bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluorinated Polyethylenimine to Enable Transmucosal Delivery of Photosensitizer‐Conjugated Catalase for Photodynamic Therapy of Orthotopic Bladder Tumors Postintravesical Instillation
Authors: Li Guangzhi , Yuan Simin , Deng Dashi , Ou Tong , Li Yuqing , Sun Rui , Lei Qifang , Wang Xisheng , Shen Wanwan , Cheng Yiyun , Liu Zhuang , Wu Song 
Published: August 2019

AbstractPhotodynamic therapy (PDT) by insertion of an optical fiber into the bladder cavity has been applied in the clinic for noninvasive treatment of bladder tumors. To avoid systemic phototoxicity, bladder intravesical instillation of a photosensitizer may be an ideal approach for PDT treatment of bladder cancer, in comparison to conventional intravenous injection. However, the instillation‐based PDT for bladder cancer treatment remains to be less effective due to the poor urothelial uptake of photosensitizer, as well as the tumor hypoxia‐associated PDT resistance. Herein, it is uncovered that fluorinated polyethylenimine (F‐PEI) achieved by mixing with Chorin‐e6‐conjugated catalase (CAT‐Ce6) is able to form self‐assembled CAT‐Ce6/F‐PEI nanoparticles, which show greatly improved cross‐membrane, transmucosal, and intratumoral penetration capacities compared with CAT‐Ce6 alone or nonfluorinated CAT‐Ce6/PEI nanoparticles. Owing to the decomposition of tumor endogenous H2O2 by CAT‐Ce6/F‐PEI nanoparticles penetrating into bladder tumors, the tumor hypoxia would be effectively relieved to further favor PDT. Therefore, bladder intravesical instillation with CAT‐Ce6/F‐PEI nanoparticles could offer remarkably improved photodynamic therapeutic effect to destruct orthotopic bladder tumors with reduced systemic toxicity compared to hematoporphyrin, the first‐line photosensitizer used for bladder cancer PDT in clinic. This work presents a unique photosensitizer nanomedicine formulation, promising for clinical translation in instillation‐based PDT to treat bladder tumors.
Hochenergieeffiziente Hallenbäder
Authors: Gollwitzer Esther , Peper Søren , Grove‐Smith Jessica 
Published: August 2019

AbstractIn den letzten Jahren wurden die ersten Passivhaus‐Hallenbäder intensiv untersucht. Bereits bei diesen Pilotprojekten konnte der Heizwärme‐ und der Stromverbrauch in erheblichem Umfang gesenkt werden. Aufgrund dieser Erfahrungen können in zukünftigen Bädern noch weitere Potenziale genutzt werden. Dabei ist es entscheidend, die Möglichkeiten des Zusammenspiels von Architektur, Technik und Betrieb zu nutzen, um damit die Energiekosten im langjährigen Betrieb zu senken. Im aktuellen Forschungsprojekt wurden Untersuchungen (rechnerisch und messtechnisch) u. a. zu Verdunstungsraten, Energiebilanz des Beckenwassers, Schadstoffkonzentrationen und Lüftungsregelung durchgeführt. Die gewonnenen Erkenntnisse und Planungswerte erleichtern es, die wesentlichen Einflussfaktoren für die Planung, den Bau und den Betrieb von energieeffizienten Hallenbädern zu identifizieren und zu optimieren. Schon mit dem Entwurf (Zonierung, Lüftungszonen, Verglasungsanteil, Rohrlängen, Höhenunterschiede etc.) können die Weichen für ein kostengünstiges und gleichzeitig höchst energieeffizientes Bad gestellt werden. Als Hilfestellung für weitere Bäder (Neubau und Sanierung) bieten sich der erschienene Leitfaden mit Planungshinweisen und die Checklisten für Inbetriebnahme bzw. Betriebsoptimierung an [2].
Longitudinal analysis of pre‐ and post‐treatment measurements with equal baseline assumptions in randomized trials
Authors: Funatogawa Ikuko , Funatogawa Takashi 
Published: August 2019

AbstractFor continuous variables of randomized controlled trials, recently, longitudinal analysis of pre‐ and posttreatment measurements as bivariate responses is one of analytical methods to compare two treatment groups. Under random allocation, means and variances of pretreatment measurements are expected to be equal between groups, but covariances and posttreatment variances are not. Under random allocation with unequal covariances and posttreatment variances, we compared asymptotic variances of the treatment effect estimators in three longitudinal models. The data‐generating model has equal baseline means and variances, and unequal covariances and posttreatment variances. The model with equal baseline means and unequal variance–covariance matrices has a redundant parameter. In large sample sizes, these two models keep a nominal type I error rate and have high efficiency. The model with equal baseline means and equal variance–covariance matrices wrongly assumes equal covariances and posttreatment variances. Only under equal sample sizes, this model keeps a nominal type I error rate. This model has the same high efficiency with the data‐generating model under equal sample sizes. In conclusion, longitudinal analysis with equal baseline means performed well in large sample sizes. We also compared asymptotic properties of longitudinal models with those of the analysis of covariance (ANCOVA) and t‐test.
A hybrid model for simulating grazing herds in real time
Authors: Demšar Jure , Blewitt Will , Lebar Bajec Iztok 
Published: August 2019

