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CDK4/6 inhibitors such as palbociclib in combination with endocrine therapy (ET) have remarkablyimproved the outcome of patients with ER+/HER2- metastatic breast cancer (MBC). However, manypatients are intrinsically resistant to CDK4/6i therapy, and those who respond eventually acquireresistance. Although high baseline CCNE1 expression and rare alterations in RB1 and FAT1 geneshave been shown to be associated with CDK4/6i resistance, the molecular mechanisms of CDK4/6iresistance are complex and remain poorly understood. To better understand and overcome CDK4/6iresistance, we performed multi-omics profiling of paired tumor biopsies from ER+/HER2- MBCpatients treated with palbociclib combined with ET. Tumor biopsies taken at pre-treatment, on-treatment, and progressive disease (PD) from 71 patients were profiled using whole-exomesequencing (WES), whole-transcriptome sequencing (RNA-Seq) and IHC analysis. Ourcomprehensive analysis identified several tumor intrinsic molecular markers associated with worsePFS, including the Luminal B subtype (p=0.012, HR=2.593), BRCA1/2 pathogenic mutation (p=0.012,HR=2.67) and mutation signatures linked to APOBEC enzymatic activity (p=0.002, HR=3.19).Conversely, the estrogen response signature (p=0.006, HR=0.43) was associated with favorableprognosis. Unsupervised analysis revealed a cluster of tumors enriched in homologousrecombination deficiency (HRD) linked genomic scars that was associated with poor prognosis(p=0.005, HR=2.49). Of note, these HRD-high tumors responded even more poorly to treatment whenco-occurring with TP53 somatic mutations. Integrative analysis further identified three poorprognosis clusters (IC2-4) enriched in Luminal B, proliferative and HRD features when compared tothe favorable prognosis cluster (IC1).Comparing baseline vs. PD samples, we observed a pattern of post-treatment enrichment for the poorprognosis markers. In addition, breast cancer-associated genes such as BRCA1/2, TP53 and PTENharbored a higher prevalence of genomic alterations including somatic mutation, amplification,. deletion and gene fusion at PD. Cell cycle gene expression and signatures also markedly increased atPD compared to baseline whereas estrogen response signatures decreased. Upon diseaseprogression, tumors had frequently switched to molecular subtypes with aggressive and estrogenindependent characteristics, demonstrating high plasticity in response to CDK4/6i and ET treatment.These patterns of acquired resistance were validated by IHC analysis of cyclins E1 and E2, Ki67 andpRb. To investigate the genomic alterations responsible for acquired resistance, we compared 21paired baseline and PD samples. We observed that PD-specific RB1 loss-of-function events occurredwith higher prevalence than previously reported, underscoring a major role of cell cycle de-regulation in conferring resistance to CDK4/6 inhibition. In this prospective longitudinal multi-omicsstudy, we identified novel candidate biomarkers that can be used to improve prediction of responseto CDK4/6i. In addition, we derived new insights into the molecular mechanisms of drug resistanceto palbociclib plus ET that will help guide therapeutic strategies and drug development inHR+/HER2− MBC. Citation Format: Zhengyan Kan, Seock-Ah Im, Kyunghee Park, Ji Wen, Kyung-Hun Lee, Yoon-La Choi, Won-Chul Lee, Ahrum Min, Vinicius Bonato, Seri Park, Sripad Ram, Dae-Won Lee, Ji-Yeon Kim, Su Kyeong Lee, Won-Woo Lee, Jisook Lee, Miso Kim, Scott L. Weinrich, Han Suk Ryu, Tae Yong Kim, Stephen Dann, Diane Fernandez, Jiwon Koh, Song Yi Park, Shibing Deng, Eric Powell, Rupesh Kanchi Ravi, Jadwiga Bienkowska, Paul A. Rejto, Woong-Yang Park, Yeon Hee Park. Serial genomic profiling reveals molecular mechanisms of breast cancer resistance to palbociclib [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD2-08.

PURPOSE: Although 3D food printing is expected to enable the creation of visually appealing pureed food for people with disability and dysphagia, little is known about the user experience in engaging with 3D food printing or the feasibility of use with populations who need texture-modified foods. The aim of this study was to explore the feasibility and usability of using domestic-scale 3D food printer as an assistive technology to print pureed food into attractive food shapes for people with dysphagia. MATERIALS AND METHODS: In total, 16 participants engaged in the unfamiliar, novel process of using a domestic-scale 3D food printer (choosing, printing, tasting), designed for printing pureed food, and discussed their impressions in focus group or individual interviews. RESULTS AND CONCLUSIONS: Overall, results demonstrated that informed experts who were novice users perceived the 3D food printing process to be fun but time consuming, and that 3D food printers might not yet be suitable for people with dysphagia or their supporters. Slow response time, lack of user feedback, scant detail on the appropriate recipes for the pureed food to create a successful print, and small font on the user panel interface were perceived as barriers to accessibility for people with disability and older people. Participants expected more interactive elements and feedback from the device, particularly in relation to resolving printer or user errors. This study will inform future usability trials and food safety research into 3D printed foods for people with disability and dysphagia. IMPLICATIONS FOR REHABILITATION3D food printers potentially have a role as an assistive technology in the preparation of texture-modified foods for people with disability and dysphagia.To increase feasibility, 3D food printers should be co-designed with people with disability and their supporters and health professionals working in the field of dysphagia and rehabilitation.Experts struggled to be able to print 3D pureed shapes owing to relatively low usability of the 3D food printer tested with problems using the interface and resolving problems in the print.3D food printing is a fun and novel activity and may help to engage people with disability and dysphagia in making choices around the shape of the food to be printed.

