| 1. |
- Birgersson, Madeleine, et al.
(author)
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Intestinal estrogen receptor beta modulates the tumor immune microenvironment in a mouse model of colitis-associated cancer
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Other publication (other academic/artistic)abstract
- Chronic inflammation promotes the development of colorectal cancer (CRC), as evidenced by patients with inflammatory bowel disease (IBD), and sex disparities are evident in CRC. The tumor microenvironment (TME) is composed of stromal cells and infiltrating immune cells that directly affect processes including antitumor immunity. We have previously shown that intestinal estrogen receptor beta (ERβ) protects against colitis and colitis-induced cancer (CAC) by modulating inflammatory signaling and that males are more sensitive to the induction of colitis and cancer. However, sex differences between tumors and the impact of ERβ the tumor immune microenvironment have not been investigated. In this study, we have analyzed colon samples from AOM/DSS-treated wild-type and ERβKOVil mice (that lack intestinal ERβ) and profiled the differences in the transcriptome and immune response to CAC on the basis of sex and ERβ expression. RNA-sequencing revealed differences in gene expression and enriched biological processes depending on sex and genotype, and the immune response to cancer appears altered between tumors from female WT and ERβKOVil mice. Immunostaining subsequently showed that tumors from ERβKOVil mice display significantly increased CD68+ macrophage infiltration, decreased CD3+ T cell infiltration, and, strikingly, impaired NK cell infiltration. Here, for the first time, we show that intestinal ERβ modulates the tumor immune microenvironment during CAC and that lack of intestinal ERβ appears to promote the formation of an immunosuppressive TME. Our findings indicate that activation of ERβ could be used to treat CRC, possibly together with immunotherapies, and provide a foundation for future studies investigating ERβ and immunity.
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| 2. |
- Holm, Astrid, et al.
(author)
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Cohort study of the characteristics and outcomes in patients with COVID-19 and in-hospital cardiac arrest
- 2021
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:11
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Journal article (peer-reviewed)abstract
- Objective We studied characteristics, survival, causes of cardiac arrest, conditions preceding cardiac arrest, predictors of survival and trends in the prevalence of COVID-19 among in-hospital cardiac arrest (IHCA) cases.Design and setting Registry-based observational study.Participants We studied all cases (>= 18 years of age) of IHCA receiving cardiopulmonary resuscitation in the Swedish Registry for Cardiopulmonary Resuscitation during 15 March 2020 to 31 December 2020. A total of 1613 patients were included and divided into the following groups: ongoing infection (COVID-19+; n=182), no infection (COVID-19-; n=1062) and unknown/not assessed (n=369).Main outcomes and measures We studied monthly trends in proportions of COVID-19 associated IHCAs, causes of IHCA in relation to COVID-19 status, clinical conditions preceding the cardiac arrest and predictors of survival.Results The rate of COVID-19+ patients suffering an IHCA increased to 23% during the first pandemic wave (April), then abated to 3% in July, and then increased to 19% during the second wave (December). Among COVID-19+ cases, 43% had respiratory insufficiency or infection as the underlying cause of the cardiac arrest, compared with 18% among COVID-19- cases. The most common clinical sign preceding cardiac arrest was hypoxia (57%) among COVID-19+ cases. OR for 30-day survival for COVID-19+ cases was 0.50 (95% CI 0.33 to 0.76), compared with COVID-19- cases.Conclusion During pandemic peaks, up to one-fourth of all IHCAs are complicated by COVID-19, and these patients have halved chance of survival, with women displaying the worst outcomes.
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| 3. |
- Holm, Matilda, et al.