AbstractComputer simulations of animal groups are usually performed via individual‐based modelling, where simulated animals are designed on the level of individuals. With this approach, developers are able to capture behavioural nuances of real animals. However, modelling each individual as its own entity has the downside of having a high computational cost, meaning that individual‐based models are usually not suitable for real‐time simulations of very large groups. A common alternative approach is flow‐based modelling, where the dynamics of animal congregations are designed on the group level. This enables researchers to create real‐time simulations of massive phenomena at the cost of biological authenticity. A novel approach called hybrid modelling tries to mix the best of both worlds—precision of individual‐based models and speed of flow‐based ones. An unknown surrounding hybrid model is the question of their biological authenticity and relevance. In this study, we develop a hybrid model for the simulation of herds of grazing sheep. Through Bayesian data analysis, we show that such an approach can encompass several aspects of real‐world sheep behaviour. Our hybrid model is also extremely efficient, capable of simulating herds of more than 1,000 individuals in real time without resorting to graphics processing unit execution.
Enantiomeric separation of vilanterol trifenatate by chiral liquid chromatography
Authors: Guo Yajun , Yang Yulei , Peng Jiajuan , Zhu Xueyan , Ji Zongde 
Published: August 2019

AbstractVilanterol trifenatate is a novel chiral long‐acting β2‐agonist developed. Vilanterol combined with inhaled corticosteroids can treat COPD and asthma. A simple liquid chromatographic method is developed for the quantitative determination of R‐vilanterol and S‐vilanterol (impurity S). HPLC separation was achieved on Chiralpak ID (250 × 4.6 mm; particle size 5 μm) column using hexane‐ethanol‐ethanolamine (75:25:0.1, v/v/v) as mobile phase at a flow rate of 1.0 mL/min. The resolution is greater than 3.3. Ethanolamine in the mobile phase is vital to enhance chromatographic efficiency and resolution between the isomers. The method was validated with respect to accuracy, specificity, precision, LOD, LOQ, linearity, and robustness as ICH guidelines.
Asymmetric Difluoromethylthiolation of Carbon Nucleophiles with Optically Pure Difluoromethylthiolating Reagents Derived from Camphorsultam
Authors: Zhang He , Wan Xiaolong , Shen Qilong 
Published: August 2019

Summary of main observation and conclusionThe invention of a family of optically pure electrophilic difluoromethylthiolating reagents 9a–c based on the camphorsultam skeleton was described. These reagents reacted with a variety of soft carbon nucleophiles such as oxazolone, oxindole, benzolactone and β‐ketoester in good to excellent enantioselectivities.
Obesity and breast cancer screening: Cross‐sectional survey results from the behavioral risk factor surveillance system
Authors: Miles Randy C. , Lehman Constance D. , Mercaldo Sarah F. , Tamimi Rulla M. , Dontchos Brian N. , Narayan Anand K. 
Published: August 2019

BackgroundPostmenopausal obese women demonstrate an elevated breast cancer risk and experience increased breast cancer morbidity and mortality compared with women with a normal body mass index (BMI). However, to the authors' knowledge, prior studies have yielded inconclusive results regarding the effects of obesity on mammography screening adherence. Using national cross‐sectional survey data, the objective of the current study was to assess the current association between increasing BMI and use of mammography screening.MethodsCross‐sectional survey data from the 2016 Behavioral Risk Factor Surveillance System, a state‐based national telephone survey of noninstitutionalized adults in the United States, was used to identify the association between mammography screening use and increasing incremental BMI categories, including normal (18.5‐24.9 kg/m2), overweight (25‐29.9 kg/m2), obese class I (30‐34.9 kg/m2), obese class II (35‐39.9 kg/m2), and obese class III (>40 kg/m2), with adjustments for potential confounders. A multivariable logistic regression model was used to evaluate the effect of each BMI category on self‐reported mammography use, using unadjusted and adjusted odds ratios. Effect modification by race/ethnicity was determined by testing interaction terms using Wald tests.ResultsOf 116,343 survey respondents, 33.5% (38,984 respondents) had a normal BMI, 32.6% (37,969 respondents) were overweight, 19.3% (22,416 respondents) were classified as obese class I, 8.4% (9791 respondents) were classified as obese class II, and 6.2% (7183 respondents) were classified as obese class III. There was no statistically significant difference (P < .05) observed with regard to mammography use between women with a normal BMI and obese women from each obese class (classes I‐III) when compared individually. There also was no evidence of effect modification by race (P = .53).ConclusionsIn contrast to prior reports, the results of the current study demonstrated no association between obesity and adherence to screening mammography. These findings may relate to the increasing social acceptance of obesity among women from all racial/ethnic groups and the removal of weight‐related facility‐level barriers over time.
CytoLyt fixation significantly inhibits MIB1 immunoreactivity whereas alternative Ki‐67 clone 30‐9 is not susceptible to the inhibition: Critical diagnostic implications
Authors: Buonocore Darren J. , Konno Fumiko , Jungbluth Achim A. , Frosina Denise , Fayad Mariam , Edelweiss Marcia , Lin Oscar , Rekhtman Natasha 
Published: August 2019