Purpose This paper aims to present a new model of marketing analysis that is capable of using the embedded knowledge that sits untapped in the history of marketing thought to solve contemporary marketing problems – the conceptual-historical analytical research model (CHARM). Design/methodology/approach This paper outlines the evolution of historical analysis methods (HAM), along with critiques and enhancements of the prior processes offered by Savitt (1980), Nevett (1991) and Golder (2000). From these foundations, the paper outlines the components of the model of historical analysis, detailing the development of the analytical template design. It also details the four-step process of engaging structured revisits of past knowledge for contemporary problem-solving. Findings The CHARM for problem-solving in marketing is a knowledge-gathering system that informs marketing decisions addressing contemporary problems. This is achieved through the use of embedded knowledge from a corpus of historical texts. Research limitations/implications This paper provides a method for future researchers to apply for replicable examination of historical texts and to assist intercoder reliability for multi-author history projects through the application of structured templates. Practical implications The CHARM for problem-solving in marketing is a knowledge-gathering system that informs marketing decisions addressing contemporary problems. This is achieved through the use of embedded knowledge from a corpus of historical texts. Originality/value The CHARM process applies a systematic protocol for engaging qualitative sources for historical analysis through preset data collection templates, structured analysis frameworks and definitional understanding templates for improved replicability. This paper presents a new model of approaching historical analysis through a problem-solving lens, whereby historical sources become the foundations for the solution to a problem, rather than just the literature review that identifies the presence of gap.

CDK2 is a core cell-cycle enzyme that phosphorylates a variety of substrates to drive progression through the cell cycle. CDK2 is hyperactivated in multiple cancers and is therefore an attractive therapeutic target. Here, application of a novel small molecule CDK2/4/6 inhibitor, PF-06873600, enabled in-depth interrogation of CDK2 substrate phosphorylation, cell-cycle progression, and drug adaptation in preclinical models. CDK2-specific inhibition leads to rapid loss of substrate phosphorylation, but unexpectedly, CDK2 substrate phosphorylation rebounds within several hours. Whereas CDK1 is known to compensate for loss of CDK2 in Cdk2-/- mice, here we demonstrate an early dependence on CDK4/6 activity. CDK2 inhibition reveals latent CDK4/6 activity throughout S phase that backstops the proliferative program by maintaining Rb1 hyperphosphorylation, active E2F transcription, and Cyclin A2 expression, enabling re-activation of CDK2. Our results augment our understanding of CDK plasticity and indicate that co-inhibition of CDK2 and CDK4/6 is required to suppress adaptation to CDK2 inhibitors. Citation Format: Mansi Arora, Justin Moser, Timothy E. Hoffman, Lotte P. Watts, Mingwei Min, Monica Musteanu, Yao Rong, Jordan Schneider, C Ryland Ill, Varuna Nangia, Manuel Sanclemente, John Lapek, Lisa Nguyen, Sherry Niessen, Stephen Dann, Todd van Arsdale, Mariano Barbacid, Nichol Miller, Sabrina L. Spencer. Cells rapidly adapt to CDK2 inhibitors via plasticity of the CDK2/4/6-Rb-E2F axis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5992.

Aim:of this study was to examine the Twitter experiences and networks of six adults with cognitive-communication disability after a traumatic brain injury (TBI).Method:Using mixed methods, the study integrated: (a) quantitative analysis of Twitter networks using computational and manual coding of tweets; and (b) narrative analysis of in-depth interviews.Results:Diverse experiences were evident, with two experienced and four novice users of the platform. However, all reported feeling connected and included, and identified both positive and negative experiences in their use of Twitter. Developing a supportive network facilitated higher frequency of tweets and increased feelings of enjoyment and connectedness. All expressed a desire to continue using or learning to use Twitter but novices lacked support from rehabilitation professionals or experienced Twitter users, and relied instead on a “trial and error” approach.Conclusion:Proactive integration of Twitter use during rehabilitation after TBI is warranted to support safe, enjoyable, and meaningful use.

Introduction: The cell cycle cyclin-dependent kinases (CDKs) play a critical role in controlling the transition between cell cycle phases, as well as cellular transcription. Aberrant CDK activation...

Control of the cell cycle through selective pharmacological inhibition of CDK4/6 has proven beneficial in the treatment of breast cancer. Extending this level of control to additional cell cycle CDK isoforms represents an opportunity to expand to additional tumor types and potentially provide benefits to patients that develop tumors resistant to selective CDK4/6 inhibitors. However, broad-spectrum CDK inhibitors have a long history of failure due to safety concerns. In this approach, we describe the use of structure-based drug design and Free-Wilson analysis to optimize a series of CDK2/4/6 inhibitors. Further, we detail the use of molecular dynamics simulations to provide insights into the basis for selectivity against CDK9. Based on overall potency, selectivity, and ADME profile, PF-06873600 (22) was identified as a candidate for the treatment of cancer and advanced to phase 1 clinical trials.

