bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B017: Analysis of Wnt signaling and metastasis related protein in invasive ductal carcinoma
Authors: Adeshina Anuoluwapo A. , Ajayi Babajide O.
Published: December 2022

Ductal carcinoma in situ (DCIS) characterizes about 20% of all breast cancers. Breast cancer is the most common cancer among women, the number one cause of cancer mortality, and one of the leading causes of morbidity and mortality for women worldwide. Wnt signaling have been implicated in more than 45% of breast cancer patients and has been shown to decrease survival in breast cancer patients. One of the major challenges of Breast cancer treatment is that it is a heterogeneous disease comprised of four main sub types. Therefore, there is a need to investigate possible signaling pathways that may be specific for each subtype of breast cancer, so as to establish a targeted therapy and management protocol for breast cancer patients This study analyzed the expression of Wnt signaling and metastasis related protein, reversion-inducing cysteine-rich protein with kazal motif (RECK) in molecular subtypes of breast cancer samples of DCIS origin. Formalin Fixed Paraffin Embedded (FFPE) breast tumor samples were used for this study. The breast cancer tissues were divided into estrogen receptor/progesterone receptor (ER/PR) positive, ER positive, human epidermal growth factor receptor 2 (HER-2) positive, Triple negative and Triple positive based on immunohistochemical reactivity for breast cancer subtype specific antibody. These tissues were further processed for expression of Wnt signaling and metastatic related protein. Result from this study showed that Beta-catenin was highly expressed in estrogen receptor and progesterone receptor subtypes of breast cancer whereas adenomatous polyposis coli was positive for estrogen receptor and negative for the other subtypes. Furthermore, the triple negative breast cancer may metastasize earlier than other sub types of breast cancer because it has low expression of RECK when compared with other breast cancer sub-types. In conclusion, subtypes of breast cancer have different expression of Wnt signaling and metastatic related protein expression and as such Wnt signaling may correlate with metastasis in breast cancer.

Citation Format: Anuoluwapo A. Adeshina, Babajide O. Ajayi. Analysis of Wnt signaling and metastasis related protein in invasive ductal carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr B017.
Abstract IA006: Co-evolving artificial intelligence and pathology
Authors: Yuan Yinyin
Published: December 2022

A fundamental question in cancer biology is how cancers evolve heterogeneity and treatment resistance. The evolution trajectory of cancer is dictated by selective pressures from treatments and the tumor ecosystem. Artificial intelligence (AI) enables us to directly study geographical patterns of the microenvironment in pathological samples, to infer cancer habitats and niches. Significant challenges and open questions remain: how to establish multidisciplinary platforms, develop reproducible AI tools, and how to leverage pathology, genetic, molecular, and clinical data to improve personalized oncology. Charles Darwin described how the intimate coexistence between flowering plants and insects leads to reciprocal evolutionary changes; this is now known as coevolution. Today, through the demolition of disciplinary barriers, AI and pathology can co-evolve to create evolutionary changes and new paradigms. I will discuss our latest progress on combining AI and experimental technologies for spatial histology and omics data analysis. We aim to understand how cancer evolves within diverse environmental conditions. Our work has revealed a high level of geospatial variation in the tumor microenvironment, with profound implications for early diagnosis, biomarker development, and cancer therapeutics.

Citation Format: Yinyin Yuan. Co-evolving artificial intelligence and pathology [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA006.
Abstract IA019: Surgery for DCIS: If, what and when
Authors: Thompson Alastair M. , Bonefas Elizabeth , Carter Stacey , marin Ivan , Javaid Huma , Montalvan Jessica
Published: December 2022

DCIS is traditionally viewed as a surgical problem managed in a comparable way to invasive breast cancer, by breast conservation or mastectomy, to prevent the evolution of intraductal to invasive disease. The need for surgery has been challenged by retrospective case series demonstrating that progression from DCIS to invasive disease is variable, increases with time, but may be modified by endocrine therapy. This data has led to the innovative trials currently under way of active monitoring compared with surgery – the “if” of whether surgery is needed. What surgery to perform requires pathology confirmation of the diagnosis, awareness of the heterogeneity of DCIS (and the potential for sampling to miss invasive disease) together with imaging by mammography, ultrasound and/or MRI. Clinical impressions, imaging and pathology findings direct treatment options. Surgery comprises lumpectomy versus simple, skin sparing or nipple sparing mastectomy (with consideration for reconstruction) potentially partnered with axillary node surgery, at least for those undergoing mastectomy. When (and how) to perform surgical and allied techniques is undergoing change. The required surgical margins of 2mm (for pure DCIS) at the time of conservation to reduce local recurrence remains challenging, with technologies such as optical coherence tomography demonstrating promise for intraoperative determination of adequate margins. Rather than routine sentinel lymph node biopsy, with the attendant risks of lymphedema, iron oxide/dextran coated particles injected prior to surgery, rapidly migrate to and lodge in the axillary nodes and provide an option for delayed axillary surgery if invasive disease is identified. Neoadjuvant approaches to DCIS, targeting the estrogen receptor or HER2, to downstage the extent of surgery are less favored than for invasive breast cancers, but DCIS may be the residue left after neoadjuvant treatment for invasive disease. However, adjuvant endocrine therapy and adjuvant radiotherapy may each have an impact on reducing the chance of re-occurrence of DCIS or development of invasive cancer. Currently, surgery remains the primary treatment for DCIS. If surgery is performed, what is done and when surgery takes place varies with the nature, the extent of the DCIS and is influenced by patient preference.

