bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concise Review: Process Development Considerations for Cell Therapy
Authors: Campbell Andrew , Brieva Thomas , Raviv Lior , Rowley Jon , Niss Knut , Brandwein Harvey , Oh Steve , Karnieli Ohad 
Published: August 2015

Abstract

The development of robust and well-characterized methods of production of cell therapies has become increasingly important as therapies advance through clinical trials toward approval. A successful cell therapy will be a consistent, safe, and effective cell product, regardless of the cell type or application. Process development strategies can be developed to gain efficiency while maintaining or improving safety and quality profiles. This review presents an introduction to the process development challenges of cell therapies and describes some of the tools available to address production issues. This article will provide a summary of what should be considered to efficiently advance a cellular therapy from the research stage through clinical trials and finally toward commercialization. The identification of the basic questions that affect process development is summarized in the target product profile, and considerations for process optimization are discussed. The goal is to identify potential manufacturing concerns early in the process so they may be addressed effectively and thus increase the probability that a therapy will be successful.

Significance
The present study contributes to the field of cell therapy by providing a resource for those transitioning a potential therapy from the research stage to clinical and commercial applications. It provides the necessary steps that, when followed, can result in successful therapies from both a clinical and commercial perspective.
Perforation of acquired small bowel diverticulum
Authors: Schock Jeffrey , Mainster Harris 
Published: August 2015

Abstract
A 77-year old woman was seen with an unusual pathologic entity after emergentabdominal exploration-a 'ruptured small bowel div·erticulum. This patient had a known previous history of colonic diverticulosis when she had acute onset of severe abdominal pain. The patient underwent an exploratory laparotomy with resection of representative segments of small and large bowel. The large bowel had evidence of diverticulosis, while the small bowel resected segment had evidence of diverticulitis with rupture. An extensive review of the literature revealed a very small number of reported cases in the world literature (less than 150 cases). We reviewed the history of reported cases of ruptured and nonruptured small bowel diverticular disease, as well as this case.
Professional Emotion Management as a Rehearsal Process
Authors: Bergman Blix Stina 
Published: August 2015

The work of stage actors has long been used as a simile for every day role playing, generating theoretical concepts to describe how people work to present themselves in general and how they manage their emotions in particular. Building on this tradition, this article analyses professional stage actors’ deliberate emotion management as an embodied professionalisation process, focusing the relation between emotional experience and expression through the concepts of decoupling, double agency and habituation. Observations and interviews with theatre actors rehearsing for a role revealed how they gradually develop a capacity for double agency, decoupling the experience from the expression of emotions, which are eventually habituated in a form adapted to the role character. This process of professionalising emotion management is beneficial to the presentation of role-appropriate emotions and furthers the ability to cope with the endeavour of managing emotions at work. Implications for professions outside the artistic domain are discussed.
Keywords: decoupling, deep acting, embodiment, emotion management, habituation, stage actors, surface acting
Low‐latitude 10 eV electrons: Nighttime plasma line as a new research capability
Authors: Carlson Herbert C. , Djuth Frank T. , Perillat Phil , Sulzer Mike 
Published: August 2015

AbstractThe incoherent scatter radar (ISR) plasma line (PL) in daylight is excited by photoelectrons. Measurement of its intensity (κTp) has long been used for their study. At night, despite the absence of any other excitation mechanism, the PL intensity should have a thermal amplitude level κTe, determined by the electron gas temperature Te. To the contrary Carlson et al. (1982) found nighttime PLs over Arecibo enhanced >3 times above thermal intensities despite the absence of any known causative mechanism. Here we present discovery that nighttime PLs frequently recur, with quite variable enhancement. In the absence of direct solar EUV, these enhanced PLs must be produced by particle precipitation, manifested by the presence of variable recurring F region ~10 eV electron fluxes. We see this as offering a new tool for space environment studies, opening a new era of particle precipitation research and ISR calibration.
Network analysis of geomagnetic substorms using the SuperMAG database of ground‐based magnetometer stations
Authors: Dods J. , Chapman S. C. , Gjerloev J. W. 
Published: August 2015

