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| 3. |
- Borglin, Gunilla, et al.
(author)
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Registered nurse’s working at elderly care centers experience of depressive symptoms among older people : a qualitative descriptive study
- 2019
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In: BMC Nursing. - : BioMed Central. - 1472-6955. ; 18
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Journal article (peer-reviewed)abstract
- Background: Depressive symptoms and/or depression are commonly experienced by older people. Both are underdiagnosed, undertreated and regularly overlooked by healthcare professionals. Healthcare facilities for people aged ≥ 75 years have been in place in Sweden since 2015. The aim of these care centres, which are managed by registered nurses (RNs), is to offer care adjusted to cater to the complex needs and health problems of older people. Although the mental health of older people is prioritised in these centres, research into the experience of RNs of depressive symptoms and/or depression in older people in this setting is limited. Therefore, this study aimed to illuminate RNs, working at care centres for older people, experience of identifying and intervening in cases of depressive symptoms. Methods: The data for this qualitative descriptive study were collected through interviews (n = 10) with RNs working at 10 care centres for older people in southern Sweden. The transcribed texts were analysed using inductive content analysis. Results: The participants’ experiences could be understood from four predominant themes: (1) challenging to identify, (2) described interventions, (3) prerequisites for identification, and (4) contextual influences. Key findings were that it was difficult to identify depression as it often manifested as physical symptoms; evidence-based nursing interventions were generally not the first-line treatment used; trust, continuity and the ability of RNs to think laterally; and the context influenced the ability of RNs to manage older people’s depressive symptoms and/or depression. Conclusions: The process of identifying depressive symptoms and performing an appropriate intervention was found to be complex, especially as older people were reluctant to present at the centres and provided obscure reasons for doing so. A nurse-patient relationship that was built on trust and was characterised by continuity of care was identified as a necessary prerequisite. Appropriate nursing interventions—afforded the same status as pharmacological treatment—are warranted as the first-line treatment of depression. Further research is also needed into efficacious nursing interventions targeting depressive symptoms and/or depression.
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| 4. |
- Carstam, Louise, et al.
(author)
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WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas.
- 2021
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In: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 11
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Journal article (peer-reviewed)abstract
- Background: While molecular insights to diffuse lower-grade glioma (dLGG) have improved the basis for prognostication, most established clinical prognostic factors come from the pre-molecular era. For instance, WHO grade as a predictor for survival in dLGG with isocitrate dehydrogenase (IDH) mutation has recently been questioned. We studied the prognostic role of WHO grade in molecularly defined subgroups and evaluated earlier used prognostic factors in the current molecular setting.Material and Methods: A total of 253 adults with morphological dLGG, consecutively included between 2007 and 2018, were assessed. IDH mutations, codeletion of chromosomal arms 1p/19q, and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions were analyzed.Results: There was no survival benefit for patients with WHO grade 2 over grade 3 IDH-mut dLGG after exclusion of tumors with known CDKN2A/B homozygous deletion (n=157) (log-rank p=0.97). This was true also after stratification for oncological postoperative treatment and when astrocytomas and oligodendrogliomas were analyzed separately. In IDH-mut astrocytomas, residual tumor volume after surgery was an independent prognostic factor for survival (HR 1.02; 95% CI 1.01-1.03; p=0.003), but not in oligodendrogliomas (HR 1.02; 95% CI 1.00-1.03; p=0.15). Preoperative tumor size was an independent predictor in both astrocytomas (HR 1.03; 95% CI 1.00-1.05; p=0.02) and oligodendrogliomas (HR 1.05; 95% CI 1.01-1.09; p=0.01). Age was not a significant prognostic factor in multivariable analyses (astrocytomas p=0.64, oligodendrogliomas p=0.08).Conclusion: Our findings suggest that WHO grade is not a robust prognostic factor in molecularly well-defined dLGG. Preoperative tumor size remained a prognostic factor in both IDH-mut astrocytomas and oligodendrogliomas in our cohort, whereas residual tumor volume predicted prognosis in IDH-mut astrocytomas only. The age cutoffs for determining high risk in patients with IDH-mut dLGG from the pre-molecular era are not supported by our results.
