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1.	Glasbey, JC, et al. (författare) 2021 swepub:Mat__t
2.	Adamina, M, et al. (författare) The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study 2022 Ingår i: Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. - : Wiley. - 1463-1318. ; 24:6, s. 708-726 Tidskriftsartikel (refereegranskat)
3.	Glasbey, JC, et al. (författare) Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study 2021 Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - : American Society of Clinical Oncology. - 1527-7755 .- 0732-183X. ; 39:1, s. 66- Tidskriftsartikel (refereegranskat)
4.	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)
5.	Simoes, JFF, et al. (författare) Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study 2021 Ingår i: Anaesthesia. - : Wiley. - 1365-2044 .- 0003-2409. ; 76:11, s. 1454-1464 Tidskriftsartikel (refereegranskat)
6.	Asano, H., et al. (författare) Spectroscopic study of the Λ(1405) resonance via the d (K-, n) reaction at J-PARC 2019 Ingår i: 13th International Conference on Hypernuclear and Strange Particle Physics, HYP 2018. - : AIP Publishing. - 9780735418721 ; 2130 Konferensbidrag (refereegranskat)abstract The structure of the Λ(1405) hyperon is an important and long-standing issue related to the K̄-nucleus interaction. The J-PARC E31 experiment has been performed to investigate the Λ(1405) spectrum shape. Because it is hard to form the Λ(1405) directly by a K̄N scattering in free space, E31 uses the d(K-, n) reaction with an incident kaon momentum of 1 GeV/c. We will identify three final states - ς-π+, ς+π-, ς0π0-so that the isospin structure of hyperon resonance states produced can be decomposed. The first physics run of the E31 experiment was performed in 2016. To enhance the statistics of the data set, we have performed the second physics run in the beginning of 2018. During the second run of E31, around 3.9×1010 kaons impacted on the deuteron target.
7.	van Bragt, JJMH, et al. (författare) Characteristics and treatment regimens across ERS SHARP severe asthma registries 2020 Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1 Tidskriftsartikel (refereegranskat)abstract Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
8.	Lozano, Rafael, et al. (författare) Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017 2018 Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138 Tidskriftsartikel (refereegranskat)abstract Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
9.	Murray, Christopher J. L., et al. (författare) Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017 2018 Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051 Tidskriftsartikel (refereegranskat)abstract Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
10.	Stanaway, Jeffrey D., et al. (författare) Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017 2018 Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994 Tidskriftsartikel (refereegranskat)abstract Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
11.	Abbafati, Cristiana, et al. (författare) 2020 Tidskriftsartikel (refereegranskat)
12.	Rodriguez, D., et al. (författare) MATS and LaSpec : High-precision experiments using ion traps and lasers at FAIR 2010 Ingår i: The European physical journal. Special topics. - : Springer Science and Business Media LLC. - 1951-6355 .- 1951-6401. ; 183, s. 1-123 Forskningsöversikt (refereegranskat)abstract Nuclear ground state properties including mass, charge radii, spins and moments can be determined by applying atomic physics techniques such as Penning-trap based mass spectrometry and laser spectroscopy. The MATS and LaSpec setups at the low-energy beamline at FAIR will allow us to extend the knowledge of these properties further into the region far from stability. The mass and its inherent connection with the nuclear binding energy is a fundamental property of a nuclide, a unique ""fingerprint"". Thus, precise mass values are important for a variety of applications, ranging from nuclear-structure studies like the investigation of shell closures and the onset of deformation, tests of nuclear mass models and mass formulas, to tests of the weak interaction and of the Standard Model. The required relative accuracy ranges from 10(-5) to below 10(-8) for radionuclides, which most often have half-lives well below 1 s. Substantial progress in Penning trap mass spectrometry has made this method a prime choice for precision measurements on rare isotopes. The technique has the potential to provide high accuracy and sensitivity even for very short-lived nuclides. Furthermore, ion traps can be used for precision decay studies and offer advantages over existing methods. With MATS (Precision Measurements of very short-lived nuclei using an Advanced Trapping System for highly-charged ions) at FAIR we aim to apply several techniques to very short-lived radionuclides: High-accuracy mass measurements, in-trap conversion electron and alpha spectroscopy, and trap-assisted spectroscopy. The experimental