bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A005: Identification of lipid pharmacodynamic biomarkers in FAP model
Authors: Beach Ryan , Mohammed Altaf , Rosenberg Daniel W.
Published: December 2022

Familial Adenomatous Polyposis (FAP) is a genetic disorder characterized by the development of numerous polyps in the colon, that unless removed by colectomy, inevitably progress to colorectal cancer (CRC). Although there is currently no FDA-approved treatment to delay colectomy, a common target for chemoprevention is cyclooxygenase-2 (COX-2). Non-steroidal anti-inflammatory drugs (NSAIDs) and omega-3 fatty acids are known to alter COX metabolism and affect downstream eicosanoids involved in CRC progression. In this study, we examined the chemopreventive efficacy of the NSAID naproxen alone, or in combination with TP-252, a novel, chemically-stable analogue of the omega-3 fatty acid, eicosapentaenoic acid (EPA), in the intestinal tumorigenesis Apcam1137 PIRC rat model. Over the course of this 20-week study, rats were fed a modified AIN-93G diet supplemented with 200 ppm naproxen, alone or in combination with TP-252 (1.5%, or 3% by weight). Rats treated with 200 ppm naproxen had 66% (p < 0.0001) fewer colon tumors than controls (AIN-93G) and an 81% (p < 0.0001) reduction in tumor size. However, when Naproxen was combined with high-dose TP-252 (3%), tumor number and size were reduced by 95% (p < 0.0001) and 98% (p < 0.0001) respectively, when compared to controls. Since the primary mechanisms of action for naproxen and EPA target COX metabolic activity, we performed a comprehensive lipidomic analysis on colon tissue and plasma to determine lipidomic changes associated with drug treatment. Increased formation of several EPA-derived eicosanoids, including 9-HEPE, 12-HEPE, 18-HEPE, and resolvin E2, whose mucosal levels correlated with both reduced tumor number and volume, were observed.

These metabolites were also concomitantly elevated in the plasma of treated animals, representing potential pharmacodynamic (PD) biomarkers of CRC prevention. Future studies will decipher potential mechanisms that underlie these EPA-derived PD biomarkers and their role in tumor suppression. (Supported by the NCI Prevent Program 75N91019D00019, Task Order 75N91019F00132).

Citation Format: Ryan Beach, Altaf Mohammed, Daniel W. Rosenberg. Identification of lipid pharmacodynamic biomarkers in FAP model [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A005.
Abstract A006: Shared gene expression and immune pathway changes associated with progression from nevi to melanoma
Authors: Borden Elizabeth S. , Adams Anngela C. , Buetow Kenneth H. , Wilson Melissa A. , Bauman Julie E. , Curiel-Lewandrowski Clara , Chow H.-H. Sherry , LaFleur Bonnie J. , Hastings Karen Taraszka
Published: December 2022

There is a need to identify biomarkers of melanoma progression to assist the development of chemoprevention strategies to lower melanoma incidence. In this study, we assessed the feasibility of creating a molecular signature for melanomagenesis using three publicly available RNA sequencing and microarray expression datasets. We performed differential expression and regularized regression analyses across nevi and melanoma samples to identify consistent genes associated with melanomagenesis. The regularized regression models demonstrated that a small number of genes could successfully distinguish between nevi and melanoma, providing evidence for the feasibility of creating a molecular signature. Differential expression analysis identified consistent upregulation of C1QB, CXCL9, CXCL10, DFNA5 (GSDME), FCGR1B, and PRAME in melanoma and consistent downregulation of SCGB1D2 in melanoma compared to nevi. Additionally, each of these genes demonstrated a linear association with the progression from benign nevi to dysplastic nevi, to radial growth phase melanoma to vertical growth phase melanoma, providing additional evidence for their role in melanomagenesis. Subsequent pathway analysis demonstrated significant enrichment of immune-related pathways among the differentially expressed genes. Overall, this study 1) demonstrates the feasibility of creating a gene signature for melanomagenesis and 2) highlights genes and pathways of interest for melanoma progression. We are in the process of generating a new dataset with benign nevi, dysplastic nevi, and melanoma with which to build and validate a molecular signature of melanoma.

Citation Format: Elizabeth S. Borden, Anngela C. Adams, Kenneth H. Buetow, Melissa A. Wilson, Julie E. Bauman, Clara Curiel-Lewandrowski, H.-H. Sherry Chow, Bonnie J. LaFleur, Karen Taraszka Hastings. Shared gene expression and immune pathway changes associated with progression from nevi to melanoma [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A006.
Abstract A009: Effects of commonly prescribed β-blockers on tobacco carcinogen induced reactive oxygen species in human non-tumorigenic lung epithelial cells
Authors: Lee Jenny , Shahid Ayaz , Huang Ying
Published: December 2022

Lung cancer is a detrimental disease to humans and tobacco smoking causes more than 80% of lung cancer deaths. Chemoprevention is currently the major strategy to prevent smoking related lung cancer deaths. Key components that contribute to tobacco carcinogenicity are benzo(a)pyrene [B(a)P] and its diol epoxide metabolite BPDE. The goal of this study is to evaluate the level of reactive oxygen species (ROS), a mediator for cellular DNA damage leading to cancer, when pre-treated with the β-blockers carvedilol and nebivolol, and the antioxidant resveratrol.

