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1.	Klionsky, Daniel J, et al. (författare) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). 2016 Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 12:1, s. 1-222 Tidskriftsartikel (refereegranskat)
2.	Huyghe, Jeroen R., et al. (författare) Discovery of common and rare genetic risk variants for colorectal cancer 2019 Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76- Tidskriftsartikel (refereegranskat)abstract To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
3.	Razavi, Homie A., et al. (författare) Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries 2023 Ingår i: JOURNAL OF HEPATOLOGY. - : Elsevier. - 0168-8278 .- 1600-0641. ; 79:2, s. 576-580 Tidskriftsartikel (refereegranskat)abstract Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV in-fections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Ac-curate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This re-quires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive in-dividuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.
4.	Razavi-Shearer, Devin M., et al. (författare) Adjusted estimate of the prevalence of hepatitis delta virus in 25 countries and territories 2024 Ingår i: JOURNAL OF HEPATOLOGY. - 0168-8278 .- 1600-0641. ; 80:2, s. 232-242 Tidskriftsartikel (refereegranskat)abstract Background & Aims: Hepatitis delta virus (HDV) is a satellite RNA virus that requires the hepatitis B virus (HBV) for assembly and propagation. Individuals infected with HDV progress to advanced liver disease faster than HBV-monoinfected individuals. Recent studies have estimated the global prevalence of anti-HDV antibodies among the HBV-infected population to be 5-15%. This study aimed to better understand HDV prevalence at the population level in 25 countries/territories. Methods: We conducted a literature review to determine the prevalence of anti-HDV and HDV RNA in hepatitis B surface antigen (HBsAg)-positive individuals in 25 countries/territories. Virtual meetings were held with experts from each setting to discuss the findings and collect unpublished data. Data were weighted for patient segments and regional heterogeneity to estimate the prevalence in the HBV-infected population. The findings were then combined with The Polaris Observatory HBV data to estimate the anti-HDV and HDV RNA prevalence in each country/territory at the population level. Results: After adjusting for geographical distribution, disease stage and special populations, the anti-HDV prevalence among the HBsAg+ population changed from the literature estimate in 19 countries. The highest anti-HDV prevalence was 60.1% in Mongolia. Once adjusted for the size of the HBsAg+ population and HDV RNA positivity rate, China had the highest absolute number of HDV RNA+ cases. Conclusions: We found substantially lower HDV prevalence than previously reported, as prior meta-analyses primarily focused on studies conducted in groups/regions that have a higher probability of HBV infection: tertiary care centers, specific risk groups or geographical regions. There is large uncertainty in HDV prevalence estimates. The implementation of reflex testing would improve estimates, while also allowing earlier linkage to care for HDV RNA+ individuals. The logistical and economic burden of reflex testing on the health system would be limited, as only HBsAg+ cases would be screened.
5.	Amare, Azmeraw T, et al. (författare) Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder. 2023 Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261 Tidskriftsartikel (refereegranskat)abstract Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
6.	Hou, Liping, et al. (författare) Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study. 2016 Ingår i: Lancet (London, England). - 1474-547X. ; 387:10023, s. 1085-1093 Tidskriftsartikel (refereegranskat)abstract Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified.
7.	Hou, Liping, et al. (författare) Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder. 2016 Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94 Tidskriftsartikel (refereegranskat)abstract Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p=5.87×10(-9); odds ratio=1.12) and markers within ERBB2 (rs2517959, p=4.53×10(-9); odds ratio=1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
8.	Amare, Azmeraw T, et al. (författare) Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study. 2018 Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 65-74 Tidskriftsartikel (refereegranskat)abstract Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association.A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017.Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained.Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P<5×10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
9.	Cearns, Micah, et al. (författare) Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach - CORRIGENDUM. 2022 Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 221:2 Tidskriftsartikel (refereegranskat)
10.	Coombes, Brandon J, et al. (författare) Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study. 2021 Ingår i: Complex psychiatry. - : S. Karger AG. - 2673-3005 .- 2673-298X. ; 7:3-4, s. 80-89 Tidskriftsartikel (refereegranskat)abstract Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = -0.14; 95% confidence interval [CI]: -0.24 to -0.03; p value = 0.010) and MDD (β = -0.16; 95% CI: -0.27 to -0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34-1.93; p value = 2e-7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.
11.	Herrera-Rivero, Marisol, et al. (författare) Exploring the genetics of lithium response in bipolar disorders. 2023 Ingår i: Research square. Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
12.	Ou, Anna H., et al. (författare) Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study 2024 Ingår i: TRANSLATIONAL PSYCHIATRY. - 2158-3188. ; 14:1 Tidskriftsartikel (refereegranskat)abstract Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
13.	Whittaker, Jackie L., et al. (författare) OPTIKNEE 2022 : Consensus recommendations to optimise knee health after traumatic knee injury to prevent osteoarthritis 2022 Ingår i: British journal of sports medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 56:24, s. 1393-1405 Tidskriftsartikel (refereegranskat)abstract The goal of the OPTIKNEE consensus is to improve knee and overall health, to prevent osteoarthritis (OA) after a traumatic knee injury. The consensus followed a seven-step hybrid process. Expert groups conducted 7 systematic reviews to synthesise the current evidence and inform recommendations on the burden of knee injuries; risk factors for post-traumatic knee OA; rehabilitation to prevent post-traumatic knee OA; and patient-reported outcomes, muscle function and functional performance tests to monitor people at risk of post-traumatic knee OA. Draft consensus definitions, and clinical and research recommendations were generated, iteratively refined, and discussed at 6, tri-weekly, 2-hour videoconferencing meetings. After each meeting, items were finalised before the expert group (n=36) rated the level of appropriateness for each using a 9-point Likert scale, and recorded dissenting viewpoints through an anonymous online survey. Seven definitions, and 8 clinical recommendations (who to target, what to target and when, rehabilitation approach and interventions, what outcomes to monitor and how) and 6 research recommendations (research priorities, study design considerations, what outcomes to monitor and how) were voted on. All definitions and recommendations were rated appropriate (median appropriateness scores of 7-9) except for two subcomponents of one clinical recommendation, which were rated uncertain (median appropriateness score of 4.5-5.5). Varying levels of evidence supported each recommendation. Clinicians, patients, researchers and other stakeholders may use the definitions and recommendations to advocate for, guide, develop, test and implement person-centred evidence-based rehabilitation programmes following traumatic knee injury, and facilitate data synthesis to reduce the burden of knee post-traumatic knee OA.