setup of MATS is a unique combination of an electron beam ion trap for charge breeding, ion traps for beam preparation, and a high-precision Penning trap system for mass measurements and decay studies. For the mass measurements, MATS offers both a high accuracy and a high sensitivity. A relative mass uncertainty of 10(-9) can be reached by employing highly-charged ions and a non-destructive Fourier-Transform Ion-Cyclotron-Resonance (FT-ICR) detection technique on single stored ions. This accuracy limit is important for fundamental interaction tests, but also allows for the study of the fine structure of the nuclear mass surface with unprecedented accuracy, whenever required. The use of the FT-ICR technique provides true single ion sensitivity. This is essential to access isotopes that are produced with minimum rates which are very often the most interesting ones. Instead of pushing for highest accuracy, the high charge state of the ions can also be used to reduce the storage time of the ions, hence making measurements on even shorter-lived isotopes possible. Decay studies in ion traps will become possible with MATS. Novel spectroscopic tools for in-trap high-resolution conversion-electron and charged-particle spectroscopy from carrier-free sources will be developed, aiming e. g. at the measurements of quadrupole moments and E0 strengths. With the possibility of both high-accuracy mass measurements of the shortest-lived isotopes and decay studies, the high sensitivity and accuracy potential of MATS is ideally suited for the study of very exotic nuclides that will only be produced at the FAIR facility. Laser spectroscopy of radioactive isotopes and isomers is an efficient and model-independent approach for the determination of nuclear ground and isomeric state properties. Hyperfine structures and isotope shifts in electronic transitions exhibit readily accessible information on the nuclear spin, magnetic dipole and electric quadrupole moments as well as root-mean-square charge radii. The dependencies of the hyperfine splitting and isotope shift on the nuclear moments and mean square nuclear charge radii are well known and the theoretical framework for the extraction of nuclear parameters is well established. These extracted parameters provide fundamental information on the structure of nuclei at the limits of stability. Vital information on both bulk and valence nuclear properties are derived and an exceptional sensitivity to changes in nuclear deformation is achieved. Laser spectroscopy provides the only mechanism for such studies in exotic systems and uniquely facilitates these studies in a model-independent manner. The accuracy of laser-spectroscopic-determined nuclear properties is very high. Requirements concerning production rates are moderate; collinear spectroscopy has been performed with production rates as few as 100 ions per second and laser-desorption resonance ionization mass spectroscopy (combined with beta-delayed neutron detection) has been achieved with rates of only a few atoms per second. This Technical Design Report describes a new Penning trap mass spectrometry setup as well as a number of complementary experimental devices for laser spectroscopy, which will provide a complete system with respect to the physics and isotopes that can be studied. Since MATS and LaSpec require high-quality low-energy beams, the two collaborations have a common beamline to stop the radioactive beam of in-flight produced isotopes and prepare them in a suitable way for transfer to the MATS and LaSpec setups, respectively.
13.	Johnson, Candice, et al. (författare) Skin sensitization in silico protocol 2020 Ingår i: Regulatory toxicology and pharmacology. - : Elsevier BV. - 0273-2300 .- 1096-0295. ; 116 Tidskriftsartikel (refereegranskat)abstract The assessment of skin sensitization has evolved over the past few years to include in vitro assessments of key events along the adverse outcome pathway and opportunistically capitalize on the strengths of in silico methods to support a weight of evidence assessment without conducing a test in animals. While in silico methods vary greatly in their purpose and format; there is a need to standardize the underlying principles on which such models are developed and to make transparent the implications for the uncertainty in the overall assessment. In this contribution, the relationship between skin sensitization relevant effects, mechanisms, and endpoints are built into a hazard assessment framework. Based on the relevance of the mechanisms and effects as well as the strengths and limitations of the experimental systems used to identify them, rules and principles are defined for deriving skin sensitization in silico assessments. Further, the assignments of reliability and confidence scores that reflect the overall strength of the assessment are discussed. This skin sensitization protocol supports the implementation and acceptance of in silico approaches for the prediction of skin sensitization.