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| 5. |
- Chen, Dongfeng, et al.
(author)
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CD99 expression is strongly associated with clinical outcome in children with B-cell precursor acute lymphoblastic leukaemia
- 2019
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In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 184:3, s. 418-423
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Journal article (peer-reviewed)abstract
- Our study aimed to determine the expression pattern and clinical relevance of CD99 in paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). Our findings demonstrate that high expression levels of CD99 are mainly found in high-risk BCP-ALL, e.g. BCR-ABL1 and CRLF2 Re/Hi, and that high CD99 mRNA levels are strongly associated with a high frequency of relapse, high proportion of positive for minimal residual disease at day 29 and poor overall survival in paediatric cohorts, which indicate that CD99 is a potential biomarker for BCP-ALL.
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| 6. |
- Chen, Dongfeng, et al.
(author)
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The Expression Pattern of the Pre-B Cell Receptor Components Correlates with Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia.
- 2016
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 11:9
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Journal article (peer-reviewed)abstract
- Precursor-B cell receptor (pre-BCR) signaling represents a crucial checkpoint at the pre-B cell stage. Aberrant pre-BCR signaling is considered as a key factor for B-cell precursor acute lymphoblastic leukemia (BCP-ALL) development. BCP-ALL are believed to be arrested at the pre-BCR checkpoint independent of pre-BCR expression. However, the cellular stage at which BCP-ALL are arrested and whether this relates to expression of the pre-BCR components (IGHM, IGLL1 and VPREB1) is still unclear. Here, we show differential protein expression and copy number variation (CNV) patterns of the pre-BCR components in pediatric BCP-ALL. Moreover, analyzing six BCP-ALL data sets (n = 733), we demonstrate that TCF3-PBX1 ALL express high levels of IGHM, IGLL1 and VPREB1, and are arrested at the pre-B stage. By contrast, ETV6-RUNX1 ALL express low levels of IGHM or VPREB1, and are arrested at the pro-B stage. Irrespective of subtype, ALL with high levels of IGHM, IGLL1 and VPREB1 are arrested at the pre-B stage and correlate with good prognosis in high-risk pediatric BCP-ALL (n = 207). Our findings suggest that BCP-ALL are arrested at different cellular stages, which relates to the expression pattern of the pre-BCR components that could serve as prognostic markers for high-risk pediatric BCP-ALL patients.
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| 7. |
- Deland, Lily, et al.
(author)
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Discovery of a rare GKAP1-NTRK2 fusion in a pediatric low-grade glioma, leading to targeted treatment with TRK-inhibitor larotrectinib
- 2021
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In: Cancer Biology & Therapy. - : Taylor & Francis. - 1538-4047 .- 1555-8576. ; 22:3, s. 184-195
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Journal article (peer-reviewed)abstract
- Here we report a case of an 11-year-old girl with an inoperable tumor in the optic chiasm/hypothalamus, who experienced several tumor progressions despite three lines of chemotherapy treatment. Routine clinical examination classified the tumor as a BRAF-negative pilocytic astrocytoma. Copy-number variation profiling of fresh frozen tumor material identified two duplications in 9q21.32–33 leading to breakpoints within the GKAP1 and NTRK2 genes. RT-PCR Sanger sequencing revealed a GKAP1-NTRK2 exon 10–16 in-frame fusion, generating a putative fusion protein of 658 amino acids with a retained tyrosine kinase (TK) domain. Functional analysis by transient transfection of HEK293 cells showed the GKAP1-NTRK2 fusion protein to be activated through phosphorylation of the TK domain (Tyr705). Subsequently, downstream mediators of the MAPK- and PI3K-signaling pathways were upregulated in GKAP1-NTRK2 cells compared to NTRK2 wild-type; phosphorylated (p)ERK (3.6-fold), pAKT (1.8- fold), and pS6 ribosomal protein (1.4-fold). Following these findings, the patient was enrolled in a clinical trial and treated with the specific TRK-inhibitor larotrectinib, resulting in the arrest of tumor growth. The patient’s condition is currently stable and the quality of life has improved significantly. Our findings highlight the value of comprehensive clinical molecular screening of BRAF-negative pediatric low-grade gliomas, to reveal rare fusions serving as targets for precision therapy.
