bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Foot Self-Care in Patients With Diabetes
Authors: Navarro-Flores Emmanuel , Gijón-Noguerón Gabriel , Cervera-Marín José Antonio , Labajos-Manzanares María Teresa
Published: May 2015

Introduction. The purpose of this article is to assess the current status of the relationship between foot self-care and self-examination and the development of complications of diabetes mellitus. Methodology. A systematic review of articles. We extracted assessments of health habits with regard to educational and training interventions intended for diabetic foot health care. We included clinical trials, meta-analysis, and Cochrane Reviews from 2008 to December 2014. Results. We included 34 articles in this review. The initial number of articles selected was 35, including 12 from PubMed, 12 from Webs of Knowledge, and 4 Cochrane reviews that were considered valid as they complied with the requirements set: they related to interventions reducing foot complications caused by diabetes. Conclusion. Strategies aimed at behavioral changes are effective for the metabolic control of the disease and for the reduction of amputations. However, given the current methodology deficit existing in most studies with regard to sample selection and length of the study, it is necessary to validate a reliable tool or measurement to indicate the status of healthy behavior development and to sustain such measures over time.

Levels of Evidence: Therapeutic, Level III: Systematic review of level I-III studies
Pictorial Review and Basic Principles of Foot and Ankle Hardware Extraction
Authors: Wagoner Matthew R. , Creech Corine L. , Nolan Christine K. , Meyr Andrew J.
Published: May 2015

This pictorial review presents basic principles of the types of hardware extraction commonly encountered in foot and ankle surgical practice. We review the indications, contraindications and complications of hardware removal including pain, intra-articular fixation, and carcinogenesis, as well as special considerations in pediatric patients and in the setting of infection. Figures are then used to describe the appropriate techniques for use of the screwdriver shafts, conical extraction screws, extraction bolts, hollow reamers, and other instruments found in most hardware extraction sets.

Levels of Evidence: Therapeutic, Level V: Expert opinion
In Vivo Talocrural Joint Contact Mechanics With Functional Ankle Instability
Authors: Kobayashi Takumi , Suzuki Eiichi , Yamazaki Naohito , Suzukawa Makoto , Akaike Atsushi , Shimizu Kuniaki , Gamada Kazuyoshi
Published: May 2015

Background. Functional ankle instability (FAI) may involve abnormal kinematics and contact mechanics during ankle internal rotation. Understanding of these abnormalities is important to prevent secondary problems in patients with FAI. However, there are no in vivo studies that have investigated talocrural joint contact mechanics during weightbearing ankle internal rotation. The objective of this study to determine talocrural contact mechanics during weightbearing ankle internal rotation in patients with FAI. Methods. Twelve male subjects with unilateral FAI (age range, 18-26 years) were enrolled. Computed tomography and fluoroscopic imaging of both lower extremities were obtained during weightbearing passive ankle joint complex rotation. Three-dimensional bone models created from the computed tomographic images were matched to the fluoroscopic images to compute 6 degrees of freedom for talocrural joint kinematics. The closest contact area in the talocrural joint in ankle neutral rotation and maximum internal rotation during either dorsiflexion or plantar flexion was determined using geometric bone models and talocrural joint kinematics data. Results. The closest contact area in the talus shifted anteromedially during ankle dorsiflexion–internal rotation, whereas it shifted posteromedially during ankle plantar flexion–internal rotation. The closest contact area in FAI joints was significantly more medial than that in healthy joints during maximum ankle internal rotation and was associated with excessive talocrural internal rotation or inversion. Discussion. This study demonstrated abnormal talocrural kinematics and contact mechanics in FAI subjects. Such abnormal kinematics may contribute to abnormal contact mechanics and may increase cartilage stress in FAI joints.

Level of Evidence: Therapeutic, Level IV: cross-sectional case-control study
Intraorbital Granular Cell Tumor Ophthalmologic and Radiologic Findings
Authors: de la Vega Gabriela , Villegas Victor M , Velazquez Jose , Barrios Mirelys , Murray Timothy G , Elhammady Mohamed Samy , Sidani Charif
Published: May 2015

Granular cell tumor is a rare soft tissue neoplasm that commonly affects the head and neck regions. We describe a case of a granular cell tumor of the orbit including its clinical presentation, histopathology, and magnetic resonance imaging findings.
Brain MR diffusion tensor imaging in Kennedy’s disease
Authors: Garaci Francesco , Toschi Nicola , Lanzafame Simona , Marfia Girolama A , Marziali Simone , Meschini Alessandro , Di Giuliano Francesca , Simonetti Giovanni , Guerrisi Maria , Massa Roberto , Floris Roberto
Published: May 2015

Introduction

Kennedy’s disease (KD) is a progressive degenerative disorder affecting lower motor neurons. We investigated the correlation between disease severity and whole brain white matter microstructure, including upper motor neuron tracts, by using diffusion-tensor imaging (DTI) in eight patients with KD in whom disease severity was evaluated using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS).

Methods

From DTI acquisitions we obtained maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (L1) and radial diffusivities (L2, L3). We then employed tract-based spatial statistics (TBSS) to investigate within-patient correlations of DTI invariants with ALSFRS and disease duration (DD).

