bluuebunny/crossref_metadata_2025_split huggingface dataset:
BQ323636.1, a Novel Splice Variant toNCOR2, as a Predictor for Tamoxifen-Resistant Breast Cancer
Authors: Gong Chun , Man Ellen P.S. , Tsoi Ho , Lee Terence K.W. , Lee Paul , Ma Sai-Ting , Wong Lai-San , Luk Mai-Yee , Rakha Emad A. , Green Andrew R. , Ellis Ian O. , Lam Eric W.-F. , Cheung Kwok-Leung , Khoo Ui-Soon 
Published: February 2018

AbstractPurpose: Adjuvant tamoxifen treatment revolutionized the management of estrogen receptor (ER)–positive breast cancers to prevent cancer recurrence; however, drug resistance compromises its clinical efficacy. The mechanisms underlying tamoxifen resistance are not fully understood, and no robust biomarker is available to reliably predict those who will be resistant. Here, we study BQ323636.1, a novel splice variant of the NCOR2 gene, and evaluate its efficacy in predicting tamoxifen resistance in patients with breast cancer.Experimental Design: A monoclonal anti-BQ323636.1 antibody that specifically recognizes the unique epitope of this splice variant was generated for in vitro mechanistic studies and for in vivo analysis by immunohistochemistry on tissue microarrays of two independent cohorts of 358 patients with more than 10 years clinical follow-up data, who had ER-positive primary breast cancer and received adjuvant tamoxifen treatment. An orthotopic mouse model was also used.Results: Overexpression of BQ323636.1 conferred resistance to tamoxifen in both in vitro and in an orthotopic mouse model. Mechanistically, coimmunoprecipitation showed BQ323636.1 could bind to NCOR2 and inhibit the formation of corepressor complex for the suppression of ER signaling. Nuclear BQ3232636.1 overexpression in patients samples was significantly associated with tamoxifen resistance (P = 1.79 × 10−6, sensitivity 52.9%, specificity 72.0%). In tamoxifen-treated patients, nuclear BQ323636.1 overexpression was significantly correlated with cancer metastasis and disease relapse. Nuclear BQ323636.1 was also significantly associated with poorer overall survival (P = 1.13 × 10−4) and disease-specific survival (P = 4.02 × 10−5).Conclusions: These findings demonstrate that BQ323636.1 can be a reliable biomarker to predict tamoxifen resistance in patients with ER-positive breast cancer. Clin Cancer Res; 24(15); 3681–91. ©2018 AACR.See related commentary by Jordan, p. 3480
Durable Clinical Benefit in Metastatic Renal Cell Carcinoma Patients Who Discontinue PD-1/PD-L1 Therapy for Immune-Related Adverse Events
Authors: Martini Dylan J. , Hamieh Lana , McKay Rana R. , Harshman Lauren C. , Brandao Raphael , Norton Craig K. , Steinharter John A. , Krajewski Katherine M. , Gao Xin , Schutz Fabio A. , McGregor Bradley , Bossé Dominick , Lalani Aly-Khan A. , De Velasco Guillermo , Michaelson M. Dror , McDermott David F. , Choueiri Toni K. 
Published: February 2018

Abstract
The current standard of care for treatment of metastatic renal cell carcinoma (mRCC) patients is PD-1/PD-L1 inhibitors until progression or toxicity. Here, we characterize the clinical outcomes for 19 mRCC patients who experienced an initial clinical response (any degree of tumor shrinkage), but after immune-related adverse events (irAE) discontinued all systemic therapy. Clinical baseline characteristics, outcomes, and survival data were collected. The primary endpoint was time to progression from the date of treatment cessation (TTP). Most patients had clear cell histology and received anti–PD–1/PD-L1 therapy as second-line or later treatment. Median time on PD-1/PD-L1 therapy was 5.5 months (range, 0.7–46.5) and median TTP was 18.4 months (95% CI, 4.7–54.3) per Kaplan–Meier estimation. The irAEs included arthropathies, ophthalmopathies, myositis, pneumonitis, and diarrhea. We demonstrate that 68.4% of patients (n = 13) experienced durable clinical benefit off treatment (TTP of at least 6 months), with 36% (n = 7) of patients remaining off subsequent treatment for over a year after their last dose of anti–PD-1/PD-L1. Three patients with tumor growth found in a follow-up visit, underwent subsequent surgical intervention, and remain off systemic treatment. Nine patients (47.4%) have ongoing irAEs. Our results show that patients who benefitted clinically from anti–PD-1/PD-L1 therapy can experience sustained beneficial responses, not needing further therapies after the initial discontinuation of treatment due to irAEs. Investigation of biomarkers indicating sustained benefit to checkpoint blockers are needed. Cancer Immunol Res; 6(4); 402–8. ©2018 AACR.
Transdisciplinaridade do Design: Niveis de Realidade Distintos
Authors: Vieira Sonia Liliana da Silva 
Published: February 2018

