for use with bendamustine in patients with rituximab‐relapsed/refractory FL.MethodsUsing a previously described population pharmacokinetic (PK) model of obinutuzumab in patients with non‐Hodgkin lymphoma and CLL, we conducted an exposure‐response analysis using data from 6 clinical trials in patients with CD20+ B‐cell malignancies (CLL11, GADOLIN, GATHER, GAUDI, GAUGUIN and GAUSS) to describe the PK properties of obinutuzumab, identify covariates influencing exposure, and explore how exposure affects safety, efficacy and pharmacodynamics.ResultsA 2‐compartment model with linear and time‐dependent clearance described obinutuzumab PK. Disease type and subtype, body weight, baseline tumour size, and sex had the largest effects on PK. Obinutuzumab exposure was not associated with occurrence or severity of adverse events, but higher exposure appeared to be associated with greater efficacy, particularly longer progression‐free survival. However, in multivariate Cox regression analysis, progression‐free survival benefit in the obinutuzumab plus bendamustine arm was independent of exposure.ConclusionThe updated population PK model reported here accurately describes the PK of obinutuzumab patients with non‐Hodgkin lymphoma and CLL. The selected obinutuzumab dosing regimen offers clinical benefit in a majority of rituximab‐refractory FL patients treated with bendamustine, irrespective of variability in exposure, whilst minimising adverse events.
The association between attention deficit hyperactivity disorder severity and risk of mild traumatic brain injury in children with attention deficit hyperactivity disorder in the United States of America: A cross‐sectional study of data from the National Survey of Children with Special Health Care Needs
Authors: Karic Semir , DesRosiers Michael , Mizrahi Briana , Zevallos Juan , Rodriguez Pura , Barengo Noël C. 
Published: May 2019

AbstractBackgroundAs children with attention deficit hyperactivity disorder (ADHD) have shown to be at higher risk of accidents and injury, one may assume that they may also bear a higher likelihood of mild traumatic brain injuries (mTBI). However, the current scientific evidence whether ADHD severity is associated with traumatic brain injuries is controversial. The objective of this study was too assess the association between the severity of ADHD and prevalence of mTBI in 0‐ to 18‐year‐old children with ADHD in the United States.MethodsCross‐sectional study using secondary data gathered in 2009/10 from the National Survey of Children with Special Healthcare Needs. After excluding comorbidity and those with nonspecific attention deficits, the final study population consisted of 10,739 children with ADHD from 40,052 households. The main exposure variable was self‐reported ADHD severity (mild, moderate, or severe). The main outcome was mTBI, defined as head injury, traumatic brain injury, and/or concussion). Covariates included age, gender and race, medication status. Unadjusted and adjusted logistic regression analysis were used.ResultsChildren with more severe ADHD had consistently increased incidences of mTBI. Adjusted logistic regression analysis revealed a statistically significant association between severity of ADHD and occurrence of mTBI. The corresponding odds ratios were 1.57 (95% confidence interval (CI) [1.13, 2.18] for moderate, and 1.79 (95% CI [1.18, 2.72]) for severe ADHD, respectively, compared with mild ADHD. In males, children with moderate and severe ADHD had increased odds of mTBI. The corresponding odds ratio for mTBI in those with moderate ADHD was 1.60 (95% CI [1.07, 2.39]) and 1.86 (95% CI [1.15, 3.00]) for severe ADHD, respectively. No associations between severity and mTBI were found in girls.ConclusionsAs ADHD severity was associated with incidence of mTBI, it is important to identify those who need increased attention and counselling to prevent injury.
Silver nanoparticles exert concentration‐dependent influences on biofilm development and architecture
Authors: Guo Jingyang , Qin Simin , Wei Yan , Liu Shima , Peng Hongzhen , Li Qingnuan , Luo Liqiang , Lv Min 
Published: May 2019

