| 1. |
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| 2. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- Delios, A., et al.
(author)
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Examining the generalizability of research findings from archival data
- 2022
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
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Journal article (peer-reviewed)abstract
- This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability-for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples.
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| 5. |
- Tierney, W., et al.
(author)
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A creative destruction approach to replication : Implicit work and sex morality across cultures
- 2021
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In: Journal of Experimental Social Psychology. - : Elsevier BV. - 0022-1031 .- 1096-0465. ; 93
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Journal article (peer-reviewed)abstract
- How can we maximize what is learned from a replication study? In the creative destruction approach to replication, the original hypothesis is compared not only to the null hypothesis, but also to predictions derived from multiple alternative theoretical accounts of the phenomenon. To this end, new populations and measures are included in the design in addition to the original ones, to help determine which theory best accounts for the results across multiple key outcomes and contexts. The present pre-registered empirical project compared the Implicit Puritanism account of intuitive work and sex morality to theories positing regional, religious, and social class differences; explicit rather than implicit cultural differences in values; self-expression vs. survival values as a key cultural fault line; the general moralization of work; and false positive effects. Contradicting Implicit Puritanism's core theoretical claim of a distinct American work morality, a number of targeted findings replicated across multiple comparison cultures, whereas several failed to replicate in all samples and were identified as likely false positives. No support emerged for theories predicting regional variability and specific individual-differences moderators (religious affiliation, religiosity, and education level). Overall, the results provide evidence that work is intuitively moralized across cultures.
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| 6. |
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| 7. |
- Elvsashagen, T, et al.
(author)
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The genetic architecture of human brainstem structures and their involvement in common brain disorders
- 2020
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4016-
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Journal article (peer-reviewed)abstract
- Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson’s disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.
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| 10. |
- Barregård, Lars, 1948, et al.
(author)
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Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine
- 2013
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In: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
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Journal article (peer-reviewed)abstract
- Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.
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| 11. |
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| 12. |
- Chng, Kern Rei, et al.
(author)
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Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment
- 2020
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 26, s. 941-951
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Journal article (peer-reviewed)abstract
- Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections. Spatiotemporal characterization of microbial diversity and antibiotic resistance in a tertiary-care hospital reveals broad distribution and persistence of antibiotic-resistant organisms that could cause opportunistic infections in a healthcare setting.
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| 13. |
- Coppo, Rosanna, et al.
(author)
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Risk factors for progression in children and young adults with IgA nephropathy : an analysis of 261 cases from the VALIGA European cohort
- 2017
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In: Pediatric nephrology (Berlin, West). - : Springer Science and Business Media LLC. - 0931-041X .- 1432-198X. ; 32:1, s. 139-150
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Journal article (peer-reviewed)abstract
- There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease. Data on 261 young patients [age < 23 years; mean follow-up of 4.9 (range 2.5-8.1) years] enrolled in VALIGA, a study designed to validate the Oxford Classification of IgAN, were assessed. Renal biopsies were scored for the presence of mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1-2) (MEST score) and crescents (C1). Progression was assessed as end stage renal disease and/or a 50 % loss of estimated glomerular filtration rate (eGFR) (combined endpoint) as well as the rate of renal function decline (slope of eGFR). Cox regression and tree classification binary models were used and compared. In this cohort of 261 subjects aged < 23 years, Cox analysis validated the MEST M, S and T scores for predicting survival to the combined endpoint but failed to prove that these scores had predictive value in the sub-group of 174 children aged < 18 years. The regression tree classification indicated that patients with M1 were at risk of developing higher time-averaged proteinuria (p < 0.0001) and the combined endpoint (p < 0.001). An initial proteinuria of ae0.4 g/day/1.73 m(2) and an eGFR of < 90 ml/min/1.73 m(2) were determined to be risk factors in subjects with M0. Children aged < 16 years with M0 and well-preserved eGFR (> 90 ml/min/1.73 m(2)) at presentation had a significantly high probability of proteinuria remission during follow-up and a higher remission rate following treatment with corticosteroid and/or immunosuppressive therapy. This new statistical approach has identified clinical and histological risk factors associated with outcome in children and young adults with IgAN.
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| 14. |
- Danko, David, et al.
(author)
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A global metagenomic map of urban microbiomes and antimicrobial resistance
- 2021
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In: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 184:13, s. 3376-3393
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Journal article (peer-reviewed)abstract
- We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.
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| 15. |
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| 16. |
- Gracias, J., et al.
(author)
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Cerebrospinal fluid concentration of complement component 4A is increased in first episode schizophrenia
- 2022
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- Schizophrenia risk has been associated with the complement component 4 (C4) genes. Here the authors show that C4A is elevated in individuals with schizophrenia. Postsynaptic density is reduced in schizophrenia, and risk variants increasing complement component 4A (C4A) gene expression are linked to excessive synapse elimination. In two independent cohorts, we show that cerebrospinal fluid (CSF) C4A concentration is elevated in patients with first-episode psychosis (FEP) who develop schizophrenia (FEP-SCZ: median 0.41 fmol/ul [CI = 0.34-0.45], FEP-non-SCZ: median 0.29 fmol/ul [CI = 0.22-0.35], healthy controls: median 0.28 [CI = 0.24-0.33]). We show that the CSF elevation of C4A in FEP-SCZ exceeds what can be expected from genetic risk variance in the C4 locus, and in patient-derived cellular models we identify a mechanism dependent on the disease-associated cytokines interleukin (IL)-1beta and IL-6 to selectively increase neuronal C4A mRNA expression. In patient-derived CSF, we confirm that IL-1beta correlates with C4A controlled for genetically predicted C4A RNA expression (r = 0.39; CI: 0.01-0.68). These results suggest a role of C4A in early schizophrenia pathophysiology.
