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Background/Aim: Epithelial ovarian cancer (EOC) is usually diagnosed in advanced stages and has a high mortality rate. In this study, we used the proximity extension assay from Olink Proteomics to search for new plasma protein biomarkers to predict overall survival (OS) in patients with EOC. Materials and Methods: Peripheral blood samples were obtained preoperatively from 116 EOC patients undergoing primary debulking surgery: 28 early EOC cases (FIGO stage I-II) and 88 advanced EOC cases (FIGO stage III-IV). Proteins were measured using the Olink Oncology II and Inflammation panels. In total, 177 unique protein biomarkers were analysed. Cross-validation and LASSO regression were combined to select prediction models for OS. Results: The model including age and the three-biomarker combination of neurotrophin-3 (NT-3)+transmembrane glycoprotein NMB (GPNMB)+mesothelin (MSLN) predicted worse OS with AUC=0.79 (p=0.004). Adding cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) to the model further improved performance (AUC=0.83; p=0.003). In a postoperative model including age and stage (III+IV vs. I+II), the three-biomarker panel of chemokine (C-C motif) ligand 28 (CCL28)+T-cell leukaemia/lymphoma protein 1A (TCL1A)+GPNMB improved the prediction of OS (from AUC=0.83 to AUC=0.90; p=0.05). In the postoperative model including age and dichotomized stage (III vs. I+II), the biomarkers CCL28 and GPNMB1 improved the prediction of OS (AUC=0.86; p

Recent studies using murine models have shown that SRY box transcription factor 9 (SOX9) is activated during repair of renal tubular cells. In this study, we showed that SOX9-positive cells represent a proportion of scattered tubular cells found in the uninjured human kidney. Furthermore, we suggest that expression of LBR, HMGA2, and HIPK3 is altered by SOX9 in the kidney tubular epithelium, suggesting the involvement of these gene products in kidney injury and regeneration.

Supplementary Data from Branching Copy-Number Evolution and Parallel Immune Profiles across the Regional Tumor Space of Resected Pancreatic Cancer

Tumor-associated macrophages (TAMs) have emerged as key players in tumor immunology but demonstrate a continuum of functional states being either tumor suppressive or promoting. Moreover, chemotherapeutic agents have been shown to alter the tumor microenvironment. Perioperative chemotherapy is a standard treatment option for resectable esophageal and gastric (EG) adenocarcinoma. The aim of this study was to investigate the influence of neoadjuvant chemotherapy (NAC) on TAMs to improve the prognostication and treatment course for these patients. The study cohort comprised 148 patients, all of whom were diagnosed with resectable EG adenocarcinoma and treated with NAC. Immunohistochemistry was applied to assess the total infiltration and infiltration into tumor nests (TN) of CD68+/CD163−, CD68+/CD163+, and MARCO+ TAMs, on paired biopsies from primary tumors (PT) pre-NAC, and resected PT and lymph node metastases post-NAC. In pre-NAC specimens, high CD68+/CD163+ infiltration into TN was an unfavorable prognostic factor. No association was found between TAM density in PT pre-NAC and histopathological regression. The density of CD68+/CD163+ TAMs was increased in PT post-NAC, while the density of MARCO+ TAMs was decreased. CD68+/CD163− TAM density was not altered. In post-NAC specimens, higher total as well as TN infiltration of CD68+/CD163− TAMs were adverse prognostic factors. In conclusion, these results suggest that NAC may alter certain TAM subsets in EG adenocarcinoma, along with their functional properties and thus their prognostic value.

The aim of this research review is to investigate how digital games can contribute to effective language learning; what attitudes teachers have toward digital games in language teaching; and what attitudes pupils have towards digital games in language teaching. This was answered in a literature review on the subjects in question retrieved through searches of scientific articles in databases. The results of the research reviews show that digital games contribute to effective language learning because they help in the development of many competences and can easily be adapted to the needs and level of pupils. The results also showed that teachers feel uncertainties and negative attitudes towards the use of digital games, while many pupils have more positive attitudes towards applying digital games in teaching. The conclusion of the research review shows that the effectiveness of learning is affected by the attitudes of teachers and pupils towards the use of digital games in teaching.

In this thesis I will use a ‘men’s rights’ influencers fanbase as an example of a new generation of people who values toxic and traditional masculinity. I will do so by doing a critical discourse analysis on 1200 comments from the platform Reddit, using Fairclough's three-dimensional model as inspiration. Furthermore, to deepen the analysis I have chosen to analyze the comments in relation to parasocial relationships, hegemonic masculinity as well as the concepts of traditional and toxic masculinity. I found through my analysis that the fanbase views the influencer as a form of ‘beacon of truth’, and made a plethora of external references in regards to the movie 'The Matrix’. Moreover, the fans articulate masculinity in a way where ‘strength’ is prevalent, and is in line with traditional and toxic masculinity - whilst holding the influencer as a form of ideal of this form. In the discussion I draw parallels to how referencing the Matrix as a concept could speak of a mistrust towards the government, and how the countermovement to ‘modern’ masculinity could result in dangerous practices. To conclude, I highlight how there is still more research to be done on the field of alternative influencers and what consequences this ‘countermovement’ may have.

Checkpoint therapy; Lung cancer; Tumour microenvironment Terapia de puntos de control; Cáncer de pulmón; Microambiente tumoral Teràpia de punts de control; Càncer de pulmó; Microambient tumoral Introduction: Immune cells in the tumour microenvironment are associated with prognosis and response to therapy. We aimed to comprehensively characterise the spatial immune phenotypes in the mutational and clinicopathological background of non-small cell lung cancer (NSCLC). Methods: We established a multiplexed fluorescence imaging pipeline to spatially quantify 13 immune cell subsets in 359 NSCLC cases: CD4 effector cells (CD4-Eff), CD4 regulatory cells (CD4-Treg), CD8 effector cells (CD8-Eff), CD8 regulatory cells (CD8-Treg), B-cells, natural killer cells, natural killer T-cells, M1 macrophages (M1), CD163+ myeloid cells (CD163), M2 macrophages (M2), immature dendritic cells (iDCs), mature dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs). Results: CD4-Eff cells, CD8-Eff cells and M1 macrophages were the most abundant immune cells invading the tumour cell compartment and indicated a patient group with a favourable prognosis in the cluster analysis. Likewise, single densities of lymphocytic subsets (CD4-Eff, CD4-Treg, CD8-Treg, B-cells and pDCs) were independently associated with longer survival. However, when these immune cells were located close to CD8-Treg cells, the favourable impact was attenuated. In the multivariable Cox regression model, including cell densities and distances, the densities of M1 and CD163 cells and distances between cells (CD8-Treg-B-cells, CD8-Eff-cancer cells and B-cells-CD4-Treg) demonstrated positive prognostic impact, whereas short M2-M1 distances were prognostically unfavourable. Conclusion: We present a unique spatial profile of the in situ immune cell landscape in NSCLC as a publicly available data set. Cell densities and cell distances contribute independently to prognostic information on clinical outcomes, suggesting that spatial information is crucial for diagnostic use. This study was partly supported by Swedish Cancer Society, The Lions Cancer Foundation Uppsala, Sweden, Selanders Foundation and The Sjöberg Foundation, Sweden.

