bluuebunny/crossref_metadata_2025 huggingface dataset:
Macroscopic optical physiological parameters correlate with microscopic proliferation and vessel area breast cancer signatures
Authors: Chung So Hyun , Feldman Michael D. , Martinez Daniel , Kim Helen , Putt Mary E. , Busch David R. , Tchou Julia , Czerniecki Brian J. , Schnall Mitchell D. , Rosen Mark A. , DeMichele Angela , Yodh Arjun G. , Choe Regine
Published: May 2015

Introduction

Non-invasive diffuse optical tomography (DOT) and diffuse correlation spectroscopy (DCS) can detect and characterize breast cancer and predict tumor responses to neoadjuvant chemotherapy, even in patients with radiographically dense breasts. However, the relationship between measured optical parameters and pathological biomarker information needs to be further studied to connect information from optics to traditional clinical cancer biology. Thus we investigate how optically measured physiological parameters in malignant tumors such as oxy-, deoxy-hemoglobin concentration, tissue blood oxygenation, and metabolic rate of oxygen correlate with microscopic histopathological biomarkers from the same malignant tumors, e.g., Ki67 proliferation markers, CD34 stained vasculature markers and nuclear morphology.

Methods

In this pilot study, we investigate correlations of macroscopic physiological parameters of malignant tumors measured by diffuse optical technologies with microscopic histopathological biomarkers of the same tumors, i.e., the Ki67 proliferation marker, the CD34 stained vascular properties marker, and nuclear morphology.

Results

The tumor-to-normal relative ratio of Ki67-positive nuclei is positively correlated with DOT-measured relative tissue blood oxygen saturation (R = 0.89, p-value: 0.001), and lower tumor-to-normal deoxy-hemoglobin concentration is associated with higher expression level of Ki67 nuclei (p-value: 0.01). In a subset of the Ki67-negative group (defined by the 15 % threshold), an inverse correlation between Ki67 expression level and mammary metabolic rate of oxygen was observed (R = −0.95, p-value: 0.014). Further, CD34 stained mean-vessel-area in tumor is positively correlated with tumor-to-normal total-hemoglobin and oxy-hemoglobin concentration. Finally, we find that cell nuclei tend to have more elongated shapes in less oxygenated DOT-measured environments.

Conclusions

Collectively, the pilot data are consistent with the notion that increased blood is supplied to breast cancers, and it also suggests that less conversion of oxy- to deoxy-hemoglobin occurs in more proliferative cancers. Overall, the observations corroborate expectations that macroscopic measurements of breast cancer physiology using DOT and DCS can reveal microscopic pathological properties of breast cancer and hold potential to complement pathological biomarker information.
Intradiscal application of rhBMP-7 does not induce regeneration in a canine model of spontaneous intervertebral disc degeneration
Authors: Willems Nicole , Bach Frances C , Plomp Saskia G M , van Rijen Mattie HP , Wolfswinkel Jeannette , Grinwis Guy CM , Bos Clemens , Strijkers Gustav J , Dhert Wouter JA , Meij Björn P , Creemers Laura B , Tryfonidou Marianna A
Published: May 2015

Introduction

Strategies for biological repair and regeneration of the intervertebral disc (IVD) by cell and tissue engineering are promising, but few have made it into a clinical setting. Recombinant human bone morphogenetic protein 7 (rhBMP-7) has been shown to stimulate matrix production by IVD cells in vitro and in vivo in animal models of induced IVD degeneration. The aim of this study was to determine the most effective dose of an intradiscal injection of rhBMP-7 in a spontaneous canine IVD degeneration model for translation into clinical application for patients with low back pain.

Methods

Canine nucleus pulposus cells (NPCs) were cultured with rhBMP-7 to assess the anabolic effect of rhBMP-7 in vitro, and samples were evaluated for glycosaminoglycan (GAG) and DNA content, histology, and matrix-related gene expression. Three different dosages of rhBMP-7 (2.5 μg, 25 μg, and 250 μg) were injected in vivo into early degenerated IVDs of canines, which were followed up for six months by magnetic resonance imaging (T2-weighted images, T1rho and T2 maps). Post-mortem, the effects of rhBMP-7 were determined by radiography, computed tomography, and macroscopy, and by histological, biochemical (GAG, DNA, and collagen), and biomolecular analyses of IVD tissue.

Results

In vitro, rhBMP-7 stimulated matrix production of canine NPCs as GAG deposition was enhanced, DNA content was maintained, and gene expression levels of ACAN and COL2A1 were significantly upregulated. Despite the wide dose range of rhBMP-7 (2.5 to 250 μg) administered in vivo, no regenerative effects were observed at the IVD level. Instead, extensive extradiscal bone formation was noticed after intradiscal injection of 25 μg and 250 μg of rhBMP-7.

Conclusions

An intradiscal bolus injection of 2.5 μg, 25 μg, and 250 μg rhBMP-7 showed no regenerative effects in a spontaneous canine IVD degeneration model. In contrast, intradiscal injection of 250 μg rhBMP-7, and to a lesser extent 25 μg rhBMP-7, resulted in extensive extradiscal bone formation, indicating that a bolus injection of rhBMP-7 alone cannot be used for treatment of IVD degeneration in human or canine patients.
KIAA1199 as a potential diagnostic biomarker of rheumatoid arthritis related to angiogenesis
Authors: Yang Xinyu , Qiu Pengcheng , Chen Bingbing , Lin Yaoyao , Zhou Zhonghao , Ge Renshan , Zou Hai , Wang Jianmin , Wang Jianguang
Published: May 2015

Introduction

Our previous proteomic study on fibroblast-like synoviocytes (FLSs) derived from the synovial tissues found that the expression of KIAA1199 was higher in rheumatoid arthritis (RA) patients than in healthy controls. The aim of this study was to examine the biological function of KIAA1199 and evaluate its clinical diagnosis value in RA.