AbstractObjectivesTo investigate the impact of silver nanoparticles (AgNPs) on the biofilm growth and architecture.Materials and methodsSilver nitrate was reduced by d‐maltose to prepare AgNPs in the presence of ammonia and sodium hydroxide. The physicochemical properties of AgNPs were characterized by transmission electron microscopy, ultraviolet‐visible spectroscopy and inductively coupled plasma mass spectrometry. The development of biofilm with and without AgNPs was explored by crystal violet stain. The structures of mature biofilm were visually studied by confocal laser scanning microscopy and scanning electron microscopy. Bacterial cell, polysaccharide and protein within biofilm were assessed quantitatively by colony‐counting method, phenol‐sulphuric acid method and Bradford assay, respectively.ResultsThe spherical AgNPs (about 30 nm) were successfully synthesized. The effect of AgNPs on Pseudomonas aeruginosa biofilm development was concentration‐dependent. Biofilm was more resistant to AgNPs than planktonic cells. Low doses of AgNPs exposure remarkably delayed the growth cycle of biofilm, whereas high concentration (18 μg/mL) of AgNPs fully prevented biofilm development. The analysis of biofilm architecture at the mature stage demonstrated that AgNPs exposure at all concentration led to significant decrease of cell viability within treated biofilms. However, sublethal doses of AgNPs increased the production of both polysaccharide and protein compared to control, which significantly changed the biofilm structure.ConclusionsAgNPs exert concentration‐dependent influences on biofilm development and structure, which provides new insight into the role of concentration played in the interaction between antibacterial nanoparticles and biofilm, especially, an ignored sublethal concentration associated with potential unintended consequences.
Response of 1,5‐anhydroglucitol level to intensive glucose‐ and blood‐pressure lowering interventions, and its associations with clinical outcomes in the ADVANCE trial
Authors: Selvin Elizabeth , Wang Dan , McEvoy John William , Juraschek Stephen P. , Lazo Mariana , Hamet Pavel , Cooper Mark E. , Marre Michel , Williams Bryan , Harrap Stephen , Chalmers John , Woodward Mark 
Published: May 2019

AbstractAimsTo evaluate 1,5‐anhydroglucitol (1,5‐AG) according to clinical outcomes and assess the effects of glucose‐ and blood pressure‐lowering interventions on change in 1,5‐AG levels in people with type 2 diabetes.MethodsWe measured 1,5‐AG in 6826 stored samples at baseline and in a random subsample of 684 participants at the 1‐year follow‐up visit in the ADVANCE trial. We examined baseline 1,5‐AG [< 39.7, 39.7‐66.2, ≥ 66.2 μmol/L (<6, 6‐10, ≥10 μg/mL)] and microvascular and macrovascular events and mortality using Cox regression models during 5 years of follow‐up. Using an intention‐to‐treat approach, we examined 1‐year change in 1,5‐AG (mean and percent) in response to the glucose‐ and blood pressure‐lowering interventions in the subsample.ResultsLow 1,5‐AG level [<39.7 μmol/L vs ≥ 66.2 μmol/L (<6 μg/mL vs ≥10 μg/mL)] was associated with microvascular events (hazard ratio 1.28, 95% confidence interval 1.03‐1.60) after adjustment for risk factors and baseline glycated haemoglobin (HbA1c); however, the associations for macrovascular events and mortality were not independent of HbA1c. The glucose‐lowering intervention was associated with a significant 1‐year increase in 1,5‐AG (vs standard control) of 6.69 μmol/L (SE 2.52) [1.01 μg/mL (SE 0.38)], corresponding to an 8.26% (SE 0.10%) increase from baseline. We also observed an increase in 1,5‐AG of similar magnitude in response to the blood pressure intervention independent of the glucose‐lowering effect.ConclusionsOur results suggest that 1,5‐AG is a marker of risk in adults with type 2 diabetes, but only for microvascular events independently of HbA1c. We found that 1,5‐AG was improved (increased) in response to an intensive glucose‐lowering intervention, although the independent effect of the blood pressure‐lowering intervention on 1,5‐AG suggests potential non‐glycaemic influences.
Weight loss enhances cardiac energy metabolism and function in heart failure associated with obesity
Authors: Karwi Qutuba G. , Zhang Liyan , Altamimi Tariq R. , Wagg Cory S. , Patel Vaibhav , Uddin Golam M. , Joerg Alice R. , Padwal Raj S. , Johnstone David E. , Sharma Arya , Oudit Gavin Y. , Lopaschuk Gary D. 
Published: May 2019