14.	Koszorús, Agota, et al. (författare) Charge radii of exotic potassium isotopes challenge nuclear theory and the magic character of N = 32 2021 Ingår i: Nature Physics. - : Springer Science and Business Media LLC. - 1745-2481 .- 1745-2473. ; 17:4, s. 439-443 Tidskriftsartikel (refereegranskat)abstract Nuclear charge radii are sensitive probes of different aspects of the nucleon–nucleon interaction and the bulk properties of nuclear matter, providing a stringent test and challenge for nuclear theory. Experimental evidence suggested a new magic neutron number at N = 32 (refs. 1–3) in the calcium region, whereas the unexpectedly large increases in the charge radii4,5 open new questions about the evolution of nuclear size in neutron-rich systems. By combining the collinear resonance ionization spectroscopy method with β-decay detection, we were able to extend charge radii measurements of potassium isotopes beyond N = 32. Here we provide a charge radius measurement of 52K. It does not show a signature of magic behaviour at N = 32 in potassium. The results are interpreted with two state-of-the-art nuclear theories. The coupled cluster theory reproduces the odd–even variations in charge radii but not the notable increase beyond N = 28. This rise is well captured by Fayans nuclear density functional theory, which, however, overestimates the odd–even staggering effect in charge radii. These findings highlight our limited understanding of the nuclear size of neutron-rich systems, and expose problems that are present in some of the best current models of nuclear theory.
15.	Micah, Angela E., et al. (författare) Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050 2021 Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343 Forskningsöversikt (refereegranskat)abstract Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
16.	Richards, Stephen, et al. (författare) The genome of the model beetle and pest Tribolium castaneum. 2008 Ingår i: Nature. - 1476-4687. ; 452:7190, s. 949-55 Tidskriftsartikel (refereegranskat)abstract Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
17.	Seiffge, D. J., et al. (författare) Recanalization Therapies in Acute Ischemic Stroke Patients Impact of Prior Treatment With Novel Oral Anticoagulants on Bleeding Complications and Outcome A Pilot Study 2015 Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 132:13, s. 1261-1269 Tidskriftsartikel (refereegranskat)abstract Background-We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in patients with ischemic stroke on non-vitamin K antagonist oral anticoagulants (NOACs, last intake <48 hours) in comparison with patients (1) taking vitamin K antagonists (VKAs) or (2) without previous anticoagulation (no-OAC). Methods and Results-This is a multicenter cohort pilot study. Primary outcome measures were (1) occurrence of intracranial hemorrhage (ICH) in 3 categories: any ICH (ICH any), symptomatic ICH according to the criteria of the European Cooperative Acute Stroke Study II (ECASS-II) (sICH ECASS-II) and the National Institute of Neurological Disorders and Stroke (NINDS) thrombolysis trial (sICH NINDS); and (2) death (at 3 months). Cohorts were compared by using propensity score matching. Our NOAC cohort comprised 78 patients treated with IVT/IAT and the comparison groups of 441 VKA patients and 8938 no-OAC patients. The median time from last NOAC intake to IVT/IAT was 13 hours (interquartile range, 8-22 hours). In VKA patients, median pre-IVT/IAT international normalized ratio was 1.3 (interquartile range, 1.1-1.6). ICH any was observed in 18.4% NOAC patients versus 26.8% in VKA patients and 17.4% in no-OAC patients. sICH ECASS-II and sICH NINDS occurred in 2.6%/3.9% NOAC patients, in comparison with 6.5%/9.3% of VKA patients and 5.0%/7.2% of no-OAC patients, respectively. At 3 months, 23.0% of NOAC patients in comparison with 26.9% of VKA patients and 13.9% of no-OAC patients had died. Propensity score matching revealed no statistically significant differences. Conclusions-IVT/IAT in selected patients with ischemic stroke under NOAC treatment has a safety profile similar to both IVT/IAT in patients on subtherapeutic VKA treatment or in those without previous anticoagulation. However, further prospective studies are needed, including the impact of specific coagulation tests.