Citation Format: Alastair M. Thompson, Elizabeth Bonefas, Stacey Carter, Ivan marin, Huma Javaid, Jessica Montalvan. Surgery for DCIS: If, what and when [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA019.
Abstract IA035: DCIS to IDC progression - a key step of immune escape
Authors: Polyak Kornelia
Published: December 2022

The cellular and molecular mechanisms underlying ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) transition are poorly understood. We have analyzed genetic, gene expression, epigenetic profiles of cells composing the tumor and identified cell type-specific changes during tumor progression. Importantly, we detected significant changes in the immune cell composition during tumor progression implying immune escape in invasive tumors and active adaptive immune response in DCIS. We demonstrate that these progression stage-specific alterations are also present in a rat model of breast cancer and that combined targeting of multiple components of the tumor ecosystem increases the efficacy of anti-cancer therapies. Our data highlight the role of microenvironmental, especially immune-related changes in driving breast tumor progression and emphasize the importance of studying pre-invasive tumors.

Citation Format: Kornelia Polyak. DCIS to IDC progression - a key step of immune escape [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA035.
Abstract A001: 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 A001.
Abstract A017: Lung cancer chemoprevention with the β-blocker carvedilol
Authors: Shahid Ayaz , Chen Mengbing , Lin Carol , Andresen Bradley T. , Parsa Cyrus , Orlando Robert , Huang Ying
Published: December 2022

Chronic exposure to carcinogens that are present in tobacco smoke is a causative factor for lung carcinogenesis. Although smoking cessation successfully reduced the prevalence of cigarette use in the US, lung cancer risk for current and former smokers remains high, for whom no effective chemopreventive agent currently exists. In the present study, carvedilol, an FDA-approved β-blocker was examined on lung carcinogenesis induced by the tobacco carcinogen benzo(a)pyrene [B(a)P] in vitro and in vivo. In non-tumorigenic human bronchial epithelial cell culture BEAS-2B, carvedilol inhibited benzo(a)pyrene diol epoxide (BPDE)-induced malignant transformation at non-toxic concentrations in a dose-dependent manner. Although β-adrenergic receptors (β-ARs) are expressed in BEAS-2B cells, the anticancer activity of carvedilol is independent of β-blockade since the non-β-blocking R-carvedilol enantiomer also blocked transformation while the β-blockers atenolol (β1-AR selective blocker), ICI-118,551 (β2-AR selective blocker), and propranolol (nonselective blocker) had no effect. Carvedilol’s anti-transformation activity is possibly mediated by aryl hydrocarbon receptor signaling because carvedilol, R- and S-carvedilol all inhibited B(a)P-activated xenobiotic responsive element (XRE) promoter and CYP1A1 mRNA expression. In a B(a)P-induced acute lung toxicity model in CD-1 mice, pretreatment with carvedilol, R- or S-carvedilol (20 mg/kg/day) for 7 days significantly attenuated increased plasma levels of lactate dehydrogenase and malondialdehyde, inflammatory cell infiltration, histopathologic changes, and overexpression of COX-2 in the lung. In a B(a)P-induced lung carcinogenesis model in A/J mice, carvedilol at 3.2 and 20 mg/kg significantly attenuated tumor multiplicity and burden, to a similar degree as the EGFR inhibitor gefitinib. Our study reveals a previously unexplored role for the FDA approved cardiovascular drug carvedilol in the prevention of tobacco carcinogen-associated lung cancer.

Citation Format: Ayaz Shahid, Mengbing Chen, Carol Lin, Bradley T. Andresen, Cyrus Parsa, Robert Orlando, Ying Huang. Lung cancer chemoprevention with the β-blocker carvedilol [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 A017.
Abstract IA017: Iloprost for lung cancer prevention
Authors: Keith Robert
Published: December 2022

Iloprost is a prostacyclin analogue with anti-metastatic, vasodilatory and anti-inflammatory properties. Increased prostacyclin is protective in pre-clinical murine models of adenocarcinoma and squamous cell carcinoma (SCC), including tobacco smoke. The chemoprotective properties are independent of the single cell surface prostacyclin receptor, as knockout animals are still protected. Clinical studies of iloprost have included both oral and inhaled preparations. Oral iloprost improves endobronchial dysplasia (pre-cursor lesions for invasive SCC) in former smokers. Dysplastic lesions are now being characterized beyond histology to better understand lesion evolution. Investigations into the mechanism of iloprost associated cancer prevention (including effects on basal progenitor cells, progenitor multi-potentiality, and differentiation) and biomarkers predicting response will be presented, along with an outline for an upcoming clinical trial in former smokers.