BackgroundThe Ki‐67 proliferation marker has multiple diagnostic and prognostic applications. Although several clones to the Ki‐67 antigen are commercially available, the MIB1 clone is widely recommended in the surgical pathology literature for neuroendocrine tumors. In our cytopathology practice, we have encountered unexpectedly low MIB1 immunoreactivity in CytoLyt‐fixed cell blocks (CBs). The current study evaluated the impact of fixatives, CB processing, and immunocytochemical (ICC) procedures on Ki‐67 immunoreactivity.MethodsTest CBs were prepared from freshly resected tumors, and multiple variables in the MIB1 ICC procedure were tested, including CytoLyt versus formalin collection media, MIB1 versus other Ki‐67 clones including 30‐9, and other variables. MIB1 versus Ki‐67 30‐9 clones were tested in parallel on CytoLyt‐fixed CBs from clinical samples of small cell lung carcinoma (SCLC).ResultsIn the test CBs (n = 10), the mean MIB1 labeling index was 10% in CytoLyt versus 47% in formalin (P = .0116), with a mean loss of reactivity in matched CBs of 37% (up to 70%). None of the procedure modifications tested in 223 individual ICC reactions recovered MIB1 reactivity in CytoLyt except for switching to the Ki‐67 30‐9 antibody. In CytoLyt‐fixed SCLC samples (n = 14), the Ki‐67 30‐9 antibody demonstrated expected ranges of reactivity (mean, 83%; range, 60%‐100%), whereas MIB1 demonstrated markedly inhibited labeling (mean, 60%; range, 10%‐95%) (P = .0058).ConclusionsCytoLyt fixation substantially inhibits MIB1 immunoreactivity, whereas the Ki‐67 30‐9 clone is not susceptible to inhibition. Markedly discrepant MIB1 reactivity may present a pitfall in the diagnosis of SCLC and may lead to the incorrect prognostic stratification of other tumor types. For laboratories using CytoLyt, we recommend using the Ki‐67 30‐9 antibody rather than the MIB1 antibody.
Pharmacokinetics and Pharmacodynamics of Insulin Tregopil in Relation to Premeal Dosing Time, Between Meal Interval, and Meal Composition in Patients With Type 2 Diabetes Mellitus
Authors: Khedkar Anand , Lebovitz Harold , Fleming Alexander , Cherrington Alan , Jose Vinu , Athalye Sandeep N. , Vishweswaramurthy Ashwini 
Published: August 2019

AbstractWe evaluated the pharmacokinetics and pharmacodynamics of oral insulin tregopil in relation to premeal dosing time, between‐meal interval, and meal composition type in type 2 diabetes mellitus patients in a randomized, placebo‐controlled, crossover study consisting of 3 sequential cohorts. In Cohort 1, insulin tregopil administered 10 to 20 minutes before a meal resulted in optimal postmeal exposure and demonstrated better postprandial glucose‐lowering effect (glucose area under concentration‐time curve [AUC]) compared to the 30‐minute group. In Cohort 2, insulin tregopil pharmacokinetic exposure (plasma AUC) showed a progressive increase through 4, 5, and 6 hours of between‐meal interval. The 6‐hour between‐meal interval resulted in better absorption of insulin tregopil in comparison to 4‐ and 5‐hour intervals. However, no significant differences were observed in pharmacodynamic parameters except for higher glucose AUC0‐180min in the insulin tregopil 4‐hour group during the afternoon meal as compared to the morning meal. In Cohort 3, a high‐fiber meal had the least impact on insulin tregopil absorption and resulted in the highest reduction in plasma glucose levels in the afternoon. A high‐fat meal reduced insulin tregopil absorption in the afternoon meal; however, pharmacodynamic response was not diminished significantly. Insulin tregopil has a rapid onset of action of approximately 10 minutes and, when administered 10 to 20 minutes before a meal, demonstrated up to 13% to 18% reduction in blood glucose levels compared to baseline. A 5‐hour between‐meal interval minimizes the impact of a meal on absorption of subsequent (afternoon) insulin tregopil dose, and the pharmacodynamic response of insulin tregopil is not altered by meal composition. Insulin tregopil was well tolerated in patients with type 2 diabetes mellitus.
Effect of KMnO4 on the Structure and Adsorption Behavior of Hydrous Manganese Dioxide Toward Pb(II) and Cd(II)
Authors: Wu Shanshan , Xie Fencun 
Published: August 2019