18.	Acs, B, et al. (författare) Systematically higher Ki67 scores on core biopsy samples compared to corresponding resection specimen in breast cancer: a multi-operator and multi-institutional study 2022 Ingår i: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. - : Elsevier BV. - 1530-0285. ; 35:10, s. 1362-1369 Tidskriftsartikel (refereegranskat)
19.	Birkebaek, Niels H., et al. (författare) Impact of the COVID-19 pandemic on long-term trends in the prevalence of diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes: an international multicentre study based on data from 13 national diabetes registries 2022 Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 10:11, s. 786-794 Tidskriftsartikel (refereegranskat)abstract Background An increased prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in children was observed in various diabetes centres worldwide during the COVID-19 pandemic. We aimed to evaluate trends in the prevalence of diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes before and during the COVID-19 pandemic, and to identify potential predictors of changes in diabetic ketoacidosis prevalence during the pandemic.Methods For this international multicentre study, we used data from 13 national diabetes registries (Australia, Austria, Czechia, Denmark, Germany, Italy, Luxembourg, New Zealand, Norway, Slovenia, Sweden, USA [Colorado], and Wales). The study population comprised 104 290 children and adolescents aged 6 months to younger than 18 years, who were diagnosed with type 1 diabetes between Jan 1, 2006, and Dec 31, 2021. The observed diabetic ketoacidosis prevalence in 2020 and 2021 was compared to predictions based on trends over the pre-pandemic years 2006-19. Associations between changes in diabetic ketoacidosis prevalence and the severity of the COVID-19 pandemic and containment measures were examined with excess all-cause mortality in the whole population and the Stringency Index from the Oxford COVID-19 Government Response Tracker.Findings 87 228 children and adolescents were diagnosed with type 1 diabetes between 2006 and 2019, 8209 were diagnosed in 2020, and 8853 were diagnosed in 2021. From 2006 to 2019, diabetic ketoacidosis at diagnosis of type 1 diabetes was present in 23 775 (27middot3%) of 87 228 individuals and the mean annual increase in the prevalence of diabetic ketoacidosis in the total cohort from 2006 to 2019 was 1middot6% (95% CI 1middot3 to 1middot9). The adjusted observed prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes was 39middot4% (95% CI 34middot0 to 45middot6) in 2020 and 38middot9% (33middot6 to 45middot0) in 2021, significantly higher than the predicted prevalence of 32middot5% (27middot8 to 37middot9) for 2020 and 33middot0% (28middot3 to 38middot5) for 2021 (p<0middot0001 for both years). The prevalence of diabetic ketoacidosis was associated with the pandemic containment measures, with an estimated risk ratio of 1middot037 (95% CI 1middot024 to 1middot051; p<0middot0001) per ten-unit increase in the Stringency Index for 2020 and 1middot028 (1middot009 to 1middot047; p=0middot0033) for 2021, but was not significantly associated with excess all-cause mortality.Interpretation During the COVID-19 pandemic, there was a marked exacerbation of the pre-existing increase in diabetic ketoacidosis prevalence at diagnosis of type 1 diabetes in children. This finding highlights the need for early and timely diagnosis of type 1 diabetes in children and adolescents.Funding German Federal Ministry for Education and Research, German Robert Koch Institute, German Diabetes Association, German Diabetes Foundation, Slovenian Research Agency, Welsh Government, Central Denmark Region, and Swedish Association of Local Authorities and Regions.Copyright (c) 2022 Elsevier Ltd. All rights reserved.
20.	Larson, DJ, et al. (författare) Analysis of bulk dielectrics with atom probe tomography 2008 Ingår i: Microscopy and Microanalysis. - 1435-8115 .- 1431-9276. ; 14:SUPPL. 2, s. 1254-1255 Tidskriftsartikel (refereegranskat)
21.	Sattui, Sebastian E., et al. (författare) Outcomes of COVID-19 in patients with primary systemic vasculitis or polymyalgia rheumatica from the COVID-19 Global Rheumatology Alliance physician registry : a retrospective cohort study 2021 Ingår i: The Lancet Rheumatology. - : Elsevier. - 2665-9913. ; 3:12, s. E855-E864 Tidskriftsartikel (refereegranskat)abstract Background Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. Methods In this retrospective cohort study, adult patients (aged >= 18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behcet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. Findings Of 1202 eligible patients identified in the registry, 733 (61.0%) were women arid 469 (39.0%) were men, and their mean age was 63.8 years (SD 17.1). A total of 374 (31.1%) patients had polymyalgia rheumatica, 353 (29.4%) had ANCA-associated vasculitis, 183 (15.2%) had giant cell arteritis, 112 (9.3%) had Behcet's syndrome, and 180 (15.0%) had other vasculitis. Of 1020 (84. 9%) patients with outcome data, 512 (S0.2%) were not hospitalised, 114 (11.2%) were hospitalised and did not receive supplemental oxygen, 239 (23 - 4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15.2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1.44 [95% CI 1. 31-1- 571), were male compared with female (1.38 [1.05-1.801), had more comorbidities (per each additional comorbidity 1.39 [1- 23-1- 581), were taking 10 mg/day or more of prednisolone compared with none (2.14 [1.50-3.04J), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2.12 [1.49-3.021). Risk factors varied among different disease subtypes. Interpretation Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to info rm mitigation strategies for patients with these diseases.