Citation Format: Robert Keith. Iloprost for lung 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 IA017.
Terrorismos e pontes do musicar local: Linn da Quebrada e seu artivismo de reXistência e desidentificação
Authors: Grunvald Vi
Published: December 2022

Este artigo se insere em um conjunto de elucubrações sobre arte e política que venho realizando ao longo da última década. Diversamente de outras publicações, meu foco aqui é a relação entre música e política ou, antes, o musicar terrorista de uma artista específica, Linn da Quebrada. Interessa-me como esse musicar afeta a construção de uma localidade e é construído mutuamente por ela, criando coalizões que servem de semente para comunidades imaginadas dissidentes que são também comunidades de prática. Posteriormente, utilizo tanto desidentificação, tal como conceituada por José Estebán Muñoz, quanto a noção de reXistência (nossa, política, cotidiana) para refletir sobre algumas motivações inerentes a esse musicar, atentando de que maneira a aproximação entre música e política faz qualquer sentido formalista de estilo musical hesitar. Por fim, em minhas alucinações finais, aciono questões relacionadas à colonialidade do pensamento e dos corpos para pensar que musicar e localidade confluem na criação de esferas públicas éticas e estéticas na qual a lógica dominante do CIStema colonial e necropolítico não é régua comum.
A bibliographic review of the history of Dexiinae (Diptera, Tachinidae) taxonomy in the Neotropical Region with bibliographic notes on Dominik Bilimek and Fritz Plaumann
Authors: De Santis Marcelo Domingos
Published: December 2022

The knowledge of Dexiinae and Tachinidae diversity in the Neotropical Region, in contrast to other regions, e.g., the Palaearctic Region, is in a poor condition. The history of these taxa has gradually increased since the 18th Century from the works of European and North American authors such as Johan C. Fabricius, Christian R.W. Wiedemann, Jean B. Robineau-Desvoidy, Pierre J.-M. Macquart, Jacques M.F. Bigot, Francis Walker, Victor von Röeder, Ermanno Giglio-Tos, Friedrich M. Brauer and Julius E. Bergenstamm, Frederik M. van der Wulp, Charles H. Curran, John M. Aldrich, Charles H.T. Townsend, Henry J. Reinhard and William R. Thompson. It was only in the first half of the 20th Century that scientists born or established in South America began to enter tachinidology. Dipterists like Jean Brèthes and Everardo E. Blanchard from Argentina, Rául E. Cortés Peña from Chile and José H. Guimarães from Brazil, are the most memorable names for, not only to Neotropical Dexiinae, but, indeed for the whole family. Herein, a brief chronological review of tachinidology, with emphasis on Dexiinae and based on a literature review, is given. The history is divided into four periods: the pre-Linnaean period of the 16th and 17th Centuries, the 18th Century, the 19th Century and the first half of the 20th Century. After the first half of 20th Century, the emphasis is focused on European and North American dipterists with an overview of their contributions on Dexiinae taxonomy. Later, with presence of the South American dipterists, the emphasis is directed to them. Then a few notes are given on the Czech Dominik Bilimek, a poorly known collector from the 19th Century and Fritz Plaumann, a well-known German immigrant who collected in Brazil during the earlier 20th Century. Finally, some notes and perspectives about the 21st Century dexiinidology from the Neotropics is briefly discussed.
As rapineiras neotropicais na Europa dos séculos XVI e XVII (Aves, Falconidae, Accipitridae)
Authors: Teixeira Dante Martins
Published: December 2022

O intenso fluxo de animais do Neotrópico observado na Europa durante o início da Idade Moderna incluiria demandas muito singulares vindas de determinados atores sociais. Este parece ser exatamente o caso das aves de rapina, em geral destinadas a uma nobreza entusiasta da falcoaria que concentrava desmedido poder e se mostrava disposta a oferecer atrativas recompensas por exemplares trazidos do além-mar. Vigente ao menos desde 1509, esse tráfico abarcava tanto representantes dos Accipitridae quanto dos Falconidade, havendo registros documentais ou iconográficos para o japacanim (Spizaetus ornatus), o falcão-peregrino (Falco peregrinus) e o falcão-de-coleira (Falco femoralis) – provavelmente o misterioso "aleto" pelo qual se pagavam quantias exorbitantes. A documentação disponível também menciona a surpreendente captura de um gerifalte (Falco rusticolus) ao largo da costa do Brasil – a primeira referência conhecida dessa espécie para o hemisfério sul. Tal como foi comprovado para vários outros grupos zoológicos no continente americano, os dados existentes sugerem a forte possibilidade de algumas rapineiras neotropicais terem sido bem mais numerosas no período colonial.
Naruto, um artista ou um intruso na aula de arte? Interferências de memórias audiovisuais no discurso criativo da criança ao desenhar
Authors: Pereira Isac dos Santos , Magno Maria Ignes Carlos
Published: December 2022