Induction of SRY box transcription factor 9 (SOX9) has been shown to occur in response to kidney injury in rodents, where SOX9-positive cells proliferate and regenerate the proximal tubules of injured kidneys. Additionally, SOX9-positive cells demonstrate a capacity to differentiate toward other nephron segments. Here, we characterized the role of SOX9 in normal and injured human kidneys. SOX9 expression was found to colocalize with a proportion of so-called scattered tubular cells in the uninjured kidney, a cell population previously shown to be involved in kidney injury and regeneration. Following injury and in areas adjacent to inflammatory cell infiltrates, SOX9-positive cells were increased in number. With the use of primary tubular epithelial cells (PTECs) obtained from human kidney tissue, SOX9 expression was spontaneously induced in culture and further increased by transforming growth factor-β1, whereas it was suppressed by interferon-γ. siRNA-mediated knockdown of SOX9 in PTECs followed by analysis of differential gene expression, immunohistochemical expression, and luciferase promoter assays suggested lamin B receptor (

Material family of zinc blende structure semiconductors (ZBSSs) is important for novel technique such as spintronics. A study of the ZBSS spin-splitting structure in momentum space is essential when seeking to understand the exotic properties of the material. The Dresselhaus field predominates in the bulk, but the Rashba field plays important roles in states near the surface. Here, we used circular dichroism in angle-resolved photoemission spectroscopy (CD-ARPES) to explore the spin-splitting structure of bulk ZBSS in momentum space. The observed structure was well-explained by a Dresselhaus field attributable to the lack of inversion symmetry in ZBSS crystals. We show that CD-ARPES usefully reveals spin-splitting in momentum space. CD-ARPES combined with hard x-ray incident-beam would be useful to investigate the spin-splitting structures of the interface states in the ZBSS heterostructure.

European Regional Development Fund (grant No. TK-141 HiTechDevices 2014-2020.4.01.15-0011 to University of Tartu; grant No. MAX-TEENUS 2014-2020.4.01.20-0278 to University of Tartu; grant No. Eesti Kiirekanal SLOFY11156T/1 to University of Tartu); Estonian Research Council (grant No. PRG-629 to University of Tartu); Jane & Aatos Erkko Foundation (grant No. SOFUS); Business Finland (grant No. 1464/31/2019); Academy of Finland (grant No. 319042; grant No. 326461; grant No. 326406; grant No. 320165); University of Oulu; University of Turku; Tampere University; University of Tartu., FinEstBeAMS (Finnish-Estonian Beamline for Atmospheric and Materials Sciences) is a multidisciplinary beamline constructed at the 1.5 GeV storage ring of the MAX IV synchrotron facility in Lund, Sweden. The beamline covers an extremely wide photon energy range, 4.5-1300 eV, by utilizing a single elliptically polarizing undulator as a radiation source and a single grazing-incidence plane grating monochromator to disperse the radiation. At photon energies below 70 eV the beamline operation relies on the use of optical and thin-film filters to remove higher-order components from the monochromated radiation. This paper discusses the performance of the beamline, examining such characteristics as the quality of the gratings, photon energy calibration, photon energy resolution, available photon flux, polarization quality and focal spot size. © 2021 International Union of Crystallography. All rights reserved. --//-- Chernenk, K., Kivimäki, A., Pärna, R., Wang, W., Sankari, R., Leandersson, M., . . . Huttula, M. (2021). Performance and characterization of the FinEstBeAMS beamline at the MAX IV laboratory. Journal of Synchrotron Radiation, 28, 1620-1630. doi:10.1107/S1600577521006032., ERDF TK-141 HiTechDevices 2014-2020.4.01.15-0011; MAX-TEENUS 2014-2020.4.01.20-0278; Eesti Kiirekanal SLOFY11156T/1; Estonian Research Council grant No. PRG-629; Jane & Aatos Erkko Foundation SOFUS; Business Finland 1464/31/2019; Academy of Finland 319042, 326461, 326406, 320165; University of Oulu; University of Turku; Tampere University; University of Tartu. Institute of Solid State Physics, University of Latvia as the Center of Excellence has received funding from the European Union’s Horizon 2020 Framework Programme H2020-WIDESPREAD-01-2016-2017-TeamingPhase2 under grant agreement No. 739508, project CAMART2.

Background Circulating tumor DNA (ctDNA), which is shed from tumor cells into the blood, is a promising minimal-invasive method for cancer diagnostics and monitoring. The aim of this study was to evaluate preoperative ctDNA levels in the plasma of patients with ovarian cancer and correlate the levels to clinicopathological parameters and patient outcome. Methods Tumor DNA was extracted from ovarian tumor tissue from 41 patients. Targeted sequencing using a panel of 127 genes recurrently mutated in cancer was performed to identify candidate somatic mutations in the tumor DNA. SAGAsafe digital PCR (dPCR) assays targeting the candidate mutations were used to measure ctDNA levels in patient plasma samples, obtained prior to surgery, to evaluate ctDNA levels in terms of mutant copy number/mL and variant allele frequency. Results Somatic mutations were found in 24 tumors, of which seven were from patients with borderline, and 17 with invasive cancer diagnosis. TP53 was the most frequently mutated gene. Fifteen of 24 patients had detectable ctDNA levels in pre-operative plasma. Plasma ctDNA mutant concentration increased with higher stage (ptrend

International audience; Atomic staircases are among the simplest lateral nanostructures. In particular, electrons belonging to Shockley states of (111)-oriented noble metal surfaces are excellent test systems to explore the basic electronic properties in onedimensional superlattices by means of angular photoemission (ARPES) . These surfaces are characterized by strong emissions from free-electron-like surface states that scatter at step edges.The scattering of electrons at surface defects, such as atomic and molecular adsorbates and monatomic steps, has been made widely popular by scanning tunnelling microscopy (STM) . Observed interference patterns mirror fundamental properties of solid crystals related to electron transport and quantum confinement, such as the inelastic lifetime and quantum coherence of a scattered electron. However, even at noble metal surfaces, considered as model systems, the nature of the step potential is more complex and fundamental questions remain open . InAs(111) A and B surfaces are known to support a two-dimensional electron gas (2DEG) exhibiting a multitude of fundamental physical phenomena that can be of major importance for technological applications. The 2DEG, observed for the first time by Olsson et al. is related to the charge accumulation layer induced by band bending. We have investigated by ARPES the electronic structure of the InAs(111) prepared by molecular beam epitaxy (MBE). On InAs(111)-B we obtained a large splitting in the 2DEG than cannot be explained by the Rashba or Dresselhaus effects. STM images on the MBE prepared surface show array of equally spaced, monatomic, parallel steps. So, the 2DEG splitting can be attributed to the superlattice band folding depending on the step lattice constant

Local tumor-associated immune cells hold prognostic and predictive value in various forms of malignancy. The role of systemic, circulating leukocytes is, however, not well-characterized. In this prospective and explorative study, we aim to delineate the clinical relevance of a broad panel of circulating immune cells in 32 patients with newly diagnosed metastatic breast cancer (MBC) before the start of systemic treatment. Freshly isolated peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry and evaluated for potential associations to clinicopathological variables and patient outcome. We show that the levels of specific circulating leukocyte populations are associated with clinical parameters such as hormone receptor status, histological subtype, number of circulating tumor cells (CTCs) and metastatic burden. Importantly, high levels of CD8+ cytotoxic T lymphocytes (CTLs) are significantly linked to improved overall survival (OS). In patients with estrogen receptor (ER)-positive primary tumors, high levels of circulating CTLs and non-classical (CD14+CD16++) monocytes were associated with improved OS, whereas in patients with ER-negative tumors low levels of circulating natural killer (NK) cells potentially associate with improved OS. We propose that the levels of specific circulating immune cell populations, such as CD8+ CTLs, may be used to predict clinical outcomes in MBC patients. Thus, larger studies are warranted to validate these findings.

