7,275 research outputs found

    Cumulative incidence and risk factors for cutaneous squamous-cell carcinoma metastases in organ transplant recipients:the SCOPE-ITSCC metastases study, a prospective multi-center study

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    INTRODUCTION: Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous-cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors.METHODS: In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases.RESULTS: Of 514 SOTRs who presented with 623 primary cSCCs, 37 developed metastases with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size &gt;2cm, clinical ulceration, poor differentiation grade, perineural invasion and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9% - 68.4%).CONCLUSIONS: SOTRs have a high risk of cSCC metastases and well-established clinical and histological risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis.</p

    Nitrate Radicals Suppress Biogenic New Particle Formation from Monoterpene Oxidation

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    Highly oxygenated organic molecules (HOMs) are a major source of new particles that affect the Earth’s climate. HOM production from the oxidation of volatile organic compounds (VOCs) occurs during both the day and night and can lead to new particle formation (NPF). However, NPF involving organic vapors has been reported much more often during the daytime than during nighttime. Here, we show that the nitrate radicals (NO3), which arise predominantly at night, inhibit NPF during the oxidation of monoterpenes based on three lines of observational evidence: NPF experiments in the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber at CERN (European Organization for Nuclear Research), radical chemistry experiments using an oxidation flow reactor, and field observations in a wetland that occasionally exhibits nocturnal NPF. Nitrooxy-peroxy radicals formed from NO3 chemistry suppress the production of ultralow-volatility organic compounds (ULVOCs) responsible for biogenic NPF, which are covalently bound peroxy radical (RO2) dimer association products. The ULVOC yield of α-pinene in the presence of NO3 is one-fifth of that resulting from ozone chemistry alone. Even trace amounts of NO3 radicals, at sub-parts per trillion level, suppress the NPF rate by a factor of 4. Ambient observations further confirm that when NO3 chemistry is involved, monoterpene NPF is completely turned off. Our results explain the frequent absence of nocturnal biogenic NPF in monoterpene (α-pinene)-rich environments

    Strain-induced bands of Büngner formation promotes axon growth in 3D tissue-engineered constructs

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    Treatment of peripheral nerve lesions remains a major challenge due to poor functional recovery; hence, ongoing research efforts strive to enhance peripheral nerve repair. In this study, we aimed to establish three-dimensional tissue-engineered bands of Büngner constructs by subjecting Schwann cells (SCs) embedded in fibrin hydrogels to mechanical stimulation. We show for the first time that the application of strain induces (i) longitudinal alignment of SCs resembling bands of Büngner, and (ii) the expression of a pronounced repair SC phenotype as evidenced by upregulation of BDNF, NGF, and p75 NTR . Furthermore, we show that mechanically aligned SCs provide physical guidance for migrating axons over several millimeters in vitro in a co-culture model with rat dorsal root ganglion explants. Consequently, these constructs hold great therapeutic potential for transplantation into patients and might also provide a physiologically relevant in vitro peripheral nerve model for drug screening or investigation of pathologic or regenerative processes

    Compassionate leadership in remote work: examining the influence of working remotely on compassionate leadership´s impact on perceived leadership authenticity and supervisor-employee relationship

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    The present research examines the relation between compassionate leadership and leader-member exchange (LMX). After reviewing past scholar, the author hypothesizes a positive relationship between compassionate leadership and supervisor-subordinate relationship mediated by perceived leadership authenticity. Most research has focused on traditional work arrangement. Given the rising popularity of working remotely, the study investigates the extent to which working remotely moderates the impact of compassionate leadership on perceived authenticity. Based on a survey of 108 employees who worked to different levels remotely, the results showed no significant moderation. However, leadership authenticity significantly mediated the relationship between compassion and LMX

    Systematic development of ionizable lipid nanoparticles for placental mRNA delivery using a design of experiments approach