14.	Kalman, Janos L, et al. (författare) Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study. 2019 Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75 Tidskriftsartikel (refereegranskat)abstract Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
15.	Watson, Hunna J., et al. (författare) Common Genetic Variation and Age of Onset of Anorexia Nervosa 2022 Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
16.	Kehoe, Laura, et al. (författare) Make EU trade with Brazil sustainable 2019 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341- Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
17.	Minoia, F, et al. (författare) Clinical features, treatment, and outcome of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a multinational, multicenter study of 362 patients 2014 Ingår i: Arthritis & rheumatology (Hoboken, N.J.). - : Wiley. - 2326-5205 .- 2326-5191. ; 66:11, s. 3160-3169 Tidskriftsartikel (refereegranskat)
18.	Pastor-Marazuela, Ines, et al. (författare) Chromatic periodic activity down to 120 megahertz in a fast radio burst 2021 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 596:7873, s. 505-508 Tidskriftsartikel (refereegranskat)abstract Fast radio bursts (FRBs) are extragalactic astrophysical transients(1) whose brightness requires emitters that are highly energetic yet compact enough to produce the short, millisecond-duration bursts. FRBs have thus far been detected at frequencies from 8 gigahertz (ref. (2)) down to 300 megahertz (ref. (3)), but lower-frequency emission has remained elusive. Some FRBs repeat(4-6), and one of the most frequently detected, FRB 20180916B(7), has a periodicity cycle of 16.35 days (ref. (8)). Using simultaneous radio data spanning a wide range of wavelengths (a factor of more than 10), here we show that FRB 20180916B emits down to 120 megahertz, and that its activity window is frequency dependent (that is, chromatic). The window is both narrower and earlier at higher frequencies. Binary wind interaction models predict a wider window at higher frequencies, the opposite of our observations. Our full-cycle coverage shows that the 16.3-day periodicity is not aliased. We establish that low-frequency FRB emission can escape the local medium. For bursts of the same fluence, FRB 20180916B is more active below 200 megahertz than at 1.4 gigahertz. Combining our results with previous upper limits on the all-sky FRB rate at 150 megahertz, we find there are 3-450 FRBs in the sky per day above 50 Jy ms. Our chromatic results strongly disfavour scenarios in which absorption from strong stellar winds causes FRB periodicity. We demonstrate that some FRBs are found in 'clean' environments that do not absorb or scatter low-frequency radiation. The fast radio burst FRB 20180916B repeats with a periodicity of 16 days, and is now found to emit down to a frequency of 120 MHz, much lower than previously observed.
19.	Ruperto, N., et al. (författare) The Pediatric Rheumatology International Trials Organization/American College of Rheumatology provisional criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus : prospective validation of the definition of improvement 2006 Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 55:3, s. 355-363 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: To use the Pediatric Rheumatology International Trials Organization (PRINTO) core set of outcome measures to develop a validated definition of improvement for the evaluation of response to therapy in juvenile systemic lupus erythematosus (SLE).METHODS: Thirty-seven experienced pediatric rheumatologists from 27 countries, each of whom had specific experience in the assessment of juvenile SLE patients, achieved consensus on 128 patient profiles as being clinically improved or not improved. Using the physicians' consensus ratings as the gold standard measure, the chi-square, sensitivity, specificity, false-positive and false-negative rates, area under the receiver operating characteristic curve, and kappa level of agreement for 597 candidate definitions of improvement were calculated. Only definitions with a kappa value greater than 0.7 were retained. The top definitions were selected based on the product of the content validity score multiplied by its kappa statistic.RESULTS: The definition of improvement with the highest final score was at least 50% improvement from baseline in any 2 of the 5 core set measures, with no more than 1 of the remaining worsening by more than 30%.CONCLUSION: PRINTO proposes a valid and reproducible definition of improvement that reflects well the consensus rating of experienced clinicians and that incorporates clinically meaningful change in core set measures in a composite end point for the evaluation of global response to therapy in patients with juvenile SLE. The definition is now proposed for use in juvenile SLE clinical trials and may help physicians to decide whether a child with SLE responded adequately to therapy.
20.	Carrick, Richard T., et al. (författare) Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe 2024 Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. Tidskriftsartikel (refereegranskat)abstract Background and Aims Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC.Methods This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed.Results One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans.Conclusions North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.
21.	Davi, S, et al. (författare) Clinical and Therapeutic Features of 312 Patients with Macrophage Activation Syndrome Enrolled in a Multinational Survey 2012 Ingår i: ARTHRITIS AND RHEUMATISM. - 0004-3591. ; 64:10, s. S500-S501 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
22.	Gasman, Danny, et al. (författare) MINDS Abundant water and varying C/O across the disk of Sz 98 as seen by JWST/MIRI 2023 Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 679 Tidskriftsartikel (refereegranskat)abstract Context. The Mid-InfraRed Instrument (MIRI) Medium Resolution Spectrometer (MRS) on board the James Webb Space Telescope (JWST) allows us to probe the inner regions of protoplanetary disks, where the elevated temperatures result in an active chemistry and where the gas composition may dictate the composition of planets forming in this region. The disk around the classical T Tauri star Sz 98, which has an unusually large dust disk in the millimetre with a compact core, was observed with the MRS, and we examine its spectrum here.Aims. We aim to explain the observations and put the disk of Sz 98 in context with other disks, with a focus on the H2O emission through both its ro-vibrational and pure rotational emission. Furthermore, we compare our chemical findings with those obtained for the outer disk from Atacama Large Millimeter/submillimeter Array (ALMA) observations.Methods. In order to model the molecular features in the spectrum, the continuum was subtracted and local thermodynamic equilibrium (LTE) slab models were fitted. The spectrum was divided into different wavelength regions corresponding to H2O lines of different excitation conditions, and the slab model fits were performed individually per region.Results. We confidently detect CO, H2O, OH, CO2, and HCN in the emitting layers. Despite the plethora of H2O lines, the isotopo-logue (H2O)-O-18 is not detected. Additionally, no other organics, including C2H2, are detected. This indicates that the C/O ratio could be substantially below unity, in contrast with the outer disk. The H2O emission traces a large radial disk surface region, as evidenced by the gradually changing excitation temperatures and emitting radii. Additionally, the OH and CO2 emission is relatively weak. It is likely that H2O is not significantly photodissociated, either due to self-shielding against the stellar irradiation, or UV shielding from small dust particles. While H2O is prominent and OH is relatively weak, the line fluxes in the inner disk of Sz 98 are not outliers compared to other disks.Conclusions. The relative emitting strength of the different identified molecular features points towards UV shielding of H2O in the inner disk of Sz 98, with a thin layer of OH on top. The majority of the organic molecules are either hidden below the dust continuum, or not present. In general, the inferred composition points to a sub-solar C/O ratio (<0.5) in the inner disk, in contrast with the larger than unity C/O ratio in the gas in the outer disk found with ALMA.