The presence of CD169+ macrophages in the draining lymph nodes of cancer patients is, for unknown reasons, associated with a beneficial prognosis. We here investigated the prognostic impact of tumor-infiltrating CD169+ macrophages in primary tumors (PTs) and their spatial relation to tumor-infiltrating B and T cells. Using two breast cancer patient cohorts, we show that CD169+ macrophages were spatially associated with the presence of B and T cell tertiary lymphoid-like structures (TLLSs) in both PTs and lymph node metastases (LNMs). While co-infiltration of CD169+/TLLS in PTs correlated with a worse prognosis, the opposite was found when present in LNMs. RNA sequencing of breast tumors further confirmed that SIGLEC1 (CD169) expression was associated with mature tertiary lymphoid structure (TLS), and Treg and Breg signatures. We propose that the negative prognostic value related to CD169+ macrophages in PTs is a consequence of an immunosuppressive tumor environment rich in TLSs, Tregs and Bregs.

Background: Cancer immunity is based on the interaction of a multitude of cells in the spatial context of the tumour tissue. Clinically relevant immune signatures are therefore anticipated to fundamentally improve the accuracy in predicting disease progression. Methods: Through a multiplex in situ analysis we evaluated 15 immune cell classes in 1481 tumour samples. Single-cell and bulk RNAseq data sets were used for functional analysis and validation of prognostic and predictive associations. Findings: By combining the prognostic information of anti-tumoural CD8+ lymphocytes and tumour supportive CD68+CD163+ macrophages in colorectal cancer we generated a signature of immune activation (SIA). The prognostic impact of SIA was independent of conventional parameters and comparable with the state-of-art immune score. The SIA was also associated with patient survival in oesophageal adenocarcinoma, bladder cancer, lung adenocarcinoma and melanoma, but not in endometrial, ovarian and squamous cell lung carcinoma. We identified CD68+CD163+ macrophages as the major producers of complement C1q, which could serve as a surrogate marker of this macrophage subset. Consequently, the RNA-based version of SIA (ratio of CD8A to C1QA) was predictive for survival in independent RNAseq data sets from these six cancer types. Finally, the CD8A/C1QA mRNA ratio was also predictive for the response to checkpoint inhibitor therapy. Interpretation: Our findings extend current concepts to procure prognostic information from the tumour immune microenvironment and provide an immune activation signature with high clinical potential in common human cancer types.

Source data for "Observation of a linked-loop quantum state in a topological magnet" by I. Belopolski et al.

Local tumor-associated immune cells hold prognostic and predictive value in various forms of malignancy. The role of systemic, circulating leukocytes is, however, not well-characterized. In this prospective and explorative study, we aim to delineate the clinical relevance of a broad panel of circulating immune cells in 32 patients with newly diagnosed metastatic breast cancer (MBC) before the start of systemic treatment. Freshly isolated peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry and evaluated for potential associations to clinicopathological variables and patient outcome. We show that the levels of specific circulating leukocyte populations are associated with clinical parameters such as hormone receptor status, histological subtype, number of circulating tumor cells (CTCs) and metastatic burden. Importantly, high levels of CD8

The β-catenin/Wnt signaling pathway plays an important role in all stages of T cell development. Nemo-like kinase (NLK) is an evolutionary conserved serine/threonine kinase and a negative regulator of the Wnt signaling pathway. NLK can directly phosphorylate histone deacetylase 1 (HDAC1), as well as T cell factor/lymphoid enhancer–binding factor (TCF/LEF), causing subsequent repression of target gene transcription. By engineering mice lacking NLK in early stages of T cell development, we set out to characterize the role NLK plays in T cell development and found that deletion of NLK does not affect mouse health or lymphoid tissue development. Instead, these mice harbored a reduced number of single-positive (SP) CD8+ thymocytes without any defects in the SP CD4+ thymocyte population. The decrease in SP CD8+ thymocytes was not caused by a block in differentiation from double-positive CD4+CD8+ cells. Neither TCR signaling nor activation was altered in the absence of NLK. Instead, we observed a significant increase in cell death and reduced phosphorylation of LEF1 as well as HDAC1 among NLK-deleted SP CD8+ cells. Thus, NLK seems to play an important role in the survival of CD8+ thymocytes. Our data provide evidence for a new function for NLK with regard to its involvement in T cell development and supporting survival of SP CD8+ thymocytes.

The pharma industry designs increasingly less cytochrome P450 dependent and more metabolically stable drugs, and consequently UGT-metabolism becomes more frequently involved. This study compares 2 glucuronidation RAF-scaling approaches, product formation and substrate depletion, regarding their potential for prediction of in vivo DDI and the relative contribution of UGT-mediated phase II reactions in an industrial setting. RAFs were developed for UGT1A1, 1A3, 1A4, 1A6, 1A9, 2B7 and 2B15 recombinant UGT isoforms and a large 150-donor pooled human liver microsome batch. The RAF-values ranged from small values of 0.06 (UGT1A3), over 0.24 and 0.48 (UGT1A9 and UGT1A4), to values around 1 (1.11 for UGT2B7, 1.14 for UGT1A1), and high RAFs of 4.8 (UGT1A6) and 6.57 (UGT2B15). Both approaches identified the same primarily involved isoforms (≥75% relative contribution) of 5 clinical reference compounds (raloxifene, haloperidol, laropiprant, telmisartan and naloxone), in concordance with reported in vitro (R2 = 0.65) and clinical results for UGT1A1, 1A3, 1A4, 1A9, 2B7 and 2B15. This study is distinctive in that it is reporting the glucuronide formation in addition to substrate depletion. The product formation approach proved more sensitive and enables UGT phenotyping of slowly metabolized drugs, additionally it allows identification of structurally different glucuronides.

