bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population Pharmacokinetic Modeling of Guselkumab, a Human IgG1λ Monoclonal Antibody Targeting IL‐23, in Patients with Moderate to Severe Plaque Psoriasis
Authors: Yao Zhenling , Hu Chuanpu , Zhu Yaowei , Xu Zhenhua , Randazzo Bruce , Wasfi Yasmine , Chen Yang , Sharma Amarnath , Zhou Honghui 
Published: January 2018

AbstractPsoriasis is a common inflammatory skin disorder that requires chronic treatment and is associated with multiple comorbidities. Guselkumab, a human immunoglobulin‐G1‐lambda monoclonal antibody, binds to interleukin‐23 with high specificity and affinity and is effective in treating moderate to severe plaque psoriasis. As part of the guselkumab psoriasis clinical trial program, using a confirmatory approach, a population pharmacokinetics (PopPK) model was established using 13 014 PK samples from 1454 guselkumab‐treated patients across 3 phase 2/3 trials. Observed serum guselkumab concentrations were adequately described by a 1‐compartment linear PK model with first‐order absorption and elimination. The final PK model was robust and stable, with apparent clearance (CL/F), apparent volume of distribution (V/F), and absorption rate constant (ka) estimates of 0.516 L/day, 13.5 L, and 1.11 day‐1, respectively. A model‐derived elimination half‐life of 18.1 days indicated achievement of steady‐state serum guselkumab concentrations within 12–14 weeks. The primary covariate contributing to the observed PK variability was body weight, which accounted for only 28% (CL/F) and 32% (V/F) of the interindividual proportion of variance. Diabetes was identified to marginally reduce guselkumab exposure, owing to 12% higher CL/F in diabetic versus nondiabetic patients, but its contribution was not clinically relevant. None of the other covariates tested (eg, age, sex, ethnicity, immune response to guselkumab, or concomitant medications) had a clinically relevant effect on guselkumab exposure.
A novel synthesis of 6′′‐[18F]‐fluoromaltotriose as a PET tracer for imaging bacterial infection
Authors: Namavari Mohammad , Gowrishankar Gayatri , Srinivasan Ananth , Gambhir Sanjiv S. , Haywood Thomas , Beinat Corinne 
Published: January 2018

The aim of this study was to develop a positron emission tomography (PET) tracer to visualize and monitor therapeutic response to bacterial infections. In our continued efforts to find maltose based PET tracers that can image bacterial infections, we have designed and prepared 6′′‐[18F]fluoromaltotriose as a second generation PET imaging tracer targeting the maltodextrin transporter of bacteria. We have developed methods to synthesize 6′′‐deoxy‐6′′‐[18F]fluoro‐α‐D‐glucopyranosyl‐(1‐4)‐O‐α‐D‐glucopyranosyl‐(1‐4)‐O‐D‐glucopyranose (6′′‐[18F]‐fluoromaltotriose) as a bacterial infection PET imaging agent. 6′′‐[18F]fluoromaltotriose was prepared from precursor, 2′′,3′′,4′′‐tri‐O‐acetyl‐6′′‐O‐nosyl‐α‐D‐glucopyranosyl‐(1‐4)‐O‐2′,3′,6′‐tri‐O‐acetyl‐α‐D‐glucopyranosyl‐(1‐4)‐1,2,3,6‐tetra‐O‐acetyl‐D‐glucopyranose (per‐O‐acetyl‐6′′‐O‐nosyl‐maltotriose 4). This method utilizes the reaction between precursor 4 and anhydrous [18F]KF/Kryptofix 2.2.2 in dimethylformamide (DMF) at 85°C for 10 minutes to yield per‐O‐acetyl‐6′′‐deoxy‐6‐′′ [18F]‐fluoromaltotriose (7). Successive acidic and basic hydrolysis of the acetyl protecting groups in 7 produced 6′′‐[18F]fluoromaltotriose (8). Also, cold 6′′‐ [19F]fluoromaltotriose was prepared from per‐O‐acetyl‐6′′‐hydroxymaltotriose via a diethylaminosulfur trifluoride reaction followed by a basic hydrolysis. A successful synthesis of 6′′‐[18F]‐fluoromaltotriose has been accomplished in 8 ± 1.2% radiochemical yield (decay corrected). Total synthesis time was 120 minutes. Serum stability of 6′′‐[18F]fluoromaltotriose at 37°C indicated that 6′′‐[18F]‐fluoromaltotriose remained intact up to 2 hours. In conclusion, we have successfully synthesized 6′′‐[18F]‐fluoromaltotriose via direct fluorination of an appropriate precursor of a protected maltotriose.
89Zr‐ImmunoPET companion diagnostics and their impact in clinical drug development
Authors: McKnight Brooke N. , Viola‐Villegas Nerissa T. 
Published: January 2018