23.	Gasperetti, Alessio, et al. (författare) Programmed Ventricular Stimulation as an Additional Primary Prevention Risk Stratification Tool in Arrhythmogenic Right Ventricular Cardiomyopathy : A Multinational Study 2022 Ingår i: Circulation. - : Lippincott, Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 146:19, s. 1434-1443 Tidskriftsartikel (refereegranskat)abstract Background: A novel risk calculator based on clinical characteristics and noninvasive tests that predicts the onset of clinical sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been proposed and validated by recent studies. It remains unknown whether programmed ventricular stimulation (PVS) provides additional prognostic value. Methods: All patients with a definite ARVC diagnosis, no history of sustained VAs at diagnosis, and PVS performed at baseline were extracted from 6 international ARVC registries. The calculator-predicted risk for sustained VA (sustained or implantable cardioverter defibrillator treated ventricular tachycardia [VT] or fibrillation, [aborted] sudden cardiac arrest) was assessed in all patients. Independent and combined performance of the risk calculator and PVS on sustained VA were assessed during a 5-year follow-up period. Results: Two hundred eighty-eight patients (41.0±14.5 years, 55.9% male, right ventricular ejection fraction 42.5±11.1%) were enrolled. At PVS, 137 (47.6%) patients had inducible ventricular tachycardia. During a median of 5.31 [2.89-10.17] years of follow-up, 83 (60.6%) patients with a positive PVS and 37 (24.5%) with a negative PVS experienced sustained VA (P<0.001). Inducible ventricular tachycardia predicted clinical sustained VA during the 5-year follow-up and remained an independent predictor after accounting for the calculator-predicted risk (HR, 2.52 [1.58-4.02]; P<0.001). Compared with ARVC risk calculator predictions in isolation (C-statistic 0.72), addition of PVS inducibility showed improved prediction of VA events (C-statistic 0.75; log-likelihood ratio for nested models, P<0.001). PVS inducibility had a 76% [67-84] sensitivity and 68% [61-74] specificity, corresponding to log-likelihood ratios of 2.3 and 0.36 for inducible (likelihood ratio+) and noninducible (likelihood ratio-) patients, respectively. In patients with a ARVC risk calculator-predicted risk of clinical VA events <25% during 5 years (ie, low/intermediate subgroup), PVS had a 92.6% negative predictive value. Conclusions: PVS significantly improved risk stratification above and beyond the calculator-predicted risk of VA in a primary prevention cohort of patients with ARVC, mainly for patients considered to be at low and intermediate risk by the clinical risk calculator.
24.	Holm, Patur M., et al. (författare) The Effects of Different Management Strategies or Rehabilitation Approaches on Knee Joint Structural and Molecular Biomarkers Following Traumatic Knee Injury : A Systematic Review of Randomized Controlled Trials for the OPTIKNEE Consensus 2023 Ingår i: Journal of Orthopaedic and Sports Physical Therapy. - : Journal of Orthopaedic & Sports Physical Therapy (JOSPT). - 0190-6011 .- 1938-1344. ; 53:4, s. 172-193 Forskningsöversikt (refereegranskat)abstract OBJECTIVE: To summarize the effectiveness of management strategies and rehabilitation approaches for knee joint structural and molecular biomarker outcomes following anterior cruciate ligament (ACL) and/or meniscal tear. DESIGN: Intervention systematic review. LITERATURE SEARCH: We searched the MEDLINE, Embase, CINAHL, CENTRAL, and SPORTDiscus databases from their inception up to November 3, 2021. STUDY SELECTION CRITERIA: We included randomized controlled trials (RCTs) investigating the effectiveness of management strategies or rehabilitation approaches for structural/molecular biomarkers of knee joint health following ACL and/or meniscal tear. DATA SYNTHESIS: We included 5 RCTs (9 papers) with primary ACL tear (n = 365). Two RCTs compared initial management strategies (rehabilitation plus early vs optional delayed ACL surgery), reporting on structural biomarkers (radiographic osteoarthritis, cartilage thickness, meniscal damage) in 5 papers and molecular biomarkers (inflammation, cartilage turnover) in 1 paper. Three RCTs compared different post-ACL reconstruction (ACLR) rehabilitation approaches (high vs low intensity plyometric exercises, accelerated vs nonaccelerated rehabilitation, continuous passive vs active motion), reporting on structural biomarkers (joint space narrowing) in 1 paper and molecular biomarkers (inflammation, cartilage turnover) in 2 papers. RESULTS: There were no differences in structural or molecular biomarkers between post-ACLR rehabilitation approaches. One RCT comparing initial management strategies demonstrated that rehabilitation plus early ACLR was associated with greater patellofemoral cartilage thinning, elevated inflammatory cytokine response, and reduced incidence of medial meniscal damage over 5 years compared to rehabilitation with no/delayed ACLR. CONCLUSION: Very low-certainty evidence suggests that different initial management strategies (rehabilitation plus early vs optional delayed ACL surgery) but not postoperative rehabilitation approaches may influence the incidence of meniscal damage, patellofemoral cartilage loss and cytokine concentrations over 5 years post-ACL tear.