Results

We found a significant correlation between low ALSFRS and 1) low FA values in association commissural and projection fibers, and 2) high L3 values in commissural tracts and fronto-parietal white matter. Additionally, we found a significant association between longer DD and 1) low FA in the genu and body of corpus callosum, association fibers and midbrain and 2) high L1 in projection and association tracts.

Conclusions

The associations between clinical variables and white matter microstructural changes in areas thought to be spared by the disease process support the hypothesis of a multisystem involvement in the complex pathogenic mechanisms responsible for the clinical disability of these patients.
Diffusion characteristics of pediatric pineal tumors
Authors: Choudhri Asim F , Whitehead Matthew T , Siddiqui Adeel , Klimo Paul , Boop Frederick A
Published: May 2015

Background

Diffusion weighted imaging (DWI) has been shown to be helpful in characterizing tumor cellularity, and predicting histology. Several works have evaluated this technique for pineal tumors; however studies to date have not focused on pediatric pineal tumors.

Objective

We evaluated the diffusion characteristics of pediatric pineal tumors to confirm if patterns seen in studies using mixed pediatric and adult populations remain valid.

Materials and methods

This retrospective study was performed after Institutional Review Board approval. We retrospectively evaluated all patients 18 years of age and younger with pineal tumors from a single institution where preoperative diffusion weighted imaging as well as histologic characterization was available.

Results

Twenty patients (13 male, 7 female) with pineal tumors were identified: seven with pineoblastoma, four with Primitive Neuroectodermal Tumor (PNET), two with other pineal tumors, and seven with germ cell tumors including two germinomas, three teratomas, and one mixed germinoma-teratoma. The mean apparent diffusion coefficient (ADC) values in pineoblastoma (544 ± 65 × 10–6 mm2/s) and pineoblastoma/PNET (595 ± 144 × 10–6 mm2/s) was lower than that of the germ cell tumors (1284 ± 334 × 10–6 mm2/s; p < 0.0001 vs pineoblastoma). One highly cellular germinoma had an ADC value of 694 × 10–6 mm2/s.

Conclusion

ADC values can aid in differentiation of pineoblastoma/PNET from germ cell tumors in a population of children with pineal masses.
Neurocutaneous melanosis: Review of a rare non-familial neuroectodermal dysplasia with newer association of cerebellopontine angle cistern lipoma
Authors: Siddiqui Mohammed Azfar , Siddiqui Shaista , Zaman Nuzhat , Ahmad Ibne , Ullah Ekram
Published: May 2015

Neurocutaneous melanosis is a rare neuroectodermal dysplasia with a grave prognosis. It is actually a disorder of neuronal migration at the time of the embryogenesis hence classified as a neurocristopathy. The patients are initially identified by the skin manifestations of the disease in the form of melanocytic naevus which can be hairy or non-hairy. These patients may or may not present with neurological symptoms but often show CNS abnormalities especially on MRI of the brain and the spine. A lot has been described about the disease since the first case described by Rokitansky in 1861, but every time a new CNS pathology is being added to the long list of currently documented pathologies. Herein we describe a case of a 5 yr old boy with seizures and hairy melanocytic naevus over the trunk and back who was diagnosed as a case of Neurocutaneous melanosis on subsequent evaluation by CT and MRI. We also describe the new association of CP angle cistern lipoma with neurocutaneous melanosis.
From Noxious to Public? Tracing Ethical Dynamics of Social Media Platform Conversions
Authors: Ananny Mike
Published: May 2015

Sometimes, some social media marketplaces turn from noxious to public. Why do such conversions happen, what do they reveal about a platform’s definition of “public,” and when should they happen? Drawing on contemporary examples, this article examines some of the empirical and normative dimensions of platform conversions.
What Do We Talk about When We Talk About Animation
Authors: Gershon Ilana
Published: May 2015

What if performance is no longer the dominant trope for understanding the mediated self? What if animation is as or more important as a trope? This essay explores what questions scholars would ask if they were to begin with animation as the starting point.
Up and Out: Journalism, Social Media, and Historical Sensibility
Authors: Anderson C. W.
Published: May 2015

Much of the modern theorizing about journalism and communication attained its robustness due to a powerful convergence of distinct middle-range scholarly findings that emerged primarily in the 1970s and 1980s. In the present day, when we turn our analytical gaze to the relationship between journalism and social media, we thus need to strike a delicate balance between conducting new qualitative research, re-conceptualizing and re-interrogating the classic conclusions of political communication scholarship, and linking these two aspects of research together. However, we might also wish to extend our analytical gaze “out,” interrogating the movement of journalistic technology across history, as well as “up,” looking at how journalism fits within larger structural explanations regarding the shape of political life.
Making Sense of Society Through Social Media
Authors: Bruns Axel
Published: May 2015

All media are social—they are after all media, in between, intermediating between producers and consumers of content, information, conversation, between the actors in the media and the audiences who read, listen, and watch. And the sociality of the media does not stop there: the processes of media production are social processes just as much as the activities of media audiencing. So strictly speaking, all media are social media. But only a particular subset of all media are fundamentally defined by their sociality, and thus distinguished from the mainstream media of print, radio, and television. It is the actual uses which are made of any medium which determine whether it is indeed a social medium—so let us investigate their roles in and interplay with the societies in which they operate.
What’s Social About Social Media?
Authors: Jensen Klaus Bruhn
Published: May 2015