Purpose The aim of the study was to investigate the experiences of people with traumatic brain injury (TBI) and rehabilitation professionals in use of social media after TBI. Design Metasynthesis of a multilevel mixed-methods research design was used in the study. Method A qualitative metasynthesis of (a) evidence in the literature regarding the use of communication technologies and social media after TBI, (b) Twitter data and network analysis, (c) interviews with people with TBI ( n = 13), (d) focus groups with TBI rehabilitation professionals ( n = 11), and (e) a review of current guidance on safe use of social media was conducted. Results People with TBI adopt a trial-and-error approach to using social media. Their meaningful use and a sense of connection enable them to develop social media mastery. TBI rehabilitation professionals' concerns regarding potential risks associated with using social media might lead them to restrict social media use during rehabilitation. Conclusions Access to proactive training in social media use and a supportive network of rehabilitation professionals, family, and friends can enable people with TBI to develop social media mastery through working collaboratively on social media goals. This metasynthesis of research culminates in an evidence-based protocol for assessing and supporting a person with TBI's social media goals to guide clinical practice and future research in the field.

This abstract was withdrawn by the authors. Citation Format: Dann S, Chionis J, Eisele K, Zhang Q, Liu C, Yuan J, Miller N, Murray B, Xu M, Solowiej J, Wei P, Weinrich S, Sutton S, Behenna D, Ninkovic S, Hoffman R, Freeman-Cook K, Jessen B, Huser N, Zhang C, Visswanathan R, Boras B, VanArsdale T, White MA. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-20-06.

To be effective in the workforce, engineering and computing graduates need both technical and professional skills. The latter includes, for example, confidence to communicate and work ethically in diverse teams to solve problems. In the Australian National University (ANU) postgraduate programs, the initial development of professional skills is currently embedded in two sequential courses: Professional Practice 1 and 2 (PP2). This Work-in-Progress explores the application of Lego® Serious Play™ (LSP) with PP2 students as they work together to solve real-world problems in project challenges. We adapted and tested the LSP facilitation for its capacity to integrate into the engineering and computing classroom environment and help our students develop the confidence needed to collaborate with their industry partners to solve the project challenge. We measured the effectiveness of our approach using questionnaires and reflections. The evidence-based insights will help to improve curriculum design for professional skill development in engineering and computing and further our understanding of the challenges presented by innovation in science and technology.

Lego Serious Play was founded within the Lego Corporation in the mid-90s as a response to an unusual problem why a company that sold creativity by the kilo was struggling for market share, profit and new thinking. Built from the ground up as a make-or-break proposition, the LSP process is an industry strength business solution designed to create conducive conditions for problem recognition, knowledge creation, and shared understanding. Based on these condition, and the 2010 open source licence of the protocol, this paper outlines the Lego Serious Play process, the history and origin of the method, and the seven principles underpinning its operation. The paper then outlines the adaptation of the LSP method from industry to academy, to showcase how to bring the technique into the classroom. Educators can use the step by step guide to construct a classroom activity that draws on Lego Serious Play to further promote key graduate outcomes of communication, creativity and shared understanding.

© 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Purpose: Articles 19, 26 and 27 of the Universal Declaration of Human Rights and Articles 4, 9 and 21 of the Convention on the Rights of Persons with Disabilities promote the human rights of communication, education, use of technology and access to information. Social media is an important form of online communication, and Twitter increases users’ visibility, influence and reach online. The aim of this sociotechnical research was to determine the impact of teaching three people who use Augmentative and Alternative Communication (AAC) to use Twitter. Method: Three participants were trained in ways of using Twitter strategically. Data collected from participants’ Twitter profiles were examined to determine the impact of training on Twitter follower count, frequency of tweeting, tweet content and the development of social networks. Data were also examined using (1) KH Coder software analysis and visualisation of co-occurring networks in the text data, based on word frequencies; and (2) Gephi software analysis to show the Twitter network for each participant. Result: Two participants showed an improvement in Twitter skills and strategies. Conclusions: Twitter can be used to improve social connectedness of people who use AAC, and should not be overlooked in relation to communication rights.

Summary The CDK4/6 inhibitor, palbociclib (PAL), significantly improves progression-free survival in HR+/HER2− breast cancer when combined with anti-hormonals. We sought to discover PAL resistance mechanisms in preclinical models and through analysis of clinical transcriptome specimens, which coalesced on induction of MYC oncogene and Cyclin E/CDK2 activity. We propose that targeting the G1 kinases CDK2, CDK4, and CDK6 with a small-molecule overcomes resistance to CDK4/6 inhibition. We describe the pharmacodynamics and efficacy of PF-06873600 (PF3600), a pyridopyrimidine with potent inhibition of CDK2/4/6 activity and efficacy in multiple in vivo tumor models. Together with the clinical analysis, MYC activity predicts (PF3600) efficacy across multiple cell lineages. Finally, we find that CDK2/4/6 inhibition does not compromise tumor-specific immune checkpoint blockade responses in syngeneic models. We anticipate that (PF3600), currently in phase 1 clinical trials, offers a therapeutic option to cancer patients in whom CDK4/6 inhibition is insufficient to alter disease progression.