B(a)P and BPDE were used to induce ROS in human lung epithelial cells (BEAS-2B). The non- fluorescent and non-polar 2’,7- dichlorofluorescein diacetate (DCFH-DA) probe was added to the cells. DCFH-DA was converted to DCFH in the cells by hydrolyzation of DCFH. ROS then induced the conversation of DCFH into 2,7-dichlorofluorescein (DCF). Florescence of DCF was measured by flow cytometry to detect ROS level.

B(a)P at concentrations 10 and 100 μM failed to induce ROS while BPDE successfully induced ROS dose-dependently during our pilot study. As a result, different concentrations of BPDE(2 μM and 4 μM) were used to induce ROS. When BEAS-2B was pre-treated with resveratrol (50 μM), ROS was reduced by 42% compared to the cells treated with 2 μM BPDE alone. Additionally, there was a decrease in ROS when pre-treated with nebivolol and carvedilol (5 μM). Nebivolol reduced 52% and 64% of the ROS induced by BPDE 2 μM and 4 μM, respectively. Carvedilol reduced 31% and 10% of the ROS induced by BPDE 2 μM and 4 μM, respectively.

These results suggest that some commonly used anti-hypertensive agents, such as the β-blockers , may block or reduce tobacco carcinogen induced ROS and thus can be used as chemopreventive agents for lung cancer.

Citation Format: Jenny Lee, Ayaz Shahid, Ying Huang. Effects of commonly prescribed β-blockers on tobacco carcinogen induced reactive oxygen species in human non-tumorigenic lung epithelial cells [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A009.
Abstract A010: Chemopreventive effects of carvedilol and nebivolol in benzo(a)pyrene-induced transformation of non-tumorous human bronchial epithelial cell
Authors: Lin Carol
Published: December 2022

Lung cancer is among the most common cancers worldwide. The primary risk factor for the development of lung cancer is cigarette smoking and there are a large amount of studies has confirmed the association between smoking and lung cancer. Chemopreventive drug would be beneficial among patients who are in high risk due to chronic exposure to carcinogens. In the previous study of chemopreventive activity of carvedilol, it significantly delayed and reduced skin squamous cell carcinoma development. The aim of the present study was to explore the role of carvedilol and nebivolol in benzo(a)pyrene induced transformation of the non-tumorous human bronchial epithelial cells. To evaluate the effects of carvedilol and nebivolol on chemopreventive activity against BPDE-induced lung carcinogenesis, anchorage-independent growth assay in soft agar was used to determine the degree of malignant transformation of BEAS-2b cells. Before the investigation of carvedilol and nebivolol, the appropriate drug concentration aiming minimum cytotoxicity on normal BEAS-2b cells were determined by MTT assay. The MTT assay was used to measure cellular metabolic activity as an indicator of cytotoxicity. Carvedilol at 10 μM or lower and Nebivolol at 1 μM or lower did not cause significant cytotoxicity. In non-tumorigenic human bronchial epithelial cell culture BEAS-2B vitro assays, carvedilol and nebivolol exert a protective effect against BPDE-indued transformation at non-toxic concentrations in a dose dependent manner. As shown in the figure below, Nebivolol (1 μM and 0.5 μM) and Carvedilol (1 μM and 0.5 μM) both significantly attenuated colony formation compared with BPDE control. However, the anti-transformation mechanism is unknown, further studies of carvedilol and nebivolol are needed to investigate their chemoprevention activity.

Citation Format: Carol Lin. Chemopreventive effects of carvedilol and nebivolol in benzo(a)pyrene-induced transformation of non-tumorous human bronchial epithelial cell [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A010.
Abstract A014: Targeting TAK1 for intercepting PanIN progression to ductal adenocarcinoma in an inducible KC mouse model
Authors: Madka Venkateshwar , Pathuri Gopal , Kuma Gaurav , Singh Anil , Stratton Nicole , Houchen Courtney , Mohammed Altaf , Rao Chinthalapally V.
Published: December 2022

Despite advances in our knowledge of human pancreatic ductal adenocarcinoma (PDAC), targeted therapies have not yet significantly translated to an improved overall survival for patients. Pancreatic tumor microenvironment enriched by infiltrating immune cells and consisting of dense fibrotic stroma is characterized by desmoplasia, the major contributors of tumor-associated inflammation. Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) is widely accepted as a key player in the TNF-α and TGF-β -induced signaling, and principal contributor of tumor fibrosis, inflammation and cell proliferation. Here, we show that pancreatic tumors over- express TAK1, and are associated with fibrotic-stroma and infiltrating immune cells. Also, p-TAK1(ser412) expression is correlated with progression of pancreatic intraepithelial neoplasia (PanIN) lesions to PDAC. Thus, we hypothesized TAK1 as an important target for inhibition of the tumor-associated fibrosis, inflammation and PanIN progression to PDAC.

To prove above hypothesis, we tested a selective TAK1 inhibitor, Takinib for its toxicity and efficacy against PanIN progression in the inducible Ptf1CreERT.LSL-KrasG12D (KC) mouse model. Takinib was synthesized and fed to wild type C57BL/6J mice (n=6) at 250 ppm and 500ppm in diet for 6 weeks to determine toxicity. Bodyweight gain, organ weights and serum enzyme analysis did not indicate any toxicity at the tested doses. For efficacy study, LSL-KrasG12D mice were bred with Ptf1-CreERTmice. Pups were genotyped and randomized to groups (n=12).