All media are social, in the sense that they establish and maintain relations between and among humans as individuals and collectives, increasingly across space and time. No medium is more social than any other medium. But each medium is social in distinctive ways. So-called social media are distinguished by their potential for many-to-many communication, drawing on and feeding into networks of one-to-one and one-to-many communication, as well.
Social Media: A Phenomenon to be Analyzed
Authors: boyd danah
Published: May 2015

The phenomenon of “social media” has more to do with its cultural positioning than its technological affordances. Rooted in the broader “Web 2.0” landscape, social media helped engineers, entrepreneurs, and everyday people reimagine the role that technology could play in information dissemination, community development, and communication. While the technologies invoked by the phrase social media have a long history, what unfolded in the 2000s reconfigured socio-technical practices in significant ways. Reflecting on the brief history of social media, this essay argues for the need to better understand this phenomenon.
A Call for Compassion in Social Media Studies
Authors: Deuze Mark
Published: May 2015

In social media we can see ourselves live, as much as we are blind to media. Compassion is therefore key in studying the role of social media in everyday life.
Social Media: Human Life
Authors: Couldry Nick
Published: May 2015

This article explores the idea that research into media communications and information has recently undergone a normative turn as more and more writers reflect on the ever deeper embedding of our lives in media, and the possible costs that this entails. Possible ways forward for deepening and addressing this normative turn are explored, based on the particular contribution to media and communications research of social theory.
Going Public on Social Media
Authors: Elmer Greg
Published: May 2015

This brief essay questions the disconnect between the financial goals of social media properties and the concerns of privacy advocates and other new media critics. It is argued that critics of social media often fail to recognize the financial imperative of social media companies, one that requires users to divulge and publicize ever more granular aspects of their daily lives, thoughts, and feelings.
How I Learned to Stop Worrying and Love the Bots
Authors: Jones Steve
Published: May 2015

This articles inquires about the consequences of social bots for the study and understanding of social media.
Platforms Intervene
Authors: Gillespie Tarleton
Published: May 2015

Social media platforms don’t just guide, distort, and facilitate social activity, they also delete some of it. They don’t just link users together, they also suspend them. They don’t just circulate our images and posts, they also algorithmically promote some over others. Platforms pick and choose.
The Social Media Political Subject Is an Infant
Authors: Karatzogianni Athina
Published: May 2015

Any random sampling of a Facebook timeline or Twitter feed, to take the obvious examples, provides a prepackaged view of global politics. It is restrictive because we choose it to reflect our own pet subjects, groups, likes, and world interests. The lens is prejudiced to reflect our race, class, gender, sexuality, ideology, and affective positionality. We enter a social media world as many as 10 or 50 times a day that has ourselves as the center of the universe. This communication world is similar to an infant’s world: Someone else decides what we can see, what we can consume, what is that extra treat we can earn, if we are good: in social media terms, if we pay for it by reputational capital, or simply, if we spend enough money.
Social Media and Distribution Studies
Authors: Braun Josh
Published: May 2015

Social media increasingly trouble our traditional distinctions between distribution concerns on the one hand and editorial concerns on the other. Sites like Facebook and reddit simultaneously serve as distribution platforms, circulating messages addressed to individuals and publics, and as mechanical editors, deciding algorithmically which posts and topics warrant inclusion in the continuous and often overwhelming feed of information delivered to each of our screens. Recent controversies surrounding the manner in which social media companies develop and test software and editorial strategies for curating content may have brought this editor–distributor duality into sharp relief in ways that feel new and at times uncomfortable. But as a number of critical scholars—most notably Michael Warner—have illustrated, the boundary between editorial and distribution concerns has always been highly porous. Framing social media as centers of reflexive distribution not only opens up sociologically interesting questions about how such distribution infrastructures are forged but also about how they affect the “concatenation of texts through time” and the sense of shared attention and imagined community that enable public discourse. This essay argues that the emerging field of “distribution studies” is a compelling lens for the considering social media and their place in society and public life.
My First Piece About Social Media: The Good, the Bad, and the Ugly
Authors: Christensen Christian
Published: May 2015

There is nothing quite like looking back at something you wrote 6 years ago, particularly when the piece was about “new” technology. Your solid points seem extra solid, and your weak points seem unbearably weak. Most importantly, however, you can see the extent to which your thinking was influenced by dominant understandings and frameworks of the time. So, when I was asked to contribute a short thought-piece on social media for this inaugural issue, it occurred to me that it might be of value to look back rather than forward: to re-read something I had written about Twitter and Facebook years ago, and to identify what I got right and what I got wrong. I decided to go all the way back and to look at the very first thing I wrote about social media. This was not an academic piece, but a popular article written for Le Monde Diplomatique on the use of Twitter and Facebook in the aftermath of the 2009 Iranian elections.
Optimization of the Dutch Matrix Test by Random Selection of Sentences From a Preselected Subset
Authors: Houben Rolph , Dreschler Wouter A.
Published: May 2015