Background Pancreatic cancer is a devastating disease with a dismal prognosis. Despite profound medical advances in systemic therapies for other types of aggressive tumours during recent years, a diagnosis of pancreatic cancer is still often synonymous with a fatal outcome. The term periampullary cancer includes pancreatic cancer and applies to the group of tumours found in proximity to the ampulla of Vater. Molecular events and immune response in the host during chemotherapy remain largely unexplored in this group of tumours. Therefore, the “Chemotherapy, Host Response and Molecular Dynamics in Periampullary Cancer (CHAMP)” study aims to monitor these processes to gain new insight into this perplexing disease. Methods The CHAMP study is a prospective, single-arm observational study. All patients diagnosed with pancreatic or other periampullary adenocarcinoma undergoing adjuvant or palliative chemotherapy treatment in the Department of Oncology, Skåne University Hospital, are invited to participate. Clinical and pathological data will be compiled at study entry. A single tissue microarray (TMA) block is constructed for each patient with a resected tumour and blood samples are drawn before, during and after chemotherapy in order to sample peripheral blood mononuclear cells (PBMC), cytokines and circulating tumour DNA (ctDNA). Next generation sequencing will be performed on tumour tissue and ctDNA to detect changes in the clonal landscape over space and time. Discussion Despite the recent emergence of some promising biomarkers for periampullary cancer, there has been a lack of success in clinical implementation. Cancer cells continuously adapt and become resistant to treatment during chemotherapy. To be able to keep pace with and hopefully overtake this rapid evolution we must, with the help of new diagnostic tools, be ready to adapt and alter treatment accordingly. It seems to us that the only way forward is to gain a better understanding of the dynamics of the disease during treatment. With insights gained from the CHAMP study we hope to find answers to key questions in this largely unexplored territory. Trial registration This study has been registered 30th October 2018 at clinicaltrials.gov as NCT03724994.

The overall aim of this prospective study was to delineate the role of monocytic myeloid-derived suppressor cells (Mo-MDSCs) in patients with metastatic breast cancer (MBC). MDSCs are a heterogeneous group of immunosuppressive cells often enriched in different malignancies which hold prognostic and predictive value for clinical outcomes. Here, we assessed the clinical significance of Mo-MDSCs in 54 patients with de novo or distant recurrent MBC. We show that high levels of Mo-MDSCs significantly correlated with de novo MBC (metastatic disease at initial diagnosis), estrogen receptor (ER) negativity, and liver- and bone metastasis. A trend towards an association between high levels of Mo-MDSCs and survival (P = 0.053) was also found in patients with distant recurrent ER-positive MBC. We therefore propose that an increased population of Mo-MDSCs may be related to the metastatic or immunoregulatory switch associated with transition to a more systemic disease. Our data imply that high levels of systemic Mo-MDSCs represent patients with more aggressive disease and worse outcome. Electronic supplementary material The online version of this article (10.1007/s00262-019-02472-z) contains supplementary material, which is available to authorized users.

Supplemental data for "The injury-induced transcription factor SOX9 alters expression of LBR, HMGA2, and HIPK3 in human kidney", including differentially expressed genes between siSOX9-transfected cells and control cells from RNA-seq, predicted SOX9 binding sites in promoter regions, immunohistochemical controls, and data from proliferation assay of siSOX9-transfected cells and control cells.

STUDY QUESTION What characterizes the group of donor-conceived (DC) individuals who request information about their identity-release sperm donor in Sweden, and what are their experiences of disclosure, information receipt and donor contact? SUMMARY ANSWER Following three decades of identity-release donation in Sweden, few DC individuals have requested donor information with varying experiences of information receipt and donor contact. WHAT IS KNOWN ALREADY In 1985, Sweden was the first country worldwide to enact legislation that gave DC individuals the right to obtain identifying information about their donor. Since then, identity-release gamete donation has become available in many countries but there is limited knowledge about the individuals who request donor information. STUDY DESIGN, SIZE, DURATION A nation-wide cross-sectional survey study was performed at all seven University hospitals that provided donation treatment in Sweden during 1985–2002. During this period only donor insemination to heterosexual couples was permitted. Inclusion criteria were being 18 years of age or older, conceived with donor sperm and having requested information about the donor by December 2020. Recruitment was performed during 2016–2020. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 60 individuals had requested information about their donor. Of these, 53 were approached and 40 individuals, representing 34 families, accepted study participation (75% response rate). Participants completed a postal survey with the WHO-10 well-being index and study-specific questions about experiences of disclosure, motivations for requesting donor information, receipt of information, as well as intentions and experiences of donor contact. Independent t-test and chi-square tests were used to compare ratings of participants with early and late disclosure. MAIN RESULTS AND ROLE OF CHANCE Of ∼900 DC individuals who had reached adult age, a total of 60 (≈7%) had requested information about the donor. Most of the 40 study participants (78%) made their requests within 2 years after reaching 18 years of age, or following disclosure at later ages (up to 32 years). Several participants had adult DC siblings in the family who had not requested any donor information. All except five participants received identifying information about the donor from the clinic. However, some donors had died or lacked contact information. Among those participants who were able to contact their donor, 41% had done so at the time of the study, while a third of the participants were unsure about potential contact. Several had met the donor in person and a few were in regular contact. About half of the participants had been informed about their donor conception in adolescence or adulthood (age 12–32), and there were significant differences between participants based on age at disclosure. Compared to those with early disclosure, participants with late disclosure were significantly more likely to be dissatisfied with the timing of their disclosure (P = 0.021), to react with negative emotions (P LIMITATIONS, REASONS FOR CAUTION The limited population available for inclusion resulted in a small sample size, despite a high response rate. In addition, men’s lower participation rate must be taken into consideration when interpreting the results. WIDER IMPLICATIONS OF THE FINDINGS The small number of individuals requesting information about their identity-release sperm donor is surprising. While not all DC individuals appear to be interested in donor information, it is reasonable to assume that some are unaware of their donor conception and thus unable to make informed decisions regarding their genetic origins. During the coming years, young women and men in many countries will become eligible to access identifying information about their donor. In order to meet the needs of these individuals, and to support positive outcomes for all involved parties, it is essential that adequate protocols and resources are developed. STUDY FUNDING/COMPETING INTEREST Financial support from The Swedish Research Council. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.

Supplemental data for "Kidney injury increases expression of the transcription factor SOX9 that regulates LBR, HMGA2, and HIPK3", including differentially expressed genes between siSOX9-transfected cells and control cells from RNA-seq, predicted SOX9 binding sites in promoter regions, and data from proliferation assay of siSOX9-transfected cells and control cells.