Objective The aims of this study were to: (a) determine how Twitter is used by people with traumatic brain injury (TBI) and TBI organisations, (b) analyse the Twitter networks and content of tweets tagged with TBI-related hashtags, and (c) identify any challenges people with TBI encounter in using Twitter. Research design Mixed methods in a Twitter hashtag study. Methods Mixed methods in a Twitter hashtag study. Tweets tagged with TBI-related hashtags were harvested from the Twitter website over a one-month period in 2016 and analysed qualitatively and quantitatively. Results The sample of 29,199 tweets included tweets sent by 893 @users, 219 of whom had a brain injury. Twitter was used to: (a) discuss health issues, (b) raise awareness of TBI, (c) talk about life after TBI, (d) talk about sport and concussion, and (e) communicate inspirational messages. Conclusions Twitter is an important platform for research and knowledge translation on TBI, and for hearing the voices of people with TBI as they express their personal views and stories of living with TBI and become more visible and influential in Twitter communities. TBI clinicians could use these narratives of people with TBI in Twitter to develop more effective and personally meaningful rehabilitation goals.

S-Adenosyl-L-methionine (SAM) is an enzyme cofactor used in methyl transfer reactions and polyamine biosynthesis. The biosynthesis of SAM from ATP and L-methionine is performed by the methionine adenosyltransferase enzyme family (Mat; EC 2.5.1.6). Human methionine adenosyltransferase 2A (Mat2A), the extrahepatic isoform, is often deregulated in cancer. We identified a Mat2A inhibitor, PF-9366, that binds an allosteric site on Mat2A that overlaps with the binding site for the Mat2A regulator, Mat2B. Studies exploiting PF-9366 suggested a general mode of Mat2A allosteric regulation. Allosteric binding of PF-9366 or Mat2B altered the Mat2A active site, resulting in increased substrate affinity and decreased enzyme turnover. These data support a model whereby Mat2B functions as an inhibitor of Mat2A activity when methionine or SAM levels are high, yet functions as an activator of Mat2A when methionine or SAM levels are low. The ramification of Mat2A activity modulation in cancer cells is also described.

PURPOSE Rehabilitation professionals support people with traumatic brain injury (TBI) to return to meaningful participation in life and society - which now includes the use of social media. However, the role of health professionals in supporting the use of social media by adults with TBI is not yet known. This study aimed to investigate the experiences and views of rehabilitation professionals on the use of social media by people with TBI during rehabilitation. METHOD Two focus groups were conducted and analysed qualitatively for content themes. RESULTS Eleven rehabilitation professionals, including allied health, recreational therapy, and service management, took part in this study. Participants identified potential benefits to people with TBI using social media, including reduced social isolation. However, they expressed concerns about social media risks relating to the vulnerability, exploitation, and reputation management for people with TBI. Rehabilitation professionals viewed their role as being to protect people from these risks of harm, either through imposing restrictions on social media use or responding to problems after these occurred. CONCLUSION A knowledge translation approach might help guide and support rehabilitation professionals in enabling adults with TBI to safely access and experience the benefits of meaningful engagement in social media during rehabilitation.Implications for rehabilitationRehabilitation professionals can start addressing social media use during collaborative goal setting, in order to support people with traumatic brain injury to use social media successfully during rehabilitation and beyond. To do this, professionals can inquire as to the person's previous social media use and identify priority areas for the person for short- and long-term goals.Rehabilitation targeting social media use should include instruction for participation in social media platforms, providing education and feedback that is positive and constructive, as well as risk management education.Policy and guidance is needed for rehabilitation professionals to more actively support people with traumatic brain injury to access social media for improved participation and inclusion in online communities.Addressing social media goals in rehabilitation should be informed by existing successful traumatic brain injury rehabilitation approaches (e.g., functional rehabilitation) and adopting strategies used in rehabilitation supporting other higher risk goals (e.g., return to driving).

The human capacity to address complex problems depends on the ability and willingness to effectively engage and problem-solve with individuals who hold different views from one’s own. Bridging repr...

Overcoming checkpoints to cell cycle control is the basis for tumorigenesis and malignant growth. Therefore, models that recapitulate clinically relevant cell cycle deregulation enhance our understanding of defined tumors subsets. Specifically, pancreatic ductal adenocarcinomas (PDAs) frequently delete the 9p21 locus which contains the cyclin dependent kinase (CDK) inhibitors CDKN2A (p16, p14) and CDKN2B (p15), as well as methylthioadenosine phosphorylase (MTAP), a metabolic gene required for methionine salvage from methylthioadenosine. No model currently exists that accurately represents loss of the entire locus in a relevant disease context. Moreover, the contribution of MTAP to tumor progression remains largely unknown. Therefore, we have developed a novel genetically engineered mouse model (GEMM) of PDA which combines loss of the orthologous murine 9p21 region (4qC4) with activated KRAS [Pdx-Cre; LSL-KrasG12D; 9p21L/L (K9C)], which results in rapid adenocarcinoma formation and subsequent mortality in mice homozygous for 9p21 deletion. Single-cell RNA sequencing revealed a remarkable level of inter- and intra-tumoral heterogeneity, including a significant immune and stromal component that contribute to tumor growth and progression. Additionally, K9C derived cell lines are responsive to Pfizer's first-in class CDK2/4/6 selective inhibitor while displaying de novo resistance to CDK4/6 inhibitor Palbociclib. Allograft and single-cell RNA sequencing experiments corroborated these findings and implicate Myc in contributing to CDK2/4/6i sensitivity. Furthermore, phenotypic-based screens revealed synthetic-lethal hits with 9p21 loss, indicating ample opportunities for combination strategies in this select patient population. Thus, we show that the K9C model recapitulates salient aspects of PDA and is amenable to novel therapeutic intervention strategies that may aid in improving the outcomes of patients with this precise genetic background. *All procedures performed on animals were in accordance with regulations and established guidelines and were reviewed and approved by an Institutional Animal Care and use committee Citation Format: Christina Adams, Lynn Wang, Tim S. Wang, Nichol Miller, Elizabeth McMillan, Monica Ramstetter, John Chionis, Koleen Eisele, Jonathan Almaden, Timothy Affolter, Smitha Pillai, Todd VanArsdale, Chris Dillon, Stephen G. Dann. A novel mouse model of pancreatic cancer reveals new insights into cell cycle deregulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2960.