Therapeutic monoclonal antibodies have been used in cancer treatment for 30 years, with around 24 mAb and mAb:drug conjugates approved by the FDA to date. Despite their specificity, efficacy has remained limited, which, in part, derails nascent initiatives towards precision medicine. An image‐guided approach to reinforce treatment decisions using immune positron emission tomography (immunoPET) companion diagnostic is warranted. This review provides a general overview of current translational research using Zr‐89 immunoPET and opportunities for utilizing and harnessing this tool to its full potential. Patient case studies are cited to illustrate immunoPET probes as tools for profiling molecular signatures. Discussions on its utility in reinforcing clinical decisions as it relates to histopathological tumor assessment and standard diagnostic methods, and its potential as predictive biomarkers, are presented. We finally conclude with an overview of practical considerations to its utility in the clinic.
Electrochemical monitoring of aflatoxin M1 in milk samples using silver nanoparticles dispersed on α‐cyclodextrin‐GQDs nanocomposite
Authors: Shadjou Rana , Hasanzadeh Mohammad , Heidar‐poor Mohammad , Shadjou Nasrin 
Published: January 2018

AbstractAflatoxins are potential food pollutants produced by fungi. One of important toxins is aflatoxin M1 (AFM1). A great deal of concern is associated with AFM1 toxicity. In the present study, an innovative electrochemical interface for quantitation of AFM1 based on ternary signal amplification strategy was fabricated. In this work, silver nanoparticles was electrodeposited onto green and biocompatible nanocomposite containing α‐cyclodextrin as conductive matrix and graphene quantum dots as amplification element. Therefore, a multilayer film based on α‐cyclodextrin, graphene quantum dots, and silver nanoparticles was exploited to develop a highly sensitive electrochemical sensor for detection of AFM1. Fully electrochemical methodology was used to prepare a transducer on a glassy carbon electrode, which provided a high surface area toward sensitive detection of AFM1. The surface morphology of electrode surface was characterized by high‐resolution field emission scanning electron microscope. The proposed sensing platform provides a simple tool for AFM1 detection. Under optimized condition, the calibration curve for AFM1 concentration was linear in 0.015mM to 25mM with low limit of quantification of 2μM. The practical analytical utility of the modified electrode was illustrated by determination of AFM1 in unprocessed milk samples.
Cerebral blood volume mapping with ferumoxytol in dynamic susceptibility contrast perfusion MRI: Comparison to standard of care
Authors: Varallyay Csanad G. , Nesbit Eric , Horvath Andrea , Varallyay Peter , Fu Rongwei , Gahramanov Seymur , Muldoon Leslie L. , Li Xin , Rooney William D. , Neuwelt Edward A. 
Published: January 2018