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| 17. |
- Rizzoli, René, et al.
(author)
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Osteonecrosis of the jaw and bisphosphonate treatment for osteoporosis.
- 2008
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In: Bone. - : Elsevier BV. - 8756-3282. ; 42:5, s. 841-7
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Journal article (peer-reviewed)abstract
- A potential side effect associated with bisphosphonates, a class of drugs used in the treatment of osteoporosis, Paget's disease and metastatic bone disease, is osteonecrosis of the jaw (ONJ). The incidence of ONJ in the general population is unknown; this rare condition also may occur in patients not receiving bisphosphonates. Case reports have discussed ONJ development in patients with multiple myeloma or metastatic breast cancer receiving bisphosphonates as palliation for bone metastases. These patients are also receiving chemotherapeutic agents that might impair the immune system and affect angiogenesis. The incidence or prevalence of ONJ in patients taking bisphosphonates for osteoporosis seems to be very rare. No causative relationship has been unequivocally demonstrated between ONJ and bisphosphonate therapy. A majority of ONJ occurs after tooth extraction. Furthermore, the underlying risk of developing ONJ may be increased in osteoporotic patients by comorbid diseases. Treatment for ONJ is generally conservative.
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| 18. |
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| 19. |
- Schwarz, E, et al.
(author)
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Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder
- 2019
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In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 12-
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Journal article (peer-reviewed)abstract
- Schizophrenia is a severe mental disorder characterized by numerous subtle changes in brain structure and function. Machine learning allows exploring the utility of combining structural and functional brain magnetic resonance imaging (MRI) measures for diagnostic application, but this approach has been hampered by sample size limitations and lack of differential diagnostic data. Here, we performed a multi-site machine learning analysis to explore brain structural patterns of T1 MRI data in 2668 individuals with schizophrenia, bipolar disorder or attention-deficit/ hyperactivity disorder, and healthy controls. We found reproducible changes of structural parameters in schizophrenia that yielded a classification accuracy of up to 76% and provided discrimination from ADHD, through it lacked specificity against bipolar disorder. The observed changes largely indexed distributed grey matter alterations that could be represented through a combination of several global brain-structural parameters. This multi-site machine learning study identified a brain-structural signature that could reproducibly differentiate schizophrenia patients from controls, but lacked specificity against bipolar disorder. While this currently limits the clinical utility of the identified signature, the present study highlights that the underlying alterations index substantial global grey matter changes in psychotic disorders, reflecting the biological similarity of these conditions, and provide a roadmap for future exploration of brain structural alterations in psychiatric patients.
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| 20. |
- Sellgren, C. M., et al.
(author)
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GRK3 deficiency elicits brain immune activation and psychosis
- 2021
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 6820-6832
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Journal article (peer-reviewed)abstract
- The G protein-coupled receptor kinase (GRK) family member protein GRK3 has been linked to the pathophysiology of schizophrenia and bipolar disorder. Expression, as well as protein levels, of GRK3 are reduced in post-mortem prefrontal cortex of schizophrenia subjects. Here, we investigate functional behavior and neurotransmission related to immune activation and psychosis using mice lacking functional Grk3 and utilizing a variety of methods, including behavioral, biochemical, electrophysiological, molecular, and imaging methods. Compared to wildtype controls, the Grk3(-/-) mice show a number of aberrations linked to psychosis, including elevated brain levels of IL-1 beta, increased turnover of kynurenic acid (KYNA), hyper-responsiveness to D-amphetamine, elevated spontaneous firing of midbrain dopamine neurons, and disruption in prepulse inhibition. Analyzing human genetic data, we observe a link between psychotic features in bipolar disorder, decreased GRK expression, and increased concentration of CSF KYNA. Taken together, our data suggest that Grk3(-/-) mice show face and construct validity relating to the psychosis phenotype with glial activation and would be suitable for translational studies of novel immunomodulatory agents in psychotic disorders.
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| 24. |
- Yeung, Andy Wai Kan, et al.
(author)
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Dietary natural products and their potential to influence health and disease including animal model studies
- 2018
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In: Animal Science Papers and Reports. - : POLSKA AKAD NAUK, INST GENETYKI I HODOWLI ZWIERZAT. - 0860-4037. ; 36:4, s. 345-358
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Research review (peer-reviewed)abstract
- Although biological and pharmacological effects of dietary natural products have been intensively studied, there has been no bibliometric analysis performed on this research field up to now. The current study has aimed to identify and analyze the manuscripts on dietary natural products and their potential to influence health and disease including studies using animal models. Data, including words from titles and abstracts, publication and citation data, have been extracted from Web of Science database and analyzed by the VOSviewer software. Our search has yielded 1,014 manuscripts. The ratio of original articles to reviews was identified to be 1.5:1. Over half of the manuscripts have been published since 2010. The manuscripts have been contributed by 4,301 authors from 1,445 organizations in 76 countries/territories and published in 499 journals. The results from the current study point out that scientific research focusing on the potential of dietary natural products to affect health and disease status (including animal model studies) is expanding, and suggests an increasing significance of this scientific area. With the progressive development and improvement of animal studies, it should be expected that animal models of different human diseases (especially civilization ones) would be an integral part of the research for the evaluation of pharmaceuticals originated from dietary natural products like plants or plant materials. Moreover, natural products can also be fed to animals to improve the quality of animal products, with numerous resulting functional effects.
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