O artigo desenvolve como breve tema geral, mesmo que de forma implícita as discussões acerca da inserção dos produtos audiovisuais dentro do campo da Arte/Educação contemporânea, salientando sua importância e mudança na maneira de se ensinar e aprender Arte na atualidade, e posteriormente, de forma preponderante, a construção poética das crianças ao desenharem nutridas audiovisualmente, principalmente pela animação Naruto, estando elas muito mais propícias a serem criativas. Logo, tem-se em vista que compreender as produções gráficas das crianças como objetos de Arte conformados dentro do contexto contemporâneo, é também ao mesmo tempo entendê-las como status documentais/memórias da Arte/Educação afeitos à época da comunicação audiovisual e inerentes ao processo criativo.
Literacias para a Cidadania Global
Authors: Cunha Isabel Maria Ribeiro Ferin
Published: December 2022

Este texto discute a pertinência, atualidade e princípios do conceito de literacias para uma cidadania global. Após descrever historicamente a emrgência e o enquadramento do conceito de literacia, na década de sessenta do século passado, abordam-se os fatores que impelem à sua expansão num mundo global. Descreve-se o entendimento de ler o mundo, como capacidade de buscar, agregar e interpretar  informação, a partir de múltiplas fontes e dispositivos, com o objetivo de compreender fenómenos e situações. Defende-se que o objetivo da literacia para uma cidadania global deve dirigir-se a todos os grupos sociais,  identificados por caracrterísticas próprias e merecedores de abordagens específicas.  A metodologia utilizada está sustentada na revisão bibliográfica e assume-se o pendor ensaístico e exploratório da exposição.
Diálogo em Paulo Freire nas interfaces com a comunicação popular e comunitária e a pesquisa participante
Authors: Peruzzo Cicilia Maria Khroling , Bassi Ingrid Gomes , Silva Junior Carlos Humberto Ferreira
Published: December 2022

O artigo objetiva discutir a questão do diálogo em Freire, como base do processo de comunicação e, em interação com outros autores, relacioná-lo às interrelações entre Comunicação e Educação, em especial na Comunicação Popular e Comunitária no contexto dos movimentos sociais cívicos e na pesquisa participante. O estudo se fundamenta em pesquisa bibliográfica. Conclui-se que as relações entre Comunicação e Educação facilitam a constituição do diálogo, tanto nos ambientes da educação formal quanto no contexto dos movimentos sociais populares brasileiros que, desde o fim da década de 1970, vivenciam o diálogo, tanto na construção coletiva das suas formas de organização e mobilização quanto na formulação das estratégias e táticas desenvolvidas tendo em vista as lutas denunciativas da opressão e reivindicativas de direitos. O diálogo é uma questão transcendental e indissociável às práticas educativas. O diálogo pode ser entendido como ação-reflexão que valoriza a participação dos sujeitos – como sujeitos – na construção do conhecimento.
Ciências da Comunicação contra a desinformação
Authors: Bucci Eugenio
Published: December 2022

A partir do entendimento de informação, não apenas pela etimologia, mas pela história do uso social do termo, procuro desenvolver o conceito de desinformação. Mais do que boatos, mais do que um rastilho de mentiras, a desinformação, a meu ver, deve ser vista como um subproduto tóxico da Superindústria do Imaginário, pondo em risco a normalidade democrática e impulsionando discursos com traços fascistas. Se a informação ajuda a tecer laços de confiança na esfera pública, a desinformação dissolve esses laços. Nos marcos da Superindústria do Imaginário – um estágio do capitalismo em que o valor da imagem da mercadoria supera o valor do corpo da mercadoria –, a comunicação deixa de ser uma atividade acessória (a serviço de organizações públicas ou privadas) para se tornar o centro da atividade econômica e da política, definindo o estatuto da desinformação – um padrão comunicacional que comprime o pensamento e a verificação dos fatos em proveito das identificações libidinais, das paixões e do desejo. Tanto isso é verdade que os conglomerados monopolistas globais (as big techs, como Meta, Apple ou Alphabet) alcançam os maiores valores de mercado da história, na casa dos trilhões de dólares.
A educação midiática, diálogos e práticas possíveis com crianças no ambiente educacional da favela
Authors: Oliveira Thaiane Moreira de , Sousa Lumárya Souza de
Published: December 2022

A partir dos pressupostos da metodologia da pesquisa-ação, o artigo apresenta experiências do projeto FavelAção, que promoveu atividades de educação midiática em uma escola pública na favela carioca com crianças entre 9 e 12 anos de idade. São apontadas percepções midiáticas dos educandos a partir das diferentes formas que se relacionam, utilizam, consomem e entendem as mídias, apontando como essa relação é permeada por invisibilidades e disputas por autoridade e reconhecimento dos seus processos intersubjetivos. Os resultados apontam para indivíduos já letrados midiaticamente, tanto no sentido crítico quanto produtivo das mídias, mas que também reivindicam por espaços dialógicos que os reconheçam enquanto sujeitos.
Social-Ecological Measurement of Daily Life: How Relationally Focused Ambulatory Assessment Can Advance Clinical Intervention Science
Authors: Kaplan Deanna M.
Published: December 2022

