Intrinsic and extrinsic mechanisms for B-cell lymphoma development and progression studied by global gene expression profiling

Mantle cell lymphoma (MCL) is a rare hematopoietic malignancy characterized by frequent relapses and poor survival, partly due to minimal residual disease, whereby a subset of malignant cells, harbored in protective niches, survive treatment. In vitro and ex vivo experiments have shown that MCL cells can be rescued from apoptosis through interactions with non- malignant cells such as stromal cells. The present thesis investigates the effect that extrinsic microenvironmental interactions may exert on MCL cells and discuss the presumptive role of these as well as intrinsic mechanisms in the development and progression of lymphomas. MCL cells commonly grow in suspension but when co-cultured with stromal cells a fraction of the MCL cells strongly attached to the stromal cell monolayer. Analysis of transcript levels by next generation sequencing and species-specific read separation we identified sets of genes with altered transcript levels between the adherent MCL cells and those that remained in suspension. These genes could broadly be divided into four functional themes of which three exhibited increased transcript levels in the adherent fraction: B-cell signaling, antiapoptosis and cell adhesion/migration, and one, early mitosis for which the associated genes exhibited lower transcript levels in the adherent MCL fraction. Additionally, we observed a significant overlap between the changed genes in the present co-culture model system and genes that change at the mRNA level between lymph node and cells in circulation in material from MCL and chronic lymphocytic leukemia patients. Suggesting that the model system faithfully represent aspects of microenvironment-promoted changes to the lymphoma cells also observed in vivo. As different MCL cell lines were subject to similar co-culture conditions we observed differences in engagement of and dependency on cell surface molecules, including the B cell receptor, for adhesion to stromal cells. Different responses to microenvironmental interactions for different MCL cells may therefore affect how different patients or different subsets of MCL cells within a patient will respond to different therapy regimens. The transcription factor SOX11 is a key diagnostic marker in MCL. Commonly not expressed in hematological malignancies it is expressed in 90% of MCL cases and most importantly identifies cyclin D1 negative MCL. Its role in MCL development and progression is however debated. Here we show that in the context of the non-malignant pre-B-cell-like cell line Ba/F3 SOX11 does not exhibit oncogenic properties. MYC is a transcription factor that is capable of regulating the expression of a vast and diverse set of genes and has a role in lymphoma development, progression and disease prognosis for many lymphoma types, including MCL. Here we show that progressively increasing MYC levels in B-cells lead to the gradual change in expression in a large set of genes and importantly the gradual increase of two lymphoma-associated MYC mutants significantly altered transcript levels differently from wild type MYC. Gene set enrichment analysis identified functions previously associated with regulation by MYC such as ribosome biogenesis and purine metabolism, while other, novel functions such as those related to Bcell identity and chemotaxis were observed. The MYC regulated genes overlapped with previous gene signatures observed in the Eµ-Myc mouse model and also with recently identified direct MYC targets, collectively indicating the utility of the present model system with inducible MYC for the identification of MYC dependent functions in lymphomagenesis. Two studied lymphoma-associated MYC mutants differentially affect largely distinct subsets on Myc-regulated genes via different mechanisms

Investigating cognitive impairment, biopsychosocial barriers, and predictors of return to daily life among older stroke survivors

PurposeThe aim was to investigate the associations between cognitive impairment and biopsychosocial factors among older stroke survivors and predictors of poststroke return to daily life.Materials and methodsThis cross-sectional study involved 117 stroke survivors (61% men) with an average age of 77 years (range 65–91). The participants completed two questionnaires (Riksstroke and Short Form 36 questionnaires). The Montreal Cognitive Assessment (MoCA) was used to assess cognitive abilities. The International Classification of Functioning, Disability, and Health (ICF) framework guided the selection of biopsychosocial variables. We used Spearman’s correlation coefficient and multiple logistic regression in the analyses.ResultsThe average MoCA score was 21.7 points (range: 4–30, SD 5.6). The need for assistance from relatives and professionals, need for help with dressing and household chores, reliance on others for mobility, and reading and balance problems were correlated with more severe cognitive impairment (r = 0.20–0.33). Cognitive impairment, fatigue, and balance issues predicted an unfavorable return to daily life (odds ratio: 6.2–6.8).ConclusionThe study indicated that cognitive impairment is associated with difficulties in all ICF domains. Cognitive impairment, fatigue, and balance issues are associated with an unsuccessful return to daily life. Prioritizing these factors and screening for cognitive impairment with objective assessment tools may improve rehabilitation outcomes and enhance overall quality of life poststroke