22.	Zamora, Juan Carlos, et al. (författare) Considerations and consequences of allowing DNA sequence data as types of fungal taxa 2018 Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185 Tidskriftsartikel (refereegranskat)abstract Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
23.	Acs, Balazs, et al. (författare) Abstract P5-02-01: Analytical validation and prognostic potential of an automated digital scoring protocol for Ki67: An International Ki67 Working Group study 2020 Ingår i: Cancer research. Supplement. - 1538-7445. ; 80:4 Suppl Konferensbidrag (övrigt vetenskapligt/konstnärligt)
24.	Akter, Shaheda T. (författare) Experimental characterization and numerical modeling of compression perpendicular to the grain in wood and cross-laminated timber 2022 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Compression perpendicular to the grain (CPG) of wood is a typical loading situation in timber structures. It has been an extensively studied research topic for decades, due to the highly ductile behavior of wood under such loading, the large variations in mechanical properties, and the relevance of these properties in structural design. Among others, the main influencing factors for CPG properties are stressed volume, load and support configurations, and annual ring orientations to the loading direction. After the innovation of the massive, engineered wood based product, cross-laminated timber (CLT) and its application in high rise buildings, CPG of wood has gained further importance. The development of a non-homogeneous, undesired and combined stress state under CPG in solid wood, due to the material anisotropy in the radial-tangential plane, can build up a complex multi-axial stress state in CLT. As a comparatively new product, the study of the influencing factors for CPG properties of CLT, and an understanding of the local material behavior under such loading, is essential for product characterization and for the development of design guidelines to ensure safe and efficient design.The main aim of the doctoral thesis is to establish a relationship betweenthe anisotropic behavior of clear wood in the transverse plane and the structural response of CLT under CPG loading. Both experimental and numerical studies were adopted herein, to enhance the understanding of the basic material behavior and the product and structural behavior. On the clear wood scale, the focus was on developing a test setup for uniaxial and biaxial loading in the radial-tangential(RT) plane. The potential of the developed test setup for the biaxial testing in the transverse plane was exploited for the investigation of the moisture and time dependent behavior of clear wood under radial compression and rolling shear loading. For data acquisition, in addition to the force and displacement data measured by the internal actuators of the testing machine and an external load cell,a contact-free digital image correlation (DIC) system was used in the experimental investigations. A numerical model was developed, which can describe the elasto-plastic behavior of wood under compression in the transverse plane and predict the structural behavior of solid wood and CLT. For that purpose, a novel Quadratic multi-surface (QMS) failure criterion and a simplified Hoffman failure criterion were implemented in a user-subroutine in the finite element software Abaqus®, and their suitability was compared with the Abaqus implemented Hill’s criterion.The validation of the material models was based on the experimental investigations of failure behavior of clear wood under stress perpendicular to the grain with rolling shear interaction. The material models were further utilized to predict the structural response of solid wood and CLT wall-to-floor connections under CPG loading. The predicted response of CLT connections under CPG by using the above-mentioned material models was compared with experiments, which investigated the influences of different connection types, wall and floor thicknesses, positions of walls, and outer deck layer orientations. The models were then applied to investigate the influence of the pith location in the boards, the number of layers and the thickness of walls and the floor on the stiffness and strength of CLT connections. Moreover, the CLT connection’s rotational rigidity as a consequence of compressive force from the upper floor in a multi-story building was studied by means of finite element calculations.The DIC measured strain fields from the experiments on clear wood confirmed the dependence of strain field on the curvature of the annual rings. As regards the material models, Hill’s model resulted in significantly higher force carrying capacity than experiments on clear wood, whereas Hoffman’s and QMS models predicted reasonably well the force-displacement relationships as found in experiments. The Hoffman’s and QMS models predicted stiffness was about 5–10% higher than corresponding experimental results on clear wood, and about 25% higher for CLT connections. The higher difference in the latter case is due to the difference in material properties of clear wood and structural timber, and the contact behavior between the structural members. The results from CLT wall-to-floor connections revealed a strong influence of loading and supporting configurations, wall thickness and pith locations on their stiffness and strength. A compressive loading on the CLT wall showed a positive effect on the rotational stiffness of CLT wall-to-floor connections, which considerably reduces the CLT floor mid-span deflection in comparison to a simply-supported floor.The thesis work contributes to an enhanced understanding of the anisotropic material behavior of wood in the RT-plane and of its effects on structural timber and CLT under CPG loading. The outcomes of the thesis are beneficial to the product design and standardization of CLT and can be applied in further product development and in optimized structural design.
