The Transcription Factor Twist1 Has a Significant Role in Mycosis Fungoides (MF) Cell Biology: An RNA Sequencing Study of 40 MF Cases

The purpose of this RNA sequencing study was to investigate the biological mechanism underlying how the transcription factors (TFs) Twist1 and Zeb1 influence the prognosis of mycosis fungoides (MF). We used laser-captured microdissection to dissect malignant T-cells obtained from 40 skin biopsies from 40 MF patients with stage I–IV disease. Immunohistochemistry (IHC) was used to determinate the protein expression levels of Twist1 and Zeb1. Based on RNA sequencing, principal component analysis (PCA), differential expression (DE) analysis, ingenuity pathway analysis (IPA), and hub gene analysis were performed between the high and low Twist1 IHC expression cases. The DNA from 28 samples was used to analyze the TWIST1 promoter methylation level. In the PCA, Twist1 IHC expression seemed to classify cases into different groups. The DE analysis yielded 321 significant genes. In the IPA, 228 significant upstream regulators and 177 significant master regulators/causal networks were identified. In the hub gene analysis, 28 hub genes were found. The methylation level of TWIST1 promoter regions did not correlate with Twist1 protein expression. Zeb1 protein expression did not show any major correlation with global RNA expression in the PCA. Many of the observed genes and pathways associated with high Twist1 expression are known to be involved in immunoregulation, lymphocyte differentiation, and aggressive tumor biology. In conclusion, Twist1 might be an important regulator in the disease progression of MF

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome - Update 2023.

On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier versions published in 2006 and 2017 this document provides an updated standard for the treatment of mycosis fungoides and Sézary syndrome (MF/SS). It considers recent relevant publications and treatment options introduced into clinical practice after 2017. Consensus was established among the authors through a series of consecutive consultations in writing and a round of discussion. Treatment options are assigned to each disease stage and, whenever possible and clinically useful, separated into first- and second line options annotated with levels of evidence. Major changes to the previous version include the incorporation of chlormethine, brentuximab vedotin, and mogamulizumab, recommendations on the use of pegylated interferon α (after withdrawal of recombinant unpegylated interferons), and the addition of paragraphs on supportive therapy and on the care of older patients. Still, skin-directed therapies are the most appropriate option for early-stage MF and most patients have a normal life expectancy but may suffer morbidity and impaired quality of life. In advanced disease treatment options have expanded recently. Most patients receive multiple consecutive therapies with treatments often having a relatively short duration of response. For those patients prognosis is still poor and only for a highly selected subset long term remission can be achieved with allogeneic stem cell transplantation. Understanding of the disease, its epidemiology and clinical course, and its most appropriate management are gradually advancing, and there is well-founded hope that this will lead to further improvements in the care of patients with MF/SS

Kasvatuksen taide ja taidekasvatus:estetiikan ja taidekasvatuksen merkitys John Deweyn naturalistisessa pragmatismissa