Methods

The over-expression of KIAA1199 was verified by quantitative real-time polymerase chain reaction (qPCR), Immunohistochemistry, Immunofluorescence and enzyme linked immunosorbent assay (ELISA) in inactive and active RA patients and healthy controls. The effect of KIAA1199 expression on FLSs proliferation, angiogenesis and related pathway were analyzed by MTT, cell migration, tube formation, chorioallantoic membrane (CAM) assay, qPCR and western-blotting after KIAA1199 knockdown and over-expression.

Results

The verification results show the up-regulation of KIAA1199 in RA patients at mRNA and protein level as compared to that in healthy controls. ELISA and receiver operator characteristic (ROC) analysis shows that KIAA1199 concentration in serum, synovial fluid and synovial tissues could be used as dependable biomarkers for the diagnosis of active RA, provided an area under roc curve (AUC) of 0.83, 0.92 and 0.92. Sensitivity and specificity, which were determined by cut-off points, reached 72% 84% and 80% in sensitivity and 80%, 93.3%, 93.3% in specificity, respectively. Moreover, KIAA1199 also enhance the proliferation and angiogenesis of synovial membrane, and KIAA1199/ PLXNB3/ SEMA5A/CTGF axis may be a newly found pathway enhancing cell proliferation and angiogenesis.

Conclusion

KIAA1199 may be a potential diagnostic biomarker of RA related to angiogenesis.
Early biomarkers of joint damage in rheumatoid and psoriatic arthritis
Authors: Mc Ardle Angela , Flatley Brian , Pennington Stephen R. , FitzGerald Oliver
Published: May 2015

Joint destruction, as evidenced by radiographic findings, is a significant problem for patients suffering from rheumatoid arthritis and psoriatic arthritis. Inherently irreversible and frequently progressive, the process of joint damage begins at and even before the clinical onset of disease. However, rheumatoid and psoriatic arthropathies are heterogeneous in nature and not all patients progress to joint damage. It is therefore important to identify patients susceptible to joint destruction in order to initiate more aggressive treatment as soon as possible and thereby potentially prevent irreversible joint damage. At the same time, the high cost and potential side effects associated with aggressive treatment mean it is also important not to over treat patients and especially those who, even if left untreated, would not progress to joint destruction. It is therefore clear that a protein biomarker signature that could predict joint damage at an early stage would support more informed clinical decisions on the most appropriate treatment regimens for individual patients. Although many candidate biomarkers for rheumatoid and psoriatic arthritis have been reported in the literature, relatively few have reached clinical use and as a consequence the number of prognostic biomarkers used in rheumatology has remained relatively static for several years. It has become evident that a significant challenge in the transition of biomarker candidates to clinical diagnostic assays lies in the development of suitably robust biomarker assays, especially multiplexed assays, and their clinical validation in appropriate patient sample cohorts. Recent developments in mass spectrometry-based targeted quantitative protein measurements have transformed our ability to rapidly develop multiplexed protein biomarker assays. These advances are likely to have a significant impact on the validation of biomarkers in the future. In this review, we have comprehensively compiled a list of candidate biomarkers in rheumatoid and psoriatic arthritis, evaluated the evidence for their potential as biomarkers of bone (joint) damage, and outlined how mass spectrometry-based targeted and multiplexed measurement of candidate biomarker proteins is likely to accelerate their clinical validation and the development of clinical diagnostic tests.
Linking classification and therapeutic management of vasculitides
Authors: Baldwin Corisande , Carette Simon , Pagnoux Christian
Published: May 2015

Vasculitides are classified by the size, type and location of the predominantly involved vessels and by their primary or secondary nature. Their treatment depends on the type of vasculitis, its etiology (when known), and its severity and must be further adjusted by the individual characteristics and comorbidities of patients. In this paper, we review how the classification and definition of vasculitides have evolved over the past years and how it has affected therapeutic changes. As new genetic markers are being discovered and the pathogenesis of vasculitides continues to be elucidated, further modifications in classification and treatment can be expected.
Dislocated quasi-b-metric spaces and fixed point theorems for cyclic contractions
Authors: Klin-eam Chakkrid , Suanoom Cholatis
Published: May 2015

In this paper, we establish dislocated quasi-b-metric spaces and introduce the notions of Geraghty type dqb-cyclic-Banach contraction and dqb-cyclic-Kannan mapping and derive the existence of fixed point theorems for such spaces. Our main theorem extends and unifies existing results in the recent literature.
Shot- and angle-domain wave-equation traveltime inversion of reflection data: Theory
Authors: Zhang Sanzong , Luo Yi , Schuster Gerard
Published: May 2015