BackgroundCerebral blood volume (CBV) mapping with a dynamic susceptibility contrast (DSC) perfusion technique has become a clinical tool in diagnosing and follow‐up of brain tumors. Ferumoxytol, a long‐circulating iron oxide nanoparticle, has been tested for CBV mapping, but the optimal dose has not been established.PurposeTo compare ferumoxytol DSC of two different doses to standard of care gadoteridol by analyzing time–intensity curves and CBV maps in normal‐appearing brain regions.Study TypeRetrospective.SubjectsFifty‐four patients with various brain disorders.Field Strength/Sequence3T MRI. DSC‐MRI was performed with 0.1 mmol/kg gadoteridol and 1 day later with ferumoxytol in doses of 1 or 2 mg/kg.AssessmentSignal changes during first pass, relative CBV (rCBV) in normal‐appearing thalamus, putamen, and globus pallidus, and contrast‐to‐noise ratio (CNR) of the CBV maps were compared between gadoteridol and various doses of ferumoxytol using an automated method. To subjectively assess the quality of the CBV maps, two blinded readers also assessed visual conspicuity of the putamen.Statistical TestsLinear mixed effect model was used for statistical comparison.ResultsCompared to gadoteridol, 1 mg/kg ferumoxytol showed no difference in CNR (P = 0.6505), peak ΔR2*, and rCBV in the putamen (P = 0.2669, 0.0871) or in the thalamus (P = 0.517, 0.9787); 2 mg/kg ferumoxytol increased peak ΔR2* as well as the CNR (P < 0.0001), but also mildly increased rCBV in putamen and globus pallidus (P = 0.0005, 0.0012). Signal intensities during first pass remained highly above the noise level, with overlapping of 95% confidence intervals with noise only in 3 out of 162 tested regions. Compared to gadoteridol, the visual image quality showed mild improvement with 1 mg/kg (P = 0.02) and marked improvement with 2 mg/kg ferumoxytol (P < 0.0001).Data Conclusion1 mg/kg ferumoxytol provides similar imaging results to standard gadoteridol for DSC‐MRI, and 2 mg/kg has a benefit of increased CNR, but may also result in mildly increased rCBV values.Level of Evidence: 3Technical Efficacy: Stage 1J. MAGN. RESON. IMAGING 2018;48:441–448.
Characterization of Adrenal Lesions on Unenhanced MRI Using Texture Analysis: A Machine‐Learning Approach
Authors: Romeo Valeria , Maurea Simone , Cuocolo Renato , Petretta Mario , Mainenti Pier Paolo , Verde Francesco , Coppola Milena , Dell'Aversana Serena , Brunetti Arturo 
Published: January 2018

BackgroundAdrenal adenomas (AA) are the most common benign adrenal lesions, often characterized based on intralesional fat content as either lipid‐rich (LRA) or lipid‐poor (LPA). The differentiation of AA, particularly LPA, from nonadenoma adrenal lesions (NAL) may be challenging. Texture analysis (TA) can extract quantitative parameters from MR images. Machine learning is a technique for recognizing patterns that can be applied to medical images by identifying the best combination of TA features to create a predictive model for the diagnosis of interest.Purpose/HypothesisTo assess the diagnostic efficacy of TA‐derived parameters extracted from MR images in characterizing LRA, LPA, and NAL using a machine‐learning approach.Study TypeRetrospective, observational study.Population/Subjects/Phantom/Specimen/Animal ModelSixty MR examinations, including 20 LRA, 20 LPA, and 20 NAL.Field Strength/SequenceUnenhanced T1‐weighted in‐phase (IP) and out‐of‐phase (OP) as well as T2‐weighted (T2‐w) MR images acquired at 3T.AssessmentAdrenal lesions were manually segmented, placing a spherical volume of interest on IP, OP, and T2‐w images. Different selection methods were trained and tested using the J48 machine‐learning classifiers.Statistical TestsThe feature selection method that obtained the highest diagnostic performance using the J48 classifier was identified; the diagnostic performance was also compared with that of a senior radiologist by means of McNemar's test.ResultsA total of 138 TA‐derived features were extracted; among these, four features were selected, extracted from the IP (Short_Run_High_Gray_Level_Emphasis), OP (Mean_Intensity and Maximum_3D_Diameter), and T2‐w (Standard_Deviation) images; the J48 classifier obtained a diagnostic accuracy of 80%. The expert radiologist obtained a diagnostic accuracy of 73%. McNemar's test did not show significant differences in terms of diagnostic performance between the J48 classifier and the expert radiologist.Data ConclusionMachine learning conducted on MR TA‐derived features is a potential tool to characterize adrenal lesions.Level of Evidence: 4Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2018.
Population growth and status of california sea lions
Authors: Laake Jeffrey L. , Lowry Mark S. , DeLong Robert L. , Melin Sharon R. , Carretta James V. 
Published: January 2018