Abstract John Dewey has been widely accepted as a modern classic in educational philosophy. Dewey's general philosophy has gained new interest lately, as well. This interest reflects both a need to find alternatives for analytic and continental philosophies, as well as a need for a naturalistic critique of the modernist presuppositions of Cartesian and transcendental philosophies. Dewey's reconstructive philosophy has encouraged the approach of this study. The reconstructive approach combines the synchronic and diachronic analyses of philosophical concepts with a pragmatist critique that trusts in the power of philosophy to guide human practice. The possibility of such pragmatist critique explains the central role of pedagogy in Dewey's philosophy: Dewey saw pedagogy as a social laboratory where philosophical concepts are tested for their pragmatic potential in enhancing democratic cultural formation. The present study is guided by the central idea that the naturalistic outlook of Dewey's mature philosophy can serve as a thematic framework for contemporary philosophies of art and music. Recent readings of Dewey's work suggest important links between his pedagogy and aesthetics. If Dewey's later philosophy is examined systematically, it becomes clear that his concept of (a)esthetic experience has an important summative function; it unifies his ideas concerning epistemology, ontology, and moral theory in a "soft" naturalistic anthropologic-pedagogical perspective. Dewey finds the core of existence in the process of human growth where experience is continually transformed into culture through communicative practice. Ideally, human growth involves both an immediate, aesthetic dimension, as well as a mediated, instrumental dimension. An important function of art is to bring out the aesthetic moments of growth. With this thesis in mind, Dewey radically extends his concept of art to comprise all cultural practices that balance their means with their ends. Art educates as it is worked out in means-ends-praxis, that is, in social practice that aims both at mediate and immediate good. In the framework of Dewey's naturalistic pragmatism, art education has two crucial functions: (1) to work out the possibilities of aesthetic expression and perception in a pragmatic process of learning by doing; and 2) to point out the paradigmatic moments of meaning making in the best of art. To the philosophers of music education, Dewey's philosophy can open up a new critical horizon where both aesthetic and praxial outlooks can meet in the experimental terms of naturalistic pragmatism.Tiivistelmä John Deweyn asema pedagogiikan klassikkona on tunnustettu jo vuosikymmeniä. Myös Deweyn laajempi filosofia on saanut osakseen uutta kiinnostusta. Tämä kiinnostus liittyy sekä vaihtoehtojen hakemiseen analyyttiselle ja mannermaiselle filosofialle että modernin filosofian kartesiolaisten ja transsendentaalisten lähtökohtien naturalistiseen kritiikkiin. Deweyn filosofialle ominainen rekonstruktiivinen lähestymistapa on innoittanut käsillä olevaa tutkimusta. Rekonstruktiivinen lähestymistapa edellyttää filosofisten käsitysten synkronisen ja diakronisen analyysin ohella pragmatistista kritiikkiä, johon liittyy luottamus filosofian voimaan ohjata inhimillisiä käytäntöjä. Pragmatistisen kritiikin mahdollisuus selittää pedagogiikan keskeisen aseman Deweyn filosofiassa. Deweylle kasvatus on laboratorio, joka tarjoaa mahdollisuuden koetella filosofisten käsitysten pragmatistista toimivuutta demokraattisen kulttuurin rakennusaineina. Tämän tutkimuksen temaattisena johtolankana toimii ajatus Deweyn myöhäiskauden naturalistisen pragmatismin soveltuvuudesta oman aikamme taide- ja musiikkikasvatusfilosofiseksi tarkastelutavaksi. Uudemmassa Dewey-tutkimuksessa onkin tuotu esiin Deweyn estetiikkaan ja pedagogiikan välisiä yhtymäkohtia. Tarkasteltaessa Deweyn myöhäiskauden filosofiaa kokonaisuutena, mikä on tämän työn tavoitteena, on lisäksi helppo huomata, että esteettisen kokemuksen käsitteellä on tärkeä asema hänen tiedonfilosofiansa, ontologiansa ja moraalifilosofiansa täydentäjänä. Deweylle inhimillisen eksistenssin ytimessä on kasvuprosessi, jossa kokemuksesta muovataan demokraattista kulttuuria kommunikatiivisessa toiminnassa. Tähän pragmatistiseen merkityksen tuoton prosessiin (ja siihen liittyvään pedagogiseen projektiin) liittyy parhaimmillaan esteettinen ulottuvuus. Kasvu sulkee sisäänsä sekä välineellisiä että välittömästi koettuja momentteja. Taiteen tärkeänä tehtävänä on tuoda esiin kasvuprosessiin liittyviä esteettisiä momentteja osana pragmaattista merkityksen tuottoa. Taide käsittääkin Deweylla kaiken kulttuurisen toiminnan, johon liittyy keinojen ja päämäärien välinen tasapaino. Kasvattavana toimintana taide on means-ends-praksista, keinonsa ja päämääränsä tasapainottavaa yhteiskunnallista käytäntöä, joka pyrkii samanaikaisesti sekä välilliseen että välittömään hyvään. Taidekasvatukselle jäsentyy Deweyn naturalistisessa pragmatismissa kaksi päätehtävää: (1) harjoituttaa esteettisen ilmaisun ja havainnon mahdollisuuksia pragmaattisessa tekemällä oppimisessa ja (2) osoittaa taiteissa kulminoituvia inhimillisen merkityksentuoton paradigmaattisia momentteja. Musiikkikasvatusfilosofeille Deweyn filosofia voi avata uuden kriittisen horisontin, jossa sekä perinteinen esteettinen näkökulma että uudempi praksiaalinen näkökulma voivat kohdata toisensa naturalistisen pragmatismin eksperimentaalisessa viitekehyksessä