Mixed-species RNAseq analysis of human lymphoma cells adhering to mouse stromal cells identifies a core gene set that is also differentially expressed in the lymph node microenvironment of mantle cell lymphoma and chronic lymphocytic leukemia patients

A subset of hematologic cancer patients is refractory to treatment or suffers relapse, due in part to minimal residual disease, whereby some cancer cells survive treatment. Cell-adhesion-mediated drug resistance is an important mechanism, whereby cancer cells receive survival signals via interaction with e.g. stromal cells. No genome-wide studies of in vitro systems have yet been performed to compare gene expression in different cell subsets within a co-culture and cells grown separately. Using RNA sequencing and species-specific read mapping, we compared transcript levels in human Jeko-1 mantle cell lymphoma cells stably adhered to mouse MS-5 stromal cells or in suspension within a co-culture or cultured separately as well as in stromal cells in co-culture or in separate culture. From 1050 differentially expressed transcripts in adherent mantle cell lymphoma cells, we identified 24 functional categories that together represent four main functional themes, anti-apoptosis, B-cell signaling, cell adhesion/migration and early mitosis. A comparison with previous mantle cell lymphoma and chronic lymphocytic leukemia studies, of gene expression differences between lymph node and blood, identified 116 genes that are differentially expressed in all three studies. From these genes, we suggest a core set of genes (CCL3, CCL4, DUSP4, ETV5, ICAM1, IL15RA, IL21R, IL4I1, MFSD2A, NFKB1, NFKBIE, SEMA7A, TMEM2) characteristic of cells undergoing cell-adhesion-mediated microenvironment signaling in mantle cell lymphoma/chronic lymphocytic leukemia. The model system developed and characterized here together with the core gene set will be useful for future studies of pathways that mediate increased cancer cell survival and drug resistance mechanisms

A Protein Intrinsic Disorder Approach for Characterising Differentially Expressed Genes in Transcriptome Data: Analysis of Cell-Adhesion Regulated Gene Expression in Lymphoma Cells

Conformational protein properties are coupled to protein functionality and could provide a useful parameter for functional annotation of differentially expressed genes in transcriptome studies. The aim was to determine whether predicted intrinsic protein disorder was differentially associated with proteins encoded by genes that are differentially regulated in lymphoma cells upon interaction with stromal cells, an interaction that occurs in microenvironments, such as lymph nodes that are protective for lymphoma cells during chemotherapy. Intrinsic disorder protein properties were extracted from the Database of Disordered Protein Prediction (D2P2), which contains data from nine intrinsic disorder predictors. Proteins encoded by differentially regulated cell-adhesion regulated genes were enriched in intrinsically disordered regions (IDRs) compared to other genes both with regard to IDR number and length. The enrichment was further ascribed to down-regulated genes. Consistently, a higher proportion of proteins encoded by down-regulated genes contained at least one IDR or were completely disordered. We conclude that down-regulated genes in stromal cell-adherent lymphoma cells encode proteins that are characterized by elevated levels of intrinsically disordered conformation, indicating the importance of down-regulating functional mechanisms associated with intrinsically disordered proteins in these cells. Further, the approach provides a generally applicable and complementary alternative to classification of differentially regulated genes using gene ontology or pathway enrichment analysis

A qualitative study on how new employees’ sense of belonging is affected during digital onboarding