ABSTRACTThe California sea lion (Zalophus californianus) population in the United States has increased steadily since the early 1970s. The Marine Mammal Protection Act of 1972 (MMPA) established criteria for management of marine mammals based on the concept of managing populations within the optimal sustainable population (OSP), defined as a range of abundance from the maximum net productivity level (MNPL) to carrying capacity (K). Recent declines in California sea lion pup production and survival suggest that the population may have stopped growing, but the status of the population relative to OSP and MNPL is unknown. We used a time series of pup counts from 1975 to 2014 and a time series of mark‐release‐resight‐recovery data from 1987 to 2015 for survival estimates to numerically reconstruct the population and evaluate the current population status relative to OSP using a generalized logistic model. We demonstrated that the population size in 2014 was above MNPL and within its OSP range. However, we also showed that population growth can be dramatically decreased by increasing sea surface temperature associated with El Niño events or similar regional ocean temperature anomalies. In this analysis we developed a critical tool for management of California sea lions that provides a better understanding of the population dynamics and a scientific foundation upon which to base management decisions related to complex resource issues involving this species. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.
Reversible Semicrystalline Polymer as Actuators Driven by Organic Solvent Vapor
Authors: Hou Guohui , Wang Fengle , Qu Zhe , Cheng Zhiqiang , Zhang Yingchao , Cai Shisheng , Xie Tao , Feng Xue 
Published: January 2018

AbstractA semicrystalline polymer actuator, which is responsive to solvent vapor with fast and large scale locomotion, is described. The thermoset semicrystalline polymer can be easily synthesized from crystallizable polyester segment poly (ε‐caprolactone) and isophorone diisocyanate trimer. Organic solvent vapor is used to induce the reversible swelling‐crystallization conversion of the crystallizable polyester segment, resulting in its expansion/shrinkage. The contraction of the polymer actuator (1 mm thick) needs only ≈4 s in room temperature. When exposed to air the polymer actuator can exhibit a fast self‐oscillation. Then, a soft crawler based on this polymer is demonstrated. Driven by organic solvent it walks rapidly and steadily. The microscope images show the fast swelling‐crystallization conversion that gives rise to reversible shape changes of the polymer.
Disulfide bond based polymeric drug carriers for cancer chemotherapy and relevant redox environments in mammals
Authors: Zhang Pei , Wu Jilian , Xiao Fengmei , Zhao Dujuan , Luan Yuxia 
Published: January 2018

AbstractIncreasing numbers of disulfide linkage‐employing polymeric drug carriers that utilize the reversible peculiarity of this unique covalent bond have been reported. The reduction‐sensitive disulfide bond is usually employed as a linkage between hydrophilic and hydrophobic polymers, polymers and drugs, or as cross‐linkers in polymeric drug carriers. These polymeric drug carriers are designed to exploit the significant redox potential difference between the reducing intracellular environments and relatively oxidizing extracellular spaces. In addition, these drug carriers can release a considerable amount of anticancer drug in response to the reducing environment when they reach tumor tissues, effectively improving antitumor efficacy. This review focuses on various disulfide linkage‐employing polymeric drug carriers. Important redox thiol pools, including GSH/GSSG, Cys/CySS, and Trx1, as well as redox environments in mammals, will be introduced.
Stachyose Improves Inflammation through Modulating Gut Microbiota of High‐Fat Diet/Streptozotocin‐Induced Type 2 Diabetes in Rats
Authors: Liu Guimei , Bei Jia , Liang Li , Yu Guoyong , Li Lu , Li Quanhong 
Published: January 2018