25.	Kamp, Inga, et al. (författare) The chemical inventory of the inner regions of planet-forming disks - the JWST/MINDS program 2023 Ingår i: Faraday discussions. - 1359-6640 .- 1364-5498. ; 245, s. 112-137 Tidskriftsartikel (refereegranskat)abstract The understanding of planet formation has changed recently, embracing the new idea of pebble accretion. This means that the influx of pebbles from the outer regions of planet-forming disks to their inner zones could determine the composition of planets and their atmospheres. The solid and molecular components delivered to the planet-forming region can be best characterized by mid-infrared spectroscopy. With Spitzer low-resolution (R = 100, 600) spectroscopy, this approach was limited to the detection of abundant molecules, such as H2O, C2H2, HCN and CO2. This contribution will present the first results of the MINDS (MIRI mid-INfrared Disk Survey, PI:Th Henning) project. Due do the sensitivity and spectral resolution provided by the James Webb Space Telescope (JWST), we now have a unique tool to obtain the full inventory of chemistry in the inner disks of solar-type stars and brown dwarfs, including also less-abundant hydrocarbons and isotopologues. The Integral Field Unit (IFU) capabilities will enable at the same time spatial studies of the continuum and line emission in extended sources such as debris disks, the flying saucer and also the search for mid-IR signatures of forming planets in systems such as PDS 70. These JWST observations are complementary to ALMA and NOEMA observations of outer-disk chemistry; together these datasets will provide an integral view of the processes occurring during the planet-formation phase.
26.	Markt, Sarah C., et al. (författare) ABO Blood Group Alleles and Prostate Cancer Risk : results from the Breast and Prostate Cancer Cohort Consortium (BPC3) 2015 Ingår i: The Prostate. - : John Wiley & Sons. - 0270-4137 .- 1097-0045. ; 75:15, s. 1677-1681 Tidskriftsartikel (refereegranskat)abstract BACKGROUND. ABO blood group has been associated with risk of cancers of the pancreas, stomach, ovary, kidney, and skin, but has not been evaluated in relation to risk of aggressive prostate cancer. METHODS. We used three single nucleotide polymorphisms (SNPs) (rs8176746, rs505922, and rs8176704) to determine ABO genotype in 2,774 aggressive prostate cancer cases and 4,443 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). Unconditional logistic regression was used to calculate age and study-adjusted odds ratios and 95% confidence intervals for the association between blood type, genotype, and risk of aggressive prostate cancer (Gleason score >= 8 or locally advanced/metastatic disease (stage T3/T4/N1/M1). RESULTS. We found no association between ABO blood type and risk of aggressive prostate cancer (Type A: OR = 0.97, 95% CI = 0.87-1.08; Type B: OR = 0.92, 95% CI = n0.77-1.09; Type AB: OR = 1.25, 95% CI = 0.98-1.59, compared to Type O, respectively). Similarly, there was no association between "dose" of A or B alleles and aggressive prostate cancer risk. CONCLUSIONS. ABO blood type was not associated with risk of aggressive prostate cancer. Prostate 75: 1677-1681, 2015. (C) 2015 Wiley Periodicals, Inc.
27.	Morger, Jennifer, et al. (författare) Distinct haplotype structure at the innate immune receptor Toll-like receptor 2 across bank vole populations and lineages in Europe 2015 Ingår i: Biological Journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4066. ; 116:1, s. 124-133 Tidskriftsartikel (refereegranskat)abstract Parasite-mediated selection may contribute to the maintenance of genetic variation at host immune genes over long time scales. To date, the best evidence for the long-term maintenance of immunogenetic variation in natural populations comes from studies on the major histocompatibility complex (MHC) genes, whereas evidence for such processes from other immune genes remains scarce. In the present study, we show that, despite pronounced population differentiation and the occurrence of numerous private alleles within populations, the innate immune gene Toll-like receptor 2 (TLR2) displays a distinct haplotype structure in 21 bank vole (Myodes glareolus) populations across Europe. Haplotypes from all populations grouped in four clearly differentiated clusters, with the three main clusters co-occurring in at least three previously described mitochondrial lineages. This pattern indicates that the distinct TLR2 haplotype structure may precede the split of the mitochondrial lineages 0.19-0.56Mya and suggests that haplotype clusters at this innate immune receptor are maintained over prolonged time in wild bank vole populations.
28.	Quadri, Marialuisa, et al. (författare) LRP10 genetic variants in familial Parkinson's disease and dementia with Lewy bodies : a genome-wide linkage and sequencing study 2018 Ingår i: The Lancet Neurology. - 1474-4422. ; 17:7, s. 597-608 Tidskriftsartikel (refereegranskat)abstract Background: Most patients with Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies do not carry mutations in known disease-causing genes. The aim of this study was to identify a novel gene implicated in the development of these disorders. Methods: Our study was done in three stages. First, we did genome-wide linkage analysis of an Italian family with dominantly inherited Parkinson's disease to identify the disease locus. Second, we sequenced the candidate gene in an international multicentre series of unrelated probands who were diagnosed either clinically or pathologically with Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. As a control, we used gene sequencing data from individuals with abdominal aortic aneurysms (who were not examined neurologically). Third, we enrolled an independent series of patients diagnosed clinically with Parkinson's disease and controls with no signs or family history of Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies from centres in Portugal, Sardinia, and Taiwan, and screened them for specific variants. We also did mRNA and brain pathology studies in three patients from the international multicentre series carrying disease-associated variants, and we did functional protein studies in in-vitro models, including neurons from induced pluripotent stem-like cells. Findings: Molecular studies were done between Jan 1, 2008, and Dec 31, 2017. In the initial kindred of ten affected Italian individuals (mean age of disease onset 59·8 years [SD 8·7]), we detected significant linkage of Parkinson's disease to chromosome 14 and nominated LRP10 as the disease-causing gene. Among the international series of 660 probands, we identified eight individuals (four with Parkinson's disease, two with Parkinson's disease dementia, and two with dementia with Lewy bodies) who carried different, rare, potentially pathogenic LRP10 variants; one carrier was found among 645 controls with abdominal aortic aneurysms. In the independent series, two of these eight variants were detected in three additional Parkinson's disease probands (two from Sardinia and one from Taiwan) but in none of the controls. Of the 11 probands from the international and independent cohorts with LRP10 variants, ten had a positive family history of disease and DNA was available from ten affected relatives (in seven of these families). The LRP10 variants were present in nine of these ten relatives, providing independent—albeit limited—evidence of co-segregation with disease. Post-mortem studies in three patients carrying distinct LRP10 variants showed severe Lewy body pathology. Of nine variants identified in total (one in the initial family and eight in stage 2), three severely affected LRP10 expression and mRNA stability (1424+5delG, 1424+5G→A, and Ala212Serfs*17, shown by cDNA analysis), four affected protein stability (Tyr307Asn, Gly603Arg, Arg235Cys, and Pro699Ser, shown by cycloheximide-chase experiments), and two affected protein localisation (Asn517del and Arg533Leu; shown by immunocytochemistry), pointing to loss of LRP10 function as a common pathogenic mechanism. Interpretation: Our findings implicate LRP10 gene defects in the development of inherited forms of α-synucleinopathies. Future elucidation of the function of the LRP10 protein and pathways could offer novel insights into mechanisms, biomarkers, and therapeutic targets. Funding: Stichting ParkinsonFonds, Dorpmans-Wigmans Stichting, Erasmus Medical Center, ZonMw—Memorabel programme, EU Joint Programme Neurodegenerative Disease Research (JPND), Parkinson's UK, Avtal om Läkarutbildning och Forskning (ALF) and Parkinsonfonden (Sweden), Lijf and Leven foundation, and cross-border grant of Alzheimer Netherlands–Ligue Européene Contre la Maladie d'Alzheimer (LECMA).