The main difficulty with iterative waveform inversion is that it tends to get stuck in local minima associated with the waveform misfit function. To mitigate this problem and avoid the need to fit amplitudes in the data, we have developed a wave-equation method that inverts the traveltimes of reflection events, and so it is less prone to the local minima problem. Instead of a waveform misfit function, the penalty function was a crosscorrelation of the downgoing direct wave and the upgoing reflection wave at the trial image point. The time lag, which maximized the crosscorrelation amplitude, represented the reflection-traveltime residual (RTR) that was back projected along the reflection wavepath to update the velocity. Shot- and angle-domain crosscorrelation functions were introduced to estimate the RTR by semblance analysis and scanning. In theory, only the traveltime information was inverted and there was no need to precisely fit the amplitudes or assume a high-frequency approximation. Results with synthetic data and field records revealed the benefits and limitations of wave-equation reflection traveltime inversion.
The effect of micrite content on the acoustic velocity of carbonate rocks
Authors: El Husseiny Ammar , Vanorio Tiziana
Published: May 2015

We have demonstrated the effect of micrite content on the acoustic properties of well-controlled microstructures that are created in the laboratory to closely mimic those of carbonate rocks. In particular, we examined the effect of micrite content on the acoustic velocity, sensitivity of velocity to pressure, and changes in velocity resulting from dissolution upon saturation with a reactive fluid. We followed Dunham’s classification and fabricated the samples by mixing coarse (sand-sized) and very fine (micrite-sized) calcite grains in different ratios and then cold compressing the mixture. The acoustic velocities were measured under benchtop conditions and as functions of confining pressure before and after the injection of a [Formula: see text] aqueous solution. The benchtop measurements indicated that the addition of micrite made the frame of the carbonate samples stiffer. Because the sensitivity of velocity to pressure decreases as the content of micrite increases, we hypothesized a stiffer pore structure in micrite-richer fabrics. Moreover, the content of micrite seems also to affect the change in elastic moduli upon dissolution. Micrite-rich samples experience a drop in elastic moduli after fluid injection, with respect to the moduli measured under dry conditions. This was interpreted as being likely due to dissolution, which weakens the rock frame. Such an effect seems to overcome the stiffening that results from dispersion mechanisms under high-frequency conditions.
Relative location of microseismicity
Authors: Grechka Vladimir , De La Pena Alejandro , Schisselé-Rebel Estelle , Auger Emmanuel , Roux Pierre-Francois
Published: May 2015

Applying the two-point paraxial ray tracing, we develop a technique for relative location of microseismic events. Our technique assumes the availability of a perforation shot or an already located microseismic event, termed the master, for which the paraxial ray tracing has been performed. The ray-tracing output for the master makes it possible to compute the relative locations of adjacent microseismic events, as many as a data set contains, with an efficient algorithm that requires no additional ray tracing and reduces to solving a series of simple, low-dimensional and well-behaved optimization problems. The relative event-location approach discussed in our paper is especially well suited for surface microseismic monitoring because the high accuracy of the paraxial ray approximation in the directions orthogonal to the reference rays, typically spanning the stimulated horizons for surface microseismic geometries, ensures the calculation of precise event hypocenters at appreciable distances from the master. Also, since our computations operate with differences of the recorded times of microseismic events rather than with the times themselves, inaccuracies in static corrections for surface receiver stations are largely eliminated. We test the relative location technique on synthetic and field microseismic data to demonstrate its accuracy, computational efficiency, and insensitivity to velocity errors.
SV-P extraction and imaging for far-offset vertical seismic profile data
Authors: Li Yandong , Hardage Bob A.
Published: May 2015

We have analyzed vertical seismic profile (VSP) data acquired across a Marcellus Shale prospect and found that SV-P reflections could be extracted from far-offset VSP data generated by a vertical-vibrator source using time-variant receiver rotations. Optimal receiver rotation angles were determined by a dynamic steering of geophones to the time-varying approach directions of upgoing SV-P reflections. These SV-P reflections were then imaged using a VSP common-depth-point transformation based on ray tracing. Comparisons of our SV-P image with P-P and P-SV images derived from the same offset VSP data found that for deep targets, SV-P data created an image that extended farther from the receiver well than P-P and P-SV images and that spanned a wider offset range than P-P and P-SV images do. A comparison of our VSP SV-P image with a surface-based P-SV profile that traversed the VSP well demonstrated that SV-P data were equivalent to P-SV data for characterizing geology and that a VSP-derived SV-P image could be used to calibrate surface-recorded SV-P data that were generated by P-wave sources.
Ligand-Hole in [SnI6] Unit and Origin of Band Gap in Photovoltaic Perovskite Variant Cs2SnI6
Authors: Xiao Zewen , Lei Hechang , Zhang Xiao , Zhou Yuanyuan , Hosono Hideo , Kamiya Toshio
Published: May 2015

Cs2SnI6, a variant of perovskite CsSnI3, is gaining interest as a photovoltaic material. Based on a simple ionic model, it is expected that Cs2SnI6 is composed of Cs+, I−, and Sn4+ ions and that the band gap is primarily made of occupied I− 5p6 valence band maximum (VBM) and unoccupied Sn4+ 5s conduction band minimum (CBM) similar to SnO2. In this work, we performed density functional theory (DFT) calculations and revealed that the real oxidation state of the Sn ion in Cs2SnI6 is +2 similar to CsSnI3. The +2 oxidation state of Sn originates from 2 ligand holes (L+) in the [SnI6]2− octahedron unit, where the ligand [I6] cluster has the apparent [I66−L+2]4− oxidation state, because the band gap is formed mainly by occupied I 5p VBM and unoccupied I 5p CBM. The +2 oxidation state of Sn and the band gap originate from the intracluster hybridization and stabilized by the strong covalency of the Sn–I bonds.
Behavioural evidence for self-medication in bumblebees?
Authors: Baracchi David , Brown Mark J. F. , Chittka Lars
Published: May 2015