25.	Alder-Rangel, Alene, et al. (författare) The Third International Symposium on Fungal Stress – ISFUS 2020 Ingår i: Fungal Biology. - : Elsevier BV. - 1878-6146. ; 124:5, s. 235-252 Tidskriftsartikel (refereegranskat)abstract Stress is a normal part of life for fungi, which can survive in environments considered inhospitable or hostile for other organisms. Due to the ability of fungi to respond to, survive in, and transform the environment, even under severe stresses, many researchers are exploring the mechanisms that enable fungi to adapt to stress. The International Symposium on Fungal Stress (ISFUS) brings together leading scientists from around the world who research fungal stress. This article discusses presentations given at the third ISFUS, held in São José dos Campos, São Paulo, Brazil in 2019, thereby summarizing the state-of-the-art knowledge on fungal stress, a field that includes microbiology, agriculture, ecology, biotechnology, medicine, and astrobiology.
26.	Alić, Ivan, et al. (författare) Correction: Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain. 2021 Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26 Tidskriftsartikel (refereegranskat)
27.	Backes, Claudia, et al. (författare) Production and processing of graphene and related materials 2020 Ingår i: 2D Materials. - : IOP Publishing. - 2053-1583. ; 7:2 Tidskriftsartikel (refereegranskat)abstract We present an overview of the main techniques for production and processing of graphene and related materials (GRMs), as well as the key characterization procedures. We adopt a 'hands-on' approach, providing practical details and procedures as derived from literature as well as from the authors' experience, in order to enable the reader to reproduce the results. Section I is devoted to 'bottom up' approaches, whereby individual constituents are pieced together into more complex structures. We consider graphene nanoribbons (GNRs) produced either by solution processing or by on-surface synthesis in ultra high vacuum (UHV), as well carbon nanomembranes (CNM). Production of a variety of GNRs with tailored band gaps and edge shapes is now possible. CNMs can be tuned in terms of porosity, crystallinity and electronic behaviour. Section II covers 'top down' techniques. These rely on breaking down of a layered precursor, in the graphene case usually natural crystals like graphite or artificially synthesized materials, such as highly oriented pyrolythic graphite, monolayers or few layers (FL) flakes. The main focus of this section is on various exfoliation techniques in a liquid media, either intercalation or liquid phase exfoliation (LPE). The choice of precursor, exfoliation method, medium as well as the control of parameters such as time or temperature are crucial. A definite choice of parameters and conditions yields a particular material with specific properties that makes it more suitable for a targeted application. We cover protocols for the graphitic precursors to graphene oxide (GO). This is an important material for a range of applications in biomedicine, energy storage, nanocomposites, etc. Hummers' and modified Hummers' methods are used to make GO that subsequently can be reduced to obtain reduced graphene oxide (RGO) with a variety of strategies. GO flakes are also employed to prepare three-dimensional (3d) low density structures, such as sponges, foams, hydro- or aerogels. The assembly of flakes into 3d structures can provide improved mechanical properties. Aerogels with a highly open structure, with interconnected hierarchical pores, can enhance the accessibility to the whole surface area, as relevant for a number of applications, such as energy storage. The main recipes to yield graphite intercalation compounds (GICs) are also discussed. GICs are suitable precursors for covalent functionalization of graphene, but can also be used for the synthesis of uncharged graphene in solution. Degradation of the molecules intercalated in GICs can be triggered by high temperature treatment or microwave irradiation, creating a gas pressure surge in graphite and exfoliation. Electrochemical exfoliation by applying a voltage in an electrolyte to a graphite electrode can be tuned by varying precursors, electrolytes and potential. Graphite electrodes can be either negatively or positively intercalated to obtain GICs that are subsequently exfoliated. We also discuss the materials that can be amenable to exfoliation, by employing a theoretical data-mining approach. The exfoliation of LMs usually results in a heterogeneous dispersion of flakes with different lateral size and thickness. This is a critical bottleneck for applications, and hinders the full exploitation of GRMs produced by solution processing. The establishment of procedures to control the morphological properties of exfoliated GRMs, which also need to be industrially scalable, is one of the key needs. Section III deals with the processing of flakes. (Ultra)centrifugation techniques