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| 8. |
- Deland, Lily, et al.
(author)
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Novel TPR::ROS1 Fusion Gene Activates MAPK, PI3K and JAK/STAT Signaling in an Infant-type Pediatric Glioma.
- 2022
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In: Cancer genomics & proteomics. - : Anticancer Research USA Inc.. - 1109-6535 .- 1790-6245. ; 19:6, s. 711-726
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Journal article (peer-reviewed)abstract
- Although fusion genes involving the proto-oncogene receptor tyrosine kinase ROS1 are rare in pediatric glioma, targeted therapies with small inhibitors are increasingly being approved for histology-agnostic fusion-positive solid tumors.Here, we present a 16-month-old boy, with a brain tumor in the third ventricle. The patient underwent complete resection but relapsed two years after diagnosis and underwent a second operation. The tumor was initially classified as a low-grade glioma (WHO grade 2); however, methylation profiling suggested the newly WHO-recognized type: infant-type hemispheric glioma. To further refine the molecular background, and search for druggable targets, whole genome (WGS) and whole transcriptome (RNA-Seq) sequencing was performed.Concomitant WGS and RNA-Seq analysis revealed several segmental gains and losses resulting in complex structural rearrangements and fusion genes. Among the top-candidates was a novel TPR::ROS1 fusion, for which only the 3' end of ROS1 was expressed in tumor tissue, indicating that wild type ROS1 is not normally expressed in the tissue of origin. Functional analysis by Western blot on protein lysates from transiently transfected HEK293 cells showed the TPR::ROS1 fusion gene to activate the MAPK-, PI3K- and JAK/STAT- pathways through increased phosphorylation of ERK, AKT, STAT and S6. The downstream pathway activation was also confirmed by immunohistochemistry on tumor tissue slides from the patient.We have mapped the activated oncogenic pathways of a novel ROS1-fusion gene and broadened the knowledge of the newly recognized infant-type glioma subtype. The finding facilitates suitable targeted therapies for the patient in case of relapse.
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| 9. |
- Fogelstrand, Linda, 1974, et al.
(author)
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Prognostic Implications of Mutations in NOTCH1 and FBXW7 in Childhood T-ALL Treated According to the NOPHO ALL-1992 and ALL-2000 Protocols
- 2014
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In: Pediatric Blood & Cancer. - : Wiley-Blackwell. - 1545-5009 .- 1545-5017. ; 61:3, s. 424-430
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Journal article (peer-reviewed)abstract
- Background In children, T-cell acute lymphoblastic leukemia (T-ALL) has inferior prognosis compared with B-cell precursor ALL. In order to improve survival, individualized treatment strategies and thus risk stratification algorithms are warranted, ideally already at the time of diagnosis.Procedure We analyzed the frequency and prognostic implication of mutations in NOTCH1 and FBXW7 in 79 cases of Swedish childhood T-ALL treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL-1992 and ALL-2000 protocols. In a subgroup of patients, we also investigated the functional relevance of NOTCH1 mutations measured as expression of the HES1, MYB, and MYC genes.Results Forty-seven of the cases (59%) displayed mutations in NOTCH1 and/or FBXW7. There was no difference in overall (P=0.14) or event-free survival (EFS) (P=0.10) in patients with T-ALL with mutation(s) in NOTCH1/FBXW7 compared with patients with T-ALL without mutations in any of these genes. T-ALL carrying NOTCH1 mutations had increased HES1 and MYB mRNA expression (HES1 9.21.9 (mean +/- SEM), MYB 8.7 +/- 0.8 (mean +/- SEM)) compared to T-ALL with wild-type NOTCH1 (HES1 1.8 +/- 0.7, MYB 5.1 +/- 1.2, P=0.02 and 0.008, respectively). In cases of T-ALL with high HES1 expression, improved overall (P=0.02) and EFS (P=0.028) was seen.Conclusions Increased NOTCH activity, reflected by increased HES1 expression, is associated with improved outcome in pediatric T-ALL, but its role as a diagnostic tool or a therapeutic target in future clinical treatment protocols remains to be elucidated. Pediatr Blood Cancer 2014;61:424-430. (c) 2013 Wiley Periodicals, Inc.