Individuals’ daily behaviors and social interactions play a central role in the diagnosis and treatment of psychological disorders. Despite this, observational ambulatory assessment methods—research methods that allow for direct and passive assessment of individuals’ momentary activities and interactions—have a remarkably scant history in the clinical science field. Prior discussions of ambulatory assessment methods in clinical science have focused on subjective methods (e.g., ecological momentary assessment) and physiological methods (e.g., wearable heart rate monitoring). Comparatively less attention has been dedicated to ambulatory assessment methods that collect objective, relational data about individuals’ social behaviors and their interactions with their momentary environmental contexts. Drawing on extant social-ecological measurement frameworks, this article first provides a conceptual and psychometric rationale for the integration of daily relational data into clinical science research. Next, the nascent research applying such methods to clinical science is reviewed, and priorities for further research organized by the NIH Stage Model for Clinical Science Research are recommended. These data can provide unique information about the social contexts of diverse patient populations; identify social-ecological targets for transdiagnostic, precision, and culturally responsive interventions; and contribute novel data about the effectiveness of established interventions at creating behavioral and relational change.
Funding Failure: Determinants of Persistence
Authors: Baid Chandresh , Baid Devesh
Published: December 2022

Since the economic meltdown in 2008, crowdfunding has emerged as an alternate source of finance for entrepreneurs looking for funds to start or support their venture. Most research in the area of crowdfunding has focused on the determinants of successful funding. To the best of our knowledge, very few studies exist about what happens to a project with an unsuccessful funding on crowdfunding platforms. Do the entrepreneurs who failed to get funding from crowdfunding platform abandon their project or do they persist with it and try to find alternate sources to make their dream come true? In this article, we study the determinants of persistence of an entrepreneur to bring their project to life after failing to receive funding from crowdfunding platforms.
The untargeted urine volatilome for biomedical applications: methodology and volatilome database
Authors: Llambrich Maria , Brezmes Jesús , Cumeras Raquel
Published: December 2022

Chemically diverse in compounds, urine can give us an insight into metabolic breakdown products from foods, drinks, drugs, environmental contaminants, endogenous waste metabolites, and bacterial by-products. Hundreds of them are volatile compounds; however, their composition has never been provided in detail, nor has the methodology used for urine volatilome untargeted analysis. Here, we summarize key elements for the untargeted analysis of urine volatilome from a comprehensive compilation of literature, including the latest reports published. Current achievements and limitations on each process step are discussed and compared. 34 studies were found retrieving all information from the urine treatment to the final results obtained. In this report, we provide the first specific urine volatilome database, consisting of 841 compounds from 80 different chemical classes.
Improvement of erectile dysfunction using endothelial progenitor cells from fetal cerebral vasculature in the cavernous nerve injury of rats
Authors: Kim Jae Heon , Bak Sang Hong , Yang Hee Jo , Doo Seung Whan , Kim Do Kyung , Yang Won Jae , Kim Seung U. , Lee Hong J. , Song Yun Seob
Published: December 2022

Background

Because of limited differentiation to endothelium from mesenchymal stem cells, it has been strongly recommended to use endothelial progenitor cells for the regeneration of the damaged endothelium of corpora cavernosa. This study was performed to investigate the immortalized human cerebral endothelial cells and their capability for repairing erectile dysfunction in a rat model of cavernous nerve injury. Circulating endothelial progenitor cells were isolated from human fetal brain vasculature at the periventricular region of telencephalic tissues. Over 95% of CD 31-positive cells were sorted and cultured for 10 days. Human cerebral endothelial progenitor cells were injected into the cavernosa of rats with cavernous nerve injury. Erectile response was then assessed. In in vivo assays, rats were divided into three groups: group 1, sham operation: group 2, bilateral cavernous nerve injury: and group 3, treatment with human cerebral endothelial cells after cavernous nerve injury.

Results

Established immortalized circulating endothelial progenitor cells showed expression of human telomerase reverse transcriptase transcript by RT-PCR. They also showed the expression of vascular endothelial growth factor, von Willebrand factor, vascular endothelial growth factor receptor, and CD31, cell type-specific markers for endothelial cells by RT-PCR. In in vitro angiogenesis assays, they demonstrated tube formation that suggested morphological properties of endothelial progenitor cells. In in vivo assays, impaired erectile function of rat with cavernous nerve injury recovered at 2, 4, and 12 weeks after transplantation of human cerebral endothelial cells into the cavernosa.