AbstractFour kinds of hydrous manganese dioxide (HMO) with different morphologies are synthesized by one‐pot method in this work. The effect of KMnO4 on structure and adsorption behavior of HMO has been thoroughly investigated by XRD, SEM, TEM, BET, and zeta potential analysis. The HMOs prepared are all δ‐MnO2, and a higher concentration of KMnO4 leads to a disordered, lower crystallinity structure, and higher absolute zeta potential values of HMO in the same condition, which exhibits a better adsorption capacity of 478.2 mg g−1 for Pb(II) and 135.2 mg g−1 for Cd(II). The addition of KMnO4 after reaction can also affect structure and adsorption capacity of HMO, it is characterized by higher crystallinity, fewer lattice defects, and higher adsorption capacity. The SEM and TEM analyses indicate that the possible formation is divided into two steps, involving the nucleation and shell growth, in a higher concentration of KMnO4: the first step is the reaction of KMnO4 and Mn2+, the second is KMnO4 decomposition with H+. In contrast, there is only the nucleation step in insufficient KMnO4. The addition of KMnO4 after reaction also involves two steps.
Transcutaneous immunization with CD40 ligation boosts cytotoxic T lymphocyte mediated antitumor immunity independent of CD4 helper cells in mice
Authors: Bialojan Ariane , Sohl Julian , Rausch Johanna , Aranda Lopez Pamela , Denny Mark , Langguth Peter , Hartmann Ann‐Kathrin , Yagita Hideo , Probst Hans Christian , Schild Hansjörg , Radsak Markus P. 
Published: August 2019

AbstractTranscutaneous immunization (TCI) is a novel vaccination strategy that utilizes skin‐associated lymphatic tissue to induce immune responses. Employing T‐cell epitopes and the TLR7 agonist imiquimod onto intact skin mounts strong primary, but limited memory CTL responses. To overcome this limitation, we developed a novel imiquimod‐containing vaccination platform (IMI‐Sol) rendering superior primary CD8+ and CD4+ T‐cell responses. However, it has been unclear whether IMI‐Sol per se is restricted in terms of memory formation and tumor protection. In our present work, we demonstrate that the combined administration of IMI‐Sol and CD40 ligation unleashes fullblown specific T‐cell responses in the priming and memory phase, strongly enhancing antitumor protection in mice. Interestingly, these effects were entirely CD4+ T cell independent, bypassing the necessity of helper T cells. Moreover, blockade of CD70 in vivo abrogated the boosting effect of CD40 ligation, indicating that the adjuvant effect of CD40 in TCI is mediated via CD70 on professional APCs. Furthermore, this work highlights the so far underappreciated importance of the CD70/CD27 interaction as a promising adjuvant target in TCI. Summing up, we demonstrate that the novel formulation IMI‐Sol represents a powerful vaccination platform when applied in combination with sufficient adjuvant thereby overcoming current limitations of TCI.
Exercise‐induced hypoalgesia in young adult females with long‐standing patellofemoral pain – A randomized crossover study
Authors: Straszek Christian L. , Rathleff Michael S. , Graven‐Nielsen Thomas , Petersen Kristian K. , Roos Ewa M. , Holden Sinead 
Published: August 2019