CDK4/6 small molecule inhibitors represent a milestone in treating hormone receptor-positive breast cancer. PALOMA (Palbociclib: Ongoing Trials in the Management of Breast Cancer) studies have confirmed prolonged progression-free survival after CDK4/6 inhibitor and anti-estrogen therapy. Notably, disease progression is observed in a subset of patients receiving Palbociclib-Fulvestrant treatment (Turner et al., NEJM 2018). Circulating tumor DNA from PALOMA-3 patients revealed genetic mutations correlating with patient response (O'Leary et al., Cancer Discov, 2018). Compensations in CDK4/6i resistance include circumvention of CDK4/6 substrate regulation, CCNE1/2 amplification (Herrera-Abreu et al., Cancer Res. 2016), and compensatory CDK2 activity. The importance of compensatory CDK2 cancer re-wiring is highlighted by recently reported, highly efficacious CDK2/4/6i (Freeman-Cook et al., in review). Thus, mechanistic understanding of cancer cell and compensatory CDK2 activity is imperative to improve patient outcome. Acute, temporal phenotypes in CDK2-signaling have been observed by live single-cell tracking microscopy in human breast epithelial and ER+ breast cancer cells (Arora & Moser et al., in review). In extending these studies, we utilize first-in-class small molecule inhibitors against CDK2 combined with high content imaging approaches to illuminate cancer cell CDK2 signaling and identify potential synthetic lethality. We report biomarkers parsed in cycling populations as quantifiable phenotypes and identify disengaged control of several processes including S- and G2/M licensing after CDK2i. Combined with internal -omics studies, CDK2i selective molecules support a positive regulatory role of CDK2 on CCNB1-PLK1 signaling before mitotic entry. We combine our high-content techniques with proximity labeling to quantify alternative CDK-Cyclin complex formation following pharmacologic perturbation. We hypothesize that dysregulated CDK-Cyclin complex formation elicits unintended CDK2 kinase activity, revealing potential synthetic lethality with inhibition of centrosome duplication pathways in ER+ breast cancers. Citation Format: Tim Sen Wang, Jon Almaden, Chen Shen, John Lapek, Sherry Niessen, Nichol Miller, Stephen Dann, Todd VanArsdale. Identifying synthetic lethality with novel CDK2 small molecule inhibitors via integration of high-content microscopy and -omics level platforms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1954.

Purpose This paper explores the purposive use of the selfie in the construction of personal narratives that develop and support an individual’s human brand. Selfies were divided into archetypical clusters of “genres” that reflected the combined story told through Instagram image and accompanying text captions. Design/methodology/approach The analysis drew a randomized sample of 1,000 images with accompanying text from a large capture of 3,300 English language captioned selfies. Coding for semantic and semiotic data used a three-wave technique to overcome interpretive limitations. Findings Based on their structural characteristics, seven genre types emerged from the coded sample set. These primary genres of selfie meta-narratives are autobiography, parody, propaganda, romance, self-help, travel diary and coffee-table book. Research limitations/implications The research is limited in generalization to the Instagram photo-sharing app platform by design. Samples were taken from the app due both to its popularity and its capacity to annotate images. Selfies conducted in non-public, non-annotation-based apps may produce alternative genres and classifications. Practical implications The paper presents a genre classification to examine how selfies are used to “show, not tell” a portion of the consumer’s life story. Brands, firms and marketers can apply genres to examine the selfie types that best connect with the identity of their brands and consumers, based on how their consumers communicate within the Instagram network. Social implications Selfies are an oft pathologized and moralized aspect of consumer conduct. We present a view of the selfie as a deliberate, consciously considered communication approach to maintaining social bonds between friends, family and wider audience. Selfies are presented as a combined effect of consumption of a social media service (Instagram) and the co-production of valued content (the selfie) that recognizes the individual as an active constructor of their digital self. Originality/value The paper outlines a novel framework of selfie genres to classify the deliberate human-brand narratives expressed in selfies. By taking a narrative perspective to the Instagram selfie practice, the genre type captures the combined effect of the mimesis and diegesis, where the mimesis showing of self is contextualized with the diegesis of the provided captions to capture an intentional storytelling act of image and text.

SummaryPalbociclib, is a selective inhibitor of cyclin-dependent kinases 4 and 6 and used as a first-line treatment for patients with estrogen receptor positive breast cancer. It has been shown that patients have improved progression-free survival when treated in combination with fulvestrant, an estrogen receptor antagonist. However, the mechanisms for this survival advantage are not known. We sought to analyze metabolic and transcriptomic changes in MCF-7 adenocarcinoma breast cancer cells following single and combined treatments to determine if selective metabolic pathways are targeted during combination therapy. Our results showed that individually, the drugs caused metabolic disruption to the same metabolic pathways, however fulvestrant additionally attenuated the pentose phosphate pathway and the production of important coenzymes. A comprehensive effect was observed when the drugs were applied together, confirming the combinatory therapy′s synergism in the cell model. This study highlights the power of merging high-dimensional datasets to unravel mechanisms involved in cancer metabolism and therapy.Highlights○First study employing multi-omics to investigate combined therapy on breast cancer cells○Fulvestrant attenuates the pentose phosphate pathway and coenzyme production○Synergism of palbociclib and fulvestrant was confirmed in vitro○Altered key pathways have been identifiedeTOC BlurbJohnson et al. applied an innovative multi-omics approach to decipher metabolic pathways affected by single versus combination dosing of palbociclib and fulvestrant in estrogen receptor positive breast cancer. Key metabolites and genes were correlated within metabolic pathways and shown to be involved in the drugs′ synergism.