29.	Schwarz, Kamber R., et al. (författare) MINDS. JWST/MIRI Reveals a Dynamic Gas-rich Inner Disk inside the Cavity of SY Cha 2024 Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 962:1 Tidskriftsartikel (refereegranskat)abstract SY Cha is a T Tauri star surrounded by a protoplanetary disk with a large cavity seen in the millimeter continuum but has the spectral energy distribution of a full disk. Here we report the first results from JWST/Mid-InfraRed Instrument (MIRI) Medium Resolution Spectrometer (MRS) observations taken as part of the MIRI mid-INfrared Disk Survey (MINDS) GTO Program. The much improved resolution and sensitivity of MIRI-MRS compared to Spitzer enables a robust analysis of the previously detected H2O, CO, HCN, and CO2 emission as well as a marginal detection of C2H2. We also report the first robust detection of mid-infrared OH and rovibrational CO emission in this source. The derived molecular column densities reveal the inner disk of SY Cha to be rich in both oxygen- and carbon-bearing molecules. This is in contrast to PDS 70, another protoplanetary disk with a large cavity observed with JWST, which displays much weaker line emission. In the SY Cha disk, the continuum, and potentially the line, flux varies substantially between the new JWST observations and archival Spitzer observations, indicative of a highly dynamic inner disk.
30.	Sridhar, Arun R., et al. (författare) Identifying Risk of Adverse Outcomes in COVID-19 Patients via Artificial Intelligence-Powered Analysis of 12-Lead Intake Electrocardiogram. 2022 Ingår i: Cardiovascular digital health journal. - : Elsevier. - 2666-6936. ; 3:2, s. 62-74 Tidskriftsartikel (refereegranskat)abstract Background: Adverse events in COVID-19 are difficult to predict. Risk stratification is encumbered by the need to protect healthcare workers. We hypothesize that AI can help identify subtle signs of myocardial involvement in the 12-lead electrocardiogram (ECG), which could help predict complications.Objective: Use intake ECGs from COVID-19 patients to train AI models to predict risk of mortality or major adverse cardiovascular events (MACE).Methods: We studied intake ECGs from 1448 COVID-19 patients (60.5% male, 63.4±16.9 years). Records were labeled by mortality (death vs. discharge) or MACE (no events vs. arrhythmic, heart failure [HF], or thromboembolic [TE] events), then used to train AI models; these were compared to conventional regression models developed using demographic and comorbidity data.Results: 245 (17.7%) patients died (67.3% male, 74.5±14.4 years); 352 (24.4%) experienced at least one MACE (119 arrhythmic; 107 HF; 130 TE). AI models predicted mortality and MACE with area under the curve (AUC) values of 0.60±0.05 and 0.55±0.07, respectively; these were comparable to AUC values for conventional models (0.73±0.07 and 0.65±0.10). There were no prominent temporal trends in mortality rate or MACE incidence in our cohort; holdout testing with data from after a cutoff date (June 9, 2020) did not degrade model performance.Conclusion: Using intake ECGs alone, our AI models had limited ability to predict hospitalized COVID-19 patients' risk of mortality or MACE. Our models' accuracy was comparable to that of conventional models built using more in-depth information, but translation to clinical use would require higher sensitivity and positive predictive value. In the future, we hope that mixed-input AI models utilizing both ECG and clinical data may be developed to enhance predictive accuracy.
31.	Tranfa, Mario, et al. (författare) Alzheimer's Disease and Small Vessel Disease Differentially Affect White Matter Microstructure Ingår i: Annals of Clinical and Translational Neurology. - 2328-9503. Tidskriftsartikel (refereegranskat)abstract Objective: Alzheimer's disease (AD) and cerebral small vessel disease (cSVD), the two most common causes of dementia, are characterized by white matter (WM) alterations diverging from the physiological changes occurring in healthy aging. Diffusion tensor imaging (DTI) is a valuable tool to quantify WM integrity non-invasively and identify the determinants of such alterations. Here, we investigated main effects and interactions of AD pathology, APOE-ε4, cSVD, and cardiovascular risk on spatial patterns of WM alterations in non-demented older adults. Methods: Within the prospective European Prevention of Alzheimer's Dementia study, we selected 606 participants (64.9 ± 7.2 years, 376 females) with baseline cerebrospinal fluid samples of amyloid β1-42 and p-Tau181 and MRI scans, including DTI scans. Longitudinal scans (mean follow-up time = 1.3 ± 0.5 years) were obtained in a subset (n = 223). WM integrity was assessed by extracting fractional anisotropy and mean diffusivity in relevant tracts. To identify the determinants of WM disruption, we performed a multimodel inference to identify the best linear mixed-effects model for each tract. Results: AD pathology, APOE-ε4, cSVD burden, and cardiovascular risk were all associated with WM integrity within several tracts. While limbic tracts were mainly impacted by AD pathology and APOE-ε4, commissural, associative, and projection tract integrity was more related to cSVD burden and cardiovascular risk. AD pathology and cSVD did not show any significant interaction effect. Interpretation: Our results suggest that AD pathology and cSVD exert independent and spatially different effects on WM microstructure, supporting the role of DTI in disease monitoring and suggesting independent targets for preventive medicine approaches.