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    Ionizable lipid nanoparticles (LNPs) have gained attention as mRNA delivery platforms for vaccination against COVID-19 and for protein replacement therapies. LNPs enhance mRNA stability, circulation time, cellular uptake, and preferential delivery to specific tissues compared to mRNA with no carrier platform. However, LNPs are only in the beginning stages of development for safe and effective mRNA delivery to the placenta to treat placental dysfunction. Here, we develop LNPs that enable high levels of mRNA delivery to trophoblasts in vitro and to the placenta in vivo with no toxicity. We conducted a Design of Experiments to explore how LNP composition, including the type and molar ratio of each lipid component, drives trophoblast and placental delivery. Our data revealed that utilizing C12-200 as the ionizable lipid and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as the phospholipid in the LNP design yields high transfection efficiency in vitro. Analysis of lipid molar composition as a design parameter in LNPs displayed a strong correlation between apparent pKa and poly (ethylene) glycol (PEG) content, as a reduction in PEG molar amount increases apparent pKa. Further, we present one LNP platform that exhibits the highest delivery of placental growth factor mRNA to the placenta in pregnant mice, resulting in synthesis and secretion of a potentially therapeutic protein. Lastly, our high-performing LNPs have no toxicity to both the pregnant mice and fetuses. Our results demonstrate the feasibility of LNPs as a platform for mRNA delivery to the placenta, and our top LNP formulations may provide a therapeutic platform to treat diseases that originate from placental dysfunction during pregnancy

    Reduced Bone Regeneration in Rats With Type 2 Diabetes Mellitus as a Result of Impaired Stromal Cell and Osteoblast Function—A Computer Modeling Study

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    ABSTRACT Bone has the fascinating ability to self‐regenerate. However, under certain conditions, such as type 2 diabetes mellitus (T2DM), this ability is impaired. T2DM is a chronic metabolic disease known by the presence of elevated blood glucose levels that is associated with reduced bone regeneration capability, high fracture risk, and eventual non‐union risk after a fracture. Several mechanical and biological factors relevant to bone regeneration have been shown to be affected in a diabetic environment. However, whether impaired bone regeneration in T2DM can be explained due to mechanical or biological alterations remains unknown. To elucidate the relevance of either one, the aim of this study was to investigate the relative contribution of T2DM‐related alterations on either cellular activity or mechanical stimuli driving bone regeneration. A previously validated in silico computer modeling approach that was capable of explaining bone regeneration in uneventful conditions of healing was further developed to investigate bone regeneration in T2DM. Aspects analyzed included the presence of mesenchymal stromal cells (MSCs), cellular migration, proliferation, differentiation, apoptosis, and cellular mechanosensitivity. To further verify the computer model findings against in vivo data, an experimental setup was replicated, in which regeneration was compared in healthy and diabetic after a rat femur bone osteotomy stabilized with plate fixation. We found that mechanical alterations had little effect on the reduced bone regeneration in T2DM and that alterations in MSC proliferation, MSC migration, and osteoblast differentiation had the highest effect. In silico predictions of regenerated bone in T2DM matched qualitatively and quantitatively those from ex vivo μCT at 12 weeks post‐surgery when reduced cellular activities reported in previous in vitro and in vivo studies were included in the model. The presented findings here could have clinical implications in the treatment of bone fractures in patients with T2DM. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research