Purpose: Endocrine therapy, using tamoxifen or an aromatase inhibitor, remains first-line therapy for the management of estrogen receptor (ESR1)–positive breast cancer. However, ESR1 mutations or other ligand-independent ESR1 activation mechanisms limit the duration of response. The clinical efficacy of fulvestrant, a selective estrogen receptor downregulator (SERD) that competitively inhibits agonist binding to ESR1 and triggers receptor downregulation, has confirmed that ESR1 frequently remains engaged in endocrine therapy–resistant cancers. We evaluated the activity of a new class of selective estrogen receptor modulators (SERM)/SERD hybrids (SSH) that downregulate ESR1 in relevant models of endocrine-resistant breast cancer. Building on the observation that concurrent inhibition of ESR1 and the cyclin-dependent kinases 4 and 6 (CDK4/6) significantly increased progression-free survival in advanced patients, we explored the activity of different SERD– or SSH–CDK4/6 inhibitor combinations in models of endocrine therapy–resistant ESR1+ breast cancer. Experimental Design: SERDs, SSHs, and the CDK4/6 inhibitor palbociclib were evaluated as single agents or in combination in established cellular and animal models of endocrine therapy–resistant ESR1+ breast cancer. Results: The combination of palbociclib with a SERD or an SSH was shown to effectively inhibit the growth of MCF7 cell or ESR1-mutant patient-derived tumor xenografts. In tamoxifen-resistant MCF7 xenografts, the palbociclib/SERD or SSH combination resulted in an increased duration of response as compared with either drug alone. Conclusions: A SERD– or SSH–palbociclib combination has therapeutic potential in breast tumors resistant to endocrine therapies or those expressing ESR1 mutations. Clin Cancer Res; 21(22); 5121–30. ©2015 AACR. See related commentary by DeMichele and Chodosh, p. 4999

Purpose: The aim of this study was to investigate the Twitter experiences of adults with severe communication disabilities who use augmentative and alternative communication (AAC) to inform Twitter training and further research on the use of Twitter in populations with communication disabilities. Method: This mixed methods research included five adults with severe communication disabilities who use AAC. It combined (a) quantitative analysis of Twitter networks and (b) manual coding of tweets with (c) narrative interviews with participants on their Twitter experiences and results. Results: The five participants who used AAC and Twitter were diverse in their patterns and experiences of using Twitter. Twitter networks reflected interaction with a close-knit network of people rather than with the broader publics on Twitter. Conversational, Broadcast and Pass Along tweets featured most prominently, with limited use of News or Social Presence tweets. Tweets appeared mostly within each participant's micro- or meso-structural layers of Twitter. Conclusions: People who use AAC report positive experiences in using Twitter. Obtaining help in Twitter, and engaging in hashtag communities facilitated higher frequency of tweets and establishment of Twitter networks. Results reflected an inter-connection of participant Twitter networks that might form part of a larger as yet unexplored emergent community of people who use AAC in Twitter.Implications for RehabilitationTwitter can be used as an important vehicle for conversation and a forum for people with communication disabilities to exchange information and participate socially in online communities.It is important that information and resources relating to the effective use of Twitter for a range of purposes are made available to people with communication disabilities who wish to take up or maintain use of Twitter.People with communication disabilities might benefit from support in using Twitter to meet their goals relating to participation in online forums and information exchange. Practitioners need to consider how their own social media skills might impact on service delivery and supporting these goals.

In this reply to Lilienfeld, Marshall, Todd, and Shane (2015) we provide a social marketing perspective on ways that facilitated communication (FC) is presented and discussed on social media platforms, in the field of augmentative and alternative communication (AAC). The growth in uptake and use of FC in recent years has occurred in the context of rapid growth in mobile technologies and AAC integrated with social media and online learning. Social media have been used to disseminate both materials that are supportive of FC and materials that provide scientific evidence of facilitator influence over authorship in FC. In order to illustrate how social media are being used to spread information about FC, we present a limited scan of two social media sites—TwitterTM and YouTubeTM—for information about FC. In this paper we discuss barriers to evidence and facilitators for FC in social media and consider the role that social marketing might play in relation to FC. Clinical implications for using social m...