ScopeThe present study is undertaken to assess the effects of stachyose (STS) on type 2 diabetes in rats and changes in the gut microbiota compared to metformin (MET).Methods and resultsThe type 2 diabetic model is successfully established via a high‐fat diet /streptozotocin in Wistar rats, and STS or MET is administered for 4 weeks. Blood is collected to analyze biochemical parameters, pancreas for mRNA expression of related gene, and contents of colon for gut microbiota. STS or MET decreases serum LPS, mRNA expression of IL‐6, and tumor necrosis factor‐α (TNF‐α). In addition, STS and MET show a similar shifting of the structure of the gut microbiota and a selective enrichment of key species. At the genus level, STS shows selective enrichment of Phascolarctobacterium, Bilophila, Oscillospira, Turicibacter, and SMB5, but MET demonstrates a selective effect on Sutterella, Prevotella, 02d06, and rc4. The correlation analysis indicates that STS and MET decrease IL‐6 and TNF‐α and increase Akt/PI3K expression, which are relative to key species of gut microbiota.ConclusionSTS decreases pancreatic mRNA expression of IL‐6 and TNF‐α via key species of gut microbiota. The mechanism of this effect is similar to that of MET.
High frequency of MGUS in DSP
Authors: Abraham Alon , Barnett Carolina , Katzberg Hans D. , Lovblom Leif E. , Perkins Bruce A. , Bril Vera 
Published: January 2018

AbstractIntroduction: Monoclonal gammopathy has been reported in several polyneuropathies. In this study, we sought to explore the frequency and characteristics of monoclonal gammopathy in patients with diabetic sensorimotor polyneuropathy (DSP). Methods: Patients with type 1 and type 2 diabetes mellitus (DM 1, DM 2) and controls without diabetes were evaluated between November 2008 and December 2013. Results: Fifty controls, 66 patients with DM 1, and 106 patients with DM 2 were included, with average ages of 43 ± 18, 45 ± 17, and 65 ± 10 years, respectively; the frequency of monoclonal gammopathy was 0%, 8%, and 15%, respectively. In patients with DSP, the frequency of monoclonal gammopathy increased to 14% in DM 1 and 21% in DM 2; the most common monoclonal proteins were immunoglobulin (Ig) M and IgG, respectively. Discussion: DSP might be associated with a high frequency of monoclonal gammopathy, with different characteristics in DM 1 and in DM 2. Muscle Nerve 57: 1018–1021, 2018
Validation of The Individualized Neuromuscular Quality of Life in Japanese patients with myotonic dystrophy
Authors: Fujino Haruo , Saito Toshio , Takahashi Masanori P. , Takada Hiroto , Nakayama Takahiro , Ogata Katsuhisa , Rose Michael R. , Imura Osamu , Matsumura Tsuyoshi 
Published: January 2018

ABSTRACTIntroduction: The Individualized Neuromuscular Quality of Life (INQoL) is used to measure the quality of life (QoL) of patients with neuromuscular disease. We conducted this study to translate and validate the Japanese version of the INQoL in patients with myotonic dystrophy. Methods: Forward and backward translation, patient testing, and psychometric validation were performed. We used the 36‐Item Short Form Health Survey (SF‐36) and the modified Rankin scale for concurrent validation. Results: The Japanese INQoL was administered to 90 adult patients. The coefficients for internal consistency and test‐retest reliability were adequately high in most domains (Cronbach α 0.88–0.96 and intraclass coefficient 0.64–0.99). INQoL domains were moderately to strongly associated with relevant SF‐36 subscales (Spearman's ρ −0.23 to −0.74). Symptom severity, disease duration, employment status, and use of a ventilator influenced overall QoL. Discussion: The INQoL is a reliable and validated measure of QoL for Japanese patients with myotonic dystrophy. Muscle Nerve 58: 56–63, 2018
Risk factors for stress urinary incontinence recurrence after single‐incision sling
Authors: Palmieri Stefania , Frigerio Matteo , Spelzini Federico , Manodoro Stefano , Milani Rodolfo 
Published: January 2018