PanINs -PDAC was induced in the KC mice by tamoxifen (oral gavage) followed by 250ppm Takinib administration in diet for 20 weeks. After termination, pancreas tissue sections were evaluated for PanIN multiplicity and PDAC incidence/spread. Administration of Takinib led to significant reduction in PanIN 1 by 54% (p<0.02), PanIN 2 by 77% (p<0.001) and PanIN 3 by 80% (p<0.02) in the KC mice compared to untreated mice. PDAC incidence was also reduced with an increase in normal pancreas in Takinib administered KC mice. Taken together our results suggest that TAK1 is a valuable target for PDAC, and Takinib possesses efficacy against the PanIN and PDAC progression in the KC mouse model warranting further studies. (Supported by PHF Team Science grant and Kerley-Cade Endowed Chair).

Citation Format: Venkateshwar Madka, Gopal Pathuri, Gaurav Kuma, Anil Singh, Nicole Stratton, Courtney Houchen, Altaf Mohammed, Chinthalapally V. Rao. Targeting TAK1 for intercepting PanIN progression to ductal adenocarcinoma in an inducible KC mouse model [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A014.
Abstract A022: Limonene as a vehicle in topical delivery of carvedilol for skin cancer chemoprevention
Authors: Wang Janell , Chao Lawrence , Yeung Steven , Huang Ying
Published: December 2022

Skin cancer is currently one of the most common cancers and is defined as an abnormal growth of the skin cells. The goal of this study is to develop a topical delivery system of carvedilol with limonene as the vehicle. Limonene is a major component found in the rinds of citrus fruits and other herbs. It is one of many natural compounds that have demonstrated inhibitory activity in different types of cancers such as breast, lung, and stomach cancer. Furthermore, limonene has shown to increase skin permeation of drugs including carvedilol. The soft agar colony formation assay was used to evaluate anchorage-independent growth of JB6 mouse epidermal cells.

This assay tested concentrations of carvedilol (0.1, 1.0 and 10 μM); limonene (1.0, 10, 100 and 1000 μM); and a combination of carvedilol (1.0 μM) and limonene (1.0, 10 or 100 μM). Results demonstrated that carvedilol and limonene as single treatment inhibited colony formation.

The combination of carvedilol and limonene showed higher colony inhibition than single treatment, although not statistically significant. Franz diffusion cell was used to test for permeation of the drug. The device has two chambers separated by a membrane, which in this case is rat skin. The drugs, in vehicles of 40% polyethylene glycol (PEG) 400 in PBS or 40% PEG400 in PBS plus 5% limonene were applied into the donor chamber while the samples are collected through the receptor chamber as the drug permeates through the skin. The samples were collected at 16 hours, 20 hours, and 24 hours. Results showed that limonene significantly increased permeation. Therefore, our data indicate that limonene was able to increase skin permeation and the chemopreventive activity of carvedilol. This new formulation will be further examined in animal models for its efficacy against UV-induced skin cancer.

Citation Format: Janell Wang, Lawrence Chao, Steven Yeung, Ying Huang. Limonene as a vehicle in topical delivery of carvedilol for skin cancer chemoprevention [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A022.
Abstract IA003: SC144 and the next generation IL6/GP130/STAT3 inhibitors for cancer prevention
Authors: Neamati Nouri
Published: December 2022

IL6/GP130/STAT3 signaling plays a crucial role in multiple diseases, and all components of this signaling cascade are directly or indirectly implicated in tumorigenesis. Therefore, blockade of this signaling axis is expected to provide novel therapeutic opportunities to treat various diseases including cancer. IL6 binds to IL6R and GP130 to activate downstream signaling pathways to promote proliferation, survival and metastasis of cancer cells, and to stimulate angiogenesis on endothelial cells. Although GP130 is positioned at the junction of this oncogenic signaling network and is essential for activation of the network, there are no small-molecule inhibitors of GP130 under clinical development. Previously, we identified SC144 as a first-in-class, efficacious, safe, and orally active inhibitor of GP130. SC144 selectively inhibits the activation of downstream signaling pathways induced by GP130 ligands (IL6, LIF), with no significant effects on the activation by non-GP130 ligands, such as IFN-γ, SDF-1α, and PDGF. SC144 exhibits cytotoxicity in a panel of platinum-sensitive and platinum-resistant cells, with no significant cytotoxicity to human normal epithelial cells. In mouse xenograft models, SC144 significantly inhibited tumor growth through GP130 inhibition and induction of necrosis in the tumor. No toxicity was evident in normal tissues. Furthermore, SC144 showed significant in vivo efficacy in immune competent syngeneic mouse models. Unfortunately, clinical development of SC144 was delayed due to its poor solubility and metabolic instability. During the past two years, we have identified metabolic liabilities of SC144 and have undertaken an extensive medicinal chemistry lead optimization campaign to produce analogs with increased solubility and metabolic stability. The new analogs show favorable properties in single- and repeat-dosing pharmacokinetic (PK) studies. As a result, we have in hand a series of 2nd-generation analogs that are orally active, water-soluble, and display desirable PK properties suitable for advanced preclinical studies to support IND filing.