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| 12. |
- Olsson, Linda, et al.
(author)
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The clinical impact of IKZF1 deletions in paediatric B-cell precursor acute lymphoblastic leukaemia is independent of minimal residual disease stratification in Nordic Society for Paediatric Haematology and Oncology treatment protocols used between 1992 and 2013
- 2015
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In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 170:6, s. 847-858
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Journal article (peer-reviewed)abstract
- Paediatric B-cell precursor acute lymphoblastic leukaemias (BCP ALL) with IKZF1 deletions (IKZF1) are associated with a poor outcome. However, there are conflicting data as to whether IKZF1 is an independent risk factor if minimal residual disease (MRD) and other copy number alterations also are taken into account. We investigated 334 paediatric BCP ALL, diagnosed 1992-2013 and treated according to Nordic Society for Paediatric Haematology and Oncology ALL protocols, with known IKZF1 status based on either single nucleotide polymorphism array (N=218) or multiplex ligation-dependent probe amplification (N=116) analyses. IKZF1, found in 15%, was associated with inferior 10-year probabilities of event-free (60% vs. 83%; P<0001) and overall survival (pOS; 73% vs. 89%; P=0001). Adjusting for known risk factors, including white blood cell (WBC) count and MRD, IKZF1 was the strongest independent factor for relapse and death. IKZF1 was present in 27% of cases with non-informative cytogenetics (BCP-other') and a poor 10-year pOS was particularly pronounced in this group (58% vs. 90%; P<0001). Importantly, neither MRD nor WBC count predicted events in the IKZF1-positive cases. Co-occurrence of pseudoautosomal region 1 (PAR1) deletions in Xp22.33/Yp11.32 (P2RY8-CRLF2) and IKZF1 increased the risk of relapse (75% vs. 30% for cases with only IKZF1; P=0045), indicating that BCP-other ALL with both P2RY8-CRLF2 and IKZF1 constitutes a particularly high-risk group.
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| 13. |
- Paulsson, Kajsa, et al.
(author)
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The genomic landscape of high hyperdiploid childhood acute lymphoblastic leukemia
- 2015
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 47:6, s. 672-676
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Journal article (peer-reviewed)abstract
- High hyperdiploid (51-67 chromosomes) acute lymphoblastic leukemia (ALL) is one of the most common childhood malignancies, comprising 30% of all pediatric B cell-precursor ALL. Its characteristic genetic feature is the nonrandom gain of chromosomes X, 4, 6, 10, 14, 17, 18 and 21, with individual trisomies or tetrasomies being seen in over 75% of cases, but the pathogenesis remains poorly understood. We performed whole-genome sequencing (WGS) (n = 16) and/or whole-exome sequencing (WES) (n = 39) of diagnostic and remission samples from 51 cases of high hyperdiploid ALL to further define the genomic landscape of this malignancy. The majority of cases showed involvement of the RTK-RAS pathway and of histone modifiers. No recurrent fusion gene-forming rearrangement was found, and an analysis of mutations on trisomic chromosomes indicated that the chromosomal gains were early events, strengthening the notion that the high hyperdiploid pattern is the main driver event in this common pediatric malignancy.