have thus far been the most investigated to sort GRMs following ultrasonication, shear mixing, ball milling, microfluidization, and wet-jet milling. It allows sorting by size and thickness. Inks formulated from GRM dispersions can be printed using a number of processes, from inkjet to screen printing. Each technique has specific rheological requirements, as well as geometrical constraints. The solvent choice is critical, not only for the GRM stability, but also in terms of optimizing printing on different substrates, such as glass, Si, plastic, paper, etc, all with different surface energies. Chemical modifications of such substrates is also a key step. Sections IV-VII are devoted to the growth of GRMs on various substrates and their processing after growth to place them on the surface of choice for specific applications. The substrate for graphene growth is a key determinant of the nature and quality of the resultant film. The lattice mismatch between graphene and substrate influences the resulting crystallinity. Growth on insulators, such as SiO2, typically results in films with small crystallites, whereas growth on the close-packed surfaces of metals yields highly crystalline films. Section IV outlines the growth of graphene on SiC substrates. This satisfies the requirements for electronic applications, with well-defined graphene-substrate interface, low trapped impurities and no need for transfer. It also allows graphene structures and devices to be measured directly on the growth substrate. The flatness of the substrate results in graphene with minimal strain and ripples on large areas, allowing spectroscopies and surface science to be performed. We also discuss the surface engineering by intercalation of the resulting graphene, its integration with Si-wafers and the production of nanostructures with the desired shape, with no need for patterning. Section V deals with chemical vapour deposition (CVD) onto various transition metals and on insulators. Growth on Ni results in graphitized polycrystalline films. While the thickness of these films can be optimized by controlling the deposition parameters, such as the type of hydrocarbon precursor and temperature, it is difficult to attain single layer graphene (SLG) across large areas, owing to the simultaneous nucleation/growth and solution/precipitation mechanisms. The differing characteristics of polycrystalline Ni films facilitate the growth of graphitic layers at different rates, resulting in regions with differing numbers of graphitic layers. High-quality films can be grown on Cu. Cu is available in a variety of shapes and forms, such as foils, bulks, foams, thin films on other materials and powders, making it attractive for industrial production of large area graphene films. The push to use CVD graphene in applications has also triggered a research line for the direct growth on insulators. The quality of the resulting films is lower than possible to date on metals, but enough, in terms of transmittance and resistivity, for many applications as described in section V. Transfer technologies are the focus of section VI. CVD synthesis of graphene on metals and bottom up molecular approaches require SLG to be transferred to the final target substrates. To have technological impact, the advances in production of high-quality large-area CVD graphene must be commensurate with those on transfer and placement on the final substrates. This is a prerequisite for most applications, such as touch panels, anticorrosion coatings, transparent electrodes and gas sensors etc. New strategies have improved the transferred graphene quality, making CVD graphene a feasible option for CMOS foundries. Methods based on complete etching of the metal substrate in suitable etchants, typically iron chloride, ammonium persulfate, or hydrogen chloride although reliable, are time- and resource-consuming, with damage to graphene and production of metal and etchant residues. Electrochemical delamination in a low-concentration aqueous solution is an alternative. In this case metallic substrates can be reused. Dry transfer is less detrimental for the SLG quality, enabling a deterministic transfer. There is a large range of layered materials (LMs) beyond graphite. Only few of them have been already exfoliated and fully characterized. Section VII deals with the growth of some of these materials. Amongst them, h-BN, transition metal tri- and di-chalcogenides are of paramount importance. The growth of h-BN is at present considered essential for the development of graphene in (opto) electronic applications, as h-BN is ideal as capping layer or substrate. The interesting optical and electronic properties of TMDs also require the development of scalable methods for their production. Large scale growth using chemical/physical vapour deposition or thermal assisted conversion has been thus far limited to a small set, such as h-BN or some TMDs. Heterostructures could also be directly grown. Section