Onboarding av nyanställda är den process som handlar om att integrera nya medarbetare in i organisationen för att öka organisationens produktivitet. Genom onboarding kan organisationen bland annat lära nyanställda medarbetare om deras nya arbetsuppgifter, organisationens normer och att få medarbetaren att bli en del av arbetsgruppen och organisationen. Användningen av digital onboarding tog fart vid Covid 19-pandemins start år 2019 och kom att påverka hur organisationer hanterade sin onboarding framöver. Då användandet av digital onboarding är ett relativt nytt fenomen som tagit fart sedan pandemins start behövs kunskap om hur digital onboarding kan bidra till att de nyanställda upplever känslan av tillhörighet. Syftet med studien är därför att få en djupare förståelse för hur nyanställda upplever känslan av tillhörighet vid digital onboarding. Studiens valda metod är kvalitativ och har inspirerats av en fenomenologisk ansats. Åtta semistrukturerade intervjuer hölls med respondenter från den utvalda organisationen. Det empiriska materialet har sedan analyserats med inspiration av fenomenologisk analysmetod och har genomförts i fem steg. Resultatet påvisar att information, feedback, en närvarande chef samt möjlighet till digitalt relationsskapande kan bidra till att nyanställda upplever känslan av tillhörighet vid digital onboarding. Resultatet visar på hur organisationer kan skapa bättre förutsättningar för nyanställda under digital onboarding.Onboarding of new employees is the process that involves integrating new employees into the organization to increase the organization's productivity. Through onboarding the organization can, among other things, instruct newly hired employees their new tasks, educate them about the organization's norms and values and helping the employees to become part of the working group and the organization. The use of digital onboarding took off at the start of the Covid-19 pandemic in 2019 and came to affect how organizations handled their onboarding in the future. As the use of digital onboarding is relatively a new phenomenon that has gained momentum since the start of the pandemic, knowledge is needed about how digital onboarding can contribute to new employees experiencing the feeling of belonging. The purpose of the study is therefore to gain a deeper understanding on how new employees’ sense of belonging is affected during digital onboarding. The study's chosen method is qualitative method and it has been inspired by a phenomenological approach. Eight semi-structured interviews were held with respondents from the selected organization. The empirical material has been analyzed with inspiration from a phenomenological analysis method and has been carried out in five steps. The result show that information, feedback, a present manager and the opportunity for digital relationship building can contribute to newly hired employees experiencing the feeling of belonging during digital onboarding.The result indicates how organizations can create better conditions for new employees during digital onboarding

Erfarenheter efter brännskada

Bakgrund: Att råka ut för brännskador är traumatiskt.  Sjuksköterskans förmåga att ge omsorg och visa respekt gentemot patienten är vitalt för patienters upplevelser av brännskador. Om en svårt brännskadad patient överlever är det ofta med handikapp och förändrat utseende, samtidigt som en palliativ behandling innebär svåra smärtor. Att skapa ny livskvalité är ofta förknippat med en svår process för brännskadade Syfte: Studiens syfte var att belysa patienters erfarenheter efter brännskada. Metod: En systematisk litteraturstudie genomfördes där nio artiklar, fem kvalitativa och fyra kvantitativa analyserades med en modifierad innehållsanalys. Resultat: Analysen föll ut i ett övergripande tema, förändring med fem underliggande kategorier. Förändringen bestod bland annat av ändrad självbild. Närstående fick ett högre värde och gav livskvalitet. Psykisk ohälsa till följd av den långa rehabiliteringsprocessen var också en tydlig konsekvens. Slutsats: En brännskada behöver inte alltid innebära negativt lidande utan kan ge upphov till positiva erfarenheter. Det finns ett behov av forskning inom psykisk rehabilitering hos brännskadade. Nyckelord: Brännskada, Förändring, Lidande, Erfarenheter, Psykisk ohäls

