Heterogeneity in circulating tumor cells : the relevance of the stem-cell subset

The release of circulating tumor cells (CTCs) into vasculature is an early event in the metastatic process. The analysis of CTCs in patients has recently received widespread attention because of its clinical implications, particularly for precision medicine. Accumulated evidence documents a large heterogeneity in CTCs across patients. Currently, the most accepted view is that tumor cells with an intermediate phenotype between epithelial and mesenchymal have the highest plasticity. Indeed, the existence of a meta-stable or partial epithelial⁻mesenchymal transition (EMT) cell state, with both epithelial and mesenchymal features, can be easily reconciled with the concept of a highly plastic stem-like state. A close connection between EMT and cancer stem cells (CSC) traits, with enhanced metastatic competence and drug resistance, has also been described. Accordingly, a subset of CTCs consisting of CSC, present a stemness profile, are able to survive chemotherapy, and generate metastases after xenotransplantation in immunodeficient mice. In the present review, we discuss the current evidence connecting CTCs, EMT, and stemness. An improved understanding of the CTC/EMT/CSC connections may uncover novel therapeutic targets, irrespective of the tumor type, since most cancers seem to harbor a pool of CSCs, and disclose important mechanisms underlying tumorigenicity

Circular RNAs Could Encode Unique Proteins and Affect Cancer Pathways

CircRNAs constitute a novel class of RNA, generally considered as non-coding RNAs; nonetheless, their coding potential has been under scrutiny. In this work, we systematically explored the predicted proteins of more than 160,000 circRNAs detected by exome capture RNA-sequencing and collected in the MiOncoCirc pan-cancer compendium, including normal and cancer samples from different types of tissues. For the functional evaluation, we compared their primary structure and domain composition with those derived from the same linear mRNAs. Among the 4362 circRNAs potentially encoding proteins with a unique primary structure and 1179 encoding proteins with a novel domain composition, 183 were differentially expressed in cancer. In particular, eight were associated with prognosis in acute myeloid leukemia. The functional classification of the dysregulated circRNA-encoded polypeptides showed an enrichment in the heme and cancer signaling, DNA-binding, and phosphorylation processes, and disclosed the roles of some circRNA-based effectors in cancer

Calorimetry and FTIR reveal the ability of URG7 protein to modify the aggregation state of both cell lysate and amylogenic α-synuclein

Differential scanning calorimetry and FITR analyses allowed to investigate the role of URG7 (up-regulated gene clone 7) protein involved in the development of hepatocellular carcinoma induced by hepatitis B virus infection, on the physical structure both of lysates of human hepatoblastoma cells (HepG2) stressed with tunicamycin and α-synuclein, one of the proteins associated with neurogenerative diseases. The protein-water interfacial region was identified and correlated with protein structure. DSC results confirm through the interfacial water behavior that URG7 is able to act in two ways: it maintains the interfacial water stability and controls the mobile fraction level, thereby the flexibility and the protein folding. The mobile water phase increases strongly for cells exposed to α-synuclein, demonstrating an important influence on water hydration. FTIR results evidenced an increase of about 30% of cross β structures in cells exposed to α-synuclein, associated with aggregated proteins. In stress conditions, URG7 was able to maintain the same fraction of mobile water as untreated cells. URG7 was able to restore the water reorientation ability around the complex lysate system and reduced abnormal protein folding

Effective Neutralizing Antibody Response Against SARS-CoV-2 Virus and Its Omicron BA.1 Variant in Fully Vaccinated Hematological Patients

SARS-CoV-2 and its variants cause CoronaVIrus Disease 19 (COVID-19), a pandemic disease. Hematological malignancies increase susceptibility to severe COVID-19 due to immunosuppression. Anti-SARS-CoV-2 neutralizing antibodies protect against severe COVID-19. This retrospective real-life study aimed to evaluate seropositivity and neutralizing antibody rates against SARS-CoV-2 and its Omicron BA.1 variant in hematological patients. A total of 106 patients with different hematologic malignancies, who have mostly received three or more vaccine doses (73%), were included in this study. Serum was collected between May and June 2022. The primary endpoint was anti-SARS-CoV-2 antibody response against ancestral (wild type; wt) and Omicron BA.1 virus, defined as a neutralizing antibody titer ≥ 1:10. Adequate neutralizing antibody response was observed in 75 (71%) and 87 (82%) of patients for wt and Omicron BA.1 variants, respectively.However, patients with B-cell lymphoproliferative disorders and/or those treated with anti-CD20 monoclonal antibodies in the prior 12 months showed a lower seropositivity rate compared to other patients against both Omicron BA.1 variant (73% vs 91%; P = 0.02) and wt virus (64% vs 78%; P = 0.16). Our real-life experience confirmed that full vaccination against SARS-CoV-2 induces adequate neutralizing antibody protection for both the wt virus and Omicron BA.1 variants, even in hematological frail patients. However, protective measures should be maintained in hematological patients, especially those with B-cell lymphoproliferative diseases treated with anti-CD20 monoclonal antibodies, because these subjects could have a reduced neutralizing antibody production