Matrix tests are available for speech recognition testing in many languages. For an accurate measurement, a steep psychometric function of the speech materials is required. For existing tests, it would be beneficial if it were possible to further optimize the available materials by increasing the function’s steepness. The objective is to show if the steepness of the psychometric function of an existing matrix test can be increased by selecting a homogeneous subset of recordings with the steepest sentence-based psychometric functions. We took data from a previous multicenter evaluation of the Dutch matrix test (45 normal-hearing listeners). Based on half of the data set, first the sentences (140 out of 311) with a similar speech reception threshold and with the steepest psychometric function (≥9.7%/dB) were selected. Subsequently, the steepness of the psychometric function for this selection was calculated from the remaining (unused) second half of the data set. The calculation showed that the slope increased from 10.2%/dB to 13.7%/dB. The resulting subset did not allow the construction of enough balanced test lists. Therefore, the measurement procedure was changed to randomly select the sentences during testing. Random selection may interfere with a representative occurrence of phonemes. However, in our material, the median phonemic occurrence remained close to that of the original test. This finding indicates that phonemic occurrence is not a critical factor. The work highlights the possibility that existing speech tests might be improved by selecting sentences with a steep psychometric function.
The Role of CTA, MRA, and Sonography in Aortic Dissection
Authors: Sentz Amanda
Published: May 2015

Aortic dissection is an emergent condition requiring rapid diagnosis and immediate treatment. Patients with aortic dissection typically present with complaints of a sudden onset of severe abdominal and back pain. Patients with a suspected dissection may undergo a variety of imaging tests such as computed tomography angiography, sonography, and/or magnetic resonance angiography. The role of these diagnostic imaging modalities for aortic dissection is examined in detail in this literature review. These imaging modalities are compared and contrasted by reviewing their advantages, disadvantages, and overall effectiveness for aortic dissection.
Effect of surface roughness on fatigue performance of additive manufactured Ti–6Al–4V
Authors: Greitemeier D. , Dalle Donne C. , Syassen F. , Eufinger J. , Melz T.
Published: May 2015

Additive manufacturing is increasingly considered for production of high quality, metallic, aerospace parts. Despite the high potential of this manufacturing process to reduce weight and lead time, the fundamental understanding of additive manufactured Ti–6Al–4V material is still at an early stage, especially in the area of fatigue and damage tolerance. This paper covers the effects of inherent surface roughness on the fatigue life. In the as built condition, metallic parts have a poor surface texture, which is generally removed in fatigue critical areas. It is shown that the fatigue properties of Ti–6Al–4V samples, produced by direct metal laser sintering and electron beam melting, are dominated by surface roughness effects. A simple model based on an equivalent initial flaw size is formulated.
Review of Z phase precipitation in 9–12 wt-Cr steels
Authors: Danielsen H. K.
Published: May 2015

For high temperature applications, 9–12 wt-Cr steels in fossil fired power plants rely upon precipitate strengthening from (V,Nb)N MX nitrides for long term creep strength. During prolonged exposure at service temperature, another nitride precipitates: Cr(V,Nb)N Z phase. The Z phases lowly replace MX, eventually causing a breakdown in creep strength. The present paper reviews the Z phase and its behaviour in 9–12 wt-Cr steels including thermodynamic modelling, crystal structure, nucleation process and precipitation rate as a function of chemical composition. The influence of Z phase precipitation upon long term creep strength is assessed from several different 9–12wt-Cr steel grades and alloy design philosophies.
Regulation of actin polymerization by tropomodulin-3 controls megakaryocyte actin organization and platelet biogenesis
Authors: Sui Zhenhua , Nowak Roberta B. , Sanada Chad , Halene Stephanie , Krause Diane S. , Fowler Velia M.
Published: May 2015

Key Points

Tmod3-null embryos have macrothrombocytopenia due to impaired MK cytoplasmic morphogenesis with defective proplatelet formation. F-actin polymerization and organization are disrupted in Tmod3-null MKs and in their proplatelet buds.
How I treat T-cell acute lymphoblastic leukemia in adults
Authors: Litzow Mark R. , Ferrando Adolfo A.
Published: May 2015

T-cell immunophenotype of acute lymphoblastic leukemia (T-ALL) is an uncommon aggressive leukemia that can present with leukemic and/or lymphomatous manifestations. Molecular studies are enhancing our understanding of the pathogenesis of T-ALL, and the discovery of activating mutations of NOTCH1 and FBXW7 in a majority of patients has been a seminal observation. The use of pediatric intensive combination chemotherapy regimens in adolescents and young adults has significantly improved the outcome of patients with T-ALL. The use of nelarabine for relapsed and refractory T-ALL results in responses in a substantial minority of patients. Allogeneic hematopoietic cell transplantation (HCT) still plays a key role in patients with high-risk or relapsed/refractory disease. γ-Secretase inhibitors hold promise for the treatment of patients with NOTCH1 mutations, and the results of clinical trials with these agents are eagerly awaited. It is recommended that younger patients receive a pediatric-intensive regimen. Older and unfit patients can receive suitable multiagent chemotherapy and be allocated to HCT based on their response, risk factors, and comorbidities. Although advances in the treatment of T-ALL have lagged behind those of B-cell ALL, it is hoped that the molecular revolution will enhance our understanding of the pathogenesis and treatment of this aggressive lymphoid malignancy.
Central nervous system relapse in peripheral T-cell lymphomas: a Swedish Lymphoma Registry study
Authors: Ellin Fredrik , Landström Jenny , Jerkeman Mats , Relander Thomas
Published: May 2015