Extending the Tourist Season : An In-Depth Study of Tourism Relationships and Collaborations in Åre and Visby

Projektet syftar till att utforska turismsektorns dynamik med fokus på förlängning av turistsäsongen, med Åre och Visby som jämförelseobjekt. Genom en djupgående dokumentanalys och intervjuer med personer inom destinationernas turismsektor identifieras kritiska faktorer för framgångsrik och hållbar destinationsutveckling. Frågeställningarna inkluderar strategier för att attrahera turister året runt och samarbetsformer för att förlänga säsongen. Resultaten visar att båda destinationerna har unika strategier baserade på geografiska och klimatiska förutsättningar. Åre satsar på vinter och sommar och vill ses som en åretrunt-destination medan Visby arbetar med att utvidga sommarsäsongen till höst och vår. Samarbeten mellan olika aktörer, såsom kommuner och näringsliv, är avgörande för att hantera utmaningarna med lågsäsonger. Slutligen framhävs att för att vara en ledande turistdestination som Åre och Visby, krävs både strategiskt arbete för att locka turister året runt och effektiva samarbeten inom turismsektorn.  The thesis aims to explore the dynamics of the tourism sector with a focus on extending the tourist season, using Åre and Visby as comparative subjects. Through in-depth document analysis and interviews with stakeholders in the destinations' tourism sectors, critical factors for successful and sustainable destination management are identified. Key inquiries include strategies to attract tourists year-round and forms of collaboration to extend the season. The results reveal that both destinations have unique strategies based on geographical and climatic conditions. Åre focuses on winter and summer tourism, striving to be a year-round destination, while Visby aims to extend its summer season into the fall and spring. Collaborations among various stakeholders, such as municipalities and businesses, are crucial for addressing off-peak season challenges. Ultimately, it is emphasized that to be leading tourist destinations like Åre and Visby, strategic efforts to attract tourists year-round and effective collaborations within the tourism sector are essential

A qualitative study on how new employees’ sense of belonging is affected during digital onboarding

Onboarding av nyanställda är den process som handlar om att integrera nya medarbetare in i organisationen för att öka organisationens produktivitet. Genom onboarding kan organisationen bland annat lära nyanställda medarbetare om deras nya arbetsuppgifter, organisationens normer och att få medarbetaren att bli en del av arbetsgruppen och organisationen. Användningen av digital onboarding tog fart vid Covid 19-pandemins start år 2019 och kom att påverka hur organisationer hanterade sin onboarding framöver. Då användandet av digital onboarding är ett relativt nytt fenomen som tagit fart sedan pandemins start behövs kunskap om hur digital onboarding kan bidra till att de nyanställda upplever känslan av tillhörighet. Syftet med studien är därför att få en djupare förståelse för hur nyanställda upplever känslan av tillhörighet vid digital onboarding. Studiens valda metod är kvalitativ och har inspirerats av en fenomenologisk ansats. Åtta semistrukturerade intervjuer hölls med respondenter från den utvalda organisationen. Det empiriska materialet har sedan analyserats med inspiration av fenomenologisk analysmetod och har genomförts i fem steg. Resultatet påvisar att information, feedback, en närvarande chef samt möjlighet till digitalt relationsskapande kan bidra till att nyanställda upplever känslan av tillhörighet vid digital onboarding. Resultatet visar på hur organisationer kan skapa bättre förutsättningar för nyanställda under digital onboarding.Onboarding of new employees is the process that involves integrating new employees into the organization to increase the organization's productivity. Through onboarding the organization can, among other things, instruct newly hired employees their new tasks, educate them about the organization's norms and values and helping the employees to become part of the working group and the organization. The use of digital onboarding took off at the start of the Covid-19 pandemic in 2019 and came to affect how organizations handled their onboarding in the future. As the use of digital onboarding is relatively a new phenomenon that has gained momentum since the start of the pandemic, knowledge is needed about how digital onboarding can contribute to new employees experiencing the feeling of belonging. The purpose of the study is therefore to gain a deeper understanding on how new employees’ sense of belonging is affected during digital onboarding. The study's chosen method is qualitative method and it has been inspired by a phenomenological approach. Eight semi-structured interviews were held with respondents from the selected organization. The empirical material has been analyzed with inspiration from a phenomenological analysis method and has been carried out in five steps. The result show that information, feedback, a present manager and the opportunity for digital relationship building can contribute to newly hired employees experiencing the feeling of belonging during digital onboarding.The result indicates how organizations can create better conditions for new employees during digital onboarding