Partindo das noções de disciplina, design e transdisciplinaridade, este artigo faz uma revisão da literatura e desdobra perspectivas sobre e para o desenvolvimento do design transdisciplinar. O design como disciplina, engloba diversas disciplinas de projeto, disciplinas estas anfitriãs do design, que nutrindo o seu espaço particular, se sobrepõem em espaços partilhados, e a suas influências particulares são visíveis em abordagens dorsais e artefactos resultantes. Um dos desafios do design transdisciplinar passa pela identificação das suas invariantes, quer de natureza especifica ou não especifica do design, com influência transdisciplinar capaz de alcançar e influenciar outras disciplinas. Designers, investigadores e educadores almejam identificar tais características. Este conhecimento, uma vez integrado é de grande utilidade e aplicação no desenvolvimento dos processos sociais de investigação, educação e pratica do design.
Central-Eastern China Persistent Heat Waves: Evaluation of the AMIP Models
Authors: Freychet N. , Tett S. F. B. , Hegerl G. C. , Wang J. 
Published: February 2018

Abstract
Large-scale and persistent heat waves affecting central-eastern China are investigated in 40 different simulations of sea surface temperature driven global atmospheric models. The different models are compared with results from reanalysis and ground station datasets. It is found that the dynamics of heat-wave events is well reproduced by the models. However, they tend to produce too-persistent heat-wave events (lasting more than 20 days), and several hypotheses were tested to explain this bias. The daily variability of the temperatures or the seasonal signal did not explain the persistence. However, interannual variability of the temperatures in the models, and especially the sharp transition in the mid-1990s, has a large impact on the duration of heat waves. A filtering method was applied to select the models closest to the observations in terms of events persistence. The selected models do not show a significant difference from the other models for the long-term trends. Thus, the bias on the duration of the events does not impact the reliability of the model positive trends, which is mainly controlled by the changes in mean temperatures.
Stress-activated MAPKs and CRM1 regulate the subcellular localization of Net1A to control cell motility and invasion
Authors: Ulu Arzu , Oh Wonkyung , Zuo Yan , Frost Jeffrey A. 
Published: February 2018

ABSTRACT
The neuroepithelial cell transforming gene 1A (Net1A, an isoform of Net1) is a RhoA subfamily guanine nucleotide exchange factor (GEF) that localizes to the nucleus in the absence of stimulation, preventing it from activating RhoA. Once relocalized in the cytosol, Net1A stimulates cell motility and extracellular matrix invasion. In the present work, we investigated mechanisms responsible for the cytosolic relocalization of Net1A. We demonstrate that inhibition of MAPK pathways blocks Net1A relocalization, with cells being most sensitive to JNK pathway inhibition. Moreover, activation of the JNK or p38 MAPK family pathway is sufficient to elicit Net1A cytosolic localization. Net1A relocalization stimulated by EGF or JNK activation requires nuclear export mediated by CRM1. JNK1 (also known as MAPK8) phosphorylates Net1A on serine 52, and alanine substitution at this site prevents Net1A relocalization caused by EGF or JNK activation. Glutamic acid substitution at this site is sufficient for Net1A relocalization and results in elevated RhoA signaling to stimulate myosin light chain 2 (MLC2, also known as MYL2) phosphorylation and F-actin accumulation. Net1A S52E expression stimulates cell motility, enables Matrigel invasion and promotes invadopodia formation. These data highlight a novel mechanism for controlling the subcellular localization of Net1A to regulate RhoA activation, cell motility, and invasion.
Bromine-Mediated Cross-Dehydrogenative Coupling (CDC) Reactions
Authors: Wang Bin , Wong Henry N C 
Published: February 2018

AbstractSignificant advances in the development of CDC reactions have been made in recent years. However, metal-free CDC reaction remains comparatively under-developed. In view that a variety of readily available, cheap and environmentally friendly bromine reagents have been employed in bromination or oxidation in organic synthesis, we would like to summarize and discuss in this review examples of bromine-mediated CDC reactions, delineating significant and promising applications of these reagents in metal-free functionalization of C-H bonds.
Target volume motion during anal cancer image guided radiotherapy using cone-beam computed tomography
Authors: Brooks Corrinne J , Bernier Laurence , Hansen Vibeke N , Tait Diana M 
Published: February 2018

Objective:
Literature regarding image-guidance and interfractional motion of the anal canal (AC) during anal cancer radiotherapy is sparse. This study investigates interfractional AC motion during anal cancer radiotherapy.