AbstractAimsObesity is associated with high rates of cardiac fatty acid oxidation, low rates of glucose oxidation, cardiac hypertrophy and heart failure. Whether weight loss can lessen the severity of heart failure associated with obesity is not known. We therefore determined the effect of weight loss on cardiac energy metabolism and the severity of heart failure in obese mice with heart failure.Materials and methodsObesity and heart failure were induced by feeding mice a high‐fat (HF) diet and subjecting them to transverse aortic constriction (TAC). Obese mice with heart failure were then switched for 8 weeks to either a low‐fat (LF) diet (HF TAC LF) or caloric restriction (CR) (40% caloric intake reduction, HF TAC CR) to induce weight loss.ResultsWeight loss improved cardiac function (%EF was 38 ± 6% and 36 ± 6% in HF TAC LF and HF TAC CR mice vs 25 ± 3% in HF TAC mice, P < 0.05) and it decreased cardiac hypertrophy post TAC (left ventricle mass was 168 ± 7 and 171 ± 10 mg in HF TAC LF and HF TAC CR mice, respectively, vs 210 ± 8 mg in HF TAC mice, P < 0.05). Weight loss enhanced cardiac insulin signalling, insulin‐stimulated glucose oxidation rates (1.5 ± 0.1 and 1.5 ± 0.1 μmol/g dry wt/min in HF TAC LF and HF TAC CR mice, respectively, vs 0.2 ± 0.1 μmol/g dry wt/min in HF TAC mice, P < 0.05) and it decreased pyruvate dehydrogenase phosphorylation. Cardiac fatty acid oxidation rates, AMPKTyr172/ACCSer79 signalling and the acetylation of ß‐oxidation enzymes, were attenuated following weight loss.ConclusionsWeight loss is an effective intervention to improve cardiac function and energy metabolism in heart failure associated with obesity.
Spinning their wheels: a reply to Jane Humphries and Benjamin Schneider
Authors: Allen Robert C. 
Published: May 2019

AbstractJane Humphries and Benjamin Schneider have assembled several large databases of spinners’ production and wages that they believe disprove my view that high wages led to mechanization in eighteenth‐century England. This reply examines their data and shows that they have little value for understanding the incentives to mechanize. In addition, I present new evidence that substantiates my earlier estimates of productivity and earnings. The high wage hypothesis is unimpaired by the critique of Humphries and Schneider.
Model‐based evaluation of low‐dose factor VIII prophylaxis in haemophilia A
Authors: Brekkan Ari , Degerman Johanna , Jönsson Siv 
Published: May 2019

AbstractIntroductionThe optimal treatment modality for haemophilia A is lifelong prophylaxis which is expensive and may not be implementable everywhere where factor VIII (FVIII) availability is limited. A less costly alternative to prophylaxis is low‐dose prophylaxis (LDP) which was compared to conventional prophylaxis in this model‐based simulation study.AimTo explore whether LDP is motivated where standard prophylaxis is not implementable, including evaluating LDP efficacy compared to high‐dose prophylaxis and investigating the potential economic benefit of individualized dosing.MethodsFor a virtual adult haemophilia A population, FVIII activity levels were simulated following alternative treatment regimens, based on a published population PK model. The regimens included very LDP, LDP and conventional prophylaxis twice and thrice weekly. The annual probability of bleeding was predicted based on the weekly time spent below 1 IU/dL, using a previously published relationship. Additionally, PK‐based dose individualization was evaluated to determine FVIII savings using Bayesian forecasting.ResultsA treatment regimen of 10 IU/kg administered thrice weekly cost 75% less than a standard high‐dose regimen and was predicted to have a 5% higher median probability of annual bleeds. PK‐based dose individualization may result in further cost‐savings, but implementation needs benefit versus feasibility consideration.ConclusionBased on simulations, a promising LDP regimen was identified that decreased treatment costs compared with standard high‐dose prophylaxis at a small increase in bleeding risk. The results indicate that LDP is advocated where the standard‐of‐care is on‐demand treatment; however, the results should be considered in the context of any limitations of the applied models.
Conversation from Beyond the Grave? A Neo‐Confucian Ethics of Chatbots of the Dead
Authors: Elder Alexis 
Published: May 2019