Extending the Tourist Season : An In-Depth Study of Tourism Relationships and Collaborations in Åre and Visby

Projektet syftar till att utforska turismsektorns dynamik med fokus på förlängning av turistsäsongen, med Åre och Visby som jämförelseobjekt. Genom en djupgående dokumentanalys och intervjuer med personer inom destinationernas turismsektor identifieras kritiska faktorer för framgångsrik och hållbar destinationsutveckling. Frågeställningarna inkluderar strategier för att attrahera turister året runt och samarbetsformer för att förlänga säsongen. Resultaten visar att båda destinationerna har unika strategier baserade på geografiska och klimatiska förutsättningar. Åre satsar på vinter och sommar och vill ses som en åretrunt-destination medan Visby arbetar med att utvidga sommarsäsongen till höst och vår. Samarbeten mellan olika aktörer, såsom kommuner och näringsliv, är avgörande för att hantera utmaningarna med lågsäsonger. Slutligen framhävs att för att vara en ledande turistdestination som Åre och Visby, krävs både strategiskt arbete för att locka turister året runt och effektiva samarbeten inom turismsektorn.  The thesis aims to explore the dynamics of the tourism sector with a focus on extending the tourist season, using Åre and Visby as comparative subjects. Through in-depth document analysis and interviews with stakeholders in the destinations' tourism sectors, critical factors for successful and sustainable destination management are identified. Key inquiries include strategies to attract tourists year-round and forms of collaboration to extend the season. The results reveal that both destinations have unique strategies based on geographical and climatic conditions. Åre focuses on winter and summer tourism, striving to be a year-round destination, while Visby aims to extend its summer season into the fall and spring. Collaborations among various stakeholders, such as municipalities and businesses, are crucial for addressing off-peak season challenges. Ultimately, it is emphasized that to be leading tourist destinations like Åre and Visby, strategic efforts to attract tourists year-round and effective collaborations within the tourism sector are essential

A Protein Intrinsic Disorder Approach for Characterising Differentially Expressed Genes in Transcriptome Data: Analysis of Cell-Adhesion Regulated Gene Expression in Lymphoma Cells

Conformational protein properties are coupled to protein functionality and could provide a useful parameter for functional annotation of differentially expressed genes in transcriptome studies. The aim was to determine whether predicted intrinsic protein disorder was differentially associated with proteins encoded by genes that are differentially regulated in lymphoma cells upon interaction with stromal cells, an interaction that occurs in microenvironments, such as lymph nodes that are protective for lymphoma cells during chemotherapy. Intrinsic disorder protein properties were extracted from the Database of Disordered Protein Prediction (D2P2), which contains data from nine intrinsic disorder predictors. Proteins encoded by differentially regulated cell-adhesion regulated genes were enriched in intrinsically disordered regions (IDRs) compared to other genes both with regard to IDR number and length. The enrichment was further ascribed to down-regulated genes. Consistently, a higher proportion of proteins encoded by down-regulated genes contained at least one IDR or were completely disordered. We conclude that down-regulated genes in stromal cell-adherent lymphoma cells encode proteins that are characterized by elevated levels of intrinsically disordered conformation, indicating the importance of down-regulating functional mechanisms associated with intrinsically disordered proteins in these cells. Further, the approach provides a generally applicable and complementary alternative to classification of differentially regulated genes using gene ontology or pathway enrichment analysis