Cross-platform frameworks enable development for multiple platforms, such as iOS and Android, using the same codebase. Evaluation of cross-platform frameworks has traditionally been geared towards technical assessments and, more seldom, targeted usability, leaving a gap to be explored. This paper presents a usability analysis of Flutter and React Native, supported by a user study using the Cognitive Dimensions of Notations framework (CDN framework). Six developers were recruited and interviewed with the CDN framework questionnaire and a thematic analysis was performed where several usability issues, benefits and design trade-offs were identified. A recurring topic amongst the React Native developers was issues regarding hooks, while the Flutter developers unanimously identified problems relating to layout design. React Native was highlighted for its abstraction and progressive evaluation capabilities, indicating an edge toward Flutter. In contrast, comments regarding Flutters tooling capabilities and UI libraries showed an edge towards React Native. The identified usability benefits and trade-off characteristics give insight into each framework’s strengths and weaknesses. “Cross-platform”-ramverk möjliggör applikationsutveckling till ett flertal plattformar såsom iOS och Android genom användning av samma kodbas. Flutter och React Native är i dagsläget två av de mest eftersökta “cross-platform”-ramverken. Utvärdering av dessa ramverk har vanligtvis utvärderat den tekniska aspekten, och mer sällan fokuserat på användbarhet. Denna masteruppsats presenterar en användbarhetsanalys av Flutter och React Native genom en användarstudie med utgångpunkt i ramverket “Cognitive Dimensions of Notations” (CDN-ramverket). Sex utvecklare rekryterades och intervjuades genom ett formulär tillhörande CDN-ramverket. En tematisk analys genomfördes på den insamlade datan och identifierade ett flertal problem och överväganden gällande design. Ett återkommande tema bland React Native-utvecklarna var problem relaterat till “hooks” medan Flutter-utvecklarna beskrev problem avseende layout-design. React Native mottog positiva kommentarer relaterat till abstraktionkapacitet och progressiv utvärdering jämfört med Flutter. Flutter mottog positiv kritik angående verktyg samt tillhörande UI-bibliotek jämfört med React Native. Utvärderingen av Flutter och React Native ger insyn i respektive ramverks styrkor och svagheter.

In this essay we will be discussing how middle aged women have reflected upon their sexuality in relation to their age, plastic surgeries and the various beauty norms that are prevalent in our society today. We have done this through six different interviews with women within the age group 45-60. Sexuality, in this essay's meaning, is defined as the way a person dresses, talks about, acts upon and presents themselves in an attractive manner. Further we will be analyzing and discussing the interviewees answers with the help of various different theories: liberal- and socialistic feminism, erotic capital, respectability and ageism. What we have found is that although one might think that age and aging might make a woman feel insecure about the way she looks, the women we’ve interviewed have shown quite the opposite. Also, the interviewees have displayed a concern about a kind of ‘youth norm’ that has affected the way society treats and sees them. Age and aging have furthermore brought upon a new form of confidence for most of the interviewees, which differs from other found studies that have been done on middle-aged womens thoughts about aging.

Our group at NCBJ works on upgrade of 1.6-cell, SRF, XFEL-type injector in collaboration with DESY and other laboratories. The work is focused on preparation of lead-on-niobium photocathode, its positioning in the gun cavity and on the UV laser system for photocurrent excitation. RF focusing effect was used to minimize the predicted emittance and transverse size of accelerated e⁻ beam. Following beam dynamics computation, it has been proposed that the photocathode be recessed 0.45 mm into the rear wall of the gun cavity. It helps focusing e⁻ beam in its low-energy part. Preparation of sc cathodes of Pb layer on Nb plugs (*, **) is reported, aimed at reaching clean, planar and uniform Pb films. The laser system will consist of commercially available Pharos laser and a 4-th harmonic generator. A gaussian, 300 fs long, 257 nm in wavelength UV pulse will be transformed in time by a pulse stretcher/stacker and in space by pi-shaper. The planned optical system will generate cylindrical photoelectron bunch 2 - 30 ps long and 0.2 - 3 mm wide., Proceedings of the 20th International Conference on RF Superconductivity, SRF2021, East Lansing, MI, USA

Quantum phases can be classified by topological invariants, which take on discrete values capturing global information about the quantum state. Over the past decades, these invariants have come to play a central role in describing matter, providing the foundation for understanding superfluids, magnets, the quantum Hall effect, topological insulators, Weyl semimetals and other phenomena. Here we report a remarkable linking number (knot theory) invariant associated with loops of electronic band crossings in a mirror-symmetric ferromagnet. Using state-of-the-art spectroscopic methods, we directly observe three intertwined degeneracy loops in the material's bulk Brillouin zone three-torus, $\mathbb{T}^3$. We find that each loop links each other loop twice. Through systematic spectroscopic investigation of this linked loop quantum state, we explicitly draw its link diagram and conclude, in analogy with knot theory, that it exhibits linking number $(2,2,2)$, providing a direct determination of the invariant structure from the experimental data. On the surface of our samples, we further predict and observe Seifert boundary states protected by the bulk linked loops, suggestive of a remarkable Seifert bulk-boundary correspondence. Our observation of a quantum loop link motivates the application of knot theory to the exploration of exotic properties of quantum matter., See popular summary at https://research.princeton.edu/news/electrons-crystal-exhibit-linked-and-knotted-quantum-twists

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease. The only option for curative treatment is resection of the tumor followed by standard adjuvant chemotherapy. Yet, early relapse due to chemoresistance is almost inevitable. Herein, we delineated the genetic intratumor heterogeneity in resected PDAC, with the aim to identify evolutionary patterns that may be associated with overall survival (OS) following treatment with curative intent. Potential relationships with the adjacent immune microenvironment were also examined. The genetic and immune landscapes of the regional tumor space were analyzed in nine patients with resected PDAC. Targeted deep sequencing and genome wide SNP array were followed by clonal deconvolution and phylogenetic analysis. A mathematical complexity score was developed to calculate the network extent of each phylogeny. Spatial variation in abundancy and tumor nest infiltration of immune cells was analyzed by double IHC staining. Copy-number heterogeneity was denoted as the major contributing factor to the branching architectures of the produced phylogenetic trees. Increased tree complexity was significantly inversely associated with OS, and larger regional maximum aberrations (higher treetops) were associated with increased PD-L1 expression on tumor cells. Contrastingly, an FREM1 gene amplification, found in one patient, coincided with a particularly vigorous immune response. Findings from this limited case series suggest that complex evolutionary patterns may be associated with a shorter survival in surgically treated patients with PDAC. Some hypothesis-generating associations with the surrounding immune microenvironment were also detected.Evolutionary copy-number patterns may be associated with survival in patients with resected PDAC.

Simple Summary We sought to provide a detailed overview of the immune landscape of colorectal cancer in the largest study to date in terms of patient numbers and analyzed immune cell types. We applied a multiplex in situ staining method in combination with an advanced scanning and image analysis pipeline akin to flow cytometry, and analyzed 5968 individual multi-layer images of tissue defining in a total of 39,078,450 cells. We considered the location of immune cells with respect to the stroma, and tumor cell compartment and tumor regions in the central part or the invasive margin. To the best of our knowledge, this study is the first comprehensive spatial description of the immune landscape in colorectal cancer using a large population-based cohort and a multiplex immune cell identification. Abstract While the clinical importance of CD8+ and CD3+ cells in colorectal cancer (CRC) is well established, the impact of other immune cell subsets is less well described. We sought to provide a detailed overview of the immune landscape of CRC in the largest study to date in terms of patient numbers and in situ analyzed immune cell types. Tissue microarrays from 536 patients were stained using multiplexed immunofluorescence panels, and fifteen immune cell subclasses, representing adaptive and innate immunity, were analyzed. Overall, therapy-naïve CRC patients clustered into an ‘inflamed’ and a ‘desert’ group. Most T cell subsets and M2 macrophages were enriched in the right colon (p-values 0.046–0.004), while pDC cells were in the rectum (p = 0.008). Elderly patients had higher infiltration of M2 macrophages (p = 0.024). CD8+ cells were linked to improved survival in colon cancer stages I-III (q = 0.014), while CD4+ cells had the strongest impact on overall survival in metastatic CRC (q = 0.031). Finally, we demonstrated repopulation of the immune infiltrate in rectal tumors post radiation, following an initial radiation-induced depletion. This study provides a detailed analysis of the in situ immune landscape of CRC paving the way for better diagnostics and providing hints to better target the immune microenvironment.