Citation Format: Nouri Neamati. SC144 and the next generation IL6/GP130/STAT3 inhibitors for cancer prevention [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr IA003.
Abstract IA016: Lessons learned from clinical trials of MUC1 peptide vaccines for cancer prevention
Authors: Schoen Robert E.
Published: December 2022

We report on three trials of a MUC1 peptide vaccine for cancer prevention. Two trials were pilot studies evaluating vaccine immunogenicity and safety. One was in subjects with advanced colon adenomas, and the other in smokers at risk for lung cancer. The third trial was a multi-center, randomized placebo-controlled trial in subjects with advanced adenoma that included an assessment of the clinical efficacy of the vaccine to prevent recurrent adenoma. All trials successfully recruited their full complement of participants and the vaccine was well tolerated with no safety concerns. The response rate in the colon adenoma trials was 43% in the pilot study and 25% in the placebo- controlled multicenter trial. Only 10% of smokers responded to the vaccine. Higher levels of circulating myeloid derived suppressor cells (MDSC) were consistently associated with the lack of an immune response. This suggests that even in pre-malignancy immunosuppressive tendencies can impair vaccine immunogenicity. Responders to the vaccine demonstrated immune memory at one year. In the multicenter adenoma trial that evaluated the efficacy of the vaccine on adenoma recurrence, immune responders demonstrated an association with a reduced rate of adenoma recurrence. In future studies, patient selection based on circulating MDSC levels, or concomitant use of agents to counter MDSC immunosuppressive function or otherwise improve T cell function, should be considered.

Citation Format: Robert E. Schoen. Lessons learned from clinical trials of MUC1 peptide vaccines for cancer prevention [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr IA016.
Abstract IA018: Cancer immune-interception in Lynch Syndrome: Neoantigen-based vaccine development
Authors: Vilar-Sanchez Eduardo
Published: December 2022

Lynch Syndrome (LS) is the most common cause of hereditary colorectal cancer and also conveys significantly increased risks for several other malignancies, including endometrial, small bowel, gastric, ovarian, adrenocortical tumors, and others. LS results from a heterozygous germline mutation in one of four DNA mismatch repair (MMR) genes. The acquisition of a somatic “second hit” causes affected cells to lose the ability to repair DNA mismatch replication errors that frequently occur in microsatellite regions of the genome. Consequently, hundreds to thousands of small insertion/deletions (indels) accumulate in these regions, and when expressed, result in frameshift peptides that are recognized as neoantigens that are then presented on the cell surface via the major histocompatibility complexes (MHC-I/II) for immune cell recognition. Vaccine development efforts in this high-risk population have been challenged by the substantial inter-individual variability in both the set of expressed neoantigens and MHC I/II responses. Yet, recent advances in next-generation sequencing and associated bioinformatic approaches are now allowing for more accurate profiling of the most frequently recurring and shared mutated neoantigens in LS-associated tumors. This allows for identification of the most immunogenic neoantigens that can be incorporated into different vaccine platforms to test the development of a population-based vaccine. The Vilar Lab has collaborated with industry and academic partners such as Nouscom, s.r.l. and the National Cancer Institute to develop two different clinical trials to bring new vaccines to the LS population based on mutated neoantigens and tumor associated antigens. In this presentation, we will focus on mutated neoantigen-based strategies and present the Phase I clinical trial (NCT05078866) using a viral-based vaccine including 209 distinct neoantigens. The primary endpoint of this trial is safety and immunogenicity. A total of 45 participants will be enrolled to receive a prime and boost vaccination. Different secondary biomarkers will explore immunological aspects of this novel immune-interception strategy.

Citation Format: Eduardo Vilar-Sanchez. Cancer immune-interception in Lynch Syndrome: Neoantigen-based vaccine development [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr IA018.
Abstract IA020: Targeting mTOR signaling in oral premalignant lesions: From bench to clinic and back
Authors: Gutkind J. Silvio
Published: December 2022

Despite encouraging recent results from novel treatment options, such as immunotherapy, for head and neck squamous cell carcinoma (HNSCC), limited progress has been made in improving outcomes for most patients. Prevention and early detection are key to improving the prognosis of HNSCC. Our team has focused on decoding the oncogenic signaling circuitries driving HNSCC initiation and progression, aimed at identifying novel druggable targets to treat and prevent this aggressive malignancy. These efforts led to the early discovery that persistent activation of PI3K/mTOR signaling circuitry is the most frequent dysregulated signaling mechanism in HNSCC, and that in turn, the overreliance on PI3K/mTOR for HNSCC initiation and progression can be exploited for therapeutic purposes. Evidence will presented that mTOR inhibition exerts a potent antitumor activity in HNSCC patients in a recently reported window of opportunity clinical trial (NCT01195922). Thus, mTOR inhibitors can be considered for the prevention of HNSCC development and for the treatment of existing HNSCC lesions. However, their safety profile and tolerability may hamper their potential long-term use for HNSCC prevention. In this regard, we have shown that the repurposed drug metformin, which is safely used by millions of type 2 diabetes patients, decreases mTOR signaling in HNSCC and displays potent chemopreventive activity in experimental oral premalignancy models. Based on these findings, we have conducted a Phase IIa Clinical Trial using metformin for HNSCC prevention (NCT02581137) in patients with oral premalignant lesions (OPL), which was recently completed. Metformin administration resulted in mTOR inhibition, and improvement in the histological severity of 60% of the OPLs, including a subset (17%) of patients that exhibited complete responses. Ongoing experimental and planned clinical studies will be presented, which may provide a mechanistic framework for the use of metformin as a precision preventive agent for HNSCC.