AbstractDigital records, from chat transcripts to social media posts, are being used to create chatbots that recreate the conversational style of deceased individuals. Some maintain that this is merely a new form of digital memorial, while others argue that they pose a variety of moral hazards. To resolve this, I turn to classical Chinese philosophy to make use of a debate over the ethics of funerals and mourning. This ancient argument includes much of interest for the contemporary issue at hand, including the use of impersonators of the dead to help the bereaved to deal well with their grief. I connect this historical discussion with a modern trend in clinical psychology that reframes therapeutic interventions with bereaved individuals. The trend directs practitioners away from facilitating detachment and toward affirming continuing bonds. I conclude that these chatbots can offer an important source of support to mourners, but also discuss parameters and features of social context that will be important to avoid the moral hazards identified by sceptics.
Lnc‐NA inhibits proliferation and metastasis in endometrioid endometrial carcinoma through regulation of NR4A1
Authors: Sun Linying , Zhou Rongfang , Dong Jing , Liu Shuang , Jiao Yulian , Wang Laicheng , Hu Shengnan , He Pengjuan , Liu Xiaowen , Zhao Xingbo , Jiang Guosheng , Zhao Yueran 
Published: May 2019

AbstractEndometrioid endometrial carcinoma (EEC) is the most common gynaecologic malignancy worldwide. Long non‐coding RNAs have previously been demonstrated to play important roles in regulating human diseases, particularly cancer. However, the biological functions and molecular mechanisms of long non‐coding RNAs in EEC have not been extensively studied. Here, we describe the discovery of Lnc‐NA from the promoter of the transcription factor nuclear receptor subfamily 4 group A member 1 (NR4A1) gene. The role and function of Lnc‐NA in EEC remain unknown. In this study, we used quantitative real‐time polymerase chain reactions to confirm that Lnc‐NA expression was down‐regulated in 30 EEC cases (90%) and in EEC cell lines compared with that in the paired adjacent tissues and normal endometrial cells. In vitro experiments further demonstrated that overexpressing Lnc‐NA decreased EEC cell proliferation, migration and invasion and promoted apoptosis via inactivation of the apoptosis signalling pathway. Moreover, the results show that Lnc‐NA expression was positively correlated with NR4A1. Furthermore, Lnc‐NA regulated NR4A1 expression and activated the apoptosis signalling pathway to inhibit tumour progression. In summary, our results demonstrate that the Lnc‐NA‐NR4A1 axis could be a useful tumour suppressor and a promising therapeutic target for EEC.
Travesti Subjectivity and HIV Care: the Collision of the Global LGBT Rights and Evangelical Ex‐Gay Movements in Bolivia
Authors: Heckert Carina 
Published: May 2019

ResumenEste articulo analiza las experiencias de ex‐travestis en Bolivian que dejaron su identidad travesti en favor de retornar a la vida de un hombre. Se concentra primeramente en la historia de la vida de José Luis‐Natalia, y en menor grado, dos otras ex‐travestis. Explorando el tema de porque una travesti decidiría ser hombre otra vez se revela que las experiences del cuidado del VIH tiene una influencia en la subjetividad de genero, porque el cuidado del VIH es un punto de colisión entre ideologías de género contradictorias. Este articulo muestra como la presencia de ideologías contradictorias esta conectada a la historia de Bolivia en la época después de la dictadura. Además, la relación entre Bolivia y las agencias de desarrollo internacionales han contribuido a un auge en las ONGs en Bolivia que facilitó la habilidad de organizaciones GLBT y evangélicas a ser actores importantes en las intervenciones del VIH. Etnográficamente, este articulo interroga como las travestis y ex‐travestis experimentan el apoyo recibido por estas organizaciones y como estas experiencias se influyen la subjetividad de genero.
The Effects of State‐Mandated Financial Education on College Financing Behaviors
Authors: STODDARD CHRISTIANA , URBAN CARLY 
Published: May 2019

AbstractStudents entering college have limited financial experience while making complex borrowing decisions. This paper examines a policy lever that may improve these decisions: high school personal finance graduation requirements. We use a difference‐in‐difference strategy to determine their effects on financial aid decisions of incoming freshmen at 4‐year institutions. Our results suggest financial education shifts students from high‐cost to low‐cost financing. The requirements increase aid applications and acceptance of federal loans, while decreasing the likelihood of holding credit card balances. Students from less affluent family backgrounds reduce their likelihoods of working and borrowers from more affluent backgrounds reduce private loan amounts.
Exploring Women's Experiences in Accessing, Understanding, Appraising, and Applying Health Information During Pregnancy
Authors: Vamos Cheryl A. , Merrell Laura , Detman Linda , Louis Judette , Daley Ellen 
Published: May 2019