Key Points

CNS involvement at relapse/progression in PTCL occurred at a frequency similar to what is seen in aggressive B-cell lymphomas. Outcome after relapse is generally very poor in patients with PTCL and is not significantly altered by presence of CNS involvement at relapse.
Allogeneic cell transplant expands bone marrow distribution by colonizing previously abandoned areas: an FDG PET/CT analysis
Authors: Fiz Francesco , Marini Cecilia , Campi Cristina , Massone Anna Maria , Podestà Marina , Bottoni Gianluca , Piva Roberta , Bongioanni Francesca , Bacigalupo Andrea , Piana Michele , Sambuceti Gianmario , Frassoni Francesco
Published: May 2015

Key Points

Allogeneic hematopoietic stem cells colonize, other than axial niches, appendicular BM that is abandoned in normal subjects. Bone marrow expansion into distal sites differs between cord blood and adult hematopoietic stem cells.
Distributed video coding supporting hierarchical GOP structures with transmitted motion vectors
Authors: Min Kyung-Yeon , Lim Woong , Nam Junghak , Sim Donggyu , Bajić Ivan V
Published: May 2015

In this paper, we propose a new distributed video coding (DVC) method, with hierarchical group of picture (GOP) structure. Coding gain of DVC can be significantly improved by enlarging GOP size for slow-moving frames. The proposed DVC decoder estimates a side information (SI) frame and transmits motion vectors (MVs) of the SI to the proposed encoder. Using the received MVs from the decoder, the proposed encoder can generate a predicted SI (PSI), which is the same as the SI in the decoder, and estimate the quality of PSI with minimal computational complexity. The proposed method decides the best coding mode among key, Wyner-Ziv (WZ), and skip modes, by estimating rate-distortion costs. Based on the selected best coding mode, the best GOP size can be automatically determined. As the GOP size is adaptively decided depending on the SI quality, entropy and parity bits can be effectively consumed. Experimental results show that the proposed algorithm is around 0.80 dB better in Bjøntegaard delta (BD) bitrate than an existing conventional DVC system.
Prospective functional outcomes in sequential population based cohorts of stage III/ IV oropharyngeal carcinoma patients treated with 3D conformal vs. intensity modulated radiotherapy
Authors: Kerr Paul , Myers Candace L , Butler James , Alessa Mohamed , Lambert Pascal , Cooke Andrew L
Published: May 2015

Background and purpose

To compare early (3 and 6 month) and later (12 and 24 month) functional outcomes of stage III and IV (M0) oropharyngeal squamous cancer patients treated in sequential cohorts with 3D conformal (3DCRT) or intensity modulated radiotherapy (IMRT).

Patients and methods

200 patients in sequential population based cohorts of 83 and 117 patients treated at a single institution with 3DCRT and then IMRT respectively were prospectively assessed at pre-treatment and 3, 6, 12 and 24 months post treatment. A standard functional outcomes protocol including performance status (KPS, ECOG), 3 Performance Status scales for Head and Neck (PSS-HN), the Royal Brisbane Hospital Outcome Measure for Swallowing (RBHOMS), Voice Handicap Index-10 (VHI-10) and self-rated xerostomia were applied.

Results

Mean age at diagnosis was 59 years. The primary site was base of tongue in 77 and tonsil or soft palate in 123 patients. Median follow up was 2.5 years for the second cohort. Concomitant therapy was used in 159 (79.5%). Overall survival at 3 years was 75.6% and 71.5% for IMRT and 3DCRT cohorts respectively (not significant). A multiple imputation technique was used to estimate missing values in order to avoid a healthy patient bias. KPS and ECOG reached nadirs at 3 to 6 months but approached baseline values at 12 to 24 months and did not differ by treatment. The 3 PSS-HN scales, Eating in Public (p < 0.001), Understandability of Speech (p = 0.009) and Oral Diet Texture (p = 0.002) and all showed significantly better outcomes in favor of IMRT. The RBHOMS showed a difference in favor of IMRT which appeared during 3 to 6 months (p < 0.001). The VHI-10 also showed a difference in favor of IMRT (p = 0.015). Self-rated xerostomia did not differ at 3 and 6 months but was significantly better in favor of IMRT after 12 months p = 0.005

Conclusions

A prospectively administered functional outcomes protocol showed meaningful differences in favor of IMRT over 3DCRT early (3–6 months) and later (12–24 months) in the treatment of oropharyngeal carcinoma with equivalent survival. These data support the adoption of IMRT as the standard radiation treatment method for patients with stage III and IV (M0) oropharyngeal squamous carcinoma. KPS and ECOG may not be sensitive to oropharyngeal cancer patients’ functional outcomes by treatment.
Big data and deep data in scanning and electron microscopies: deriving functionality from multidimensional data sets
Authors: Belianinov Alex , Vasudevan Rama , Strelcov Evgheni , Steed Chad , Yang Sang Mo , Tselev Alexander , Jesse Stephen , Biegalski Michael , Shipman Galen , Symons Christopher , Borisevich Albina , Archibald Rick , Kalinin Sergei
Published: May 2015

