bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contact‐facilitated drug delivery with Sn2 lipase labile prodrugs optimize targeted lipid nanoparticle drug delivery
Authors: Pan Dipanjan , Pham Christine T.N. , Weilbaecher Katherine N. , Tomasson Michael H. , Wickline Samuel A. , Lanza Gregory M. 
Published: August 2015

Sn2 lipase labile phospholipid prodrugs in conjunction with contact‐facilitated drug delivery offer an important advancement in Nanomedicine. Many drugs incorporated into nanosystems, targeted or not, are substantially lost during circulation to the target. However, favorably altering the pharmacokinetics and volume of distribution of systemic drug delivery can offer greater efficacy with lower toxicity, leading to new prolonged‐release nanoexcipients. However, the concept of achieving Paul Erhlich's inspired vision of a ‘magic bullet’ to treat disease has been largely unrealized due to unstable nanomedicines, nanosystems achieving low drug delivery to target cells, poor intracellular bioavailability of endocytosed nanoparticle payloads, and the substantial biological barriers of extravascular particle penetration into pathological sites. As shown here, Sn2 phospholipid prodrugs in conjunction with contact‐facilitated drug delivery prevent premature drug diffusional loss during circulation and increase target cell bioavailability. The Sn2 phospholipid prodrug approach applies equally well for vascular constrained lipid‐encapsulated particles and micelles the size of proteins that penetrate through naturally fenestrated endothelium in the bone marrow or thin‐walled venules of an inflamed microcirculation. At one time Nanomedicine was considered a ‘Grail Quest’ by its loyal opposition and even many in the field adsorbing the pains of a long‐learning curve about human biology and particles. However, Nanomedicine with innovations like Sn2 phospholipid prodrugs has finally made ‘made the turn’ toward meaningful translational success. WIREs Nanomed Nanobiotechnol 2015, 8:85–106. doi: 10.1002/wnan.1355This article is categorized under:

Therapeutic Approaches and Drug Discovery > Emerging Technologies
Biology-Inspired Nanomaterials > Lipid-Based Structures
Recent advances in nanotechnology‐based detection and separation of circulating tumor cells
Authors: Myung Ja Hye , Tam Kevin A. , Park Sin‐jung , Cha Ashley , Hong Seungpyo 
Published: August 2015

Although circulating tumor cells (CTCs) in blood have been widely investigated as a potential biomarker for diagnosis and prognosis of metastatic cancer, their inherent rarity and heterogeneity bring tremendous challenges to develop a CTC detection method with clinically significant specificity and sensitivity. With advances in nanotechnology, a series of new methods that are highly promising have emerged to enable or enhance detection and separation of CTCs from blood. In this review, we systematically categorize nanomaterials, such as gold nanoparticles, magnetic nanoparticles, quantum dots, graphenes/graphene oxides, and dendrimers and stimuli‐responsive polymers, used in the newly developed CTC detection methods. This will provide a comprehensive overview of recent advances in the CTC detection achieved through application of nanotechnology as well as the challenges that these existing technologies must overcome to be directly impactful on human health. WIREs Nanomed Nanobiotechnol 2016, 8:223–239. doi: 10.1002/wnan.1360This article is categorized under:

Diagnostic Tools > Diagnostic Nanodevices
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Parkinson’s disease between internal medicine and neurology
Authors: Csoti Ilona , Jost Wolfgang H. , Reichmann Heinz 
Published: August 2015

AbstractGeneral medical problems and complications have a major impact on the quality of life in all stages of Parkinson’s disease. To introduce an effective treatment, a comprehensive analysis of the various clinical symptoms must be undertaken. One must distinguish between (1) diseases which arise independently of Parkinson’s disease, and (2) diseases which are a direct or indirect consequence of Parkinson’s disease. Medical comorbidity may induce additional limitations to physical strength and coping strategies, and may thus restrict the efficacy of the physical therapy which is essential for treating hypokinetic-rigid symptoms. In selecting the appropriate medication for the treatment of any additional medical symptoms, which may arise, its limitations, contraindications and interactions with dopaminergic substances have to be taken into consideration. General medical symptoms and organ manifestations may also arise as a direct consequence of the autonomic dysfunction associated with Parkinson’s disease. As the disease progresses, additional non-parkinsonian symptoms can be of concern. Furthermore, the side effects of Parkinson medications may necessitate the involvement of other medical specialists. In this review, we will discuss the various general medical aspects of Parkinson’s disease.
Genomic signatures for paclitaxel and gemcitabine resistance in breast cancer derived by machine learning
Authors: Dorman Stephanie N. , Baranova Katherina , Knoll Joan H.M. , Urquhart Brad L. , Mariani Gabriella , Carcangiu Maria Luisa , Rogan Peter K. 
Published: August 2015