(author)
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Detection of KRAS mutations in liquid biopsies from metastatic colorectal cancer patients using droplet digital PCR, Idylla, and next generation sequencing
- 2020
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:11
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Journal article (peer-reviewed)abstract
- Circulating tumor DNA (ctDNA) is released from cancer cells and oncogenic mutations in ctDNA can be measured from plasma samples. Droplet digital PCR (ddPCR) is a sensitive and specific method for the detection of mutations in ctDNA. We analyzed serial plasma samples (n = 80) from ten metastatic colorectal cancer (mCRC) patients with a known KRAS mutation in their primary tumor. The patients were undergoing oncological treatment with bevacizumab in combination with alternating capecitabine and oxaliplatin or irinotecan. Baseline ddPCR KRAS mutation allele frequency (MAF) values ranged from 0% to 63%. The first radiologic response evaluation criteria in solid tumors (RECIST) evaluation was performed 45-63 days after the initiation of treatment, and by this time three patients had an undetectable level of KRAS mutation, one had a MAF value of 0.5%, and one had a MAF value of 3% that had been reduced by 95% from the baseline value. In three of these patients the RECIST assessment was stable disease and in two partial response. In seven patients, ddPCR MAF values increased before radiological disease progression or death, while one patient remained disease-free with an undetectable KRAS mutation level. Next, we analyzed all available plasma samples with the Idylla ctKRAS system (n = 60), and found that the overall degree of agreement between ddPCR and Idylla was almost perfect (kappa value = 0.860). We used next-generation sequencing (NGS) to detect treatment-induced mutations in the last serial plasma sample of each patient, but were unable to find any new mutations when compared to the primary tumor. This study shows that ddPCR and Idylla are equally efficient for the detection of KRAS mutations in the liquid biopsies from mCRC patients and that ctDNA may indicate the disappearance of treatment responsive KRAS positive mCRC clones and serve as an early sign of disease progression.
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| 4. |
- Holm, Matilda, et al.
(author)
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Quantitative bile and serum proteomics for the screening and differential diagnosis of primary sclerosing cholangitis
- 2022
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:8
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Journal article (peer-reviewed)abstract
- Background Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by biliary strictures, cholestasis, and a markedly increased risk of cholangiocarcinoma. New markers for the screening and differential diagnosis of PSC are needed. In this pilot study, we have analyzed both the bile and serum proteomic profiles of 80 PSC patients and non-PSC controls (n = 6 for bile and n = 18 for serum). Aim The aim of this study was to discover candidates for new biomarkers for the differential diagnosis of PSC. Methods Bile and serum samples were processed and subsequently analyzed using ultra performance liquid chromatography-ultra definition mass spectrometry (UPLC-UDMSE). Further analysis included statistical analyses such as receiver operating characteristic curve analysis as well as pathway analysis using Ingenuity Pathway Analysis. Results and conclusions In bile, we discovered 64 proteins with significantly different levels between the groups, with fold changes of up to 129. In serum, we discovered 112 proteins with significantly different levels. Receiver operating characteristic curve analysis found multiple proteins with high area under the curve values, up to 0.942, indicating that these serum proteins are of value as new non-invasive classifiers of PSC. Pathway analysis revealed multiple canonical pathways that were enriched in the dataset, which have roles in bile homeostasis and metabolism. We present several serum proteins that could serve as new blood-based markers for the diagnosis of PSC after further validation. The measurement of serum levels of these proteins could be of use in the screening of patients with suspected PSC.
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| 5. |
- Holm, Sebastian, et al.