Conclusions

Telomerase reverse transcriptase-circulating endothelial progenitor cells from fetal brain vasculature could repair erectile dysfunction of rats with cavernous nerve injury.
Genome-wide characterization and expression analysis of the HAK gene family in response to abiotic stresses in Medicago
Authors: Li Qian , Du Wenxuan , Tian Xinge , Jiang Wenbo , Zhang Bo , Wang Yuxiang , Pang Yongzhen
Published: December 2022

The high-affinity K+ transporter (HAK) family plays a vital role in K+ uptake and transport as well as in salt and drought stress responses. In the present study, we identified 22 HAK genes in each Medicago truncatula and Medicago sativa genome. Phylogenetic analysis suggested that these HAK proteins could be divided into four clades, and the members of the same subgroup share similar gene structure and conserved motifs. Many cis-acting elements related with defense and stress were found in their promoter region. In addition, gene expression profiles analyzed with genechip and transcriptome data showed that these HAK genes exhibited distinct expression pattern in different tissues, and in response to salt and drought treatments. Furthermore, co-expression analysis showed that 6 homologous HAK hub gene pairs involved in direct network interactions. RT-qPCR verified that the expression level of six HAK gene pairs was induced by NaCl and mannitol treatment to different extents. In particular, MtHK2/7/12 from M. truncatula and MsHAK2/6/7 from M. sativa were highly induced. The expression level of MsHAK1/2/11 determined by RT-qPCR showed significantly positive correlation with transcriptome data. In conclusion, our study shows that HAK genes play a key role in response to various abiotic stresses in Medicago, and the highly inducible candidate HAK genes could be used for further functional studies and molecular breeding in Medicago.
Comprehensive microRNA analysis across genome-edited colorectal cancer organoid models reveals miR-24 as a candidate regulator of cell survival
Authors: Villanueva Jonathan W. , Kwong Lawrence , Han Teng , Martinez Salvador Alonso , Shanahan Michael T. , Kanke Matt , Dow Lukas E. , Danko Charles G. , Sethupathy Praveen
Published: December 2022

Somatic mutations drive colorectal cancer (CRC) by disrupting gene regulatory mechanisms. Distinct combinations of mutations can result in unique changes to regulatory mechanisms leading to variability in the efficacy of therapeutics. MicroRNAs are important regulators of gene expression, and their activity can be altered by oncogenic mutations. However, it is unknown how distinct combinations of CRC-risk mutations differentially affect microRNAs. Here, using genetically-modified mouse intestinal organoid (enteroid) models, we identify 12 different modules of microRNA expression patterns across different combinations of mutations common in CRC. We also show that miR-24-3p is aberrantly upregulated in genetically-modified mouse enteroids irrespective of mutational context. Furthermore, we identify an enrichment of miR-24-3p predicted targets in downregulated gene lists from various mutational contexts compared to WT. In follow-up experiments, we demonstrate that miR-24-3p promotes CRC cell survival in multiple cell contexts. Our novel characterization of genotype-specific patterns of miRNA expression offer insight into the mechanisms that drive inter-tumor heterogeneity and highlight candidate microRNA therapeutic targets for the advancement of precision medicine for CRC.
Evaluation of Mycobacterium tuberculosis specific antigen-stimulated CD27−CD38+IFN-γ+CD4+ T cells for discrimination of active tuberculosis
Authors: Fang Yong , Wang Na , Tang Liang , Yang Xiao-Jun , Tang Yuan , Li Lin , Wu Wen-Fei , Su Bo , Sha Wei
Published: December 2022

Background

Active tuberculosis (ATB) originates from primary Mycobacterium tuberculosis (MTB) infection or reactivation of latent tuberculosis. Besides bacteriological examination, MTB-reactive immunocytes detection can be an alternative testing for discrimination of active tuberculosis. The purpose of this study is to investigate the accuracy of peripheral blood CD27−CD38+IFN-γ+CD4+T cells in ATB diagnosis.

Methods

This prospective diagnostic accuracy study was conducted at Shanghai Pulmonary Hospital between January 2019 and December 2021. Patients with ATB, non-tuberculosis mycobacterium infection (NTM), latent tuberculosis infection (LTBI), other respiratory diseases (OD), and healthy individuals (HC) were enrolled. The accuracy of CD27−CD38+IFN-γ+CD4+/CD4+ and other phenotypic markers for ATB diagnosis was assessed.

Results

A total of 376 patients (237 ATB, 38 LTBI, 8 NTM, 50 OD, and 43 HC) were enrolled. The ratios of CD4+IFN-γ+CD27− and CD4+IFN-γ+CD27−CD38+ profiles in CD4+IFN−γ+ cells and the ratios of CD4+IFN-γ+CD38+, CD4+IFN-γ+CD27−, and CD4+IFN-γ+CD38+CD27− profiles in CD4+ cells in the ATB group were significantly higher than in the other groups. The area under the curve (AUC) of CD27−CD38+IFN-γ+CD4+/CD4+ for the diagnosis of ATB was the highest, with a value of 0.890. With the optimal cutoff value of 1.34 × 10–4, the sensitivity and specificity of CD27−CD38+IFN-γ+CD4+/CD4+ for ATB diagnosis was 0.869 and 0.849, respectively.