Transcriptomics and cancer: beyond messenger RNA

Non-coding RNAs (ncRNAs) can contribute to the alteration of biological functions in normal cells, leading to progression and malignant phenotype in cancer. Among them, microRNAs and Transcribed-ultraconserved regions (T-UCRs), a novel class of long non coding RNAs transcribed from ultraconserved regions (UCRs), can both act as key regulators of cancer gene expression. Circular RNAs (circRNAs) have been generally considered as members of the non-coding RNA family. In the last decade, an increasing number of studies focused on the evaluation of the coding potential of circRNAs. The role of ncRNAs and circRNAs in human cancer and the molecular mechanisms in which they are involved are under scrutiny. We decided to explore the cobweb of non-coding RNAs in human cancer by using in silico and in vitro approaches. In particular we focused our attention on the following themes: i) the coding potential of cancer circRNAs (evaluated in terms of novel primary structure and/or domain composition) and their differential expression in a pan-cancer dataset ii) the role of a set of T-UCRs, mutually exclusive with miR-221 expression, in the cell cycle circuitry of breast cancer cell lines; iii) the molecular network composed by non-coding RNA and their targets in breast cancer; iv) the molecular network of miRNA and their targets in the drug-resistance of colon carcinoma. These studies contribute to clarify the influence of non-coding regulators and circRNAs on various human cancer processes and might also offer hints to guide clinical applications.Gli RNA non codificanti (ncRNA) possono contribuire all’alterazione delle funzioni biologiche in cellule normali, favorendo la progressione del fenotipo tumorale. Tra questi, microRNA e regioni ultra-conservate trascritte (T-UCRs), una nuova classe di long non coding RNAs, possono entrambi agire da regolatori dell’espressione dei geni coinvolti nella carcinogenesi. Per lungo tempo gli RNA circolari (circRNA) sono stati considerati membri della famiglia degli RNA non codificanti. Nell’ultimo decennio, diversi studi si sono focalizzati sulla valutazione del potenziale codificante dei circRNA. Il ruolo dei ncRNA e circRNA nei diversi tumori dell’uomo e i meccanismi molecolari in cui essi sono coinvolti sono ancora oggetto di discussione. Abbiamo investigato sulla rete di ncRNA nel cancro dell’uomo attraverso un approccio in silico e in vitro. In particolare sono stati approfonditi i seguenti temi: i) il potenziale codificante dei circRNA (valutato in termini di novità in struttura primaria e/o composizione in domini) e la loro espressione differenziale in un dataset di pan-cancer; ii) il ruolo di una serie di T-UCRs, espressi in maniera mutualmente esclusiva rispetto al miR-221, nel circuito del ciclo cellulare in linee di cancro al seno; iii) il network molecolare composto da ncRNA e i loro target nel tumore al seno; iv) il network molecolare di miRNA e i loro target nel contesto della resistenza farmacologica nel tumore al colon retto. Questi studi contribuiscono a chiarire l’influenza dei ncRNA e circRNA sui vari processi tumorali nell’uomo e potrebbero anche offrire degli spunti per applicazioni cliniche

Ripensare le mappe argomentative nei nuovi contesti multimodali: una revisione narrativa della letteratura

Oggigiorno è richiesta un’interazione attiva e critica alla vita della società e non sempre si è in grado di elaborare le informazioni raccolte e di esprimere riflessioni in merito. Soprattutto ora che i new media, integrati nella nostra quotidianità, hanno decisamente cambiato il modo di comunicare con l’altro. Tuttavia, dato che è molto più semplice accedere e diffondere informazioni e le persone necessitano di una nuova “alfabetizzazione” per adoperare criticamente i media. Tuttavia, le strategie didattiche oggi a supporto della comprensione critica si muovono intorno a informazioni statiche. Con la nascita dei contesti dinamici, bisogna interpellare l’educazione e la formazione in forme completamente diverse, come nel caso delle mappe argomentative ripensate per forme testuali dinamiche. Sulla base di queste premesse è stata condotta una revisione narrativa della letteratura, da cui sono emersi quattro nodi concettuali, sviluppati in specifici saggi e relative bibliografie: a) il primo sulla logica argomentativa, da un’argomentazione orale ad una scritta; b) il secondo sulle mappe argomentative, come supporto alle skills argomentative e di pensiero critico; c) il terzo sul testo argomentativo, da analogico a multimodale; d) il quarto su new media e digital literacy. Con la ricostruzione di un dibattito generale, si è tratteggiata la cornice epistemologica su cui possono posare future ricerche, inclusa la ricerca dottorale al centro di questo studio. Questi risultati hanno evidenziato la rilevanza dell’argomentazione nella società del post-digitale e suggerito il focus della ricerca dottorale: un approfondimento empirico sull’impiego delle mappe argomentative per la digital literacy