32.	Tranfa, Mario, et al. (författare) Alzheimer's Disease and Small Vessel Disease Differentially Affect White Matter Microstructure 2024 Ingår i: ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY. - 2328-9503. ; 11:6, s. 1541-1556 Tidskriftsartikel (refereegranskat)abstract ObjectiveAlzheimer's disease (AD) and cerebral small vessel disease (cSVD), the two most common causes of dementia, are characterized by white matter (WM) alterations diverging from the physiological changes occurring in healthy aging. Diffusion tensor imaging (DTI) is a valuable tool to quantify WM integrity non-invasively and identify the determinants of such alterations. Here, we investigated main effects and interactions of AD pathology, APOE-epsilon 4, cSVD, and cardiovascular risk on spatial patterns of WM alterations in non-demented older adults.MethodsWithin the prospective European Prevention of Alzheimer's Dementia study, we selected 606 participants (64.9 +/- 7.2 years, 376 females) with baseline cerebrospinal fluid samples of amyloid beta 1-42 and p-Tau181 and MRI scans, including DTI scans. Longitudinal scans (mean follow-up time = 1.3 +/- 0.5 years) were obtained in a subset (n = 223). WM integrity was assessed by extracting fractional anisotropy and mean diffusivity in relevant tracts. To identify the determinants of WM disruption, we performed a multimodel inference to identify the best linear mixed-effects model for each tract.ResultsAD pathology, APOE-epsilon 4, cSVD burden, and cardiovascular risk were all associated with WM integrity within several tracts. While limbic tracts were mainly impacted by AD pathology and APOE-epsilon 4, commissural, associative, and projection tract integrity was more related to cSVD burden and cardiovascular risk. AD pathology and cSVD did not show any significant interaction effect.InterpretationOur results suggest that AD pathology and cSVD exert independent and spatially different effects on WM microstructure, supporting the role of DTI in disease monitoring and suggesting independent targets for preventive medicine approaches.
33.	Wirbel, Jakob, et al. (författare) Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer 2019 Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25:4, s. 679-689 Tidskriftsartikel (refereegranskat)abstract Association studies have linked microbiome alterations with many human diseases. However, they have not always reported consistent results, thereby necessitating cross-study comparisons. Here, a meta-analysis of eight geographically and technically diverse fecal shotgun metagenomic studies of colorectal cancer (CRC, n = 768), which was controlled for several confounders, identified a core set of 29 species significantly enriched in CRC metagenomes (false discovery rate (FDR) < 1 × 10 −5 ). CRC signatures derived from single studies maintained their accuracy in other studies. By training on multiple studies, we improved detection accuracy and disease specificity for CRC. Functional analysis of CRC metagenomes revealed enriched protein and mucin catabolism genes and depleted carbohydrate degradation genes. Moreover, we inferred elevated production of secondary bile acids from CRC metagenomes, suggesting a metabolic link between cancer-associated gut microbes and a fat- and meat-rich diet. Through extensive validations, this meta-analysis firmly establishes globally generalizable, predictive taxonomic and functional microbiome CRC signatures as a basis for future diagnostics.
34.	Baenas, Isabel, et al. (författare) Impact of COVID-19 Lockdown in Eating Disorders : A Multicentre Collaborative International Study 2022 Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 14:1 Tidskriftsartikel (refereegranskat)abstract Background. The COVID-19 lockdown has had a significant impact on mental health. Patients with eating disorders (ED) have been particularly vulnerable. Aims. (1) To explore changes in eating-related symptoms and general psychopathology during lockdown in patients with an ED from various European and Asian countries; and (2) to assess differences related to diagnostic ED subtypes, age, and geography. Methods. The sample comprised 829 participants, diagnosed with an ED according to DSM-5 criteria from specialized ED units in Europe and Asia. Participants were assessed using the COVID-19 Isolation Scale (CIES). Results. Patients with binge eating disorder (BED) experienced the highest impact on weight and ED symptoms in comparison with other ED subtypes during lockdown, whereas individuals with other specified feeding and eating disorders (OFSED) had greater deterioration in general psychological functioning than subjects with other ED subtypes. Finally, Asian and younger individuals appeared to be more resilient. Conclusions. The psychopathological changes in ED patients during the COVID-19 lockdown varied by cultural context and individual variation in age and ED diagnosis. Clinical services may need to target preventive measures and adapt therapeutic approaches for the most vulnerable patients.
35.	Furman, David, et al. (författare) Chronic inflammation in the etiology of disease across the life span 2019 Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25:12, s. 1822-1832 Tidskriftsartikel (refereegranskat)abstract Although intermittent increases in inflammation are critical for survival during physical injury and infection, recent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders. In the present Perspective we describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI.