Tumor-associated macrophages (TAMs) have emerged as key players in tumor immunology but demonstrate a continuum of functional states being either tumor suppressive or promoting. Moreover, chemotherapeutic agents have been shown to alter the tumor microenvironment. Perioperative chemotherapy is a standard treatment option for resectable esophageal and gastric (EG) adenocarcinoma. The aim of this study was to investigate the influence of neoadjuvant chemotherapy (NAC) on TAMs to improve the prognostication and treatment course for these patients. The study cohort comprised 148 patients, all of whom were diagnosed with resectable EG adenocarcinoma and treated with NAC. Immunohistochemistry was applied to assess the total infiltration and infiltration into tumor nests (TN) of CD68+/CD163-, CD68+/CD163+, and MARCO+ TAMs, on paired biopsies from primary tumors (PT) pre-NAC, and resected PT and lymph node metastases post-NAC. In pre-NAC specimens, high CD68+/CD163+ infiltration into TN was an unfavorable prognostic factor. No association was found between TAM density in PT pre-NAC and histopathological regression. The density of CD68+/CD163+ TAMs was increased in PT post-NAC, while the density of MARCO+ TAMs was decreased. CD68+/CD163- TAM density was not altered. In post-NAC specimens, higher total as well as TN infiltration of CD68+/CD163- TAMs were adverse prognostic factors. In conclusion, these results suggest that NAC may alter certain TAM subsets in EG adenocarcinoma, along with their functional properties and thus their prognostic value.

Immune cells of the tumor microenvironment are central but erratic targets for immunotherapy. The aim of this study was to characterize novel patterns of immune cell infiltration in non-small cell lung cancer (NSCLC) in relation to its molecular and clinicopathologic characteristics. Lymphocytes (CD3+, CD4+, CD8+, CD20+, FOXP3+, CD45RO+), macrophages (CD163+), plasma cells (CD138+), NK cells (NKp46+), PD1+, and PD-L1+ were annotated on a tissue microarray including 357 NSCLC cases. Somatic mutations were analyzed by targeted sequencing for 82 genes and a tumor mutational load score was estimated. Transcriptomic immune patterns were established in 197 patients based on RNA sequencing data. The immune cell infiltration was variable and showed only poor association with specific mutations. The previously defined immune phenotypic patterns, desert, inflamed, and immune excluded, comprised 30, 13, and 57% of cases, respectively. Notably, mRNA immune activation and high estimated tumor mutational load were unique only for the inflamed pattern. However, in the unsupervised cluster analysis, including all immune cell markers, these conceptual patterns were only weakly reproduced. Instead, four immune classes were identified: (1) high immune cell infiltration, (2) high immune cell infiltration with abundance of CD20+ B cells, (3) low immune cell infiltration, and (4) a phenotype with an imprint of plasma cells and NK cells. This latter class was linked to better survival despite exhibiting low expression of immune response-related genes (e.g. CXCL9, GZMB, INFG, CTLA4). This compartment-specific immune cell analysis in the context of the molecular and clinical background of NSCLC reveals two previously unrecognized immune classes. A refined immune classification, including traits of the humoral and innate immune response, is important to define the immunogenic potency of NSCLC in the era of immunotherapy. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Perioperative chemotherapy enhances the survival rates for patients with esophageal and gastric (EG) adenocarcinoma, but not all patients benefit from this additional treatment. Chemotherapeutic agents have been demonstrated to alter the immune cell (IC) composition in the tumor microenvironment. Hence, there is a rationale to investigate the influence of neoadjuvant chemotherapy (NAC) on different IC subsets, to better understand and compare their utility as complementary prognostic or predictive biomarkers in a clinically relevant context. The density of T cells (CD8+ and FoxP3+), B cells (CD20+) and the expression of PD-L1 on ICs and tumor cells (TC) was assessed by immunohistochemistry on paired biopsies from primary tumors (PT) pre-NAC, and resected PT and lymph node metastases post-NAC. The cohort encompasses 148 patients with resectable EG adenocarcinoma, all of whom received NAC. The density of CD8+ cells was decreased and the density of FoxP3+ cells and CD20+ cells was increased in PT post-NAC. PD-L1 expression was not altered following NAC. In pre-NAC specimens, high FoxP3+ density and high PD-L1 expression on ICs were favorable prognostic factors, whereas high CD8+ density was an unfavorable prognostic factor. In post-NAC specimens, however, high FoxP3+ density was an unfavorable prognostic factor, and high PD-L1 expression on TC was associated with a shorter survival. There were no significant associations between IC density or PD-L1 expression in PT pre-NAC and histopathological regression. These findings propose that NAC might alter the density and prognostic impact of some IC subsets in EG adenocarcinoma.

Background: The transcription factor signal transducer and activator of transcription 3 (STAT3) is implicated in cancer drug resistance, metastasis, and immunosuppression and has been identified as a promising therapeutic target for new anticancer drugs. Myeloid-derived suppressor cells (MDSCs) play a major role in the suppression of antitumor immunity and STAT3 is involved in the accumulation, generation, and function of MDSCs. Thus, targeting STAT3 holds the potential of reversing immunosuppression in cancer. This study aims to investigate the effect of the small molecule STAT3 inhibitor galiellalactone on prostate cancer cell– induced generation of MDSCs from monocytes and the effect on immunosuppressive factors and inflammatory cytokines. Methods: Primary human monocytes were cocultured with prostate cancer cells (DU145, PC3, and LNCaP-IL6) or with conditioned medium (CM) from prostate cancer cells in the presence or absence of the STAT3 inhibitor galiellalactone. Monocytes were analyzed by flow cytometry for an MDSC-like phenotype (CD14+ HLA-DR−/lo). The secretion and gene expression of immunosuppressive factors and inflammatory cytokines from prostate cancer cells and monocytes were investigated. Results: Galiellalactone blocked the prostate cancer cell–induced generation of MDSC-like monocytes with an immunosuppressive phenotype ex vivo. Monocytes cultured with CM from prostate cancer cells showed increased expression of phosphorylated STAT3. Prostate cancer cells increased the expression of interleukin1β (IL1β), IL10, and IL6 in monocytes which was inhibited by galiellalactone. In addition, galiellalactone decreased indoleamine 2,3-dioxygenase gene expression in monocytes. Galiellalactone reduced the levels of IL8 and granulocyte macrophage-colony stimulating factor in prostate cancer cells per se. Conclusion: The STAT3 inhibitor galiellalactone may prevent the prostate cancer cell–induced generation of MDSCs and reverse the immunosuppressive mechanisms caused by the interplay between prostate cancer cells and MDSCs. This is a potential new immunotherapeutic approach for the treatment of prostate cancer. (Less)