Increasingly, the effectiveness of adjuvant chemotherapy agents for breast cancer has been related to changes in the genomic profile of tumors. We investigated correspondence between growth inhibitory concentrations of paclitaxel and gemcitabine (GI50) and gene copy number, mutation, and expression first in breast cancer cell lines and then in patients. Genes encoding direct targets of these drugs, metabolizing enzymes, transporters, and those previously associated with chemoresistance to paclitaxel (n = 31 genes) or gemcitabine (n = 18) were analyzed. A multi‐factorial, principal component analysis (MFA) indicated expression was the strongest indicator of sensitivity for paclitaxel, and copy number and expression were informative for gemcitabine. The factors were combined using support vector machines (SVM). Expression of 15 genes (ABCC10, BCL2, BCL2L1, BIRC5, BMF, FGF2, FN1, MAP4, MAPT, NFKB2, SLCO1B3, TLR6, TMEM243, TWIST1, and CSAG2) predicted cell line sensitivity to paclitaxel with 82% accuracy. Copy number profiles of 3 genes (ABCC10, NT5C, TYMS) together with expression of 7 genes (ABCB1, ABCC10, CMPK1, DCTD, NME1, RRM1, RRM2B), predicted gemcitabine response with 85% accuracy. Expression and copy number studies of two independent sets of patients with known responses were then analyzed with these models. These included tumor blocks from 21 patients that were treated with both paclitaxel and gemcitabine, and 319 patients on paclitaxel and anthracycline therapy. A new paclitaxel SVM was derived from an 11‐gene subset since data for 4 of the original genes was unavailable. The accuracy of this SVM was similar in cell lines and tumor blocks (70–71%). The gemcitabine SVM exhibited 62% prediction accuracy for the tumor blocks due to the presence of samples with poor nucleic acid integrity. Nevertheless, the paclitaxel SVM predicted sensitivity in 84% of patients with no or minimal residual disease.
The fluid regime of crystallization of water-saturated granitic and pegmatitic magmas: a physicochemical analysis
Authors: Smirnov S.Z. 
Published: August 2015

Abstract
Miarolitic granite pegmatites are a unique natural object that makes it possible to study magmatic processes that lead to the formation of ore-forming media and systems. This paper summarizes modern views on phase transformations in aqueous silicate systems at parameters close to those of the transition from magmatic to hydrothermal crystallization. Comparison of phase diagrams and the results of study of pegmatite-forming media permits making conclusions about the crystallization of the water-saturated magmas of miarolitic granite pegmatites. The fluid regime of aqueous granite systems of simple composition, not enriched in fluxing components, is determined mainly by magma degassing or the supply of volatiles with flows of transmagmatic fluids. These processes cause the separation of essentially carbon dioxide or essentially hydrous fluid. During the evolution of such magmas, crystallization from silicate melt is separated in PT-space and, possibly, in time from the crystallization from aqueous or mixed carbon dioxide–aqueous super- and subcritical solutions. The evolution of chambers of water-saturated granitic and pegmatitic magma enriched in F, B, and alkali metals presupposes the formation of a heterogeneous mineral-forming medium in which crystallization occurs in the magmatic melt at high-temperature stages; as temperature decreases, crystallization can proceed in hydrous fluid, hydrosilicate, and/or hydrosaline liquids simultaneously. Hydrothermal crystallization can also take place in a heterogeneous medium consisting of aqueous solutions of different salinities and vapor or vapor–carbon dioxide gas mixture. The relationship between different fluid regimes during the evolution of volatile-saturated granitic and pegmatitic magmas determines the variety of postmagmatic rocks accompanying granite massifs.
Gold mineralization of the Khaak-Sair gold–quartz ore occurrence in listwänites (western Tuva)
Authors: Kuzhuget R.V. , Zaikov V.V. , Lebedev V.I. , Mongush A.A. 
Published: August 2015