AbstractBackgroundPatellofemoral pain (PFP) is a common knee pain condition where hip and knee exercises help improve treatment outcomes. This study compared the acute effect of hip versus knee exercises on anti‐nociceptive and pro‐nociceptive mechanisms in young females with long‐standing PFP.MethodsIn this randomized cross‐over study, 29 females with PFP performed hip and knee exercises in randomized order during a single day. Pressure pain thresholds (PPTs) were assessed by handheld pressure algometry at the patella, the tibialis anterior muscle, and the contralateral elbow. Cuff pressure algometry at the lower legs was used to assess pain detection threshold (cPDT) and tolerance (cPTT) as well as conditioned pain modulation (CPM: change in cPDT during contralateral cuff pain conditioning) and temporal summation of pain (TSP: ten painful cuff stimulations assessed on a visual analogue scale [VAS]).ResultsPPTs at the tibialis anterior muscle but not at the patella increased compared with baseline following both exercises (p < .002). Compared with baseline, the cPDTs and cPTTs increased after both types of exercises (p < .001). The cPTTs increased more after knee compared to hip exercises (p < .007). VAS scores for TSP were increased following hip exercises (p < .001) although the rate of VAS increase over repeated stimulations was not significantly affected by exercises. The CPM‐effect was reduced after both types of exercises (p < .001).ConclusionA general hypoalgesic response to slowly increasing pressure stimuli was observed following both hip and knee exercises as well as decreased conditioned pain modulation, potentially indicating an attenuated ability from exercise to inhibit pain.
Fabrication and biological activity of polycaprolactone/phlorotannin endotracheal tube to prevent tracheal stenosis: An in vitro and in vivo study
Authors: Lee Hyoung Shin , Jeong Min‐Seon , Ko Seok‐Chun , Heo Seong‐Yeong , Kang Hyun Wook , Kim Sung Won , Hwang Chi Woo , Lee Kang Dae , Oak Chulho , Jung Min Jung , Oh Junghwan , Park Won Sun , Choi Il‐Whan , Jung Won‐Kyo 
Published: August 2019

AbstractProlonged endotracheal intubation is the most common cause of tracheal stenosis, which may lead to serious airway obstruction. Development of an endotracheal tube coated with biomaterials that exhibit anti‐inflammatory or anti‐fibrogenic effects may prevent tracheal stenosis. This study demonstrates that an endotracheal tube coated with phlorotannin, which is present in extracts of the brown alga Ecklonia cava, can prevent tracheal stenosis in a rabbit model. An in vitro study shows that phlorotannin inhibits proliferation of human tracheal fibroblasts treated with transforming growth factor β1. Phlorotannin‐coated endotracheal tubes show steady release of phlorotannin for up to 7 days, and removal of the tube 1 week after insertion reveals a reduction in both fibrogenesis and thickening of tracheal submucosa. Western blot analysis of tracheal tissues after removal of the phlorotannin‐coated tube shows decreased protein expression levels of phenotypic markers of fibrosis such as collagen type I and α‐smooth muscle actin. The ability of phlorotannin‐coated endotracheal tube to prevent tracheal stenosis caused by endotracheal intubation indicates that phlorotannin may be considered as a candidate biomaterial for coating the cuff of endotracheal tubes to prevent tracheal stenosis.
Sex Differences in the Prevalence and Severity of Exercise‐Induced Bronchoconstriction in Kindergarteners in Japan
Authors: Shinohara Miwa , Ogawa Sigeto , Nakaya Takahiro , Niino Ryouji , Ito Masanori , Haro Kaoru , Ishii Eiichi 
Published: August 2019

AbstractBackgroundExercise‐induced bronchoconstriction (EIB), a strong positive predictor of asthma, becomes progressively less frequent with age. Although asthma tends to become less common only in boys during adolescence, sex differences in EIB, especially in preschoolers, remain unclear. To find EIB for early diagnosis and intervention asthma, mass‐screening tests considering sex differences in preschoolers are needed. In this study, we investigated whether sex differences influence the prevalence and severity of EIB in prepubertal children aged 5–6 years.MethodsFifty‐one children aged 5–6 years who were attending a kindergarten in Matsuyama City, Ehime, Japan, were enrolled in this cross‐sectional study. The children underwent a 6‐minute free‐running test in 2015. The peak expiratory flow rate (PEFR) was measured before exercise and 0, 3, 10, and 20 minutes after exercise. The severity of EIB was classified according to the reduction in PEFR, measured as the difference between the postexercise PEFR and the highest pre‐exercise PEFR.ResultsOf the 51 children (23 boys and 28 girls) enrolled, the prevalence of EIB defined as three criteria: a ≥15%, ≥20%, or ≥25% decrease was 54.9% (28/51), 41.2% (21/51), and 25.5% (13/51), respectively. The prevalence of EIB defined as ≥25% decrease was significantly higher in girls than in boys (39.3% vs 8.7%, P = .013). In girls, the mean percentage change in PEFR was significantly higher 20 minutes than 10 minutes postexercise (P = .043).ConclusionsSex difference in the prevalence and severity of EIB should be considered when evaluating EIB, even in young, prepubertal children.