Argument maps as tools to support the development of new media literacies: a systematic review. [Zenodo Data set]

The post-digital era is characterized by the vast presence of platforms imposing their digital affordances and algorithmic control on our behavior. This environment is challenging education and training, with implications for digital and transmedial literacy. Investigating instructional methodologies is crucial to foster critical comprehension of such novel informational environments. The argument maps (AM), which were first created and evaluated in static information contexts (analogical/old web), could be useful in the emergence of dynamic (post-digital) textual forms. The current paper describes a comprehensive literature review based on the assumptions above. We looked into state of the art in research on using AM to handle dynamic information. We found 150 papers using a PRISMA procedure and then examined 25 of them. Our review produced pertinent data about the current state of AM, including the sorts of texts on which they are used and the tools (especially digital and AI-based) that have been employed. Our research lays the groundwork for teaching the literacies needed in new informational settings, such as multimodal, dynamic, algorithmic, and data-driven contexts, with a specific focus on AM as an effective mediational tool. This Zenodo record presents the full dataset composed of the following sheets: 1.Codebook 2. Italian Journals 3. List of articles extracted from SCOPUS 4. List of articles extracted from ERIC 5. List of articles extracted from WOS 6. List of articles extracted from DOAJ 7. PRISMA workflow 8. Analysis - First Level (classification of 25 articles selected) 9. Analysis - Second Level (List of 19 articles selected) 10. Final Dataset 11. Interrater Agreement. As for the Keywords' Map, a primo file .txt displays the text over which basis was performed the keyword maps analysis. The second .txt file shows notes relating to the analysis procedures using the software VOS-Viewer http://www.vosviewer.com

Dataset on "Argument maps as a proxy for critical thinking development: A Lab for undergraduate students"

<p>Argumentative skills are crucial for any individual at the personal and professional levels. In recent decades, there has been an increasing concern about the weak undergraduates' skills and considerable difficulty in reworking and expressing one's own reflection on a topic. In turn, this has implications for being a critical thinker, able to express an original point of view. Tailored interventions in Higher Education could constitute a powerful approach to promote argumentative skills and extend these skills to professional and personal life. In this regard, argument maps (AM) could prove to be a valuable support to the visualization process of arguments. They don’t just create associations between concepts, but trace the logical relationships between different statements, allowing you to track the reasoning chain and understand it better. We conducted an experimental study to investigate how a path with AM could support students in increasing the level of text comprehension (CoT) competence, in terms of identifying the elements of an argumentative text, and critical thinking (CT), in terms of reconstructing meaning and building their own reflection. </p> <p>Our preliminary descriptive analysis suggested the positivity of the role of AM in increasing students’ CoT and CT proficiency levels</p> <p> </p> <p>This Zenodo record follows the full analysis process with R (https://cran.r-project.org/bin/windows/base/ ) composed of the following datasets and script:</p> <p>1. Comprehension of Text and AMs Results - ExpAM.xlsx</p> <p>2. Critical Thinking Results - CriThink.xlsx</p> <p>3. Argumentative skills in Forum - ExpForum.xlsx</p> <p>4. Selfassessment Results - Dataset_Quest.xlsx</p> <p>5. Data for Correlation and Regression - Dataset_CorRegr.xlsx</p> <p>6. Descriptive Statistics - Preliminary Analysis.R</p> <p>7. Inferential Statistics - Correlation and Regression.R</p> <p> </p> <p>Any comments or improvements are welcome!</p&gt

Argument maps as comparator for internal feedback: A Lab for undergraduate students

Internal feedback is a construct that become recently relevant for the impact it has on metacognitive and affective-relational regulation, in relation to different skills and learning contexts. In particular, the concept of comparator, i.e. the tools, interventions, or resources that activate internal feedback, requires the support of empirical research. In this contribution, we take as an initial hypothesis that the argument maps’ (AM) visual component, already linked to the development of argumentative and critical thinking skills, could be a generative source of concrete comparison, allowing for a facilitated comprehension and an improvement of the sense-making abilities within argumentative texts. In fact, AMs diagram the logical relationships between different utterances, allowing the learner to keep track and better understand the reasoning chain. To test the above hypothesis, an experimental study was conducted to investigate the extent to which a course with AMs favored students in increasing: a) internal feedback (IF), associated with b) their level of text comprehension (CoT) and hence, c) critical thinking (CT)