AbstractThe overall morphology and dynamics of magnetospheric substorms is well established in terms of the observed qualitative auroral features seen in ground‐based magnetometers. This paper focuses on the quantitative characterization of substorm dynamics captured by ground‐based magnetometer stations. We present the first analysis of substorms using dynamical networks obtained from the full available set of ground‐based magnetometer observations in the Northern Hemisphere. The stations are connected in the network when the correlation between the vector magnetometer time series from pairs of stations within a running time window exceeds a threshold. Dimensionless parameters can then be obtained that characterize the network and by extension, the spatiotemporal dynamics of the substorm under observation. We analyze four isolated substorm test cases as well as a steady magnetic convection (SMC) event and a day in which no substorms occur. These test case substorms are found to give a consistent characteristic network response at onset in terms of their spatial correlation. Such responses are differentiable from responses to the SMC event and nonsubstorm times. We present a method to optimize network parametrization with respect to the different individual station responses, the spatial inhomogeneity of stations in the Northern Hemisphere, and the choice of correlation window sizes. Our results suggest that dynamical network analysis has potential to quantitatively categorize substorms.
Sensitivity of the mean and variability of Indian summer monsoon to land surface schemes in RegCM4: Understanding coupled land‐atmosphere feedbacks
Authors: Halder Subhadeep , Dirmeyer Paul A. , Saha Subodh Kumar 
Published: August 2015

AbstractA relatively simple land surface model, the Biosphere‐Atmosphere Transfer Scheme (BATS) and the more complex Community Land Model (CLM3.5) coupled to RegCM4 are used to investigate land‐atmosphere feedback processes during the Indian summer monsoon. Model simulations for 27 years show that the mean and interannual variability of rainfall and surface air temperature are affected significantly due to differences in the formulation of evapotranspiration and hydrological processes between BATS and CLM3.5, prescribed land use, land cover data and changes in net radiation. RegCM4 with CLM3.5 (RCLM) shows a reduction in surface moisture flux and precipitation but an increase in surface air temperature over most parts of India as compared to RegCM4 with BATS (RBAT). In terms of the mean and interannual variability of rainfall over central India, RBAT performs better than RCLM. Evapotranspiration over central India is found to be less (more) sensitive to soil wetness variations in RCLM (RBAT) compared to the multimodel estimate from the Global Soil Wetness Project, that is mainly attributed to the differences in ground evaporation and transpiration. Changes in evaporation efficiency between the models also lead to a reduction in the land‐atmosphere coupling strength for precipitation in RCLM. Furthermore, such changes decrease the convective instability over central and eastern India in RCLM leading to weakened convection, reduced large‐scale moisture convergence and precipitation over land. Observations of soil moisture, surface fluxes, and radiation are needed for better understanding and improvement of coupled land‐atmosphere feedbacks in models during the Indian summer monsoon.
Remote sensing measurements of thermokarst subsidence using InSAR
Authors: Liu L. , Schaefer K. M. , Chen A. C. , Gusmeroli A. , Zebker H. A. , Zhang T. 
Published: August 2015

AbstractThawing of ice‐rich permafrost followed by surface subsidence results in irregular, depressed landforms known as thermokarst. Many remote sensing studies have identified thermokarst landforms and mapped their changes. However, the intrinsic dynamic thermokarst process of surface subsidence remains a challenge to quantify and is seldom examined using remote sensing methods. In this study we used spaceborne interferometric synthetic aperture radar (InSAR) data to map surface subsidence trends at a thermokarst landform located near Deadhorse on the North Slope of Alaska. A pipeline access road constructed in the 1970s triggered the thawing of the permafrost, causing subsequent expansion of the thermokarst landform. Using Phased Array type L band Synthetic Aperture Radar images acquired by the Advanced Land Observing Satellite‐1, our InSAR analysis reveals localized thermokarst subsidence of 2–8 cm/yr between 2006 and 2010, equivalent to an ice volume loss of about 1.2 × 107 m3/yr. Comparisons between InSAR subsidence trends and lidar microtopography suggest a characteristic time of 8 years of thermokarst development. We also quantitatively explain the difficulty, uncertainties, and possible biases in separating thermokarst‐induced, irreversible subsidence from cyclic seasonal deformation. Our study illustrates that InSAR is an effective tool for mapping and studying active thermokarst processes and quantifying ice loss.
Long‐Term Followup of a Multicenter Cohort of 101 Patients With Eosinophilic Granulomatosis With Polyangiitis (Churg‐Strauss)
Authors: Durel Cécile‐Audrey , Berthiller Julien , Caboni Silvia , Jayne David , Ninet Jacques , Hot Arnaud 
Published: August 2015