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| 14. |
- Persson, Fredrik, 1973, et al.
(author)
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Characterization of the 12q amplicons by high-resolution, oligonucleotide array CGH and expression analyses of a novel liposarcoma cell line
- 2008
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In: Cancer Letters. - : Elsevier BV. - 0304-3835. ; 260:1-2, s. 37-47
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Journal article (peer-reviewed)abstract
- The cytogenetic hallmark of well-differentiated liposarcoma (WDLS) is a giant marker chromosomes containing amplified genes from chromosome 12q13-q15. Here, we have employed SKY and high-resolution 244K oligonucleotide array CGH to characterize rearrangements and amplifications in a new WDLS cell line (GOT3) with a giant marker chromosome derived from chromosomes 12, 1, and X. The most prominent amplifications included 144 genes in 12q11-q21.2, 201 genes in 1q23.3-q44, and six genes in 13q32.1-q32.2. In the 12q amplicons, MDM2 showed the highest level of amplification followed by LYZ, HMGA2 (5'-part), TSPAN8, CNOT2, YEATS4, CDK4, GNS, HELB, and TSFM. Expression analysis of genes from the three major amplicons revealed that several highly amplified potential target genes, including HMGA2, MDM2, YEATS4, CDK4, PKP1, IPO9, and SOX21, were strongly overexpressed. Studies of cell cycle controlling proteins that interact with CDK4 and MDM2 revealed an abnormally strong expression of cyclins D1 and E. The selective high-level amplification of the 5'-part of HMGA2, including the DNA-binding domains, suggests that this gene is a major target of amplifications in WDLS. Our results also identify several novel candidate genes of potential pathogenetic and therapeutic importance for WDLS.
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| 15. |
- Persson, Fredrik, 1973, et al.
(author)
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High-resolution genomic profiling of adenomas and carcinomas of the salivary glands reveals amplification, rearrangement, and fusion of HMGA2
- 2009
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In: Genes Chromosomes Cancer. - : Wiley. - 1098-2264 .- 1045-2257. ; 48:1, s. 69-82
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Journal article (peer-reviewed)abstract
- Carcinoma ex pleomorphic adenoma (Ca-ex-PA) is an epithelial malignancy developing within a benign salivary gland pleomorphic adenoma (PA). Here we have used genome-wide, high-resolution array-CGH, and fluorescence in situ hybridization to identify genes amplified in double min chromosomes and homogeneously staining regions in PA and Ca-ex-PA and to identify additional genomic imbalances characteristic of these tumor types. Ten of the 16 tumors analyzed showed amplification/gain of a 30-kb minimal common region, consisting of the 5'-part of HMGA2 (encoding the three DNA-binding domains). Coamplification of MDM2 was found in nine tumors. Five tumors had cryptic HMGA2-WIF1 gene fusions with amplification of the fusion oncogene in four tumors. Expression analysis of eight amplified candidate genes in 12q revealed that tumors with amplification/rearrangement of HMGA2 and MDM2 had significantly higher expression levels when compared with tumors without amplification. Analysis of individual HMGA2 exons showed that the expression of exons 3-5 were substantially reduced when compared with exons 1-2 in 9 of 10 tumors with HMGA2 activation, indicating that gene fusions and rearrangements of HMGA2 are common in tumors with amplification. In addition, recurrent amplifications/gains of 1q11-q32.1, 2p16.1-p12, 8q12.1, 8q22-24.1, and 20, and losses of 1p21.3-p21.1, 5q23.2-q31.2, 8p, 10q21.3, and 15q11.2 were identified. Collectively, our results identify HMGA2 and MDM2 as amplification targets in PA and Ca-ex-PA and suggest that amplification of 12q genes (in particular MDM2), deletions of 5q23.2-q31.2, gains of 8q12.1 (PLAG1) and 8q22.1-q24.1 (MYC), and amplification of ERBB2 may be of importance for malignant transformation of benign PA.