The development of electron and scanning probe microscopies in the second half of the twentieth century has produced spectacular images of the internal structure and composition of matter with nanometer, molecular, and atomic resolution. Largely, this progress was enabled by computer-assisted methods of microscope operation, data acquisition, and analysis. Advances in imaging technology in the beginning of the twenty-first century have opened the proverbial floodgates on the availability of high-veracity information on structure and functionality. From the hardware perspective, high-resolution imaging methods now routinely resolve atomic positions with approximately picometer precision, allowing for quantitative measurements of individual bond lengths and angles. Similarly, functional imaging often leads to multidimensional data sets containing partial or full information on properties of interest, acquired as a function of multiple parameters (time, temperature, or other external stimuli). Here, we review several recent applications of the big and deep data analysis methods to visualize, compress, and translate this multidimensional structural and functional data into physically and chemically relevant information.
Genetic and cellular dissection of the activation of AM14 rheumatoid factor B cells in a mouse model of lupus
Authors: Sang Allison , Zheng Ying Yi , Choi Seung-Chul , Zeumer Leilani , Morel Laurence
Published: May 2015

The RF-specific AM14 tg BCR has been used as a model to dissect the mechanisms of B cell tolerance to ICs containing nucleic acids. We have shown previously that AM14 RF B cells break tolerance in the TC mouse model of lupus through the dual engagement of the AM14 BCR and TLR9. In this study, we showed that neither the expression of Sle1 or Sle2 susceptibility loci alone was sufficient to activate AM14 RF B cells, suggesting that the production of antichromatin IgG2aa autoAg mediated by Sle1 and an intrinsically higher B cell activation mediated by Sle2 were required. We also showed that the B6 genetic background enhanced the selection of AM14 RF B cells to the MZB cell compartment regardless of the expression of the Sle loci and therefore, of their activation into AFCs. Furthermore, some AM14 RF B cells were selected into the B-1a compartment, where they did not differentiate into AFCs. Therefore, it is unlikely that the selection of AM14 RF B cells to the MZB or B-1a cell compartments in TC.AM14a mice is responsible for their breach of tolerance. Finally, we showed that the presence of expression of Sle1 in non-tg cells, most likely T cells, is necessary for the activation of AM14 RF B cells into AFCs. Overall, these results suggest a threshold model of activation of AM14 RF B cells on the B6 background with additive genetic and cellular contribution of multiple sources.
Prediagnostic Sex Steroid Hormones in Relation to Male Breast Cancer Risk
Authors: Brinton Louise A. , Key Tim J. , Kolonel Laurence N. , Michels Karin B. , Sesso Howard D. , Ursin Giske , Van Den Eeden Stephen K. , Wood Shannon N. , Falk Roni T. , Parisi Dominick , Guillemette Chantal , Caron Patrick , Turcotte Véronique , Habel Laurel A. , Isaacs Claudine J. , Riboli Elio , Weiderpass Elisabete , Cook Michael B.
Published: May 2015

Purpose

Although previous studies have implicated a variety of hormone-related risk factors in the etiology of male breast cancers, no previous studies have examined the effects of endogenous hormones.

Patients and Methods

Within the Male Breast Cancer Pooling Project, an international consortium comprising 21 case-control and cohort investigations, a subset of seven prospective cohort studies were able to contribute prediagnostic serum or plasma samples for hormone quantitation. Using a nested case-control design, multivariable unconditional logistic regression analyses estimated odds ratios and 95% CIs for associations between male breast cancer risk and 11 individual estrogens and androgens, as well as selected ratios of these analytes.

Results

Data from 101 cases and 217 matched controls were analyzed. After adjustment for age and date of blood draw, race, and body mass index, androgens were found to be largely unrelated to risk, but circulating estradiol levels showed a significant association. Men in the highest quartile had an odds ratio of 2.47 (95% CI, 1.10 to 5.58) compared with those in the lowest quartile (trend P = .06). Assessment of estradiol as a ratio to various individual androgens or sum of androgens showed no further enhancement of risk. These relations were not significantly modified by either age or body mass index, although estradiol was slightly more strongly related to breast cancers occurring among younger (age < 67 years) than older men.

Conclusion

Our results support the notion of an important role for estradiol in the etiology of male breast cancers, similar to female breast cancers.
Course and Predictors of Cognitive Function in Patients With Prostate Cancer Receiving Androgen-Deprivation Therapy: A Controlled Comparison
Authors: Gonzalez Brian D. , Jim Heather S.L. , Booth-Jones Margaret , Small Brent J. , Sutton Steven K. , Lin Hui-Yi , Park Jong Y. , Spiess Philippe E. , Fishman Mayer N. , Jacobsen Paul B.
Published: May 2015

Purpose

Men receiving androgen-deprivation therapy (ADT) for prostate cancer may be at risk for cognitive impairment; however, evidence is mixed in the existing literature. Our study examined the impact of ADT on impaired cognitive performance and explored potential demographic and genetic predictors of impaired performance.