Abstract
We consider mineral assemblages and mineralogical and geochemical peculiarities of hypogene gold from the Khaak-Sair multistage low-sulfide gold-quartz ore occurrence in listwänites. Three productive substages of Au-and Ag-mineral formation have been recognized on the basis of mineralogical studies: gold–sulfosalt–sulfide–quartz, gold–mercury–quartz, and gold–selenide–telluride–sulfide–quartz. These substages were characterized by the following sequences of mineral formation: (1) ultrahigh-fineness gold → high-fineness gold → argental gold (medium- and low-fineness gold) → electrum + Ag-bearing and argental fahlores (up to 50 wt.% Ag) ± acanthite ± hessite; (2) high-fineness gold → Hg-bearing and mercurian gold → mercurian electrum → mercurian kustelite → Au-bearing mercurian silver; and (3) high-fineness gold → mercurian gold → mercurian electrum + naumannite + Te-bearing naumannite + fischesserite + tiemannite + hessite + coloradoite + Ag-bearing minerals of the galena–clausthalite series (up to 6 wt.% Ag) ± Se-cinnabar ± Se-imiterite. Productive mineral assemblages of the ore occurrence formed in the hypabyssal facies (depth ~ 1.5 km, P ~ 0.5 kbar) on the background of a temperature decrease from 290 to 160 °C and variations in f(O2), f(S2), f(Se2), and f(Te2).
REDISCOVERING AMERICA: POLITICAL ECONOMY OF SPANISH COLONIES ACCORDING TO THE EXPLORERS JUAN-ULLOA, MALASPINA AND HUMBOLDT
Authors: Perdices De Blas Luis , Ramos-Gorostiza José Luis 
Published: August 2015

ABSTRACTTwo scientists and sailors from the Spanish Navy, Jorge Juan and Antonio de Ulloa, the Italian sailor and explorer Alessandro Malaspina, and the German sage Alexander von Humboldt were the main actors in three great voyages to Spanish America between the second-third of the 18thcentury and the beginning of the 19thcentury. This enabled them to provide three first hand«photographs»of the state of the Spanish empire in America at three different moments in time: approximately before, during and after the implementation of colonial reforms designed in the reigns of Ferdinand VI and Charles III. This work aims, in the first place, to compare the socio-economic views of Spanish America deriving from the three expeditions, highlighting similarities and differences. Second, this work aims to connect the analysis of the weaknesses of the politico-institutional organisation of Spanish colonies, which the four travellers did at first hand, with the present debate on the role of colonial institutions in long-term economic development.
Ab initio structure determination of n-diamond
Authors: Li Da , Tian Fubo , Chu Binhua , Duan Defang , Sha Xiaojing , Lv Yunzhou , Zhang Huadi , Lu Nan , Liu Bingbing , Cui Tian 
Published: August 2015

AbstractA systematic computational study on the crystal structure of n-diamond has been performed using first-principle methods. A novel carbon allotrope with hexagonal symmetry R32 space group has been predicted. We name it as HR-carbon. HR-carbon composed of lonsdaleite layers and unique C3 isosceles triangle rings, is stable over graphite phase above 14.2 GPa. The simulated x-ray diffraction pattern, Raman and energy-loss near-edge spectrum can match the experimental results very well, indicating that HR-carbon is a likely candidate structure for n-diamond. HR-carbon has an incompressible atomic arrangement because of unique C3 isosceles triangle rings. The hardness and bulk modulus of HR-carbon are calculated to be 80 GPa and 427 GPa, respectively, which are comparable to those of diamond. C3 isosceles triangle rings are very important for the stability and hardness of HR-carbon.
On-chip aqueous two-phase system (ATPS) formation, consequential self-mixing, and their influence on drop-to-drop aqueous two-phase extraction kinetics
Authors: Wijethunga Pavithra A L , Moon Hyejin 
Published: August 2015