    Consulting report – CENTRUM Graduate Business School

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    En los últimos años, la globalización y el aumento de un nuevo grupo demográfico de estudiantes han aumentado el interés por la internacionalización y su impacto en las instituciones educativas. Ahora, COVID 19 ha contribuido al desarrollo de los avances tecnológicos, precipitando la necesidad de innovar su marketing y continuar con la captación de estudiantes. El objetivo de este proyecto es proporcionar un plan de comunicación que apoye a la Oficina de Internacionalización en el posicionamiento de CENTRUM como una escuela de negocios intercultural con un mayor reconocimiento e interconexión internacional. Sobre la base de los resultados de la investigación primaria y secundaria, incluyendo el análisis cuantitativo y cualitativo, se ha identificado una estrategia de medios sociales con un plan de implementación conciso y detallado como el enfoque más eficaz. El plan de implementación incluye requisitos previos como un sistema de apoyo a los estudiantes en inglés, se sugieren pasos adicionales para los canales tradicionales y un enfoque diversificado para China. Con un presupuesto estimado de 9.710 PEN/mes, deberían alcanzarse los siguientes resultados en un plazo de cuatro años. En primer lugar, los resultados a corto plazo incluyen: una mayor presencia en los medios sociales, el desarrollo de auditorías de SEO y expertos en medios sociales dentro de la oficina. Segundo, los resultados a medio plazo incluyen: la finalización de los requisitos previos, como los programas de tiempo completo y de inglés, y un mayor conocimiento de CENTRUM a escala mundial. Por último, los resultados a largo plazo incluyen: un aumento de las inscripciones en los primeros 18 meses que aumentará gradualmente hasta el 50% en el caso de los nuevos programas de doble titulación y el 80% en el caso de los programas en línea al final del plazo. Por último, se espera que también se alcance la marca del 30% de estudiantes extranjeros que participan en experiencias internacionales.In recent years, globalization and the increase in a new demographic of students have heightened the interest in internationalization and its impact on educational institutions. To compete globally, business schools not only have to think in a global context but also realize that international student recruitment is a relevant expansion strategy. Now, COVID-19 has contributed to the development of technology advancements, precipitating the need to innovate their marketing and continue to continue student engagement. The goal of this report is to provide a communication plan that will support the Internationalization Office in positioning CENTRUM as a cross-cultural business school with increased international recognition and interconnectedness. Based on the findings of primary and secondary research, including both quantitative and qualitative analysis a social media strategy with a concise and detailed implementation plan has been identified as the most effective approach. The implementation plan includes prerequisites such as a student support system in English, additional steps for traditional channels and a diversified approach for China are suggested. With an estimated budget of 9,710 PEN/month, the following outcomes within a time scope of four years should be achieved. First, short term outcomes include: increased social media presence, the development of SEO audits and social media experts within the office. Second, medium term outcomes include: the finalization of prerequisites such as full-time and English programs, and increased awareness of CENTRUM on a global scale. Finally, long term outcomes include: increased enrollment within the first 18 months that will gradually build up to 50% for new dual-degree programs and 80% for online programs by the end of the time scope. Finally, it is expected that the 30%-mark of foreign students participating in international experiences will be reached as well

    DEBATES SOBRE DIFERENÇAS E DESIGUALDADES NO CONTEXTO DA CONSTRUÇÃO DA NAÇÃO: PARALELISMOS ENTRE A ÍNDIA E O BRASIL

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    As sociedades indiana e brasileira apresentam diversas diferenças, mas compartilham também semelhanças que, em boa parte, têm a ver com seus passados coloniais. São marcadas por diferenças culturais internas e sobretudo por enormes desigualdades sociais. Em cada um dos países, emergiram discursos de líderes políticos e intelectuais que buscavam não somente explicar as tradições locais e o status quo das relações sociais, mas indicavam também propostas políticas para combater os constatados problemas. Este artigo propõe focar os discursos de quatro personagens importantes, responsáveis pela elaboração de abordagens que se tornariam referências paradigmáticas nas discussões em cada um dos países: Gandhi versus Ambedkar; Freyre versus Fernandes. A análise busca apontar para oposições e paralelismos nos mais diversos planos, mas sobretudo nos modos como os pensadores lidavam com os tópicos diferenças e desigualdades.Indian and Brazilian societies present many differences, but they also share similarities that largely relate to their colonial past. They are marked by internalcultural differences and above all by huge social inequalities. In each country, discourses of political and intellectual leaders emerged who sought not only to explain local traditions and the status quo of social relations, but also to suggest political proposals to combat the perceived problems. This article aims to focus on the discourses of four important personalities responsible for the elaboration of approaches that would become paradigmatic referencesin the discussions in each of the countries: Gandhi vs. Ambedkar; Freyre vs. Fernandes. The analysis seeks to point to oppositions and parallels in the mostdiverse planes, but especially in the ways in which these thinkers dealt with the topics of differences and inequalities

    Subjektlosigkeit und Verselbstständigung. Zur Verwobenheit von wissenschaftlicher Wissensproduktion und Qualifizierung

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    Susann Hofbauer setzt sich mit dem Beitrag von Wissenschaftlerinnen und Wissenschaftlern in Qualifizierungsphasen zur Erweiterung wissenschaftlichen Wissens insgesamt auseinander und fragt unter Rückgriff auf aktuelle Daten nach den Bedingungen, unter welchen diese forschen. (DIPF/Orig.)The scientific production of knowledge is closely linked to qualification projects. Both – knowledge production and qualification – are relevant to educational research. Although “qualification” may not be a genuine basic term from the perspective of educational research, it does refer to processes of subjectification and institutional processes of enabling and ways of (self-)knowledge. In all brevity, three perspectives are presented: the enabling of knowledge production in higher education, the significance of qualification work as the production of subjectlessness in the social events of science, and – following on from this – the consideration of educational research in the light of precisely these perspectives. (DIPF/Orig.
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