AimsThe aim of the study was to identify in a pure stress urinary incontinence (SUI) population risk factors for recurrence after single‐incision slings (SIS).MethodsThis retrospective study analyzed women with complaints of SUI symptoms and urodynamically proven SUI. Exclusion criteria were recurrent SUI, overactive bladder syndrome/detrusor overactivity, preoperative postvoid residual >100 mL, reduced urethral mobility (<10° at the Q‐tip test), concomitant anterior prolapse >I stage and previous history of radical pelvic surgery. Objective cure rate was assessed with stress test.ResultsA total of 192 patients were analyzed. Objective cure rate was obtained in 86.5% of patients. According to univariate analysis, recurrences had higher prevalence of severe ICIQ‐SF score (≥18 points), higher prevalence of reduced urethral mobility (Qtip ≤30°), higher prevalence of low detrusor pressures during voiding phase (opening pressure <15 cmH2O, pressure at maximum flow <20 cmH2O, closing pressure <15 cmH2O), and higher prevalence of postoperative complications According to multivariate analysis ICIQ‐SF score ≥18 points (P = 0.02; OR = 2.7) and detrusor pressure at maximum flow <20 cmH2O (P < 0.01; OR = 3.6) resulted as independent risk factors for SUI recurrence (Table 3). A trend was found for urethral mobility ≤30° (P = 0.07; OR = 2.2).ConclusionsOur study identifies SUI severity expressed with ICIQ‐SF scores and low detrusor pressure at maximum flow as independent risk factors for SUI recurrence after SIS implantation while only a trend was found for reduced urethral mobility. Therefore, preoperative assessment of symptoms and urodynamics evaluation may play a key role in improving preoperative counseling and tailoring surgical treatment.
Analytical fuel‐optimal impulsive reconfiguration of formation‐flying satellites: A revisit and new results
Authors: Li Jing 
Published: January 2018

SummaryThis paper investigates fuel‐optimal impulsive reconfiguration of formation‐ flying satellites near circular reference orbit. The author's previous work is extended to the in‐plane reconfiguration, as well as reconfigurations between different formation configurations. Analytical solutions are derived and their optimality is problem dependent. A novel kind of fuel‐optimal solutions, whose associated primer vector magnitude is identically equal to 1, has been obtained for reconfigurations with nonoptimal analytical solutions. Numerical examples are given to illustrate and validate the obtained results.
Comparing physical activity in individuals with overweight/obesity with and without binge eating disorder
Authors: Barber J. A. , Ivezaj V. , Barnes R. D. 
Published: January 2018

SummaryObjectiveDifferential participation in physical activity (PA) may partially explain the health discrepancies between individuals with or without binge‐eating disorder (BED). Yet, little is known about the PA habits of individuals with overweight/obesity and how those patterns may differ based on BED status. PA patterns and exercise self‐efficacy were examined in individuals with overweight/obesity, with and without BED.DesignNinety‐seven participants with overweight/obesity self‐reported their PA via the Godin Leisure‐Time Questionnaire and the Paffenbarger PA Questionnaire. Exercise self‐efficacy was assessed with the Marcus 5‐item Exercise Self‐Efficacy scale. Based on the Eating Disorder Examination, 27.8% (n = 27) of the participants met BED criteria. Participants were primarily female (n = 75, 77.3%), on average 47.5 years old (standard deviation = 10.4), and predominantly White/Not Hispanic (n = 67, 69.1%) or African–American/Not Hispanic (n = 18, 18.6%).ResultsHierarchical regressions, accounting for significant differences in body mass index between those with and without BED, showed that the Marcus 5‐item Exercise Self‐Efficacy Scale (but not BED status) was significantly related to PA. BED status also was unrelated to likelihood of reaching Centres for Disease Control PA guidelines, and 44.3% of all participants reported no participation in weekly sports/recreation activities.ConclusionsBoth groups participated in relatively little purposeful and moderate/strenuous PA. Exercise self‐efficacy may be important to assess and address among treatment seeking individuals with and without BED who struggle with excess weight.