The presence of antimicrobial secondary metabolites in nectar suggests that pollinators, which are threatened globally by emergent disease, may benefit from the consumption of nectars rich in these metabolites. We tested whether nicotine, a nectar secondary metabolite common inSolanaceaeandTiliaspecies, is used by parasitized bumblebees as a source of self-medication,using a series of toxicological, microbiological and behavioural experiments. Caged bees infected withCrithidia bombi had a slight preference for sucrose solution laced with the alkaloid and behavioural tests showed that the parasite infection induced an increased consumption of nicotine during foraging activity, though nicotine had an appetite-reducing effect overall. When ingested, nicotine delayed the progression of a gut infection in bumblebees by a few days, but dietary nicotine did not clear the infection, and after 10 days the parasite load approached that of control bees. Moreover, when pathogens were exposed to the alkaloid prior to host ingestion, the protozoan’s viability was not directly affected, suggesting that anti-parasite effects were relatively weak. Nicotine consumption in a single dose did not impose any cost even in starved bees but the alkaloid had detrimental effects on healthy bees if consistently consumed for weeks. These toxic effects disappeared in infected bees, suggesting that detoxification costs might have been counterbalanced by the advantages in slowing the progression of the infection. Nicotine consumption did not affect bee lifespan but the reduction in the parasite load may have other likely unexplored subtle benefits both for individual bees and their colony.  Potential evidence for self-medication is discussed. The contention that secondary metabolites in nectar may be under selection from pollinators, or used by plants to enhance their own reproductive success, remains to be confirmed.
Research Note—Investigating Firm Strategies on Offering Consumer-Customizable Products
Authors: Gu Zheyin (Jane) , Tayi Giri K.
Published: May 2015

Advances in the digital economy have driven the trend among manufacturers, particularly those in the information technology (IT) industry, to offer products that consumers can self-customize to satisfy their idiosyncratic needs. This study examines firm strategies on offering such consumer-customizable products. Our analysis shows that a monopolistic firm obtains a greater profit from offering a consumer-customizable product than from offering a preconfigured standardized product only if consumers are sufficiently capable to conduct the customization task; otherwise, it is more profitable for the firm to offer a standardized product. Moreover, consumers obtain a greater surplus when the firm offers the customizable product. We also consider the case where the firm is capable of offering both a customizable product and a standardized product and find that the firm benefits more from offering both products than offering either product if consumer customizing capability and the customization cost are not too high. Interestingly, when the firm offers both products, its effort in enhancing consumer customizability (e.g., offering free consumer training) always benefits both the firm and consumers, but its effort in increasing the value of the standardized product (e.g., offering more functions) can hurt both the firm profit and consumer surplus. Our theoretical results explain many interesting business practices and provide useful insights for marketing practitioners.
Prediction of Boron Content in Wood Pellet Products by Near-Infrared Spectroscopy
Authors: Koumbi-Mounanga Thierry , Cooper Paul A. , Yan Ning , Groves Kevin , Ung Tony , Leblon Brigitte
Published: May 2015

A rapid method assessed the potential of near-infrared spectroscopy (NIRS) to estimate boron content of wood pellet products. Based on a comparison of NIR spectra data in the 1,100- to 2,200-nm wavelength region of Eastern black spruce (Picea mariana var. mariana) wood pellets treated with preservative concentrations ranging from 0 to 2 percent and from 0 to 20 percent glycol borate–based disodium octaborate tetrahydrate (DOT), the minimum level of boric acid equivalent required to protect wood from biodegradation was revealed. Borate was indicated in the 1,700- to 1,900-nm wavelength region and the visible-NIR absorbance trended to a proportion higher for the lower borate concentrations and lower for the higher borate concentrations. These were correlated by projection to the latent structures–partial least-squares regression method and the sample-specific standard error of prediction method. Calibration sets achieved R2 values from 0.7 to 0.95, root mean square error (RMSE) ranging from 0.3 to 1.61 percent, and relative percent difference (RPD) ranging from 1.8 to 4.4, whereas validation statistics achieved R2 values from 0.64 to 0.94, RMSE ranging from 0.33 to 1.65 percent, and RPD ranging from 1.7 to 4.3. These preliminary results indicate that NIRS should be able to provide a greater quantitative and qualitative technique of predicting boron content in wood products for the preservation industry.
Looking queer? Gay men’s negotiations between masculinity and femininity in style and dress in the twenty-first century
Authors: Cole Shaun
Published: May 2015

Appearance has long been of concern to gay men, whether manifested as an identifiable visibility, an intentional invisibility or a conscious playing with gendered and social signifiers. This ties to Judith Butler’s propositions that gendered identities are performed in relation to external societal and internal personal pressures and considerations, as well as being regulated by cultural discourses. The notions of gay male femininity and the authenticity of a ‘real’ masculinity, that can be presented through choices of clothing and behavioural traits, have traditionally been a perennial concern within the urban gay male communities of Britain and America. However, perhaps given the changes in social, moral and legal conditions for, and attitudes towards, gay people that have manifested in the twenty-first century, the negotiation of this oppositional binary is no longer of such importance. Thus the question of a contemporary gay male visual identity and appearance is interesting to consider. Based on a series of interviews conducted with gay men between the ages of 19 and 46 in 2012–2013, this article will articulate some of the ways in which these British and American gay men have negotiated concerns with their sexual identity and personal appearance. It will consider the ways in which style and dress can signify meanings about the multitude of aspects that make up an individual’s identity, with a particular focus on how the acceptance and articulation of their own sexual orientation has varied between operating as a key motivator and an incidental component of the style and dress of these young gay men.
Prisoners' rights
Authors: Codd Helen
Published: May 2015