(author)
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Sociodemographic Patterns of Pediatric Patients in Specialized Burn Care in Sweden
- 2022
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In: Plastic and Reconstructive Surgery - Global Open. - : Ovid Technologies (Wolters Kluwer Health). - 2169-7574. ; 10:4
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Journal article (peer-reviewed)abstract
- Background: Trauma is a leading cause of mortality in children. Burns affect children disproportionally. Although burn incidence and mortality are decreasing, differences in the risk depend on socioeconomic status. The present study aimed to investigate the sociodemographic patterns of pediatric patients (0-17 years) managed at the two burn centers in Sweden. Uppsala, and Linkoping, between 2010 and 2020.Method: This retrospective register-based study used hospital records from the two burn centers combined with information front Statistics Sweden plus data regarding number of asylum seekers from the Swedish Migrations Agency. Choropleth maps representing the patients' geographical distribution were created. Information about income levels per geographic area was added. A Wilcoxon signed-rank test was performed to investigate differences in median income levels between the areas where the patients lived, related to Sweden's median income.Results: The study included 2455 patients. Most of the children aged below 5 years (76%) and were boys (60%). The mean percentage of total skin area was 4.2%. There was no significant increment or decrease in the incidence of pediatric burns during the study. Most patients with recorded zip codes lived in areas with an income level below the national median (n = 1974, 83%). Children with asylum status were over-represented compared with residents and/or Swedish citizens.Conclusions: In Sweden, most pediatric burns occur in families that live in areas with low-income levels. Pediatric burns affect children with asylum status disproportionally compared with those who are residents in and/or citizens of Sweden. Prevention strategies should be designed and implemented to alleviate this health inequity.
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| 6. |
- Holm, Sebastian, 1993-, et al.
(author)
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Sociodemographic Patterns of Pediatric Patients in Specialized Burn Care in Sweden
- 2022
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In: Plastic and Reconstructive Surgery - Global Open. - : Lippincott Williams & Wilkins. - 2169-7574. ; 10:4
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Journal article (peer-reviewed)abstract
- Background: Trauma is a leading cause of mortality in children. Burns affect children disproportionally. Although burn incidence and mortality are decreasing, differences in the risk depend on socioeconomic status. The present study aimed to investigate the sociodemographic patterns of pediatric patients (0-17 years) managed at the two burn centers in Sweden, Uppsala, and Linköping, between 2010 and 2020.Method: This retrospective register-based study used hospital records from the two burn centers combined with information from Statistics Sweden plus data regarding number of asylum seekers from the Swedish Migrations Agency. Choropleth maps representing the patients' geographical distribution were created. Information about income levels per geographic area was added. A Wilcoxon signed-rank test was performed to investigate differences in median income levels between the areas where the patients lived, related to Sweden's median income.Results: The study included 2455 patients. Most of the children aged below 5 years (76%) and were boys (60%). The mean percentage of total skin area was 4.2%. There was no significant increment or decrease in the incidence of pediatric burns during the study. Most patients with recorded zip codes lived in areas with an income level below the national median (n = 1974, 83%). Children with asylum status were over-represented compared with residents and/or Swedish citizens.Conclusions: In Sweden, most pediatric burns occur in families that live in areas with low-income levels. Pediatric burns affect children with asylum status disproportionally compared with those who are residents in and/or citizens of Sweden. Prevention strategies should be designed and implemented to alleviate this health inequity.
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| 7. |
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| 8. |
- Lindegaard, Tomas, et al.
(author)
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Experiences of internet-based cognitive behavioural therapy for depression and anxiety among Arabic-speaking individuals in Sweden : a qualitative study
- 2021
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In: BMC Psychiatry. - : BMC. - 1471-244X. ; 21:1
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Journal article (peer-reviewed)abstract
- BackgroundInternet-delivered cognitive behavioural therapy (ICBT) is a promising treatment for refugee and immigrant populations suffering from common mental disorders. The aim of the present study was to investigate experiences of participating in a guided ICBT program among resettled Arabic-speaking individuals suffering from symptoms of anxiety and depression.MethodsTen individuals who had previously received ICBT consented to participate and were interviewed using semi-structured telephone interviews. The interviews were conducted 10months after treatment termination. Data were transcribed and analysed using a Thematic Analysis framework.ResultsThe Thematic Analysis resulted in five overarching themes 1) The importance of being seen, 2) New ways of knowing and doing, 3) Treatment format not for everyone, 4) Changing attitudes towards mental health and help-seeking and 5) The healthcare system as a complex puzzle. Participants described varying levels of success in applying the new information learned from the treatment in their everyday lives. The results also indicate that participation in the ICBT program to some extent mitigated mental health stigma and acted as a precursor to other forms of treatment seeking.ConclusionsThe findings in the present study are largely in line with previous qualitative research studies on ICBT participants. Future research should investigate whether a more explicit focus on refugee-specific stressors and barriers to treatment engagement and implementation can increase adherence to ICBT programs in this population.