Abstract
Aqueous two-phase systems (ATPSs) allow an advantageous aqueous two-phase extraction process (ATPE), a special type of liquid–liquid extraction. Compared with conventional liquid–liquid extraction using aqueous/organic extraction media, ATPE is known to provide relatively easy mass transfer and a gentle environment for biological separation applications. Considering the recent interest in microscale ATPE, we aimed to study (i) the potential of preparing ATPS droplets on a digital microfluidic device, and (ii) the influence of the fluidic dynamics created during the formation of ATPS, with the goal of enhancing on-chip ATPE process. On-chip ATPS formation was evaluated by preparing a series of ATPSs on electrowetting on dielectric digital microfluidic chips and comparing their characteristics with the same ATPSs prepared at macroscale using conventional procedures. An enhanced on-chip drop-to-drop ATPE process was achieved by incorporating a self-mixing condition created during ATPSformation. Results indicate a successful on-chip ATPS preparation as well as enhanced extraction performance by self-mixing in the absence of forced mixing. Findings of this research suggest an alternative, simple, yet adequate technique to provide mixing for on-chip applications, such as sample preparation in portable microfluidics, for which it is unfavorable to implement complicated mixing sequences or complex device geometries.
Increased Circulating Visfatin Is Associated With Progression of Kidney Disease in Non-Diabetic Hypertensive Patients
Authors: Hsu Chien-Yi , Huang Po-Hsun , Chen Tz-Heng , Chiang Chia-Hung , Leu Hsin-Bang , Huang Chin-Chou , Chen Jaw-Wen , Lin Shing-Jong 
Published: August 2015

Abstract

BACKGROUD
Declining renal function is an independent risk factor for all-cause mortality in cardiovascular disease. Visfatin has been described as a marker of inflammation and endothelial dysfunction, but whether circulating visfatin levels are predictive to a subsequent decline in renal function remains unclear.

METHODS
In total, 200 nondiabetic, non-proteinuric hypertensive outpatients with initial serum creatinine (Sc r ) ≤1.5mg/dl were enrolled. Plasma visfatin concentration and endothelial function estimated by brachial artery flow-mediated dilatation (FMD) were determined in the study subjects. The primary endpoints were the occurrence of renal events including doubling of Sc r , 25% loss of glomerular filtration rate (GFR) from baseline values, and the occurrence of end-stage renal disease during follow-up.

RESULTS
The mean annual rate of GFR decline (ΔGFR/y) was −1.26±2.76ml/min/1.73 m 2 per year during follow-up (8.6±2.5 years). At baseline, plasma visfatin was negatively correlated with estimated GFR. In longitudinal analysis, the ΔGFR/y was correlated with visfatin, baseline GFR, FMD, systolic blood pressure, and fasting blood glucose (FBG). Multivariate analysis indicated that increased visfatin ( r = −0.331, P &lt;0.001), baseline GFR ( r = −0.234, P = 0.001), FMD ( r = 0.163, P = 0.015), and FBG ( r = −0.160, P = 0.015) are independent predictors of ΔeGFR/y. Cox regression model analysis showed that visfatin (hazard ratio (HR), 1.09; 95% confidence interval (CI), 1.05–1.13, P &lt;0.001), FBG (HR, 1.01; 95% CI, 1.00–1.02, P = 0.020), and FMD (HR, 0.87; 95% CI, 0.76–1.00, P = 0.049) were independently associated with the risk of developing future renal events.

CONCLUSIONS
Increased circulating visfatin are associated with subsequent decline in renal function in nondiabetic hypertensive patients.
Magnetic field rotations in the solar wind at kinetic scales
Authors: Chen C. H. K. , Matteini L. , Burgess D. , Horbury T. S. 
Published: August 2015

Abstract
The solar wind magnetic field contains rotations at a broad range of scales, which have been extensively studied in the magnetohydrodynamics range. Here, we present an extension of this analysis to the range between ion and electron kinetic scales. The distribution of rotation angles was found to be approximately lognormal, shifting to smaller angles at smaller scales almost self-similarly, but with small, statistically significant changes of shape. The fraction of energy in fluctuations with angles larger than α was found to drop approximately exponentially with α, with e-folding angle 9.8° at ion scales and 0.66° at electron scales, showing that large angles (α &gt; 30°) do not contain a significant amount of energy at kinetic scales. Implications for kinetic turbulence theory and the dissipation of solar wind turbulence are discussed.
X-ray variability with spectral state transitions in NS-LMXBs observed with MAXI/GSC and Swift/BAT
Authors: Asai Kazumi , Mihara Tatehiro , Matsuoka Masaru , Sugizaki Mutsumi 
Published: August 2015