Methods:
Bone matched cone beam CT (CBCT) images were acquired for 20 patients receiving anal cancer radiotherapy allowing population systematic and random error calculations. 12 were selected to investigate interfractional AC motion. Primary anal gross tumour volume and clinical target volume (CTVa) were contoured on each CBCT. CBCT CTVa volumes were compared to planning CTVa. CBCT CTVa volumes were combined into a CBCT-CTVa envelope for each patient. Maximum distortion between each orthogonal border of the planning CTVa and CBCT-CTVa envelope was measured. Frequency, volume and location of CBCT-CTVa envelope beyond the planning target volume (PTVa) was analysed.

Results:
Population systematic and random errors were 1 and 3 mm respectively. 112 CBCTs were analysed in the interfractional motion study. CTVa varied between each imaging session particularly T location patients of anorectal origin. CTVa border expansions ≥ 1 cm were seen inferiorly, anteriorly, posteriorly and left direction. The CBCT-CTVa envelope fell beyond the PTVa ≥ 50% imaging sessions (n = 5). Of these CBCT CTVa distortions beyond PTVa, 44% and 32% were in the upper and lower thirds of PTVa respectively.

Conclusion:
The AC is susceptible to volume changes and shape deformations. Care must be taken when calculating or considering reducing the PTV margin to the anus.

Advances in knowledge:
Within a limited field of research, this study provides further knowledge of how the AC deforms during anal cancer radiotherapy.
Ένα βυζαντινό οικοδομικό συνεργείο στην περιοχή του Σοφικού Κορινθίας
Authors: ΚΑΠΠΑΣ (Michalis KAPPAS) Μιχάλης 
Published: February 2018

Στο κεφαλοχώρι του Σοφικού Κορινθίας σώζεται ένα εξαιρετικού ενδιαφέροντος μνημειακό σύνολο που προσφέρεται για τη διατύπωση σκέψεων πάνω στο δυσεπίλυτο ζήτημα της διάκρισης των στοιχείων της αρχιτεκτονικής του 13ου από εκείνα του 12ου αιώνα. Συνίσταται από πέντε, τουλάχιστον, εκκλησίες στις παρυφές του οικισμού. Το παρόν άρθρο αποσκοπεί στην πληρέστερη παρουσίαση εκείνων των κατασκευαστικών και μορφολογικών στοιχείων που τεκμηριώνουν τη στενή σχέση του συγκεκριμένου μνημειακού συνόλου και ενισχύουν τη χρονολόγησή του εντός της 13ης εκατονταετίας. Εξετάζονται επιμέρους μορφολογικά στοιχεία ως προς τον τρόπο διαμόρφωσης των τρούλων, των παραθύρων και των ψευδοπαραθύρων, καθώς επίσης και ως προς τον τρόπο προσαρμογής των αγγείων στις όψεις των εκκλησιών της περιοχής του Σοφικού, και γίνονται συγκρίσεις με άλλα μνημεία από τον νότιο ελλαδικό χώρο.
An unknown work by George Klontzas: the icon of St. George the Dragonslayer in Corfu
Authors: TSIOURIS (Ιωάννης ΤΣΙΟΥΡΗΣ) Ioannis 
Published: February 2018

Η σχετικά άγνωστη εικόνα του αγίου Γεωργίου δρακοντοκτόνου φυλάσσεται στον ναό των Αγίων Πατέρων στην πόλη της Κέρκυρας. Ο τρόπος απεικόνισης του αγίου Γεωργίου, η απόδοση μορφών με δυτικότροπα ρεαλιστικά χαρακτηριστικά, η έντονη διακοσμητική διάθεση, τα είδη των πανοπλιών, η ιπποσκευή και συγκεκριμένα αρχιτεκτονικά στοιχεία συνδέουν την εικόνα με το έργο του Γεωργίου Κλόντζα. Τα εικονογραφικά και τεχνοτροπικά χαρακτηριστικά οδηγούν στην αναγνώρισή της ως αυτόγραφο έργο του Γεωργίου Κλόντζα και στη χρονολόγησή της στο τελευταίοτέταρτο του 16ου αιώνα.
Τα βημόθυρα του τέμπλου της μονής του Αγίου Νικολάου Τζώρας Ιωαννίνων
Authors: ΚΑΡΑΜΠΕΡΙΔΗ (Argyro KARAMPERIDI) Αργυρώ 
Published: February 2018