Patients and Methods

Patients with prostate cancer were assessed before or within 21 days of starting ADT (n = 58) and 6 and 12 months later. Age- and education-matched patients with prostate cancer treated with prostatectomy only (n = 84) and men without prostate cancer (n = 88) were assessed at similar intervals. Participants provided baseline blood samples for genotyping. Mean-level cognitive performance was compared using mixed models; cognitive impairment was compared using generalized estimating equations.

Results

ADT recipients demonstrated higher rates of impaired cognitive performance over time relative to all controls (P = .01). Groups did not differ at baseline (P > .05); however, ADT recipients were more likely to demonstrate impaired performance within 6 and 12 months (P for both comparisons < .05). Baseline age, cognitive reserve, depressive symptoms, fatigue, and hot flash interference did not moderate the impact of ADT on impaired cognitive performance (P for all comparisons ≥ .09). In exploratory genetic analyses, GNB3 single-nucleotide polymorphism rs1047776 was associated with increased rates of impaired performance over time in the ADT group (P < .001).

Conclusion

Men treated with ADT were more likely to demonstrate impaired cognitive performance within 6 months after starting ADT relative to matched controls and to continue to do so within 12 months after starting ADT. If confirmed, findings may have implications for patient education regarding the risks and benefits of ADT.
Phase I Study of Single-Agent AZD1775 (MK-1775), a Wee1 Kinase Inhibitor, in Patients With Refractory Solid Tumors
Authors: Do Khanh , Wilsker Deborah , Ji Jiuping , Zlott Jennifer , Freshwater Tomoko , Kinders Robert J. , Collins Jerry , Chen Alice P. , Doroshow James H. , Kummar Shivaani
Published: May 2015

Purpose

Wee1 tyrosine kinase phosphorylates and inactivates cyclin-dependent kinase (Cdk) 1/2 in response to DNA damage. AZD1775 is a first-in-class inhibitor of Wee1 kinase with single-agent antitumor activity in preclinical models. We conducted a phase I study of single-agent AZD1775 in adult patients with refractory solid tumors to determine its maximum-tolerated dose (MTD), pharmacokinetics, and modulation of phosphorylated Tyr15-Cdk (pY15-Cdk) and phosphorylated histone H2AX (γH2AX) levels in paired tumor biopsies.

Patients and Methods

AZD1775 was administered orally twice per day over 2.5 days per week for up to 2 weeks per 21-day cycle (3 + 3 design). At the MTD, paired tumor biopsies were obtained at baseline and after the fifth dose to determine pY15-Cdk and γH2AX levels. Six patients with BRCA-mutant solid tumors were also enrolled at the MTD.

Results

Twenty-five patients were enrolled. The MTD was established as 225 mg twice per day orally over 2.5 days per week for 2 weeks per 21-day cycle. Confirmed partial responses were observed in two patients carrying BRCA mutations: one with head and neck cancer and one with ovarian cancer. Common toxicities were myelosuppression and diarrhea. Dose-limiting toxicities were supraventricular tachyarrhythmia and myelosuppression. Accumulation of drug (t1/2 approximately 11 hours) was observed. Reduction in pY15-Cdk levels (two of five paired biopsies) and increases in γH2AX levels (three of five paired biopsies) were demonstrated.

Conclusion

This is the first report of AZD1775 single-agent activity in patients carrying BRCA mutations. Proof-of-mechanism was demonstrated by target modulation and DNA damage response in paired tumor biopsies.
Pancreatic Islet APJ Deletion Reduces Islet Density and Glucose Tolerance in Mice
Authors: Han Song , Englander Ella W. , Gomez Guillermo A. , Rastellini Cristiana , Quertermous Thomas , Kundu Ramendra K. , Greeley George H.
Published: May 2015

Protection and replenishment of a functional pancreatic β-cell mass (BCM) are key goals of all diabetes therapies. Apelin, a small regulatory peptide, is the endogenous ligand for the apelin receptor (APJ) receptor. The apelin-APJ signaling system is expressed in rodent and human islet cells. Apelin exposure has been shown to inhibit and to stimulate insulin secretion. Our aim was to assess the influence of a selective APJ deletion in pancreatic islet cells on islet homeostasis and glucose tolerance in mice. Cre-LoxP strategy was utilized to mediate islet APJ deletion. APJ deletion in islet cells (APJΔislet) resulted in a significantly reduced islet size, density and BCM. An ip glucose tolerance test showed significantly impaired glucose clearance in APJΔislet mice. APJΔislet mice were not insulin resistant and in vivo glucose-stimulated insulin secretion was reduced modestly. In vitro glucose-stimulated insulin secretion showed a significantly reduced insulin secretion by islets from APJΔislet mice. Glucose clearance in response to ip glucose tolerance test in obese APJΔislet mice fed a chronic high-fat (HF) diet, but not pregnant APJΔislet mice, was impaired significantly. In addition, the obesity-induced adaptive elevations in mean islet size and fractional islet area were reduced significantly in obese APJΔislet mice when compared with wild-type mice. Together, these findings demonstrate a stimulatory role for the islet cell apelin-APJ signaling axis in regulation of pancreatic islet homeostasis and in metabolic induced β-cell hyperplasia. The results indicate the apelin-APJ system can be exploited for replenishment of BCM.
The cuticle modulates ultraviolet reflectance of avian eggshells
Authors: Fecheyr-Lippens Daphne C. , Igic Branislav , D'Alba Liliana , Hanley Daniel , Verdes Aida , Holford Mande , Waterhouse Geoffrey I. N. , Grim Tomas , Hauber Mark E. , Shawkey Matthew D.
Published: May 2015