Within the family of protein kinase C (PKC) molecules, the novel isoform PRKCE (PKCɛ) acts as a bona fide oncogene in in vitro and in vivo models of tumorigenesis. Previous studies have reported expression of PKCɛ in breast, prostate and lung tumors above that of normal adjacent tissue. Data from the cancer genome atlas suggest increased copy number of PRKCE in triple negative breast cancer (TNBC). We find that overexpression of PKCɛ in a non-tumorigenic breast epithelial cell line is sufficient to overcome contact inhibition and results in the formation of cellular foci. Correspondingly, inhibition of PKCɛ in a TNBC cell model results in growth defects in two-dimensional (2D) and three-dimensional (3D) culture conditions and orthotopic xenografts. Using stable isotope labeling of amino acids in a cell culture phosphoproteomic approach, we find that CTNND1/p120ctn phosphorylation at serine 268 (P-S268) occurs in a strictly PKCɛ-dependent manner, and that loss of PKCɛ signaling in TNBC cells leads to reversal of mesenchymal morphology and signaling. In a model of Ras activation, inhibition of PKCɛ is sufficient to block mesenchymal cell morphology. Finally, treatment with a PKCɛ ATP mimetic inhibitor, PF-5263555, recapitulates genetic loss of function experiments impairing p120ctn phosphorylation as well as compromising TNBC cell growth in vitro and in vivo. We demonstrate PKCɛ as a tractable therapeutic target for TNBC, where p120ctn phosphorylation may serve as a readout for monitoring patient response.

© 2017 International Society for Augmentative and Alternative Communication. Augmentative and alternative communication (AAC) social media research is relatively new, and is built on a foundation of research on use of the Internet and social media by people with communication disabilities. Although the field is expanding to include a range of people who use AAC, there are limitations and gaps in research that will need to be addressed in order to keep pace with the rapid evolution of social media connectivity in assistive communication technologies. In this paper, we consider the aims, scope, and methodologies of AAC social media research, with a focus on social network sites. Lack of detailed attention to specific social network sites and little use of social media data limits the extent to which findings can be confirmed. Increased use of social media data across a range of platforms, including Instagram and YouTube, would provide important insights into the lives of people who use AAC and the ways in which they and their supporters use social media. New directions for AAC social media research are presented in line with those discussed at the social media research symposium at the International Society for Augmentative and Alternative Communication in Toronto, Canada, on August 12, 2016.

A sports star backed by a road safety sponsor gets caught drink driving. The sponsor moves to cancel the relationship but, used wisely, such a breach may reinforce the sponsors message, suggests Stephen Dann. Copyright 2007 Stephen Dann. No part of this article may be reproduced by any means without the written consent of the publisher.

Purpose This research was conducted to outline the capturing and analysis of composite texts. We contextualize this using selfies as image and textual data sourced from Instagram and analyzed using a three stage analysis approach from a genre perspective. Methodology/approach The capturing of composite texts is outlined for numerous services available to researchers to study social media contexts. The analysis applies a three-stage technique of (1) what is shown, (2) what is said, and (3) what is the central narrative to overcome interpretive limitations of privileging text over image or vice versa. Findings Based on their structural characteristics, seven genre types emerged from the coded sample set. Research limitations/implications Issues arise in capturing this data as social media platforms change their access and usage policies and as capturing services alter their capabilities. Originality/value The paper outlines a novel approach to capturing and understanding the mimesis and diegesis of selfies as composite texts.

In this chapter we propose a review of the influence of halal certification on consumer perceptions of food quality. As one of the few systematic studies that examines the influence of the halal sign in advertising as a quality assurance marker, this research investigates the use and effectiveness of consumers’ perceptions of halal certification as a quality assurance mark in the context of the Malaysian multicultural society. Malaysia is moving to become a global hub for halal certification and production.

Social marketing is based on the adaptation of the contemporary commercial marketing theory and practice as a means of guiding and aiding social change campaigns. This paper draws on recent developments in commercial marketing theory and prior work in social marketing definitions to create a new definition of social marketing which integrates the commercial definitions of the American Marketing Association (AMA) and Chartered Instituted of Marketing (CIM) with established social marketing definitions from the past thirty years of social marketing conceptual development. The development of the definition is supported through the use of qualitative research technique of text mining which uncovered a core series of principles consistent to the historical definitions of social marketing. Finally, the new definition also introduces clarification of several key subcomponent elements as part of an expanded definition of social marketing.

Success in social marketing is rarely clear cut and even more rarely believed to have been achieved. Social marketing practitioners are under increasing scrutiny to benchmark efficiencies of social change programs to achieve ‘success’ outcomes. Using road safety as a case study, this paper addresses the complex nature of success within a social marketing context. First, we discuss the conundrum facing road safety in articulating ‘success’ when at policy level success is quantified objectively, yet at a community level perceptions of system failure are equated with individual death. Methodologically we apply comparative empirical approaches to examine perceptual versus objective road safety outcomes. The paper concludes with a discussion and proposal of alternate strategies for measuring programmatic success, and raise issues concerning the longevity of developing competitive and sustainable benchmarks.

Political marketing theory has developed and evolved in conjunction with advancements in political science and commercial marketing. Commercial marketing has been increasingly interested in developing marketing mechanisms which allows it to satisfy the core customer groups while also meeting the broader needs of the community and other stakeholders. Political marketing has the opportunity to build a marketing framework that focuses on delivering value to a core target market (voters, supporters) and addressing the needs of society at large. The paper outlines a new definition of political marketing to meet the challenges of addressing the needs of the political marketplace, political party stakeholders, and the broader social agenda.