Το ζεύγος βημοθύρων προέρχεται από το τέμπλο του καθολικού της μονής Αγίου Νικολάου Τζώρας, στο όρος Δρίσκος Ιωαννίνων. Τα βημόθυρα, κοσμημένα με τη συνήθη παράσταση του Ευαγγελισμού χρονολογούνται στο πρώτο μισό του 16ου αιώνα, πιθανώς στην τρίτη ή τέταρτη δεκαετία. Εικονογραφικές λεπτομέρειες αλλά κυρίως η αριστοτεχνική απόδοση των μορφών, η χρωματική κλίμακα, ο γύψινος ανάγλυφος διάκοσμος του πλαισίου τους επιτρέπουν τη σύνδεση των έργων αυτών με τα μεγάλα καλλιτεχνικά ρεύματα της εποχής, και ιδιαίτερα με τον κύκλο τουζωγράφου Φράγγου Κατελάνου.
New epigraphic evidence from Mani. The Kaphiona epigrams
Authors: KATSAFADOS (Παναγιώτης Στ. ΚΑΤΣΑΦΑΔΟΣ) Panayotis St. 
Published: February 2018

Στο άρθρο γίνεται αναλυτική παρουσίαση του διασωθέντος κειμένου και προτείνεται προκαταρκτική, κατά το δυνατόν, αποκατάσταση δύο επιγραμμάτων στην εκκλησία των Αγίων Θεοδώρων στην Καφιόνα της Μέσα Μάνης. Πρόκειται για δύο από τα ελάχιστα δείγματα επιτοίχιων έμμετρων επιγραφών στην περιοχή, οι οποίες σήμερα είναι δυσανάγνωστες. Παρ’ όλα αυτά, προσεκτική επιγραφική και παλαιογραφική μελέτη αποκαλύπτει ότι πρόκειται για εξαιρετικά δείγματα από αισθητική και λόγια άποψη, τα οποία παράλληλα συνεισφέρουν τόσο στην ιστορική γνώση όσο και στις γνώμες για την εγγραμματοσύνη των κατοίκων της Μάνης, την πρώτη μετά τους Φράγκους περίοδο. Ως χρονολογία γραφής τους εκτιμάται το καλοκαίρι του 1264.
El gobierno del suelo urbano: representaciones y estrategias de articulación-acción de los actores estatales
Authors: Gargantini Daniela Mariana , Martiarena Miguel Ángel , D'Amico Desiree Alda 
Published: February 2018

Los conflictos urbanos remiten a realidades sociales producto de situaciones materiales comprobables, pero que pueden permanecer latentes si no son socialmente problematizadas. Su instalación en la agenda pública depende de los modos en que los actores sociales definen una situación como problemática e identifican sus estrategias de resolución. El acceso al suelo constituye uno de los principales conflictos urbanos dado su rol esencial en la consecución de un hábitat digno y de inclusión en la ciudad, por lo que considerar las representaciones y redes de articulación-acción de los actores involucrados favorece y potencia la comprensión sobre las miradas y posturas que condicionan la producción física y simbólica de la ciudad. En este artículo se exponen los avances sobre el estudio del gobierno del suelo urbano en Córdoba capital (Argentina) y en él se consideran las representaciones de todos los actores sociales involucrados (estatales, económicos y comunitarios); además, indaga particularmente las de los actores estatales, en sus lógicas de comprensiónacción y en sus relaciones de articulación en lo referente a este conflicto. Se busca contribuir a la comprensión de la complejidad de las problemáticas asociadas al acceso, el control y el gobierno del suelo urbano, para así facilitar su visibilización y la proposición de estrategias de resolución.
The natural history of spinal deformity in patients with Coffin-Lowry syndrome
Authors: Welborn M. , Farrell S. , Knott P. , Mayekar E. , Mardjetko S. 
Published: February 2018