Citation Format: J. Silvio Gutkind. Targeting mTOR signaling in oral premalignant lesions: From bench to clinic and back [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr IA020.
ReXistências musicais entre arte e política
Authors: Hikiji Rose Satiko Gitirana , Grunvald Vi , Guerra Paula
Published: December 2022

O que têm em comum o musicar (Small, 1998) de Apeshit, o videoclipe do casal de artistas estadunidenses Beyoncé e Jay-Z, as performances musicais de João do Crato no interior do Ceará, um projeto entre uma cantora lírica, um musicólogo e um líder indígena na Colômbia, o álbum AmerElo do rapper paulistano Emicida, o artivismo musical de Linn da Quebrada e a música de imigrantes africanos em São Paulo? À primeira vista, nada. Mas neste Dossiê estes fazeres musicais servem todos ao mesmo intuito: são formas de reXistência.[1] A ligação entre música e política é vetusta e nem sempre perceptível. Do clamor patente, ao simples comentário, do motim pessoal ao social, a música tem atuado para agitar consciências e – menos frequentemente – sistemas, instituições e estruturas (Blacking, 1995). Schreiber (2019) considera que a música é plena energia para a ação. Uma expressão de poder, não apenas sônica ou emocional. A música, especialmente quando criada em resposta aos problemas sociais do mundo, torna-se uma força única (Guerra et al., 2019). E talvez desse poder criador e criativo é que venha a insistência de DeNora (2003) para considerarmos a música uma prática social de fato e de direito e não apenas um mero reflexo da estrutura social. Portanto, a música é uma parte da nossa vida social.

 

[1] Para a noção de reXistência com a qual trabalhamos, cf. Grunvald, neste dossiê.
Editorial
Authors: Citelli Adilson Odair , Figaro Roseli , Nonato Cláudia
Published: December 2022

Editorial
#HoraDeVotar: uma experiência de media literacy durante o ensino remoto
Authors: Barsotti Adriana , Emanuel Barbara , Bertol Rachel
Published: December 2022

O #HoraDeVotar é um projeto multidisciplinar de ensino e produção de jornalismo digital desenvolvido na UFF de forma remota durante a pandemia de Covid-19. A iniciativa, de media literacy, uniu 27 discentes, dois bolsistas, três docentes e um professor em estágio docência. A oportunidade surgiu diante da proximidade das eleições municipais de 2020, em que havia grandes chances de a disseminação da desinformação crescer, o que já vinha acontecendo desde o início da pandemia. O resultado foi a criação de um site com reportagens contemplando temas de letramento midiático, uma série de podcasts, imagens e infográficos para ilustrar as reportagens e cards e vídeos para a divulgação do projeto nas redes sociais. Além de oferecer um serviço à sociedade, o projeto contribuiu para que os alunos adquirissem habilidade, capacidade, responsabilidade e comprometimento moral para se relacionarem com as mídias.
Dá para esperançar? Eu acho que sim. Entrevista com Nilma Lino Gomes
Authors: Lago Cláudia , Thamani Manuela
Published: December 2022

Nesta entrevista à Comunicação & Educação, a ex-Ministra da Igualdade Racial e Professora Titular Emérita da Faculdade de Educação da Universidade Federal de Minas Gerais (UFMG), Nilma Lino Gomes, fala da sua trajetória como mulher negra em lugares de poder. Nilma aborda, entre outros temas, a interseção entre comunicação e educação e a questão racial e a produção de saberes acadêmicos advindos dos movimentos sociais, especialmente os movimentos negros, em contrapartida à ausência de sujeitos oriundos desses locais na produção intelectual, além de fazer uma reflexão acerca do uso que as universidades públicas têm feito das ações afirmativas, principalmente as cotas raciais, e suas consequências. Ademais, ela discute a questão do racismo estrutural e dos privilégios da branquitude na sociedade brasileira. Por fim, reafirma o seu otimismo em relação ao futuro do nosso país.
Comunicação e Experiências Multiterritoriais : integração na cooperação da pós-graduação durante a pandemia
Authors: Zanetti Daniela , Patrício Edgard , Aguiar Lisiane , Rovida Mara , Rocha Paula Melani , Schoenherr Rafael , Coêlho Tamires Ferreira
Published: December 2022