Brief outline of proposed legal research on
the effects of prisons and penal policy on prisoners and the
wider community by Helen Codd, Senior Lecturer in Law, Lancashire
Law School, University of Central Lancashire. Published in Amicus
Curiae – Journal of the Society for Advanced Legal Studies at the
Institute of Advanced Legal Studies. The Journal is produced by
SALS at the IALS (Institute of Advanced Legal Studies, School of
Advanced Study, University of London).
The US electric utility deregulation: the genie is out of the bottle
Authors: Flippen Edward
Published: May 2015

Article by Edward L. Flippen (Partner, McGuire Woods LLP, Richmond, Virgina) published in Amicus Curiae - Journal of the Society for Advanced Legal Studies. The Journal is produced by the Society for Advanced Legal Studies at the Institute of Advanced Legal Studies, University of London.
Resolving the resource nationalism struggle
Authors: Connerty Anthony
Published: May 2015

Commentary by Anthony Connerty (Head of the IDR Group) on the control of national resources and the challenges for international dispute resolution. Published in Amicus Curiae – Journal of the Society for Advanced Legal Studies at the Institute of Advanced Legal Studies. The Journal is produced by SALS at the IALS (Institute of Advanced Legal Studies, School of Advanced Study, University of London).
Plus ca change? Continuity and change in UK legislative drafting practice
Authors: Laws Stephen
Published: May 2015

This article is taken from the text of the
Sir William Dale Lecture for 2008, given on November 3 2008 by
Stephen Laws CB, First Parliamentary Counsel, Office of the
Parliamentary Counsel. Article by Stephen Laws published in
Amicus Curiae - Journal of the Society for Advanced Legal
Studies. The Journal is produced by the Society for Advanced
Legal Studies at the Institute of Advanced Legal Studies,
University of London.
Climate justice is what's needed for Copenhagen success
Authors: Maniruzzaman A.F.M.
Published: May 2015

Commentary on legal issues pertinent to the international meeting on climate change in Copenhagen in 2009. Comment by Professor A.F. M. Maniruzzaman (Professor of International Law and International Business Law, University of Portsmouth) published in Amicus Curiae - Journal of the Society for Advanced Legal Studies. The Journal is produced by the Society for Advanced Legal Studies at the Institute of Advanced Legal Studies, University of London.
Pre-packed administration begins to take shape
Authors: Walton Peter
Published: May 2015

Article by Dr Peter Walton, Reader in Law
and Director of the Legal Practice Course, University of
Wolverhampton. The author looks at media and public debate around
the increasing use of pre-packed administration ("pre-pack") in
the handling of insolvency cases in the UK and considers in
particular whether the reactions of the regulator and profession
have gone far enough to counter fully the criticisms levelled at
pre-packs.
Europa an der Oder
Authors: Schwell Alexandra
Published: May 2015

Die deutsch-polnische Grenze ist seit Beginn der 1990er Jahre Schauplatz grenzpolizeilicher Kooperationen. Doch warum entschließen sich Nationalstaaten zur Zusammenarbeit in diesem sensiblen Bereich? Und wieso soll ausgerechnet die deutsch-polnische Variante so erfolgreich sein? Vor welchen Schwierigkeiten stehen deutsche und polnische Grenzschützer in der Zusammenarbeit, und wie begegnen sie ihren Kollegen in der Alltagspraxis? Die deutsch-polnische Grenzschutzkooperation steckt voller Widersprüche. Warum sie dennoch als Erfolgsmodell für bilaterale Zusammenarbeit gehandelt wird, ist Gegenstand dieser Studie.
The Political Identity of Ulama in the 2014 Indonesian Presidential Election
Authors: Winarni Leni
Published: May 2015