Innate immune responses are rapid, dynamic and highly regulated to avoid overt reactions. This regulation is executed by innate immune tolerance mechanisms that remain obscure. Wnt5a is a signalling protein mainly involved in developmental processes and cancer. The effect of Wnt5a on inflammatory myeloid cells is controversial. Here, we combine primary cell cultures, in vitro binding studies, mass spectrometry and Drosophila protein modelling to show that Wnt5a is a direct ligand of toll-like receptor (TLR) 2 and 4. The binding promotes a MyD88-non-canonical nuclear factor of kappa B (NFκB) and AP-1 signalling cascade, with contradictory profiles in mouse (pro-inflammatory) and human (anti-inflammatory) myeloid immune cells. These data reveal that the true nature of Wnt5a in inflammatory cells, is to regulate TLR signals, and in human myeloid cells it acts as an endogenous, tolerance-associated molecular pattern (TAMP), inducing IL-10 and innate immune tolerance., Meliha Mehmeti et al. show that Wnt5a is a direct ligand of toll-like receptor 2 and 4 to act as an endogenous tolerance-associated molecular pattern, triggering innate immune tolerance in human myeloid cells. This study expands the functional repertoire of Wnt5a that is mainly known as a signalling protein involved in development and cancer.

Pancreatic cancer (PC) has become one of the leading causes of cancer related deaths. Late detection and resistance to therapy are two reasons for the dismal prognosis of this disease. Hence, there is an immense need for novel treatment options as well as predictive biomarkers, to prolong the life of these patients. The Chemotherapy, Host Response and Molecular Dynamics in Periampullary Cancer, the CHAMP study (clinical trial nr NCT03724994), is an ongoing observational, prospective clinical study that includes newly diagnosed patients with PC or other periampullary cancers receiving adjuvant or first-line palliative chemotherapy. The present study aims to investigate the peripheral immune-cellome in serial blood samples obtained during treatment from 24 patients, of whom 8 had resectable tumors. Buffy coat was isolated from blood samples taken at baseline (before treatment), after one month and after three to four months of treatment. Flow cytometry with two panels of antibodies was applied to detect major immune populations in both the innate and the adaptive immune system, as well as subpopulations of T cells. Immune cell frequencies were compared between patients with progression and no progression during treatment, and the associations of different immune cell subsets with overall survival were examined. As B cells have been highlighted as being of particular clinical relevance, single-cell transcriptomics and proteomics will be applied to further delineate the dynamics and prognostic impact of individual subtypes within this lineage. The results will provide important real-world data on the longitudinal dynamics of circulating immune cells under the pressure of chemotherapy in patients with PC. These results will in the future be related to analyses of circulating tumor DNA in matched blood samples, and together they will provide a foundation for forthcoming adaptive treatment trials based on results from the CHAMP study. Citation Format: Maja Svensson, Alexandra Petersson, Viktor Sincic, Sofie Olsson Hau, Jakob Eberhard, David Gisselsson Nord, Karin Leandersson, Kristina Lundberg, Karin Jirström. Effects of chemotherapy on the peripheral immune-cellome in patients with pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A022.

Immune cells in the microenvironment shape tumor development and progression. The prognostic value of T-cell-based immune scores exceeds those of clinical parameters in colon cancer, but reflects only a part of the anti-tumor immune response. Here, we assessed 15 distinct immune cell classes and identified a simple prognostic signature based on pro- and anti-tumoral immune cells in the tumor microenvironment. The ratio of cytotoxic lymphocytes to tumor supportive macrophages predicted survival better than the state-of-art immune score in colon cancer and had the highest relative contribution to survival prediction when compared to established clinical parameters. This signature was prognostic also in other cancers with high mutation burden, such as those of the lung, bladder, esophagus, and melanomas, supporting broad clinical applicability.One Sentence SummaryThe CD8/M2 ratio in tumor tissue defines prognosis in immunogenic cancers

In connection with the COVID-19 pandemic digital tools have become increasingly common to use. This change will lead to companies finding new ways to communicate and showcase their products. This project has been very relevant when it comes to using digital tools as the project is based in the client AJ products virtual showroom. This project has been carried out with two different 3D scanners and the Artec Studio software, both scanners are from the Artec 3D brand and are handheld. The scanned products have been three different chairs. The aim of this project has been developing the most suitable approach to get a physical product to a virtual environment through 3D scanning. This project can be used to streamline scanning for the future products that have a similar shape and/or surface as the products in this work. For this technology to be made more efficient and provide more realistic model, there is now good theoretical and practical documentation of how to proceed. Information about which object and surface can be scanned well and alternatively what other solutions may be available. The result of this project has become a guide that AJ Products can follow when performing their 3D scan.

Aim: To map first-time mothers experiences of breastfeeding support provided by maternal health care, birth center and BB. Method: A quantitative survey with a cross-sectional design. The criterias to be included was first-time mothers who breastfed or wished to breastfeed and gave birth to a full-term child in the last two years. Data were collected through a web survey published on Facebook. A comfort selection was chosen and data were analyzed with descriptive statistics. Comparisons were made between two age groups Results: A total of 197 first time mothers were answered in the survey. Group 1 consisted of first-time mothers aged 21-30 years and Group 2 consisted of first-time mothers aged 31-42 years. The breastfeeding support included written, verbal and practical guidance. Positive and negative factors in breastfeeding support were identified. Both differences but mainly similarities were identified among first-time mothers’ experiences of breastfeeding support. It was 70,3% of the entire population who wanted more information about breastfeeding. A difference was that Group 2 generally estimated lower breastfeeding support compared with Group 1. Conclusion: The breastfeeding support was estimated quite low by both age groups. Almost half of the first-time mothers considered themselves to receive the best breastfeeding support from sources other than maternal health care, childbirth and BB. This indicates that the breastfeeding support that first-time mothers received was insufficient. First-time mothers requested more information about breastfeeding. High attendance of the midwife and individual guidance were positive factors. Keywords: breastfeeding, experiences, midwives, mothers, support.