Should we be imaging lymph nodes at initial diagnosis of early-stage mycosis fungoides? Results from the PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) international study

Background Early-stage mycosis fungoides (MF) includes involvement of dermatopathic lymph nodes (LNs) or early lymphomatous LNs. There is a lack of unanimity among current guidelines regarding the indications for initial staging imaging in early-stage presentation of MF in the absence of enlarged palpable LNs. Objectives To investigate how often imaging is performed in patients with early-stage presentation of MF, to assess the yield of LN imaging, and to determine what disease characteristics promoted imaging. Methods A review of clinicopathologically confirmed newly diagnosed patients with cutaneous patch/plaque (T1/T2) MF from PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) data. Results PROCLIPI enrolled 375 patients with stage T1/T2 MF: 304 with classical MF and 71 with folliculotropic MF. Imaging was performed in 169 patients (45%): 83 with computed tomography, 18 with positron emission tomography-computed tomography and 68 with ultrasound. Only nine of these (5%) had palpable enlarged (>= 15 mm) LNs, with an over-representation of plaques, irrespectively of the 10% body surface area cutoff that distinguishes T1 from T2. Folliculotropic MF was not more frequently imaged than classical MF. Radiologically enlarged LNs (>= 15 mm) were detected in 30 patients (18%); only seven had clinical lymphadenopathy. On multivariate analysis, plaque presentation was the sole parameter significantly associated with radiologically enlarged LNs. Imaging of only clinically enlarged LNs upstaged 4% of patients (seven of 169) to at least IIA, whereas nonselective imaging upstaged another 14% (24 of 169). LN biopsy, performed in eight of 30 patients, identified N3 (extensive lymphomatous involvement) in two and N1 (dermatopathic changes) in six. Conclusions Physical examination was a poor determinant of LN enlargement or involvement. Presence of plaques was associated with a significant increase in identification of enlarged or involved LNs in patients with early-stage presentation of MF, which may be important when deciding who to image. Imaging increases the detection rate of stage IIA MF, and identifies rare cases of extensive lymphomatous nodes, upstaging them to advanced-stage IVA2.Peer reviewe

Studies of the Formation and Growth of Aerosol from Molecular Iodine Precursor

The formation and growth of iodine oxide particles (IOPs), originating from molecular iodine precursor, has been studied at room temperature as a function of water vapour, and sulphuric and oxalic acid vapours. A linear variation in total IOP mass was observed over a wide range of iodine atom production rates under both dry and humid formation conditions. Particle formation was also observed in the absence of ozone, and was found to be temperature sensitive, with elevated temperatures resulting in reduced particle number and mass. Electronic structure calculations are used to show that particle formation is initiated by polymerization of I2O4 with I 2O3, or with itself. Formation of IOPs in humid conditions results in lower numbers and smaller particles than formed in the absence of water vapour, because H2O forms relatively stable complexes with molecules such as I2O3 and I2O4, inhibiting their polymerization. Addition of H2O to particles formed under dry conditions shows the collapse of fractal-like, aggregate particle structures. The uptake of sulphuric acid vapour onto humidified particles was studied over a wide range of relative humidity (RH) at room temperature, with the calculated accommodation coefficient (a) for this process increasing with RH to a value of 0.75±0.05 at RH = 90%. In contrast, growth of particles exposed to oxalic acid vapour was not observed on the experimental timescales employed, indicating an upper limit for α of 10-3. © by Oldenbourg Wissenschaftsverlag.Funding for this work from the UK Natural Environment Research Council (NERC grant NE/E005659/1) is gratefully acknowledged RK is grateful to the the Indian Government for PhD funding and Multanimal Modi (Postgraduate) College, Modinagar (U P), India for granting study leave ASM is grateful to the School of Chemistry for PhD funding BJM acknowledges NERC for a fellowship (grant NE/D009308/Peer reviewe