Conclusion

CD27−CD38+IFN-γ+CD4+/CD4+ might be a potential biomarker for active tuberculosis diagnosis.
Suicidal behaviors in the entertainment industry: a preliminary exploration of the interplay between work scheduling, social support, and wellbeing in Australia
Authors: Zarate Daniel , Sonn Christopher , Fisher Adrian , Stavropoulos Vasileios
Published: December 2022

Objective

Workers of the Australian entertainment industry exhibit disproportionately high rates of impaired psychological wellbeing and suicidal behaviors, with such rates being exacerbated by the negative impact of working long and odd hours (Work Scheduling Impact; WSI). Nonetheless, stable and secure social support networks may buffer the risks associated with such systemic difficulties.

Methods

The responses of 1302 Australian entertainment industry workers (50.3% females, Mage 38.39 years) on the Multidimensional Scale of Perceived Social Support, the Short Form Health Survey, WSI, and suicidal behaviors questions were examined via moderation analyses.

Results

Higher social support and lower WSI appeared to reduce the suicidal ideation of those experiencing poorer mental health, while lower WSI further enhanced social support’s positive effect.

Conclusions

Findings highlight the likely detrimental effect of WSI regarding the suicidal ideation reported by vulnerable Australian entertainment industry workers and stress the importance of the social support they experience.

Public health implications

Interventions attempting to increase social support could improve inherent conditions associated with the Australian entertainment industry. Similarly, the negative effect of working long and odd hours on workers’ mental health and suicidal behaviors indicates the need to regulate the industry appropriately.
Clinical outcomes and risk factor of immune checkpoint inhibitors-related pneumonitis in non-small cell lung cancer patients with chronic obstructive pulmonary disease
Authors: Zeng Zhu , Qu Jingjing , Yao Yake , Xu Fei , Lu Shan , Zhang Pei , Yao Yinan , Li Ning , Zhou Jianying , Wang Yuehong
Published: December 2022

Objectives:

Chronic obstructive pulmonary disease (COPD) is the most common co-morbidity associated with non-small cell lung cancer (NSCLC) patients. Immune checkpoint inhibitors related pneumonitis (CIP) is a common immune-related adverse event that can be life-threatening. The study aims to evaluate the association of COPD with the incidence and outcome of CIP in NSCLC patients receiving immune checkpoint inhibitors (ICIs).

Materials and methods:

We retrospectively collected data from 122 patients diagnosed with NSCLC and treated with ICIs in our department. Baseline pulmonary function was performed in the whole cohort. The incidence, risk factors, treatment and outcome of CIP patients were evaluated. Furthermore, the efficacy of ICIs in patients with COPD was analyzed.

Results:

Nineteen patients (15.5%, 19/122) developed CIP during ICIs treatment, most patients with CIP were grade 1–2, and the incidence of CIP was comparable in patients with COPD and those without COPD (18.0% vs. 13.1%, P = 0.618). In addition, an increasing trend in the incidence of CIP among patients with pulmonary fibrosis on baseline chest CT scans (27.3% vs. 13.0%, P = 0.093). There is a longer progression-free survival in COPD patients than the non-COPD patients.

Conclusion:

Coexisting COPD did not predict the higher risk of CIP in NSCLC treated with ICIs therapy. Nevertheless, pre-existing pulmonary fibrosis on CT scan may increase the risk of CIP, close monitoring is advised in these patients during ICIs.
Validity of the Osteoarthritis Research Society International (OARSI) recommended performance-based tests of physical function in individuals with symptomatic Kellgren and Lawrence grade 0–2 knee osteoarthritis
Authors: Lee Si-Huei , Kao Chi-Chun , Liang Huey-Wen , Wu Hung-Ta
Published: December 2022

Background

Performance-based physical tests have been widely used as objective assessments for individuals with knee osteoarthritis (KOA), and the core set of tests recommended by the Osteoarthritis Research Society International (OARSI) aims to provide reliable, valid, feasible and standardized measures for clinical application. However, few studies have documented their validity in roentgenographically mild KOA. Our goal was to test the validity of five performance-based tests in symptomatic KOA patients with X-ray findings of Kellgren and Lawrence (K-L) grade 0–2.

Methods

We recruited a convenience sample of thirty KOA patients from outpatient clinics and 30 age- and sex-matched asymptomatic controls from the community. They performed five OARSI-recommended physical tests and the KOA group answered the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. The tests included the 9-step stair-climbing test (9 s-SCT), timed up and go (TUG) test, 30-second chair-stand test (30sCST), 40-m fast walking-test (40MFPW) and 6-minute walking test (6MWT). The discriminant validity of these physical tests were assessed by comparisons between the KOA and control groups, receiver operating curve and multivariate logistic regression analysis. The convergent/divergent validity was assessed by correlation between the physical tests results and the three subscale scores of the WOMAC in the KOA group.