Purpose Little is known about the natural history of spinal deformities in Coffin-Lowry syndrome (CLS). Our goal was to evaluate the spinal deformity progression and clinical impact. Methods In this institutional review board-approved study, we performed a multinational retrospective review of six male CLS patients, aged 13 to 22 years at final follow-up, for a mean of 7.25 years (3 to 13). Results All showed delayed skeletal maturity. Three had calcifications of their lower cervical ligamentum flavum, all experienced neural axis abnormalities, including lower extremity weakness, numbness and tingling and in one, quadriparesis. Only two were ambulatory at final follow-up. All had significant spinal abnormalities, including severe progressive thoracic lordosis, thoracolumbar kyphosis and scoliosis. All had undergone spinal fusion or were being evaluated for surgery. Conclusion CLS is a rare X-linked mutation in the RSK2 gene, affecting between 1/50 000 to 100 000 people. There are two reports in the literature of patients with calcifications of their ligamentum flavum. Both had neural axis abnormalities and one had acute onset quadriplegia. Analysis of their ligamentum flavum found abundant central calcifications. Despite our small cohort we found 50% had calcifications and 100% had neurologic consequences associated with those calcifications. There was a 100% rate of deformity progression. They all exhibited delay in skeletal maturity, which mandates longer follow-up and has implications for surgical planning. From our cohort and literature review, the natural history of CLS supports frequent patient evaluation and a lower threshold for correction of spinal deformities. Aiming to avoid spinal cord compression and improve or avoid neurological deterioration. Level of Evidence IV - retrospective study
Binary and analogue markers of skeletal maturity: Clinical utility of the thenar and plantar sesamoids
Authors: Nicholson A. D. , Sanders J. O. , Liu R. W. , Cooperman D. R. 
Published: February 2018

Purpose We investigate the thenar and plantar sesamoids as markers of skeletal maturity, and grade appearance using two scales, a binary system (absent or present), and an analogue system that relies upon judging regular changes in morphological appearance. Methods We studied 94 healthy children (49 female and 45 male patients) between ages three and 18 years who had approximately 700 serially acquired sets of radiographs and physical examinations. The children had at least annual radiographs taken of the left hand and left foot. Velocity of growth was calculated and curves were fit to a cubic spline model to determine age of maximum height velocity, or peak height velocity (PHV). Appearance of the plantar and thenar sesamoids was recorded using a binary system classifying the sesamoids as absent or present and an analogue system classifying the sesamoid as absent, present as a small ossification centre or larger than a small ossification centre. Results The plantar sesamoids appear 1.67 years before PHV and reach mature size 1.02 years after PHV. The thenar sesamoids appear 0.32 years before PHV and reach mature size 2.25 years after PHV. The plantar sesamoids are present and thenar sesamoids are absent at a mean 1.5 years prior to PHV. No patients had the thenar sesamoids present while the plantar sesamoids were absent. Conclusion As binary markers, when the plantar and thenar sesamoids are considered together it is possible to localize maturity. As analogue markers, they offer more information. The sesamoids also allow clarification of the calcaneal and Sanders stages. Level of Evidence Not Applicable.
[Insert emoji or avatar here]: Phenomenology and digital research
Authors: Blackmon Stephanie J. 
Published: February 2018

Abstract
The way people engage and communicate with each other has changed tremendously since the advent of virtual worlds and other online learning and social networking modalities. Technological advances have made it possible for people to interact with each other and environments differently. For researchers interested in these environments and people’s experiences with them, traditional research methods may not capture the nuanced nature of these online interactions. Some researchers continue to use traditional methods to examine participants’ online experiences. However, other researchers have adapted traditional methods to fit the unique nature of online environments. In a similar fashion, this work proposes a way to conduct phenomenological research that is specific to the online environment. The work deals specifically with the way one researcher conducted a study in a virtual world, but these methods can be used in other online environments as well.
Worlds in and of motion: Agency and animation at the margins of video game aesthetics
Authors: Johnson Daniel 
Published: February 2018

Abstract
What is the relationship between player-controlled movement and animation in game media? How do game worlds respond to the movement of characters through different types of space? This article will draw on concepts such as animation, figuration and vitality to analyse some of the ways that in-game animations and graphical rendering activity are activated by player-controlled movement through three-dimensional game environments. The sudden ‘blinking in’ of environmental features in the distant horizon as the player approaches and more gradual ‘filling in’ of graphical detail in objects such as plants, rocks and shadows close to the player character/camera in games such as Red Dead Redemption and Shadow of the Colossus provide materials for considering how animation might be developed as a concept for describing the connection between player agency and game-world visual activity in the said media. Graphical rendering properties such as draw distance and texture pop-in that are tied to the spatial relationship between a player character/camera and game-world objects will be some of the primary ways this dynamic of movement and animation will be analysed.
Book Review
Authors: Henderson Brian 
Published: February 2018

Abstract
Educating in a virtual world

Learning in Virtual Worlds: Research and Applications, Sue Gregory, Mark J. W. Lee, Barney Dalgarno and Belinda Tynan (eds) (2016)
1st ed., Edmonton, Alberta: Athabasca University Press, 319 pp.,
ISBN: 9781771991339, p/bk, $39.95 (CAD)