The Indonesian presidential election of 2014 was possibly the most exciting, lively, intriguing, emotional, and brutish in the history of presidential elections since reformation in 1998. This paper explores the relationship between the political identities of ulama and their political views in the 2014 Indonesian presidential election. It  argues that their political endorsement of presidential candidates is not based on interest but on their political identity. By using constructivist ideas about identity, ulama’s political identities are constantly changing and influenced by factors beyond identity. This idea also emphasizes that identity is created and subjective. Transformation of the political identities of ulama is a way of showing their existence in the period since Indonesian independence in 1945. This paper explores how the political identities expressed by ulama influenced voters in the recent presidential election. How did their political identity affect both the kinds of political measures they took and their support for one of the president candidates? Did the ulama play a substantial political role in election of President Joko Widodo, or were there other factors? Is their political identity the salient factor in their support for either Prabowo Subianto or Joko Widodo?
[Pemilu presiden tahun 2014 memang sangat menarik, hidup, penuh emosi, bahkan penuh intrik, jika dibandingkan dengan sebelumnya sejak 1998. Paper ini meneliti hubungan politik identitas yang dibawa oleh ulama dan pandangan politiknya pada pemilihan presiden Indonesia tahun 2014. Paper ini menemukan bahwa pandangan mereka tentang calon presiden tidak sertamerta menyangkut kepentingan politik, tetapi lebih pada politik identitas. Politik identitas para ulama terus berubah dan dipengaruhi oleh banyak hal di luar identitas tersebut. Ini juga menegaskan bahwa identitas itu ciptaan dan sekaligus subjektif. Transformasi politik identitas para ulama merupakan cara mereka menampakkan keberadaannya, bahkan sejak masa kemerdekaan 1945. Paper ini meneliti politik identitas yang ditampakkan para ulama yang mempengaruhi para pemilih dalam pemilu presiden. Bagaimana politik identitas itu berpengaruh pada politik dan pilihan serta dukungan presiden? Apakah ulama memainkan sesuatu dalam proses terpilihnya Presiden Joko Widodo, atau adakah faktor lain? Apakah hanya identitas yang menjadi satu-satunya faktor  untuk mendukung Prabowo Subianto atau Joko Widodo?]
New and Promising Strategies in the Management of Bladder Cancer
Authors: Apolo Andrea B. , Vogelzang Nicholas J. , Theodorescu Dan
Published: May 2015

Bladder cancer is a complex and aggressive disease for which treatment strategies have had limited success. Improvements in detection, treatment, and outcomes in bladder cancer will require the integration of multiple new approaches, including genomic profiling, immunotherapeutics, and large randomized clinical trials. New and promising strategies are being tested in all disease states, including nonmuscle-invasive bladder cancer (NMIBC), muscle-invasive bladder cancer (MIBC), and metastatic urothelial carcinoma (UC). Efforts are underway to develop better noninvasive urine biomarkers for use in primary or secondary detection of NMIBC, exploiting our genomic knowledge of mutations in genes such as RAS, FGFR3, PIK3CA, and TP53 and methylation pathways alone or in combination. Recent data from a large, randomized phase III trial of adjuvant cisplatin-based chemotherapy add to our knowledge of the value of perioperative chemotherapy in patients with MIBC. Finally, bladder cancer is one of a growing list of tumor types that respond to immune checkpoint inhibition, opening the potential for new therapeutic strategies for treatment of this complex and aggressive disease.
Targeting the PI3K Pathway in Head and Neck Squamous Cell Carcinoma
Authors: Isaacsson Velho Pedro Henrique , Castro Gilberto , Chung Christine H.
Published: May 2015

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease arising from the mucosal epithelia in the head and neck region. The most common risk factors are tobacco use, alcohol consumption, and HPV infection, particularly in the oropharynx. The HPV-positive HNSCC is biologically and clinically distinct from the HPV-negative HNSCC; however, deregulations within the phosphatidylinositol 3-kinase (PI3K) pathway are frequent in both HPV-positive and HPV-negative HNSCC as it is the most frequently altered oncogenic pathway with a gain-of-function in HNSCC. This article reviews the basic biology and clinical data from the trials involving anticancer agents targeting the PI3K pathway in HNSCC. It also discusses the difficulties of translating the preclinical data to tangible clinical efficacy of these agents in patients with HNSCC even when there is significant preclinical data suggesting the PI3K pathway is a promising therapeutic target in HNSCC. We conclude that additional studies to determine appropriate patient selection for the activation of PI3K pathway and to develop targeted agents either as a monotherapy or combination therapy with favorable toxicity profiles are required before a broader clinical application.
Beyond Adenocarcinoma: Current Treatments and Future Directions for Squamous, Small Cell, and Rare Lung Cancer Histologies
Authors: Gerber David E. , Paik Paul K. , Dowlati Afshin
Published: May 2015

Lung cancer encompasses a diverse spectrum of histologic subtypes. Until recently, the majority of therapeutic advances were limited to the minority of patients with adenocarcinoma. With the advent of comprehensive genomic profiling of squamous and small cell lung cancers, new therapeutic targets have emerged. For squamous tumors, the most promising of these include fibroblast growth factor receptor (FGFR), the phosphatidylinositol 3-kinase (PI3K) pathway, discoidin domain receptor 2 (DDR2), and G1/S checkpoint regulators. In 2014, the antiangiogenic agent ramucirumab was approved for all non–small cell lung cancer (NSCLC) histologies, including squamous tumors. Immunotherapeutic approaches also appear to be promising for these cases. Genomic analysis of small cell lung cancer has revealed a high mutation burden, but relatively few druggable driver oncogenic alterations. Current treatment strategies under investigation are focusing on targeting mitotic, cell cycle, and DNA repair regulation, as well as immunotherapy. Pulmonary neuroendocrine tumors represent a diverse spectrum of diseases that may be treated with somatostatin analogs, cytotoxic agents, and molecularly targeted therapies. Radiolabeled somatostatin analogs and combinations with mammalian target of rapamycin (mTOR) inhibitors also show potential. Large cell neuroendocrine tumors share numerous clinical, pathologic, and molecular features with small cell lung cancer; however, whether they should be treated similarly or according to a NSCLC paradigm remains a matter of debate.
Challenges to Standardizing the Care for Adult Cancer Survivors: Highlighting ASCO's Fatigue and Anxiety and Depression Guidelines
Authors: Partridge Ann H. , Jacobsen Paul B. , Andersen Barbara L.
Published: May 2015