Utbildning för hållbar utveckling är en oumbärlig komponent för att nästkommande generation ska kunna utveckla kompetenser och färdigheter för att hantera och förebygga de klimatförändringar och miljöproblem vi människor står inför. Skolan anses vara den mest avgörande platsen när det gäller att inspirera, motivera och utbilda miljömedvetna individer. I svensk grundskola är hållbar utveckling inskrivet i läroplanen och skall genomsyra all undervisning sedan 2006. Forskare har dock visat att många lärare saknar kompetenser och självförtroende för att undervisa om hållbar utveckling, alternativt är instruktioner och begrepp för otydliga och komplexa, vilket resulterar i en bristfällig implementering. Tidigare forskning indikerar att det saknas vägledning för hur hållbar utveckling skall implementeras i undervisningen rent praktiskt, eller att de styrdokument som finns behöver uppdateras. Med denna problematik till grund gjordes en intervjustudie där tre lärare och fyra lärarstudenter på grundskolenivå intervjuades för att besvara frågeställningarna och identifiera förbättringspotential och eventuellt kunna föreslå åtgärder för framtiden. Resultaten ställdes emot teorin Dewey’s notion of learning, experience and habits i syfte att bland annat besvara frågan kring vilka metoder och strategier som är de mest effektiva för att forma medvetna individer och i förlängningen skapa hållbara städer och samhällen. Intervjustudiens svarsanalys indikerade att det som tidigare forskare påvisat, att implementeringen är bristfällig och behöver ses över, med ett utökat helhetsperspektiv. Education for sustainable development is an indispensable component to provide the coming generations with competencies and skills to cope with and prevent the sustainability issues todays’ communities are facing. Schools are one of the most crucial determinators when it comes to inspire, motivate and educate environmentally conscious individuals. Sustainable development is a part of the Swedish curriculum since 2006. However, studies on the field show that teachers are lacking competencies and confidence to educate on sustainable development, or that the guidelines and the topic is too vague and complex, which corresponds with an inadequate implementation. Current studies on the field indicate that guidance for an effective implementation is needed, or that the guidelines that exist need an update. With these identified problems, an interview study was conducted, three primary teachers and four students in the teachers’ program participated to answer the questions and identify potential for improvement and potentially give suggestions for future changes. The findings were used together with the theory Dewey’s notion of learning, experience and habits, with the aim to answer the question of which teaching methods and strategies are the most effective to form conscious individuals and eventually create sustainable cities and communities. The interview study confirmed what previous researchers have shown, that the implementation is inadequate and needs to be reviewed and updated with a holistic perspective.

Syftet med studien är att synliggöra hur förskollärare uppfattar begreppet pedagogisk dokumentation. Syftet är att ta reda på om förskollärare har barnens perspektiv eller ett vuxenperspektiv vid den pedagogiska dokumentationen. Detta bidrar till att vi vill undersöka följande frågor: Hur uppfattar förskollärare begreppet pedagogisk dokumentation? Hur anger förskollärare att de utför pedagogisk dokumentation? Vi berör även dokumentationen då den är ett förarbete till pedagogisk dokumentation. Studien utgår från fenomenografin och utvecklingspedagogiken som teoretisk utgångspunkt. Med hjälp av en kvantitativ metod med kvalitativa inslag sammanställs en pappersenkät för att få frågeställningen besvarad. Enkäterna delas ut till förskollärare på olika förskolor. Resultatet i studien visar att förskollärare har både barnens perspektiv och ett vuxenperspektiv när de utför pedagogisk dokumentation. Det visar sig att fler förskollärare har barnens perspektiv i åtanke än ett vuxenperspektiv då många fokuserar på barnens utveckling. Vid sammanställandet av enkäterna synliggörs det att förskollärare uppfattar och utför pedagogisk dokumentation olika.

Syftet med denna uppsats är att undersöka om och hur de digitala röstassistenterna Google Assistant och Apples Siri bidrar till att porträttera och förstärka könsroller år 2021, på det svenska språket. Materialet för denna studie omfattar intervjuer med dessa två röstassistenter där cirka 40 frågeställningar/påståenden ställdes till assistenterna, uppdelat på fyra intervjutillfällen. Frågeställningarna avsåg att kartlägga röstassistenternas definition av kön och identitet, respons vid sexuella trakasserier samt de egenskaper assistenterna med betraktande av ett genusperspektiv kan tillskrivas. Som teoretiskt ramverk används Judith Butlers teori om performativitet. Genom tematisk analys identifierades fem olika teman, inkluderande entiteter som på olika vis bidrar till att porträttera och förstärka könsroller; Den icke-binära assistenten, Neutralitet och motstånd, Etablering av social relation, Stereotypa könsroller samt Politisk korrekthet. Studien visar att de svensktalande röstassistenterna år 2021, trots en politisk medvetenhet i retoriken bidrar till att replikera och förstärka en diskurs vilken alltjämt befäster traditionella könsroller.

One of the more fascinating Darwinian puzzles in sexual selection is that of copulatory wounding. For those taxa displaying this behavior, and that does not engage in traumatic insemination, the function of wound infliction during copulation remains unknown. In this study, the intention was to evaluate the purpose of copulatory wounding in Drosophila melanogaster and the consequences it might have for male and female fecundity. The present study measured the size and number of wounds that males from different stocks of Darwinian fitness imposed on females, as well as the copulation duration and the resulting fecundity. The number of wounds and the total wound size showed no apparent correlation to fecundity, but a significant difference in variation of the number of wounds inflicted on females was observed between males from two different lines of fitness. Wounded females were also considerably more common than non-wounded females, as were wounds that were paired compared to non-paired copulatory wounds. The results suggests that wounding might be an adaptive male trait and a copulatory courtship interpretable to females, implying a possible case of cryptic female choice. Since most wounds were paired, this implies that a bilaterally symmetrical organ is causing these wounds. Also, wounding was not as important for fecundity as previously thought. Ett av de mer fascinerande Darwinistiska pusslen inom sexuell selektion är skadande under kopulationen. För de taxa som uppvisar detta beteende, och inte engagerar sig i traumatisk insemination, så är funktionen av kopulationsskador okänd. I denna studie så var avsikten att utvärdera syftet av kopulationsskador hos Drosophila melanogaster och de konsekvenser beteendet kan ha för det resulterande antalet avkomma. Denna studie uppmätte storleken och antalet skador som hanar av olika Darwinistisk fitness vållade honor, samt kopulationstiden och antalet avkomma. Antalet skador och den totala storleken av skador visade ingen signifikant korrelation till antalet avkommor, däremot uppvisades signifikanta variationsskillnader mellan hanar av två olika fitnessnivåer. Skadade honor visade sig också vara betydligt vanligare än icke skadade honor och parade skador var även vanligare än icke parade skador. Resultaten indikerade att kopulationsskador kan vara en adaptiv egenskap hos hanar och en form av uppvaktning som honorna kan tyda, vilket kan antyda ett möjligt fall av ”kryptiskt honligt val”. Eftersom de flesta skador var parade, så antyder detta att ett bilateralt symmetriskt organ orsakar skadorna. Kopulationsskador visade sig heller inte vara så viktiga som man tidigare antagit.

Breast cancer is the most common form of cancer in women worldwide. Although the survival among breast cancer patients has improved, there is still a large group of patients with dismal prognosis. One of the most important prognostic factors for poor prognosis is lymph node metastasis. Increasing knowledge concerning the lymph nodes of breast cancer patients indicates that they are affected by the primary tumor. In this study we show that presence of CD169+ subcapsular sinus macrophages in contact with lymph node metastases in breast cancer patients, is related to better prognosis after adjuvant tamoxifen treatment, but only in patients with PDL1+ primary tumors. This is in contrast to the prognostic effect of CD169+ primary tumor-associated macrophages (TAMs). We further show that CD169+ macrophages were spatially associated with expression of PDL1 on nearby cells, both in primary tumors and metastatic lymph node, although PDL1 expression in metastatic lymph node as such did not have further prognostic impact. Our data suggest that CD169+ resident lymph node macrophages have a unique function in targeting immune responses against breast cancer and should be further investigated in detail.