36.	Minoia, F, et al. (författare) Development and Initial Validation of the Macrophage Activation Syndrome/Primary Hemophagocytic Lymphohistiocytosis Score, a Diagnostic Tool that Differentiates Primary Hemophagocytic Lymphohistiocytosis from Macrophage Activation Syndrome 2017 Ingår i: The Journal of pediatrics. - : Elsevier BV. - 1097-6833 .- 0022-3476. ; 189, s. 72- Tidskriftsartikel (refereegranskat)
37.	Paciaroni, Maurizio, et al. (författare) Early recurrence in paroxysmal versus sustained atrial fibrillation in patients with acute ischaemic stroke. 2019 Ingår i: European stroke journal. - : SAGE Publications. - 2396-9881 .- 2396-9873. ; 4:1, s. 55-64 Tidskriftsartikel (refereegranskat)abstract The relationship between different patterns of atrial fibrillation and early recurrence after an acute ischaemic stroke is unclear.In a prospective cohort study, we evaluated the rates of early ischaemic recurrence after an acute ischaemic stroke in patients with paroxysmal atrial fibrillation or sustained atrial fibrillation which included persistent and permanent atrial fibrillation.In patients with acute ischaemic stroke, atrial fibrillation was categorised as paroxysmal atrial fibrillation or sustained atrial fibrillation. Ischaemic recurrences were the composite of ischaemic stroke, transient ischaemic attack and symptomatic systemic embolism occurring within 90 days from acute index stroke.A total of 2150 patients (1155 females, 53.7%) were enrolled: 930 (43.3%) had paroxysmal atrial fibrillation and 1220 (56.7%) sustained atrial fibrillation. During the 90-day follow-up, 111 ischaemic recurrences were observed in 107 patients: 31 in patients with paroxysmal atrial fibrillation (3.3%) and 76 with sustained atrial fibrillation (6.2%) (hazard ratio (HR) 1.86 (95% CI 1.24-2.81)). Patients with sustained atrial fibrillation were on average older, more likely to have diabetes mellitus, hypertension, history of stroke/ transient ischaemic attack, congestive heart failure, atrial enlargement, high baseline NIHSS-score and implanted pacemaker. After adjustment by Cox proportional hazard model, sustained atrial fibrillation was not associated with early ischaemic recurrences (adjusted HR 1.23 (95% CI 0.74-2.04)).After acute ischaemic stroke, patients with sustained atrial fibrillation had a higher rate of early ischaemic recurrence than patients with paroxysmal atrial fibrillation. After adjustment for relevant risk factors, sustained atrial fibrillation was not associated with a significantly higher risk of recurrence, thus suggesting that the risk profile associated with atrial fibrillation, rather than its pattern, is determinant for recurrence.
38.	Perrone, Alessio, et al. (författare) Non-conventional Cu thin films deposited on Y substrate by sputtering 2014 Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 752, s. 27-32 Tidskriftsartikel (refereegranskat)abstract Copper (Cu) thin films were deposited on yttrium (Y) substrate by sputtering. During the deposition, a small central area of the Y substrate was shielded to avoid the film deposition and was successively used to study its photoemissive properties. This configuration has two advantages: the cathode presents (i) the quantum efficiency and the work function of Y and (ii) high electrical compatibility when inserted into the conventional radio-frequency gun built with Cu bulk. The photocathode was investigated by scanning electron microscopy to determine surface morphology. X-ray diffraction and atomic force microscopy studies were performed to compare the structure and surface properties of the deposited film. The measured electrical resistivity value of the Cu film was similar to that of high purity Cu bulk. Film to substrate adhesion was also evaluated using the Daimler–Benz Rockwell-C adhesion test method. Finally, the photoelectron performance in terms of quantum efficiency was obtained in a high vacuum photodiode cell before and after laser cleaning procedures. A comparison with the results obtained with a twin sample prepared by pulsed laser deposition is presented and discussed.
39.	Raia, P., et al. (författare) Progress to extinction: increased specialisation causes the demise of animal clades 2016 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6 Tidskriftsartikel (refereegranskat)abstract Animal clades tend to follow a predictable path of waxing and waning during their existence, regardless of their total species richness or geographic coverage. Clades begin small and undifferentiated, then expand to a peak in diversity and range, only to shift into a rarely broken decline towards extinction. While this trajectory is now well documented and broadly recognised, the reasons underlying it remain obscure. In particular, it is unknown why clade extinction is universal and occurs with such surprising regularity. Current explanations for paleontological extinctions call on the growing costs of biological interactions, geological accidents, evolutionary traps, and mass extinctions. While these are effective causes of extinction, they mainly apply to species, not clades. Although mass extinctions is the undeniable cause for the demise of a sizeable number of major taxa, we show here that clades escaping them go extinct because of the widespread tendency of evolution to produce increasingly specialised, sympatric, and geographically restricted species over time.
40.	Roederer, Ian U., et al. (författare) The discovery space of ELT-ANDES. Stars and stellar populations 2024 Ingår i: Experimental Astronomy. - 0922-6435. ; 57:2 Tidskriftsartikel (refereegranskat)abstract The ArmazoNes high Dispersion Echelle Spectrograph (ANDES) is the optical and near-infrared high-resolution echelle spectrograph envisioned for the Extremely Large Telescope (ELT). We present a selection of science cases, supported by new calculations and simulations, where ANDES could enable major advances in the fields of stars and stellar populations. We focus on three key areas, including the physics of stellar atmospheres, structure, and evolution; stars of the Milky Way, Local Group, and beyond; and the star-planet connection. The key features of ANDES are its wide wavelength coverage at high spectral resolution and its access to the large collecting area of the ELT. These features position ANDES to address the most compelling questions and potentially transformative advances in stellar astrophysics of the decades ahead, including questions which cannot be anticipated today.
41.	San Sebastian, Eider, et al. (författare) Enantiospecific Response in Cross-Polarization Solid-State Nuclear Magnetic Resonance of Optically Active Metal Organic Frameworks 2020 Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 142:42, s. 17989-17996 Tidskriftsartikel (refereegranskat)abstract We report herein on a NMR-based enantiospecific response for a family of optically active metal-organic frameworks. Cross-polarization of the 1H-13C couple was performed, and the intensities of the 13C nuclei NMR signals were measured to be different for the two enantiomers. In a direct-pulse experiment, which prevents cross-polarization, the intensity difference of the 13C NMR signals of the two nanostructured enantiomers vanished. This result is due to changes of the nuclear spin relaxation times due to the electron spin spatial asymmetry induced by chemical bond polarization involving a chiral center. These experiments put forward on firm ground that the chiral-induced spin selectivity effect, which induces chemical bond polarization in the J-coupling, is the mechanism responsible for the enantiospecific response. The implications of this finding for the theory of this molecular electron spin polarization effect and the development of quantum biosensing and quantum storage devices are discussed.