ObjectiveTo assess the long‐term outcome in eosinophilic granulomatosis with polyangiitis (Churg‐Strauss) (EGPA).MethodsA total of 101 patients fulfilling the American College of Rheumatology criteria for EGPA were included between 1990 and 2011. Clinical features, antineutrophil cytoplasm autoantibodies (ANCAs), and Five‐Factors Score (FFS) were assessed at diagnosis. Overall and cumulative survival rates, relapse‐free survival, and sequelae were studied based on ANCA status and FFS.ResultsThe rate of cardiomyopathy did not differ according to ANCA status. A total of 79.6% of patients achieved first remission, but 81.1% relapsed. ANCA‐positive patients did not relapse more frequently but exhibited more severe disease with mononeuritis (P = 0.0004) and renal involvement (P = 0.02). Being Italian was the only prognostic factor associated with a higher relapse‐free survival (P = 0.01), thanks to a longer maintenance of immunosuppressive drugs, suggesting the need for prolonged low‐dose corticosteroids. Overall, survival reached 93.1% after a median followup of 6 years. No factor was associated with mortality, but patients over age 65 years with cardiomyopathy or ANCA positivity had more serious outcomes. Sequelae affected 83.2% of patients. Ear, nose, and throat (ENT) involvement was a protective factor for renal (P = 0.04) and cardiac (P = 0.03) morbidity. ANCA positivity was correlated with chronic kidney disease (P = 0.03) and chronic neurologic disability (P = 0.02).ConclusionThe actual challenges of EGPA management concern morbidity prevention and quality of life improvement. Long‐term corticosteroid treatment appears to reduce relapse risk. ENT involvement is associated with less renal and cardiac morbidity. ANCA positivity predicts renal and neurologic damage.
On Modelling Minimal Disease Activity
Authors: Jackson Christopher H. , Su Li , Gladman Dafna D. , Farewell Vernon T. 
Published: August 2015

ObjectiveTo explore methods for statistical modelling of minimal disease activity (MDA) based on data from intermittent clinic visits.MethodsThe analysis was based on a 2‐state model. Comparisons were made between analyses based on “complete case” data from visits at which MDA status was known, and the use of hidden model methodology that incorporated information from visits at which only some MDA defining criteria could be established. Analyses were based on an observational psoriatic arthritis cohort.ResultsWith data from 856 patients and 7,024 clinic visits, analysis was based on virtually all visits, although only 62.6% provided enough information to determine MDA status. Estimated mean times for an episode of MDA varied from 4.18 years to 3.10 years, with smaller estimates derived from the hidden 2‐state model analysis. Over a 10‐year period, the estimated expected times spent in MDA episodes of longer than 1 year was 3.90 to 4.22, and the probability of having such an MDA episode was estimated to be 0.85 to 0.91, with longer times and greater probabilities seen with the hidden 2‐state model analysis.ConclusionA 2‐state model provides a useful framework for the analysis of MDA. Use of data from visits at which MDA status can not be determined provide more precision, and notable differences are seen in estimated quantities related to MDA episodes based on complete case and hidden 2‐state model analyses. The possibility of bias, as well as loss of precision, should be recognized when complete case analyses are used.
Long‐Term Safety and Efficacy of Epratuzumab in the Treatment of Moderate‐to‐ Severe Systemic Lupus Erythematosus: Results From an Open‐Label Extension Study
Authors: Wallace D. J. , Hobbs K. , Clowse M. E. B. , Petri M. , Strand V. , Pike M. , Merrill J. T. , Leszczyński P. , Neuwelt C. M. , Jeka S. , Houssiau F. , Keiserman M. , Ordi‐Ros J. , Bongardt S. , Kilgallen B. , Galateanu C. , Kalunian K. , Furie R. , Gordon C. 
Published: August 2015