Este relato de experiência aborda reflexões de âmbito teórico e metodológico resultantes da oferta interinstitucional de uma disciplina sobre Comunicação e Territorialidades, reunindo estudantes de pós-graduação de seis programas das regiões Norte, Nordeste, Centro-Oeste, Sudeste e Sul do Brasil. A proposição experimental foi possibilitada pelo ensino remoto durante a pandemia de Covid-19, atravessada pelo cenário de crise política, econômica e sanitária, e constituída por contribuições advindas de rodas de conversa com a turma e de jornalistas independentes e atuantes nas periferias de diferentes regiões brasileiras. Constata-se a potência da abordagem da pluralidade de experiências (acadêmicas e alternativas contra-hegemônicas) como caminho para entender as complexas tramas territoriais que constituem processos comunicativos muito além do aparato conceitual sistematizado na literatura.
Qualidade na comunicação promotora da saúde: diálogos entre a literatura especializada e as perspectivas dos jovens
Authors: Rothberg Danilo , Ferreira Vinícius Lauriano , Muniz Aressa Joel , Mendonça Ana Valéria Machado
Published: December 2022

Estimular a adoção de comportamentos adequados com a prevenção de infecções sexualmente transmissíveis é um dos objetivos da comunicação promotora da saúde dirigida aos jovens, que deve mobilizar saberes para corresponder a anseios desse público e facilitar a interlocução. Este artigo apresenta e discute os resultados de um workshop que realizamos com jovens universitários com o objetivo de promover um diálogo entre a literatura especializada sobre diferenciais de qualidade da comunicação e as perspectivas dos participantes sobre o tema. As sugestões trazidas pelos jovens fornecem uma visão privilegiada sobre as contribuições da literatura especializada para a conceituação de qualidade da comunicação promotora da saúde.
Foto Voz – novas técnicas de pesquisa, educação e intervenção social
Authors: Costa Maria Cristina Castilho
Published: December 2022

Este texto é parte de uma pesquisa mais ampla, aprovada pelo CNPq, que busca investigar as relações entre arte, comunicação, tecnologia e educação. A partir de autores que subsidiam a importância da renovação das posturas ligadas à educação e ao conhecimento, apresenta uma metodologia de pesquisa interativa e multilinguagem que, criada nos anos 1990, recebeu o nome de Foto Voz. Integrando registro de imagens fotográficas, reflexão e discussão de situações-problema, essa metodologia tem sido utilizada em pesquisas que visam a intervenção social, com propostas ligadas à cultura dos participantes, à sua percepção da realidade e à sua subjetividade.
Studygram: os modos “instagramáveis” de ser estudante
Authors: Biadeni Bianca S. , Castro Gisela G S
Published: December 2022

Neste artigo, observamos determinados modos de ser e de se apresentar como estudante nas plataformas de redes sociais. A partir da análise de formas de produção e compartilhamento de conteúdo entre usuários da rede Instagram, que possuem perfis denominados como studygrams, procuramos compreender determinadas convocações para um modelo de subjetividade, associado ao consumo de um modo particular de estudar e de se mostrar como um estudante exemplar. Para tanto, nos inspiramos em preceitos do estudo das imagens proposto por Roland Barthes (1982) entrelaçado ao referencial teórico que mobiliza autores dedicados aos estudos da comunicação e do consumo
Association Between Copayment Amount and Filling of Medications for Angiotensin Receptor Neprilysin Inhibitors in Patients With Heart Failure
Authors: Mukhopadhyay Amrita , Adhikari Samrachana , Li Xiyue , Dodson John A. , Kronish Ian M. , Shah Binita , Ramatowski Maggie , Chunara Rumi , Kozloff Sam , Blecker Saul
Published: December 2022

Background

Angiotensin receptor neprilysin inhibitors (ARNI) reduce mortality and hospitalization for patients with heart failure. However, relatively high copayments for ARNI may contribute to suboptimal adherence, thus potentially limiting their benefits.

Methods and Results

We conducted a retrospective cohort study within a large, multi‐site health system. We included patients with: ARNI prescription between November 20, 2020 and June 30, 2021; diagnosis of heart failure or left ventricular ejection fraction ≤40%; and available pharmacy or pharmacy benefit manager copayment data. The primary exposure was copayment, categorized as $0, $0.01 to $10, $10.01 to $100, and >$100. The primary outcome was prescription fill nonadherence, defined as the proportion of days covered <80% over 6 months. We assessed the association between copayment and nonadherence using multivariable logistic regression, and nonbinarized proportion of days covered using multivariable Poisson regression, adjusting for demographic, clinical, and neighborhood‐level covariates. A total of 921 patients met inclusion criteria, with 192 (20.8%) having $0 copayment, 228 (24.8%) with $0.01 to $10 copayment, 206 (22.4%) with $10.01 to $100, and 295 (32.0%) with >$100. Patients with higher copayments had higher rates of nonadherence, ranging from 17.2% for $0 copayment to 34.2% for copayment >$100 (
P
<0.001). After multivariable adjustment, odds of nonadherence were significantly higher for copayment of $10.01 to $100 (odds ratio [OR], 1.93 [95% CI, 1.15–3.27],
P
=0.01) or >$100 (OR, 2.58 [95% CI, 1.63–4.18],
P
<0.001), as compared with $0 copayment. Similar associations were seen when assessing proportion of days covered as a proportion.