42.	Steffen, Annika, et al. (författare) Meat and Heme Iron Intake and Risk of Squamous Cell Carcinoma of the Upper Aero-Digestive Tract in the European Prospective Investigation into Cancer and Nutrition (EPIC) 2012 Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 21:12, s. 2138-2148 Tidskriftsartikel (refereegranskat)abstract Background: Evidence from prospective studies on intake of meat and fish and risk of squamous cell carcinoma (SCC) of the upper aero-digestive tract (UADT) is scarce. We prospectively investigated the association of meat and fish intake with risk of SCC of the UADT and the possible mechanism via heme iron in the large multicenter European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods: Multivariable proportional hazards models were used to estimate relative risks (RR) of SCC of the UADT in relation to intake of total meat, as well as subtypes of meat, fish, and heme iron among 348,738 individuals from 7 European countries. Results: During an average follow-up of 11.8 years, a total of 682 incident cases of UADT SCC were accrued. Intake of processed meat was positively associated with risk of SCC of the UADT in the total cohort (highest vs. lowest quintile: RR = 1.41; 95% confidence interval (CI) = 1.03-1.941, however, in stratified analyses, this association was confined to the group of current smokers (highest vs. lowest quintile: RR = 1.89; 95% CI = 1.22-2.93). Red meat, poultry, fish, and heme iron were not consistently related to UADT SCC. Conclusion: Higher intake of processed meat was positively associated with KC of the UADT among smokers. Although this finding was stable in various sensitivity analyses, we cannot rule out residual confounding by smoking. Confirmation in future studies and identification of biologic mechanisms is warranted. Impact: Smokers may further increase their risk for SCC of the UADT if they additionally consume large amounts of processed meat. Cancer Epidemiol Biomarkers Prev; 21(12); 2738-48. (C)2012 AACR.
43.	Steins Bisschop, Charlotte N, et al. (författare) Weight change later in life and colon and rectal cancer risk in participants in the EPIC-PANACEA study. 2014 Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 99:1, s. 139-147 Tidskriftsartikel (refereegranskat)abstract A moderate association exists between body mass index (BMI) and colorectal cancer. Less is known about the effect of weight change.
44.	Taïeb, David, et al. (författare) Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants : an international expert Consensus statement 2024 Ingår i: Nature Reviews Endocrinology. - : Springer Nature. - 1759-5029 .- 1759-5037. ; 20:3, s. 168-184 Forskningsöversikt (refereegranskat)abstract Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression. As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both. This Consensus statement should help guide clinicians in the diagnosis and management of patients with SDHB PPGLs.
45.	von der Lieth, Claus-Wilhelm, et al. (författare) EUROCarbDB : an open-access platform for glycoinformatics 2011 Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 21:4, s. 493-502 Tidskriftsartikel (refereegranskat)abstract The EUROCarbDB project is a design study for a technical framework, which provides sophisticated, freely accessible, open-source informatics tools and databases to support glycobiology and glycomic research. EUROCarbDB is a relational database containing glycan structures, their biological context and, when available, primary and interpreted analytical data from high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance experiments. Database content can be accessed via a web-based user interface. The database is complemented by a suite of glycoinformatics tools, specifically designed to assist the elucidation and submission of glycan structure and experimental data when used in conjunction with contemporary carbohydrate research workflows. All software tools and source code are licensed under the terms of the Lesser General Public License, and publicly contributed structures and data are freely accessible. The public test version of the web interface to the EUROCarbDB can be found at http://www.ebi.ac.uk/eurocarb.
46.	Walton, Esther, et al. (författare) Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa : A Coordinated Analysis by the ENIGMA Eating Disorders Working Group 2022 Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 92:9, s. 730-738 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and de-pendencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data.METHODS: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251).RESULTS: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of un-dernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients.CONCLUSIONS: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.
47.	Aglago, Elom K., et al. (författare) Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk : A Case-Control Study Nested within a European Prospective Cohort 2021 Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 30:1, s. 182-192 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation.METHODS: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively.RESULTS: Higher sRAGE concentrations were inversely associated with colorectal cancer (ORQ5vs.Q1, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (ORQ5vs.Q1, 1.00; 95% CI, 0.68-1.48; Pheterogeneity for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99).CONCLUSIONS: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within ADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk.IMPACT: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.
48.	Alexiadis, Alessio, et al. (författare) Comparison between CFD calculations of the flow in a rotating disk cell and the Cochran/Levich equations 2012 Ingår i: Journal of Electroanalytical Chemistry. - : Elsevier BV. - 1572-6657. ; 669, s. 55-66 Tidskriftsartikel (refereegranskat)abstract Three CFD (Computational Fluid Dynamics) models (single-phase. VOF and Euler-Euler) are employed to simulate the flow in a finite, rotating electrode cell under different operative conditions. The main dimensionless groups are derived and their effect on the flow is investigated. Except very close to the rotating electrode (i.e. in the hydrodynamic layer), the results show a flow pattern considerably different from Cochran's approximate analytical solution often used in electrochemistry. Historically, the Cochran equation was used to derive the Levich equation, which permits the calculation of the limiting current density on a rotating electrode. Despite the general inadequacy of Cochran's analytical solution, however, we show that the Levich equation often retains its validity because, in many practical situations, the concentration boundary layer is considerably smaller than the hydrodynamic boundary layer. When bubbles are generated on the electrode and a certain critical void fraction is exceeded, however, the Levich equation also becomes inaccurate. We propose, therefore, an amended version of this equation, which provides results closer to the CFD calculations.
49.	Alexiadis, Alessio, et al. (författare) Liquid-gas flow patterns in a narrow electrochemical channel 2011 Ingår i: Chemical Engineering Science. - : Elsevier BV. - 0009-2509 .- 1873-4405. ; 66:10, s. 2252-2260 Tidskriftsartikel (refereegranskat)abstract The flow in a narrow (3 mm wide) vertical gap of an electrochemical cell with gas evolution at one electrode is modeled by means of the two-phase Euler-Euler model. The results indicate that at certain conditions an unsteady type of flow with vortices and recirculation regions can occur. Such flow pattern has been observed experimentally, but not reported in previous modeling studies. Further analysis establishes that the presence of a sufficient amount of small (similar to 10 mu m) bubbles is the main factor causing this type of flow at high current densities.
50.	Alexiadis, Alessio, et al. (författare) On the electrode boundary conditions in the simulation of two phase flow in electrochemical cells 2011 Ingår i: International journal of hydrogen energy. - : Elsevier BV. - 0360-3199 .- 1879-3487. ; 36:14, s. 8557-8559 Tidskriftsartikel (refereegranskat)

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