IntroductionThis study explored pregnant women's experiences in accessing, understanding, evaluating, communicating, and using health information and services during pregnancy.MethodsPregnant participants (aged 18‐45 years) were recruited from an obstetrics and gynecology department of a large urban training hospital. Focus groups were facilitated by a moderator's guide developed from health literacy domains (access, understand, evaluate, and communicate and use), audio recorded, transcribed, and uploaded into ATLAS.ti. Constant comparative and thematic analysis were employed.ResultsParticipants (N = 17) were predominantly Hispanic (53%), married (67%), college educated (87%), employed (80%), insured (100%), and nulliparous (59%). Health care providers and online and digital sources were preferred sources of information. Participants’ understanding was facilitated by plain language, pictures and other visuals, numbers and statistics, and tailored information. Participants evaluated information credibility by source (health care provider, advertisement, multiple sources) and personal circumstances (eg, health history, gestational age). In addition, these women used the information to communicate with health care providers, family, and partners and to change health‐related behaviors.DiscussionParticipants described rich, contextual health literacy experiences. Future interventions that maximize access to health care providers and online and digital sources, while ensuring materials are easy to understand, convenient, and patient centered, could facilitate informed decision making during this critical period. Future prenatal education and counseling interventions could be developed and evaluated using established health literacy principles to ensure that information is accessible, understandable, and actionable.
Would you like to purchase a rodent with dermatophytes?
Authors: Tekin Hasan Gökcer , Sigsgaard Viktoria , Zachariae Claus , Hare Rasmus Krøger , Arendrup Maiken Cavling , Saunte Ditte Marie Lindhardt 
Published: May 2019

SummaryThe zoophilic dermatophyte Trichophyton benhamiae has received attention due to increasing infections in human in recent years. Trichophyton benhamiae has been found on asymptomatic rodents from pet shops in several countries posing a potential risk for transmission to humans. The aim of this study was to determine the prevalence of positive dermatophyte cultures from rodents in Danish pet shops in order to clarify the magnitude of potential sources of zoophilic infections and to prevent further spread. Specimen sampling was performed in 17 Danish pet shops using the brush technique (MacKenzie technique). After incubation, cultures were sent to ITS DNA sequencing for molecular species identification. Pet shop employees were asked to fulfil a five‐question survey regarding purchase and procedures of diseased animals. A total of 98 animals were sampled (N = 32 rabbits, N = 32 guinea pigs and N = 34 hamsters). Trichophyton benhamiae was found in 14/98 samples (14%); 12/32 guinea pigs (38%) were positive with T benhamiae, 2/34 (6%) hamsters and 0/32 rabbits (0%). We found that hamsters and particularly guinea pigs from Danish pet shops are common asymptomatic carriers of the dermatophyte T benhamiae. Although a larger study is warranted to test this postulate, and it raises the question if infection control measures should be implemented in pet shops.
Isavuconazole to prevent invasive fungal infection in immunocompromised adults: Initial experience at an academic medical centre
Authors: Bowen Christina D. , Tallman Gregory B. , Hakki Morgan , Lewis Ⅱ James S. 
Published: May 2019

SummaryObjectiveTo evaluate clinical and economic outcomes associated with the use of isavuconazole as antifungal prophylaxis in high‐risk immunocompromised patients.Patients/MethodsRetrospective, single‐centre cohort study of patients who received isavuconazole prophylaxis. Outcomes assessed included breakthrough IFI, early discontinuation of isavuconazole for any reason and antifungal prophylaxis prescribed at discharge. The impact on inpatient drug expenditure was evaluated using current isavuconazole and posaconazole drug costs per observed isavuconazole days of therapy (DOT) during the study period.ResultsOne hundred thirty‐eight courses of isavuconazole prophylaxis were administered to 98 inpatients (2193 DOT). Relapsed/refractory acute myelogenous leukaemia was the indication for prophylaxis in over half (59.4%) of patients. Breakthrough IFI occurred in 8 (5.8%) courses. Suspected drug‐related toxicities led to early discontinuation in 6 (4.3%) courses (five hepatotoxicity, one drug rash). At discharge, 24 (17.4%) courses lacked insurance coverage for isavuconazole. The formulary switch to isavuconazole prophylaxis resulted in an estimated mean drug cost savings of $128.25 per DOT relative to estimated posaconazole costs (P < 0.001).ConclusionIsavuconazole may be an option for antifungal prophylaxis in high‐risk immunocompromised adults and has the potential to produce significant inpatient drug cost savings. Further studies are needed to confirm the clinical efficacy and cost‐effectiveness of isavuconazole in this role.