Avian eggshells are variedly coloured, yet only two pigments, biliverdin and protoporphyrin IX, are known to contribute to the dramatic diversity of their colours. By contrast, the contributions of structural or other chemical components of the eggshell are poorly understood. For example, unpigmented eggshells, which appear white to the human eye, vary in their ultraviolet (UV) reflectance, which may be detectable by birds. We investigated the proximate mechanisms for the variation in UV-reflectance of unpigmented bird eggshells using spectrophotometry, electron microscopy, chemical analyses, and experimental manipulations. We specifically tested how UV-reflectance is affected by the eggshell cuticle, the outermost layer of most avian eggshells. The chemical dissolution of the outer eggshell layers, including the cuticle, increased UV-reflectance for only eggshells that contained a cuticle. Our findings demonstrate that the outer eggshell layers, including the cuticle, absorb UV-light, probably because they contain higher levels of organic components and other chemicals, such as calcium phosphates, compared to the predominantly calcite-based eggshell matrix. These data highlight the need to examine factors other than the known pigments in studies of avian eggshell colour.
Glypican4 promotes cardiac specification and differentiation by attenuating canonical Wnt and Bmp signaling
Authors: Strate Ina , Tessadori Federico , Bakkers Jeroen
Published: May 2015

Glypicans are heparan sulphate proteoglycans (HSPGs) attached to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor, and interact with various extracellular growth factors and receptors. The Drosophila division abnormal delayed (dally) was the first glypican loss-of-function mutant described that displays disrupted cell divisions in the eye and morphological defects in the wing. In human, as in most vertebrates, six glypican-encoding genes have been identified (GPC1-6), and mutations in several glypican genes cause multiple malformations including congenital heart defects. To understand better the role of glypicans during heart development, we studied the zebrafish knypek mutant, which is deficient for Gpc4. Our results demonstrate that knypek/gpc4 mutant embryos display severe cardiac defects, most apparent by a strong reduction in cardiomyocyte numbers. Cell-tracing experiments, using photoconvertable fluorescent proteins and genetic labeling, demonstrate that Gpc4 ‘Knypek’ is required for specification of cardiac progenitor cells and their differentiation into cardiomyocytes. Mechanistically, we show that Bmp signaling is enhanced in the anterior lateral plate mesoderm of knypek/gpc4 mutants and that genetic inhibition of Bmp signaling rescues the cardiomyocyte differentiation defect observed in knypek/gpc4 embryos. In addition, canonical Wnt signaling is upregulated in knypek/gpc4 embryos, and inhibiting canonical Wnt signaling in knypek/gpc4 embryos by overexpression of the Wnt inhibitor Dkk1 restores normal cardiomyocyte numbers. Therefore, we conclude that Gpc4 is required to attenuate both canonical Wnt and Bmp signaling in the anterior lateral plate mesoderm to allow cardiac progenitor cells to specify and differentiate into cardiomyocytes. This provides a possible explanation for how congenital heart defects arise in glypican-deficient patients.
Live imaging of endogenous protein dynamics in zebrafish using chromobodies
Authors: Panza Paolo , Maier Julia , Schmees Christian , Rothbauer Ulrich , Söllner Christian
Published: May 2015

Chromobodies are intracellular nanoprobes that combine the specificity of antibodies with the convenience of live fluorescence imaging in a flexible, DNA-encoded reagent. Here, we present the first application of this technique to an intact living vertebrate organism. We generated zebrafish lines expressing chromobodies that trace the major cytoskeletal component actin and the cell cycle marker PCNA with spatial and temporal specificity. Using these chromobodies, we captured full localization dynamics of the endogenous antigens in different cell types and at different stages of development. For the first time, the chromobody technology enables live imaging of endogenous subcellular structures in an animal, with the remarkable advantage of avoiding target protein overexpression or tagging. In combination with improved chromobody selection systems, we anticipate a rapid adaptation of this technique to new intracellular antigens and model organisms, allowing the faithful description of cellular and molecular processes in their dynamic state.
Hematopoietic development at high altitude: blood stem cells put to the test
Authors: Zovein Ann C. , Forsberg E. Camilla
Published: May 2015

In February 2015, over 200 scientists gathered for the Keystone Hematopoiesis meeting, which was held at the scenic Keystone Resort in Keystone, Colorado, USA. The meeting organizers, Patricia Ernst, Hanna Mikkola and Timm Schroeder, put together an exciting program, during which field leaders and new investigators presented discoveries that spanned developmental and adult hematopoiesis within both physiologic and pathologic contexts. Collectively, the program highlighted the increasing pace of new discoveries and the substantial progress made in the hematopoiesis field since the last Keystone meeting two years ago. In this Meeting Review, we highlight the main concepts discussed at the conference, with an emphasis on topics relevant to developmental biology.