Results

The KOA group had significantly worse performance than the control group. The percentage of difference was the largest in the 9 s-SCT (57.2%) and TUG tests (38.4%). Meanwhile, Cohen’s d was above 1.2 for the TUG test and 6MWT (1.2 ~ 2.0), and between 0.8 and 1.2 for the other tests. The areas under the curve to discriminate the two groups were mostly excellent to outstanding, except for the 30sCST. Convergent validity was documented with a moderate correlation between the 9 s-SCT and the physical function (WOMAC-PF) subscale scores (Spearman’sρ = 0.60).

Conclusions

The OARSI recommended core set was generally highly discriminative between people with K-L grade 0–2 KOA and their controls, but convergent/divergent validity was observed only in the 9 s-SCT. Further studies are required to evaluate the responsiveness of these tests and understand the discordance of physical performance and self-reported measures.
Agreement between clinical measures to classify foot posture in asymptomatic adults
Authors: Hunsawong Torkamol , Motantasuta Phornchanok , Mato Lugkana , Donpunha Wanida
Published: December 2022

Background

Various clinical measures of static foot posture have been developed and used. However, consensus among clinical measures to classify foot posture remains to be established. Therefore, this study aimed to determine the level of agreement as a reliability component between two common clinical methods in asymptomatic adults: the normalised navicular height truncated (NNHt) and the Foot Posture Index-6 (FPI-6).

Methods

The NNHt and FPI-6 were conducted on 102 asymptomatic adults. The measurement sequence was randomly arranged for each participant. Weighted Kappa (Kw) was used to determine the agreement between the methods.

Results

Both the NNHt and FPI-6 achieved similar foot posture distributions: approximately 40–50% of the participants had a normal foot, approximately 40% had a pronated foot and approximately 10–20% had a supinated foot. The agreement between the methods to classify foot posture was excellent (Kw = 0.84).

Conclusions

The present study found excellent agreement between two commonly used clinical measures. This finding highlights the NNHt and FPI-6 consensus for foot posture classification in asymptomatic adults.
Health data privacy through homomorphic encryption and distributed ledger computing: an ethical-legal qualitative expert assessment study
Authors: Scheibner James , Ienca Marcello , Vayena Effy
Published: December 2022

Background

Increasingly, hospitals and research institutes are developing technical solutions for sharing patient data in a privacy preserving manner. Two of these technical solutions are homomorphic encryption and distributed ledger technology. Homomorphic encryption allows computations to be performed on data without this data ever being decrypted. Therefore, homomorphic encryption represents a potential solution for conducting feasibility studies on cohorts of sensitive patient data stored in distributed locations. Distributed ledger technology provides a permanent record on all transfers and processing of patient data, allowing data custodians to audit access. A significant portion of the current literature has examined how these technologies might comply with data protection and research ethics frameworks. In the Swiss context, these instruments include the Federal Act on Data Protection and the Human Research Act. There are also institutional frameworks that govern the processing of health related and genetic data at different universities and hospitals. Given Switzerland’s geographical proximity to European Union (EU) member states, the General Data Protection Regulation (GDPR) may impose additional obligations.

Methods

To conduct this assessment, we carried out a series of qualitative interviews with key stakeholders at Swiss hospitals and research institutions. These included legal and clinical data management staff, as well as clinical and research ethics experts. These interviews were carried out with two series of vignettes that focused on data discovery using homomorphic encryption and data erasure from a distributed ledger platform.

Results

For our first set of vignettes, interviewees were prepared to allow data discovery requests if patients had provided general consent or ethics committee approval, depending on the types of data made available. Our interviewees highlighted the importance of protecting against the risk of reidentification given different types of data. For our second set, there was disagreement amongst interviewees on whether they would delete patient data locally, or delete data linked to a ledger with cryptographic hashes. Our interviewees were also willing to delete data locally or on the ledger, subject to local legislation.

Conclusion

Our findings can help guide the deployment of these technologies, as well as determine ethics and legal requirements for such technologies.
Role of microRNA-34b-5p in cancer and injury: how does it work?
Authors: Bai Xuechun , Zheng Lianwen , Xu Ying , Liang Yan , Li Dandan
Published: December 2022

MicroRNAs (miRNAs or miRs) are a class of noncoding single-stranded RNAs that can regulate gene expression by binding to the untranslated sequences at the 3 ' end of messenger RNAs. The microRNA-34 family is dysregulated in various human diseases. It is considered as a tumor-suppressive microRNA because of its synergistic effect with the well-known tumor suppressor p53. As a member of the miRNA-34 family, miR-34b-5p serves as a powerful regulator of a suite of cellular activities, including cell growth, multiplication, development, differentiation, and apoptosis. It promotes or represses disease occurrence and progression by participating in some important signaling pathways. This review aimed to provide an overview and update on the differential expression and function of miR-34b-5p in pathophysiologic processes, especially cancer and injury. Additionally, miR-34b-5p‐mediated clinical trials have indicated promising consequences for the therapies of carcinomatosis and injury. With the application of the first tumor-targeted microRNA drug based on miR-34a mimics, it can be inferred that miR-34b-5p may become a crucial factor in the therapy of various diseases. However, further studies on miR-34b-5p should shed light on its involvement in disease pathogenesis and treatment options.