Conclusions

We found higher rates of not filling ARNI prescriptions among patients with higher copayments, which persisted after multivariable adjustment. Our findings support future studies to assess whether reducing copayments can increase adherence to ARNI and improve outcomes for heart failure.
The Rights of God's Stewards: Property, Conscience, and the Great Awakening in Canterbury, Connecticut
Authors: Nordbye Erik
Published: December 2022

The struggle for religious liberty in Canterbury, CT, was fought over property. When the Great Awakening divided church against town, evangelical “Separates” withdrew from the establishment and launched a campaign against ecclesiastical taxation, using concepts of conscience, stewardship, and property rights to defend estates and create a voluntary religious economy.
Beyond “Sectional Superiority”: Memorializing Black History in Northern New England
Authors: Raimon Eve Allegra
Published: December 2022

New England's lingering sense of itself as the locus of abolitionist virtue makes it imperative to interrogate this self-perception while examining the cultural import of contemporary African American memorials in the region. Twenty-first century commemorations in Northern New England are attempting to correct the visual and historical record of the suppression and expulsion of African Americans by erecting memorials that celebrate New England's Black history.
Selling Books in Eighteenth-Century Boston: The Daybook of Benjamin Guild
Authors: Orr Leah
Published: December 2022

Through an analysis of the daybook of late-eighteenth-century Boston bookseller Benjamin Guild, this essay presents a microhistory of retail bookselling in Boston just after the Revolutionary War. It argues that American customers mainly bought British books and that prices varied, with implications for book history, literature, and cultural studies.
Differentiated Rehabilitation and the Geographies of Unfreedom in Post-Colonial Bombay
Authors: Thatra Geeta
Published: December 2022

The “refugee crisis” after the 1947 Partition of British India generated new contestations over urban resources, especially for securing accommodation. It resulted in a proliferation of encampment laws and policies with outcomes at multiple levels: city, neighborhood, and community. This article traces the uneven geographies produced by Bombay’s encampment laws and the (spatial) politics of refugee rehabilitation. It focuses on the state’s use of “camps” to segregate impoverished refugees and consolidate the urban periphery. The article explores the interplay between law, space, and property to illustrate how refugee entitlements created and sustained various forms of power and precarity in the metropolis. Refugee camps provided “conditional access” to shelter for indigent Sindhi refugees and became markers of social identification. Middle-class Sindhi refugees, on the other hand, secured their place in the city by establishing cooperative housing societies. This article highlights how caste and regional distinctions in pre-Partition Sindh translated into class-based spatial divisions among the displaced Sindhis in post-colonial Bombay.
Review of Adoption Theories in the Context of Blockchain
Authors: Dua Aman
Published: December 2022

Blockchain is an emerging technology, showing possibilities in many fields. It has provided its mark in finance with cryptocurrency. Its security, robustness, interoperability and reliability have promised application in various areas, but the demonstrated use of blockchain technology is rare. The stakeholders are in the process of decision-making about the adoption of blockchain and assimilating with this new technology. This article discusses blockchain technology adoption with theories that were formed on adoption, infusions and assimilation of technologies by firms and individuals. Blockchain technology will be adopted by firms, but most of the theories of adoption have been developed around individuals. Therefore, an assumption has been made that the premise for the firm will be the same as the premise for individuals, in the context of blockchain. Various firms, and the Indian government, are in the process of decision-making regarding blockchain. This article delivers explanations of constructs of different theories in the context of blockchain technology. This explanation will help practitioners to understand and analyse the adoption of blockchain technology in the context of their industry practice, and for academicians, it will act as the base to develop measurement tools for different assessments in the blockchain.
An Empirical Study of the Movement of Sectoral Indices and Macroeconomic Variables in the Indian Stock Market
Authors: Pandey Sitaram
Published: December 2022

The goal of this research is to look at how the Indian stock market sectoral indices respond to three macroeconomic variables: oil price (OP), gold price (GP) and exchange rate (ER) between 2016 and 2020. The data of sectoral indices were collected from the Bombay Stock Exchange. The underlying series is evaluated as non-stationary at the level, but stationary in the first difference, using the augmented Dickey–Fuller unit root test. The multivariate co-integration analysis and vector error correction model indicates that there are long-term links between macroeconomic variables and sectoral indices in the information technology sector. Meanwhile, the research using the vector auto regression model approach shows that there are short-run correlations between macroeconomic variables and sectoral indices, namely Basic Materials, Fast Moving Consumer Goods, Finance, Healthcare, Information Technology, Auto, Bankex, Power and Reality. The results document that OP, GP and ER simultaneously have a significant effect on sectoral indices in the Indian stock market. To stabilise the stock market post-COVID-19, the authorities are advised to put economic policies sector-wise to accelerate the economic growth and to maintain fiscal discipline. The authorities need to stabilise the aforementioned macroeconomic variables to accelerate the economic growth as the ER has a significant negative impact on all sectors.
Qualitative Innovation in the Light of the Normative: A Minimal Approach to Promoting and Measuring Successful Innovation in Business
Authors: Faix Anna-Vanadis
Published: December 2022

Innovation has now become a core issue in companies and the economy, and it is becoming the leading driver of growth and prosperity. However, there is often a lack of uniform and holistic concepts that grasp the phenomenon and integrate it interpretatively, and, therefore, business structures towards innovation cannot be defined and interpreted adequately. This article aims to take up this question and answer it within a minimal concept of innovation quality. The quality of innovation is not based on the profit of the company or other one-sided economic core variables but rather on the general creation of value and the improvement of the quality of life in a society. This makes it possible to create a normative basis for a general evaluation that can be used to interpret structures in the company that are conducive to innovation and long-term solutions towards creativity and critical thinking.
India’s Frugal Innovations: Jugaad and Unconventional Innovation Strategies
Authors: Sharma Ruchi , Mishra Nandita , Sharma Gauri
Published: December 2022