ObjectiveThe primary objective was to assess the long‐term safety of repeated courses of epratuzumab therapy in patients with moderate‐to‐severe systemic lupus erythematosus. Secondary objectives were to assess long‐term efficacy and health‐related quality of life (HRQOL).MethodsEligible patients from the 12‐week, phase IIb, randomized, placebo‐controlled EMBLEM study enrolled into the open‐label extension (OLE) study, SL0008. In the SL0008 study, patients received 1,200 mg epratuzumab infusions at weeks 0 and 2 of repeating 12‐week cycles, plus standard of care. Safety measures included treatment‐emergent adverse events (TEAEs) and serious TEAEs. Efficacy measures included combined treatment response, the British Isles Lupus Assessment Group score, the Systemic Lupus Erythematosus Disease Activity Index score, and the physician's and patient's global assessment of disease activity. Total daily corticosteroid dose and HRQOL (by the Short Form 36 health survey) were also assessed.ResultsA total of 113 of the 203 patients (55.7%) who entered the SL0008 study continued epratuzumab therapy until study closure (total cumulative exposure: 381.3 patient‐years, median exposure: 845 days, and maximum exposure: 1,185 days/approximately 3.2 years). TEAEs were reported in 192 patients (94.6%); most common were infections and infestations (68.0%, 138 patients). Serious TEAEs were reported in 51 patients (25.1%), and 14 patients (6.9%) had serious infections. In patients treated for 108 weeks (n = 116), the median corticosteroid dose was reduced from 10.0 mg/day at OLE screening to 5.0 mg/day at week 108. Improvements in efficacy and HRQOL measures in EMBLEM were maintained in the OLE, while placebo patients exhibited similar improvements in disease activity upon a switch to epratuzumab.ConclusionOpen‐label epratuzumab treatment was well tolerated for up to 3.2 years, and associated with sustained improvements in disease activity and HRQOL, while steroids were reduced.
Association of Light‐Intensity Physical Activity With Lower Cardiovascular Disease Risk Burden in Rheumatoid Arthritis
Authors: Khoja Samannaaz S. , Almeida Gustavo J. , Chester Wasko Mary , Terhorst Lauren , Piva Sara R. 
Published: August 2015

ObjectiveTo characterize physical activity (PA) in individuals with rheumatoid arthritis (RA) and to determine the associations between PA participation at light to moderate intensities and cardiovascular disease risk factors, disability, and disease activity.MethodsThe cross‐sectional study used data from 2 RA cohorts. PA was measured using an accelerometry‐based activity monitor, recording minutes/day spent in sedentary (≤1 metabolic equivalent [MET]), very light (1.1–1.9 METs), light (2–2.9 METs), and moderate activities (≥3 METs). Cardiovascular markers included body mass index, blood pressure, insulin resistance, and lipid profile. Disability and disease activity were measured using the Health Assessment Questionnaire (HAQ) and the Disease Activity Score in 28 joints (DAS28), respectively. Associations between PA at each intensity level and health markers were assessed by multiple linear regression models, adjusted for age, sex, and cohort.ResultsNinety‐eight subjects (mean ± SD age 58 ± 9 years, 85% female) were included. Subjects spent 9.8 hours/day being sedentary, 3.5 hours/day engaged in very light PA, 2.1 hours/day engaged in light PA, and 35 minutes/day engaged in moderate PA. Only 17% were physically active (≥150 minutes/week of moderate PA in 10‐minute bouts). Regression models showed that very light, light, and moderate PA were inversely associated with most cardiovascular disease risk factors and HAQ and DAS28 scores (R2Δ range 0.04–0.52, P < 0.05). The associations between PA and cardiovascular disease markers were either equivalent or stronger at very light and light intensities, as compared to moderate intensity.ConclusionIndividuals with RA are mostly active at very light and light intensities. PA at these intensity levels associates favorably with cardiovascular markers and lower disability and disease activity in RA.
Fatigue in Primary Sjögren's Syndrome: Clinical, Laboratory, Psychometric, and Biologic Associations
Authors: Karageorgas Theofanis , Fragioudaki Sofia , Nezos Adrianos , Karaiskos Dimitrios , Moutsopoulos Haralampos M. , Mavragani Clio P. 
Published: August 2015