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| 16. |
- Sangskär, Heléne, 1980, et al.
(author)
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Safety, effectiveness, women's experience, and economic costs of outpatient induction in women with uncomplicated pregnancies: A systematic review and meta-analyses.
- 2022
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In: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - : Wiley. - 1879-3479. ; 161:2, s. 343-55
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Research review (peer-reviewed)abstract
- Induction of labor is increasing worldwide, and some countries have started to introduce outpatient induction in low-risk women.To assess current knowledge concerning the safety, efficacy, women's experience, and economic costs of outpatient induction compared with inpatient induction.Multiple databases were last searched on October 19, 2021. Studies were selected according to our pre-specified inclusion, selection, and exclusion criteria.PICO; P-women with low-risk pregnancy planned for induction of labor. I-Outpatient induction C-Inpatient induction O-Outcomes according to the core outcome set for induction of labor (COSIOL).Pooled in meta-analyses. The certainty of evidence was assessed using the GRADE system.The 20 included studies, including 7956 women, showed an overall low incidence of adverse events and indicated comparable results for inpatient and outpatient induction, but the studies were underpowered for safety-related outcomes. Women's experiences of outpatient induction were mostly positive. Based on three studies, the economic costs consequence is inconclusive.Due to early randomization, heterogenic study design, and underpowered studies regarding safety outcome, the certainty of evidence is very low. It is uncertain whether outpatient induction affects the risk for neonatal and maternal complications.
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| 19. |
- Sjögren, Torsten, et al.
(author)
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Analysis of strains in cast iron joints using finite element simulations and digital image correlation techniques
- 2012
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In: 70th World Foundry Congress 2012, WFC 2012. - 9781622763825 ; , s. 396-401
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Conference paper (peer-reviewed)abstract
- The Metalock method is a mechanical joining technique most commonly employed in cracked castings of iron, aluminum and steel. The marine diesel engine designer MAN Diesel & Turbo uses the Metalock method for crack patching in large cast iron components. The service life of these components can thereby be extended, reducing both replacement costs and environmental impact. The purpose of this study is to investigate the mechanical behavior of the Metalock method. This was studied by full scale testing, using a non-contact deformation measurement technique known as digital image correlation (DIC), of cast iron specimens joined together by the Metalock method. Furthermore, finite element (FE) simulations were performed, and verified by experimental results, in order to study the mechanical behavior in detail and to carry out a parametric study on some of the components included in the joint. Experimental tests show that using the DIC technique gives a good possibility to verify the strain-field achieved by FE simulations and improving the understanding of the Metalock joining technique.
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| 20. |
- Wikhager, Carina, et al.
(author)
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High-resolution copy number array in the molecular cytogenetic diagnostics of pediatric malignant hematological disorders.
- 2012
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In: Oncology reports. - : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 27:5, s. 1429-34
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Journal article (peer-reviewed)abstract
- The presence of genetic alterations was investigated by SNP array in combination with conventional and spectral karyotyping and fluorescence insitu hybridization analysis of 75 consecutive pediatric bone marrow samples. The samples were collected at diagnosis from all children diagnosed with malignant hematological disease between 2006 and 2010 at a single diagnostic center in Gothenburg, Sweden. Conventional cytogenetic and molecular genetics techniques are up to this date essential for the clinical laboratories but there is a need for higher resolution techniques in order to identify new genetic markers that eventually can improve the management of these disorders. Here, we conclude that the addition of SNP array-based karyotyping combined with conventional cytogenetics increase the diagnostic accuracy of pediatric hematological malignancies. The two techniques enhance the cytogenetic image and should not be contrasted as they meet distinct important roles. Since balanced translocations cannot be detected with the SNP arrays of today and tumor-specific translocations are very important diagnostic and prognostic indicators we suggest that SNP-based array is a valuable adjuvant tool in the cytogenetic diagnostics of pediatric leukemias but cannot replace currently used techniques, i.e. G-banding, SKY and FISH analysis.
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