Abstract
X-ray variabilities with spectral state transitions in bright low-mass X-ray binaries containing a neutron star are investigated by using the one-day bin light curves of MAXI/GSC (Gas Slit Camera) and Swift/BAT (Burst Alert Telescope). Four sources (4U 1636−536, 4U 1705−44, 4U 1608−52, and GS 1826−238) exhibited small-amplitude X-ray variabilities with spectral state transitions. Such “mini-outbursts” were characterized by smaller amplitudes (several times) and shorter duration (less than several tens of days) than those of “normal outbursts.” A theoretical model of disk instability by Mineshige and Osaki (PASJ, 37, 1, 1985) predicts both large-amplitude outbursts and small-amplitude variabilities. We interpret the normal outbursts as the former prediction of this model, and the mini-outbursts as the latter. Here, we can also call the mini-outburst a “purr-type outburst” referring to the theoretical work. We suggest that similar variabilities lasting for several tens of days without spectral state transitions, which are often observed in the hard state, may be repeats of mini-outbursts.
Transpedicular Corpectomy and Cage Placement in the Treatment of Traumatic Lumbar Burst Fractures
Authors: Pham Martin H. , Tuchman Alexander , Chen Thomas C. , Acosta Frank L. , Hsieh Patrick C. , Liu John C. 
Published: August 2015

Study Design:
Retrospective review.

Objective:
To review the feasibility of a posterior-only approach for instrumented reconstruction in lumbar burst fractures.

Background:
Burst fractures of the lumbar spine have been treated through a variety of techniques, including anterior, posterior, or combined approaches. Here we review series of patients undergoing posterior-only transpedicular corpectomy with instrumented fusion for traumatic lumbar burst fracture.

Methods:
All patients treated at the Los Angeles County+University of Southern California (LAC+USC) Medical Center who had sustained traumatic lumbar burst fractures from February 2005 to February 2014 were reviewed.

Results:
A total of 178 traumatic lumbar burst fractures were identified of which 89 required operative intervention. Of those 89 operations, 7 patients underwent posterior-only approach for transpedicular corpectomy. Levels operated on were at L1 (4 patients), L2 (1 patient), and L4 (2 patients). The mean age was 35 years of age (range, 21–56 y), and mechanism of injury was either motor vehicle accident (5 patients) or fall (2 patients). Initial neurological examination was American Spinal Injury Association (ASIA) B in 3 patients, ASIA D in 3 patients, and 1 patient was neurologically intact. Mean thoracolumbar injury classification and severity score on presentation was 6.4 (range, 5–8), whereas the mean load sharing classification score was 7.4 (range, 7–9). Of patients who were not immediately lost to follow-up on hospital discharge, mean clinical follow-up was 45.3 months (range, 18.8–68.6 mo), whereas mean radiographic follow-up was 28.8 months (range, 1.3–63.6 mo). At the last known radiographic follow-up, no patient had gross hardware fracture, pseudoarthrosis, or adjacent segment disease. One patient with the longest radiographic follow-up of 63.6 months was noted to have some minimal subsidence of his cage with no other change in his other hardware.

Conclusion:
A posterior-only approach for transpedicular corpectomy and instrumented fusion is a viable treatment option for lumbar burst fracture which allows for reconstruction of the anterior column while avoiding many of the risks and complications associated with an anterior or combined approach.
Instability in Thoracolumbar Trauma
Authors: Abbasi Fard Salman , Skoch Jesse , Avila Mauricio J. , Patel Apar S. , Sattarov Kamran V. , Walter Christina M. , Baaj Ali A. 
Published: August 2015

Study Design:
Review of the articles.

Objective:
The objective of this study was to review all articles related to spinal instability to determine a consensus statement for a contemporary, practical definition applicable to thoracolumbar injuries.

Summary of Background Data:
Traumatic fractures of the thoracolumbar spine are common. These injuries can result in neurological deficits, disability, deformity, pain, and represent a great economic burden to society. The determination of spinal instability is an important task for spine surgeons, as treatment strategies rely heavily on this assessment. However, a clinically applicable definition of spinal stability remains elusive.

Materials and Methods:
A review of the Medline database between 1930 and 2014 was performed limited to papers in English. Spinal instability, thoracolumbar, and spinal stability were used as search terms. Case reports were excluded. We reviewed listed references from pertinent search results and located relevant manuscripts from these lists as well.

Results:
The search produced a total of 694 published articles. Twenty-five articles were eligible after abstract screening and underwent full review. A definition for spinal instability was described in only 4 of them. Definitions were primarily based on biomechanical and classification studies. No definitive parameters were outlined to define stability.

Conclusions:
Thirty-six years after White and Panjabi’s original definition of instability, and many classification schemes later, there remains no practical and meaningful definition for spinal instability in thoracolumbar trauma. Surgeon expertise and experience remains an important factor in stability determination. We propose that, at an initial assessment, a distinction should be made between immediate and delayed instability. This designation should better guide surgeons in decision making and patient counseling.