ObjectiveTo identify independent contributors of fatigue in primary Sjögren's syndrome (SS) patients, taking into account clinical, laboratory, and psychological features, and to explore the potential role of interferon (IFN)–induced gene indoleamine 2,3‐dioxygenase (IDO‐1), anti–21‐hydroxylase (anti‐21[OH]) antibodies, and soluble BAFF.MethodsDetailed clinical and laboratory characteristics were recorded for 106 primary SS patients. The Functional Assessment of Chronic Illness Therapy–Fatigue, Zung Depression Scale, State‐Trait Anxiety Inventory, Eysenck Personality Questionnaire Scale, and Athens Insomnia Scale were adopted to assess fatigue, depression, anxiety, and sleep disturbances, respectively. Peripheral whole blood expression levels of IDO‐1, as well as type I and II IFN‐induced genes were calculated using quantitative reverse transcriptase–polymerase chain reaction. Serum anti‐21(OH) antibodies and soluble BAFF levels were determined by a radioimmunoassay and an enzyme‐linked immunosorbent assay, respectively. Univariate and multivariate models were performed to identify determinants of fatigue.ResultsFatigue was detected in 32 of 106 (30.2%) primary SS patients. In univariate analysis, fatigue was associated with arthralgias/myalgias, fibromyalgia hydroxychloroquine therapy, both state and trait anxiety scores, depression, and neuroticism, as well as impaired sleep patterns. Multivariate analysis revealed neuroticism (odds ratio [OR] 6.9, [95% confidence interval (95% CI) 1.7–28.0]), depression (OR 3.0 [95% CI 0.8–11.0]), and fibromyalgia (OR 5.5 [95% CI 1.1–27.7]) as independent fatigue contributors. Soluble BAFF levels, anti‐21(OH) autoantibodies, and IDO‐1 messenger RNA expression did not significantly differ between fatigued and nonfatigued primary SS patients.ConclusionDepression, neuroticism, and fibromyalgia play a major role in primary SS–associated fatigue and should be addressed in clinical practice, with active collaboration between rheumatologists and mental health professionals. Further studies are warranted in order to explore underlying pathophysiologic pathways that might explain fatigue in the setting of primary SS.
Inkjet‐Printed Alginate Microspheres as Additional Drug Carriers for Injectable Hydrogels
Authors: CHUNG JOHNSON H. Y. , NAFICY SINA , WALLACE GORDON G. , NAFICY SINA , O'LEARY STEPHEN 
Published: August 2015

ABSTRACTLocal delivery of bioactive molecules to the inner ear via diffusion through the round window membrane is becoming an attractive approach to treat sensorineural hearing loss compared to systemic drug administration. Pluronics® (Lutrol F127) are a class of thermosensitive hydrogels that remain liquid prior to injection and rapidly gel under physiological conditions. They are, however, limited to short‐term drug release due to rapid hydrolysis in aqueous solution. Therefore, the aim of this study was to investigate an approach, using an ink‐jet printing system, to sustain the drug release by incorporating hydrogel microspheres within Lutrol F127. Various concentrations of Lutrol F127 and calcium chloride (CaCl2) were examined by rheology to determine the optimum combinations to use for injection and then blended with inkjet‐printed alginate microspheres. Drug release (FITC‐Dextran) from Lutrol F127 alone reached completion in less than 24 h. Release from alginate spheres alone showed a burst release and reached 100% in 6 h. Interestingly, the incorporation of microspheres within Lutrol F127 allowed a more sustained release profile and a slower burst release. By varying the quantity of microspheres, concentration of alginate, or ionic cross‐linking ratio, the release profile can be adjusted to suit the desired application.
Asymmetric Amination of 3‐(2‐Oxoindolin‐3‐ylidene)butanoates Catalyzed by a Cinchona‐Derived Alkaloid
Authors: Zheng Chen , Chen Wen‐Xue , Chen Fen‐Er 
Published: August 2015

AbstractHere we report the asymmetric amination of 3‐(2‐oxoindolin‐3‐ylidene)butanoates catalyzed by a cinchona‐derived alkaloid, yielding products with an N‐containing stereocenter in high yields and moderate enantioselectivity. The developed process could be an attractive approach for the synthesis of chiral amino acids.
In Vivo Endoscopic Tissue Identification by Rapid Evaporative Ionization Mass Spectrometry (REIMS)
Authors: Balog Julia , Kumar Sacheen , Alexander James , Golf Ottmar , Huang Juzheng , Wiggins Tom , Abbassi‐Ghadi Nima , Enyedi Attila , Kacska Sandor , Kinross James , Hanna George B. , Nicholson Jeremy K. , Takats Zoltan 
Published: August 2015

AbstractGastrointestinal cancers are a leading cause of mortality, accounting for 23 % of cancer‐related deaths worldwide. In order to improve outcomes from these cancers, novel tissue characterization methods are needed to facilitate accurate diagnosis. Rapid evaporative ionization mass spectrometry (REIMS) is a technique developed for the in vivo classification of human tissue through mass spectrometric analysis of aerosols released during electrosurgical dissection. This ionization technique was further developed by utilizing surface induced dissociation and was integrated with an endoscopic polypectomy snare to allow in vivo analysis of the gastrointestinal tract. We tested the classification performance of this novel endoscopic REIMS method in vivo. It was shown to be capable of differentiating between healthy layers of the intestinal wall, cancer, and adenomatous polyps based on the REIMS fingerprint of each tissue type in vivo.