There are over 14 million survivors of cancer living in the United States alone and tens of millions more worldwide, with this population expected to nearly double in the next decade. The successes of prevention, early detection, and better therapies have lead to an emerging understanding of the substantial medical and psychosocial issues for this growing population that must be tackled for individuals and from the health care system and societal perspectives.
Using Social Media to Learn and Communicate: It Is Not About the Tweet
Authors: Thompson Michael A.
Published: May 2015

Social media can be defined as the use of media to interact with social networks. Social media is not about the content of the tweet, inasmuch as the technologies and social media platforms influence how content is generated, disseminated, and used. Social media is not dead, but rather it offers rapid incoming and outgoing forms of communication, which may be utilized in a variety of “use cases” in medicine and oncology.
Application of Molecular Biology to Individualize Therapy for Patients with Liposarcoma
Authors: Abbas Manji Gulam , Singer Samuel , Koff Andrew , Schwartz Gary K.
Published: May 2015

Liposarcomas are one the most common of over 50 histologic subtypes of soft tissue sarcomas that are mostly resistant to chemotherapy. Histologically, liposarcomas themselves are heterogeneous and fall into four distinct subtypes: well-differentiated/atypical lipomatous tumor, dedifferentiated liposarcoma, myxoid (round cell) liposarcoma, and pleomorphic liposarcoma. Surgical resection with negative margins remains the mainstay for definitive treatment for operable disease. For unresectable disease, retrospective studies have identified myxoid (round cell) and pleomorphic sarcomas to be relatively responsive to chemotherapy. Recent studies have identified distinct genetic aberrations that not only aid in the diagnosis of particular liposarcoma subtypes, but represent actionable targets as they are considered central to disease pathogenesis. Cyclin-dependent kinase 4 (CDK4) and murine double minute 2 (MDM2) are overexpressed in well-differentiated and dedifferentiated liposarcomas and offer tantalizing opportunities that are being pursued in clinical trials. Myxoid (round cell) liposarcomas appear to be sensitive to trabectedin, which is currently under U.S. Food and Drug Administration (FDA) review. Liposarcomas do not represent a uniform disease and understanding the underlying molecular mechanism will help not only in accurate diagnosis but in selecting the appropriate treatment.
Early Detection of Cancer: Past, Present, and Future
Authors: Schiffman Joshua D. , Fisher Paul G. , Gibbs Peter
Published: May 2015

Screening in both healthy and high-risk populations offers the opportunity to detect cancer early and with an increased opportunity for treatment and curative intent. Currently, a defined role for screening exists in some cancer types, but each screening test has limitations, and improved screening methods are urgently needed. Unfortunately, many cancers still lack effective screening recommendations, or in some cases, the benefits from screening are marginal when weighed against the potential for harm. Here we review the current status of cancer screening: we examine the role of traditional tumor biomarkers, describe recommended imaging for early tumor surveillance, and explore the potential of promising novel cancer markers such as circulating tumor cells (CTC) and circulating tumor DNA. Consistent challenges for all of these screening tests include limited sensitivity and specificity. The risk for overdiagnosis remains a particular concern in screening, whereby lesions of no clinical consequence may be detected and thus create difficult management decisions for the clinician and patient. If treatment is pursued following overdiagnosis, patients may be exposed to morbidity from a treatment that may not provide any true benefit. The cost-effectiveness of screening tests also needs to be an ongoing focus. The improvement of genomic and surveillance technologies, which leads to more precise imaging and the ability to characterize blood-based tumor markers of greater specificity, offers opportunities for major progress in cancer screening.
Biology and Clinical Management Challenges in Meningioma
Authors: Mawrin Christian , Chung Caroline , Preusser Matthias
Published: May 2015

Meningiomas are the most frequently occurring intracranial tumors. They are characterized by a broad spectrum of histopathologic appearance. Molecular alterations driving meningioma development, which affect the NF2 gene, are found in roughly 50% of patients. Rare genetic events in benign meningiomas are mutations in TRAF7, KLF4, AKT1, and SMO; all of these mutations are exclusive of NF2 alterations. Progression to a clinically aggressive meningioma is linked to inactivation of CDKN2A/ B genes, and a plethora of signaling molecules have been described as activated in meningiomas, which supports the concept of successful clinical use of specific inhibitors. Established treatments include surgical resection with or without radiotherapy delivered in a single fraction, a few large fractions (radiosurgery), or multiple fractions (fractionated radiotherapy). For recurrent and aggressive tumors, inhibitors of the vascular endothelial growth factor (VEGF) pathway, such as vatalinib, bevacizumab, and sunitinib, showed signs of activity in small, uncontrolled studies, and prospective clinical studies will test the efficacy of the tetrahydroisoquinoline trabectedin and of SMO and AKT1 inhibitors.
Neoadjuvant Therapy for Breast Cancer: Controversies in Clinical Trial Design and Standard of Care
Authors: White Julia , DeMichele Angela
Published: May 2015