In recent years, many low-cost innovations, to solve the problems of economically weaker sections of the society has emerged, with the goal of bringing together enterprise and social welfare. In reality, all businesses were concerned that high quality and low price may cannibalise their own existence. Concurrently, the customers who were intended to be benefitted from the novel strategy, tend to evade the products, quoting, the quality of the products being inferior and talking about the social stigma of using low-cost goods or products. The researchers by using different case studies have shown how the companies can effectively and successfully reduce the uncertainties of the market and technological challenges of low-cost products for price sensitive customers. After analyzing the case studies used in the article, it appears that the most important criteria to improve customer perceptions of quality and image is to keep the cost low and provide value for money. The case studies show that organisations that use the networks of open global innovation for the overall collaborative development at various stages of the value chain representing innovation are more likely to succeed with affordability-driven innovations
Retained functional normal and preleukemic HSCs at diagnosis are associated with good prognosis in DNMT3AmutNPM1mut AMLs
Authors: Donato Elisa , Correia Nadia , Andresen Carolin , Karpova Darja , Würth Roberto , Klein Corinna , Sohn Markus , Przybylla Adriana , Zeisberger Petra , Rothfelder Kathrin , Salih Helmut , Bonig Halvard , Stasik Sebastian , Röllig Christoph , Dolnik Anna , Bullinger Lars , Buchholz Frank , Thiede Christian , Hübschmann Daniel , Trumpp Andreas
Published: December 2022

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by high rate of relapse and mortality. Current chemotherapies whilst successful in eradicating blasts, are less effective in eliminating relapse-causing leukemic stem cells (LSCs). Although LSCs are usually identified as CD34+CD38- cells, there is significant heterogeneity in surface marker expression, and CD34- LSCs exist particularly in NPM1mut AMLs. By analyzing diagnostic primary DNMT3AmutNPM1mut AML samples, we suggest a novel flow cytometry sorting strategy particularly useful for CD34neg AML subtypes. To enrich for LSCs independently of CD34 status, positive selection for GPR56 and negative selection for NKG2D ligands are used. We show that the functional reconstitution capacity of CD34- and CD34+ LSCs as well as their transcriptomes are very similar which support phenotypic plasticity. Furthermore, we show that although CD34+ subpopulations can contain next to LSCs also normal and/or preleukemic hematopoietic stem cells (HSCs), this is not the case in CD34-GPR56+NKG2DL- enriched LSCs which thus can be isolated with high purity. Finally, we show that patients with AML, who retain at the time of diagnosis a reserve of normal and/or preleukemic HSCs in their bone marrow able to reconstitute immunocompromised mice, have significantly longer relapse-free and overall survival than patients with AML in whom functional HSCs are no longer detectable.
Incidence, risk factors, and impact of early cardiac toxicity after allogeneic hematopoietic cell transplant
Authors: Pérez-Valencia Amanda Isabel , Cascos Enric , Carbonell-Ordeig Sara , Charry Paola , Gómez-Hernando Marta , Rodríguez-Lobato Luis Gerardo , Suárez-Lledó María , Martínez-Cibrian Nuria , Antelo María Gabriela , Solano María Teresa , Arcarons Jordi , Nomdedeu Meritxell , Cid Joan , Lozano Miquel , Díaz-Ricart Maribel , Rosiñol Laura , Esteve Jordi , Urbano-Ispizua Álvaro , Carreras Enric , Martínez Carmen , Fernández-Avilés Francesc , Rovira Montserrat , Salas María Queralt
Published: December 2022

This study investigates early cardiac events (ECEs) occurring during the first 180 days after allogeneic hematopoietic cell transplant (allo-HCT) in 416 adults receiving posttransplant cyclophosphamide (PTCY) (n = 258) or not receiving PTCY (n = 158). Total body irradiation (TBI) was given to 133 (31.9%) patients, of whom 111 (83.4%) received TBI combined with PTCY. The day +180 cumulative incidence function (CIF) of ECEs was 8.4%, with heart failure (n = 13) and pericardial complications (n = 11) being the most prevalent complications. The incidence of ECEs was higher in patients receiving PTCY, and receiving TBI. ECEs were more prevalent in haploidentical HCTs than in matched sibling donor, 10/10 HLA-matched unrelated donor, and 9/10 HLA-mismatched unrelated donor allo-HCTs. As for the ECE risk from the combination of PTCY and TBI, the multivariate analysis reported that patients receiving PTCY without TBI, TBI without PTCY, and TBI with PTCY were at higher risk for ECEs compared with patients receiving neither PTCY nor TBI. Pre-existing cardiac morbidity predicted ECEs. However, using high-dose CY-containing preparative regimens did not increase the risk for cardiac toxicity at +180 days after allo-HCT. ECEs were associated with higher nonrelapse mortality and lower overall survival. Considering that PTCY and TBI were predictors for ECEs, and the impact of this complication on transplant mortality, the implementation of cardiac monitoring plans could be appropriate in patients receiving these medications.