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| 9. |
- Ukkola, Iiris, et al.
(author)
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N-Glycomic Profiling of Microsatellite Unstable Colorectal Cancer
- 2023
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In: Cancers. - : MDPI AG. - 2072-6694. ; 15:14
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Journal article (peer-reviewed)abstract
- Simple Summary All human cells possess a complex glycan coating, and alterations in cell surface glycans play a role in cancer progression and immune suppression. Colorectal cancer is a heterogenous disease that can be classified into several molecular subtypes, with major variances in prognosis and therapy responses. Two important molecular markers in this regard are microsatellite instability and BRAF gene mutation, which have been largely ignored in previous glycomics studies. We analyzed the N-glycan profiles of local and advanced colorectal cancers consisting of different molecular subtypes to identify possible explanations for their differing behaviors. Our results show that the studied molecular subgroups of colorectal cancer exhibit characteristic glycan profiles, which may explain their tumorigenic properties. Aberrant glycosylation affects cancer progression and immune evasion. Approximately 15% of colorectal cancers (CRCs) demonstrate microsatellite instability (MSI) and display major differences in outcomes and therapeutic responses, as compared to corresponding microsatellite stable (MSS) tumors. We compared the N-glycan profiles of stage II and IV MSI CRC tumors, further subdivided into BRAF(V600E) wild-type and mutated subgroups (n = 10 in each subgroup), with each other and with those of paired non-neoplastic mucosal samples using mass spectrometry. Further, the N-glycans of BRAF(V600E) wild-type stage II MSI tumors were compared to corresponding MSS tumors (n = 9). Multiple differences in N-glycan profiles were identified between the MSI CRCs and control tissues, as well as between the stage II MSI and MSS samples. The MSI CRC tumors showed a lower relative abundance of high-mannose N-glycans than did the control tissues or the MSS CRCs. Among MSI CRC subgroups, acidic N-glycans showed tumor stage and BRAF mutation status-dependent variation. Specifically, the large, sulfated/phosphorylated, and putative terminal N-acetylhexosamine-containing acidic N-glycans differed between the MSI CRC subgroups, showing opposite changes in stages II and IV, when comparing BRAF mutated and wild-type tumors. Our results show that molecular subgroups of CRC exhibit characteristic glycan profiles that may explain certain carcinogenic properties of MSI tumors.
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| 10. |
- Zhang, Leiting, et al.
(author)
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Reversible Hydration Enabling High-Rate Aqueous Li-Ion Batteries
- 2024
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In: ACS Energy Letters. - : American Chemical Society (ACS). - 2380-8195. ; 9, s. 959-966
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Journal article (peer-reviewed)abstract
- Layered TiS2 has been proposed as a versatile host material for various battery chemistries. Nevertheless, its compatibility with aqueous electrolytes has not been thoroughly understood. Herein, we report on a reversible hydration process to account for the electrochemical activity and structural evolution of TiS2 in a relatively dilute electrolyte for sustainable aqueous Li-ion batteries. Solvated water molecules intercalate in TiS2 layers together with Li+ cations, forming a hydrated phase with a nominal formula unit of Li0.38(H2O)2−δTiS2 as the end-product. We unambiguously confirm the presence of two layers of intercalated water by complementary electrochemical cycling, operando structural characterization, and computational simulation. Such a process is fast and reversible, delivering 60 mAh g–1 discharge capacity at a current density of 1250 mA g–1. Our work provides further design principles for high-rate aqueous Li-ion batteries based on reversible water cointercalation.
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