Neoadjuvant therapy for breast cancer has been increasingly used in recent years as first-line treatment for operable breast cancer—serving as both a management strategy and a research tool. In addition to the established clinical benefits of down-staging more locally advanced cancers and improving breast-conservation rates, investigators have recognized the potential advantages of this approach in developing new therapies. Preoperative systemic therapy provides the opportunity for in vivo assessment of pharmacodynamic markers to assess biologic effects and allows new compounds to be tested in a more responsive, treatment-naive population. In addition, early surrogates of response, such as pathologic complete response (pCR) and residual cancer burden, provide proximate measures that correlate with long-term outcomes, thus potentially shortening the time needed to identify effective adjuvant therapies. Despite the advantages of neoadjuvant therapy for research and clinical practice, its use is characterized by persistent controversy and healthy debate regarding how to optimally use research findings and when to integrate them into the standard of care for daily management. Among the controversies surrounding neoadjuvant therapy use are questions about defining the best endpoint for assessing treatment efficacy, deciding when results from research should be used in daily clinical practice, and how the growing use of neoadjuvant therapy affects locoregional treatments.
Salvage Therapy in Patients with Germ Cell Tumors
Authors: Einhorn Lawrence H.
Published: May 2015

Testicular cancer is the most curable metastatic solid tumor. Initial chemotherapy is evidence based with risk stratification into three prognostic categories: good, intermediate, and advanced disease. Guidelines for disease management following progression after initial cisplatin combination chemotherapy are less clear. Options include salvage surgery for patients with anatomically confined relapse, standard-dose cisplatin combination chemotherapy, or high-dose chemotherapy with carboplatin plus etoposide with peripheral blood stem cell transplantation. Proper interpretation of a presumed relapse can be complicated. Growing masses on imaging studies might reflect a growing teratoma. Persistent elevations of serum human chorionic gonadotropin (hCG) or alpha fetoprotein (AFP) are only an indication for salvage therapy if there is a definitive rise in the tumor marker. Elevated and rising serum hCG as the only evidence of recurrence can be because of cross reactivity with luteinizing hormone or usage of marijuana rather than progressive cancer. Elevated liver function tests can cause rising serum AFP.
Treatment of Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia in Adults: A Broader Range of Options, Improved Outcomes, and More Therapeutic Dilemmas
Authors: Fielding Adele K.
Published: May 2015

The article addresses selected key areas of flux in the management of Philadelphia chromosome–positive acute lymphoblastic leukemia. There is no doubt that tyrosine kinase inhibitors (TKIs) have made a major contribution to higher rates of complete remission and that more patients are now surviving long term. Many patients tolerate TKIs well, and remission can be achieved with minimal toxicity. Because remissions can include a proportion of patients who become BCR-ABL1 transcript negative, the question of whether allogeneic hematopoietic stem cell transplantation can be avoided requires discussion. Despite the major progress that has been made and the relative profusion of therapeutic choice compared with 10 years ago, evidence is still lacking for many of the major possible interventions, and how to combine them is unclear. Because of the rarity of the condition and the enticing possibility of increasing traction to therapy, clinical trials and international cooperation remain paramount.
CD19 CAR Therapy for Acute Lymphoblastic Leukemia
Authors: Sadelain Michel , Brentjens Renier , Rivière Isabelle , Park Jae
Published: May 2015

Chimeric antigen receptor (CAR) therapy is an emerging immunotherapy that shows great promise for cancer, in particular acute lymphoblastic leukemia (ALL). CARs are recombinant receptors for antigen, which, in a single molecule, redirect the specificity and function of T lymphocytes. Following their genetic transfer to patient T cells, the latter acquire the ability to recognize leukemia cells and destroy them. Several years ago, we identified CD19 as an attractive target for CAR therapy for most B cell malignancies, including ALL. We and others have reported remarkable clinical outcomes in adults and children with ALL, achieving a high complete remission rate irrespective of age, prior treatments, or other prognostic markers. Severe cytokine release may develop in patients with high tumor burdens. Several interventions are available to curb the cytokine release syndrome when it occurs. Based on the impressive results obtained with CD19 CAR therapy for ALL, it is realistic to expect that CD19 CARs will become part of the armamentarium for B cell-ALL and other B cell malignancies.
Diagnosing and Managing Advanced Chronic Myeloid Leukemia
Authors: Deininger Michael W.
Published: May 2015

Clinical staging of chronic myeloid leukemia (CML) distinguishes between chronic phase (CP-CML), accelerated phase (AP-CML), and blastic phase (BP-CML), reflecting its natural history in the absence of effective therapy. Morphologically, transformation from CP-CML to AP/BP-CML is characterized by a progressive or sudden loss of differentiation. Multiple different somatic mutations have been implicated in transformation from CP-CML to AP/BC-CML, but no characteristic mutation or combination of mutations have emerged. Gene expression profiles of AP-CML and BP-CML are similar, consistent with biphasic evolution at the molecular level. Gene expression of tyrosine kinase inhibitor (TKI)–resistant CP-CML and second CP-CML resemble AP/BP-CML, suggesting that morphology alone is a poor predictor of biologic behavior. At the clinical level, progression to AP/BP-CML or resistance to first-line TKI therapy distinguishes a good risk condition with survival close to the general population from a disease likely to reduce survival. Progression while receiving TKI therapy is frequently caused by mutations in the target kinase BCR-ABL1, but progression may occur in the absence of explanatory BCR-ABL1 mutations, suggesting involvement of alternative pathways. Identifying patients in whom milestones of TKI response fail to occur or whose disease progress while receiving therapy requires appropriate molecular monitoring. Selection of salvage TKI depends on prior TKI history, comorbidities, and BCR-ABL1 mutation status. Despite the introduction of novel TKIs, therapy of AP/BP-CML remains challenging and requires accepting modalities with substantial toxicity, such as hematopoietic stem cell transplantation (HSCT).