PurposeThe paper aims to describe the application of two key service quality frameworks for improving the delivery of postgraduate research supervision. The services quality frameworks are used to identify key areas of overlap between services marketing practice and postgraduate supervision that can be used by the supervisor to improve research supervision outcomes for the student.Design/methodology/approachThe paper is a conceptual and theoretical examination of the two streams of literature that proposes a supervision gap model based on the services gap literature, and the application of services delivery frameworks of co‐creation and service quality.FindingsServices marketing literature can inform the process of designing and delivering postgraduate research supervision by clarifying student supervisor roles, setting parameters and using quality assurance frameworks for supervision delivery. The five services quality indicators can be used to examine overlooked areas of supervision delivery, and the co‐creation approach of services marketing can be used to empower student design and engaged in the quality of the supervision experience.Research limitations/implicationsAs a conceptual paper based on developing a theoretical structure for applying services marketing theory into the research supervision context, the paper is limited to suggesting potential applications. Further research studies will be necessary to test the field implementation of the approach.Practical implicationsThe practical implications of the paper include implementation suggestions for applying the supervisor gaps for assessing areas of potential breakdown in the supervision arrangement.Originality/valueThe paper draws on two diverse areas of theoretical work to integrate the experience, knowledge and frameworks of commercial services marketing into the postgraduate research supervision literature.

Social change through the use of social marketing has often grappled with the principle of “social good”. Building on the tradition of Klein and Laczniak (2009, 2012) in applying Catholic Social Teaching (CST) to commercial marketing, this paper outlines the points of similarity and divergence of contemporary social marketing frameworks with CST. As social marketing theory and practice moves away from its marketing parent discipline roots, this paper argues that CST with its focus on human dignity, subsidiary and the common good provides an increasingly relevant and compatible framework with which to evaluate ethical issues emerging in the social marketing domain. There is potential for social marketers to draw on the intellectual work underpinning CST to inform social marketing practice in engaging in the delivery of social benefit independent of the religious tradition.

Social marketing has been a discipline founded on the open and robust exchange of ideas regarding the nature of social change, the adaptation and adoption of commercial marketing, and the ethics of influencing behavior for beneficial outcomes. As a practical discipline, with a strong theoretical and philosophical framework, it also relies on the open communication between academic and practitioner to ensure those researching and those implementing are speaking the same social marketing language. In early 2006, the international social marketing mailing list (SOC-MKT) was subject to a short, albeit critical, debate on the ethics and nature of social marketing, the social marketing tool kit, and the role of social marketers. This article reports on the summary and implications of the debate among academics, practitioners, and founders of the social marketing discipline.

The paper reports on the core challenges faced by the nonprofit, political and social marketing disciplinary areas and suggests a series of research agendas to develop theory and practice to meet these challenges. � Social marketing’s research agenda involves the continued adaptation of the new developments in commercial marketing, whilst building a base of social marketing theory and best practice benchmarks that can be used to identify, clarify and classify the boundaries of social marketing against social change techniques. � Nonprofit marketing is pursuing the dual research agenda of developing the theory and practice of social entrepreneurship whilst seeking deeper consumer-based research to understand motivations for charitable behaviour and gift giving. � Political Marketing’s research agenda looks for an increase in the level of background research, core data and market research to use as a basis for developing more advanced theoretical and practical models. In addition, as political marketing is being transferred internationally between a range of political and electoral systems, there is a need for comparative research into both the relevance and effectiveness of these techniques to isolate nation independent and nation dependent political marketing strategies and campaigns.

To review the literature relating to use of social media by people with a traumatic brain injury (TBI), specifically its use for social engagement, information exchange or rehabilitation.A systematic review with a qualitative meta-synthesis of content themes was conducted. In June 2014, 10 databases were searched for relevant, peer-reviewed research studies in English that related to both TBI and social media.Sixteen studies met the inclusion criteria, with Facebook™ and Twitter™ being the most common social media represented in the included studies. Content analysis identified three major categories of meaning in relation to social media and TBI: (1) risks and benefits; (2) barriers and facilitators; and (3) purposes of use of social media. A greater emphasis was evident regarding potential risks and apparent barriers to social media use, with little focus on facilitators of successful use by people with TBI.Research to date reveals a range of benefits to the use of social media by people with TBI however there is little empirical research investigating its use. Further research focusing on ways to remove the barriers and increase facilitators for the use of social media by people with TBI is needed.

This chapter outlines a content classification framework designed to categorize content from individual and group Twitter activity. Measurement of Twitter at the individual account level can support the analysis of individual use of Twitter, and, guide the use of the platform for commercial operations. Applying a pre-existing content classification framework allows for the consistent coding of Twitter timelines into one of the five categories, with an option to further refine into a series of sub-categories. This coding approach allows for the ongoing longitudinal measurement, benchmark and analysis of how individuals or groups use their social media accounts. This chapter also outlines the potential use of the classification framework as a planning tool for guiding content creation. This approach creates a two-stage process of planned content engagement and consistent content measurement metrics from a single framework.

Social media data collection is often treated as tacit knowledge with the collation of tweets reduced to a single sentence without explanation as to means, mechanisms or relative merit of the approach. This chapter describes methods and techniques for the capture of Twitter timeline data, inclusive of first person and third party methods for data capture from personal accounts, public accounts, and keyword searches. The chapter takes a practical approach to acquiring Twitter data with a focus on individual timelines, and small to medium scale search sets. The emphasis is on being able to obtain, examine, and convert Twitter data into knowledge quickly, and with limited requirement for technical skills. This type of data collection assumes no prior programming knowledge. The chapter explains how to retrieve Twitter data from three sources: personally controlled timelines, third party timelines and ongoing search results. Finally, the chapter describes preliminary analysis that can be performed to ascertain content creation patterns, without recourse to analysis of individual tweets.