VIII discusses advances in GRM functionalization. A broad range of organic molecules can be anchored to the sp(2) basal plane by reductive functionalization. Negatively charged graphene can be prepared in liquid phase (e.g. via intercalation chemistry or electrochemically) and can react with electrophiles. This can be achieved both in dispersion or on substrate. The functional groups of GO can be further derivatized. Graphene can also be noncovalently functionalized, in particular with polycyclic aromatic hydrocarbons that assemble on the sp(2) carbon network by pi-pi stacking. In the liquid phase, this can enhance the colloidal stability of SLG/FLG. Approaches to achieve noncovalent on-substrate functionalization are also discussed, which can chemically dope graphene. Research efforts to derivatize CNMs are also summarized, as well as novel routes to selectively address defect sites. In dispersion, edges are the most dominant defects and can be covalently modified. This enhances colloidal stability without modifying the graphene basal plane. Basal plane point defects can also be modified, passivated and healed in ultra-high vacuum. The decoration of graphene with metal nanoparticles (NPs) has also received considerable attention, as it allows to exploit synergistic effects between NPs and graphene. Decoration can be either achieved chemically or in the gas phase. All LMs,
28.	Bengtsson, T, et al. (författare) Loss of alpha 10 beta 1 integrin expression leads to moderate dysfunction of growth plate chondrocytes 2005 Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 118:5, s. 929-936 Tidskriftsartikel (refereegranskat)abstract Integrin alpha 10 beta 1 is a collagen-binding integrin expressed on chondrocytes. In order to unravel the role of the alpha 10 integrin during development, we generated mice carrying a constitutive deletion of the alpha 10 integrin gene. The mutant mice had a normal lifespan and were fertile but developed a growth retardation of the long bones. Analysis of the skeleton revealed defects in the growth plate after birth characterized by a disturbed columnar arrangement of chondrocytes, abnormal chondrocyte shape and reduced chondrocyte proliferation. Electron microscopy of growth plates from newborn mice revealed an increased number of apoptotic chondrocytes and reduced density of the collagen fibrillar network compared to these structures in control mice. These results demonstrate that integrin alpha 10 beta 1 plays a specific role in growth plate morphogenesis and function.
29.	Birkebaek, Niels H., et al. (författare) Letter: Center Size and Glycemic Control: An International Study With 504 Centers From Seven Countries in DIABETES CARE, vol 42, issue 3, pp E37-E39 2019 Ingår i: Diabetes Care. - : AMER DIABETES ASSOC. - 0149-5992 .- 1935-5548. ; 42:3, s. E37-E39 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract n/a
30.	Bozdag, G. Ozan, et al. (författare) Oxygen suppression of macroscopic multicellularity 2021 Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1 Tidskriftsartikel (refereegranskat)abstract Atmospheric oxygen is thought to have played a vital role in the evolution of large, complex multicellular organisms. Challenging the prevailing theory, we show that the transition from an anaerobic to an aerobic world can strongly suppress the evolution of macroscopic multicellularity. Here we select for increased size in multicellular ‘snowflake’ yeast across a range of metabolically-available O2 levels. While yeast under anaerobic and high-O2 conditions evolved to be considerably larger, intermediate O2 constrained the evolution of large size. Through sequencing and synthetic strain construction, we confirm that this is due to O2-mediated divergent selection acting on organism size. We show via mathematical modeling that our results stem from nearly universal evolutionary and biophysical trade-offs, and thus should apply broadly. These results highlight the fact that oxygen is a double-edged sword: while it provides significant metabolic advantages, selection for efficient use of this resource may paradoxically suppress the evolution of macroscopic multicellular organisms.
31.	Bublitz, M, et al. (författare) Structural studies of P-type ATPase-ligand complexes using an X-ray free-electron laser 2015 Ingår i: IUCrJ. - 2052-2525. ; 2:Pt 4, s. 409-420 Tidskriftsartikel (refereegranskat)
32.	Charalampopoulos, Dimitrios, et al. (författare) Exploring Variation in Glycemic Control Across and Within Eight High-Income Countries: A Cross-sectional Analysis of 64,666 Children and Adolescents With Type 1 Diabetes 2018 Ingår i: Diabetes Care. - : AMER DIABETES ASSOC. - 0149-5992 .- 1935-5548. ; 41:6, s. 1180-1187 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE International studies on childhood type 1 diabetes (T1D) have focused on whole-country mean HbA(1c) levels, thereby concealing potential variations within countries. We aimed to explore the variations in HbA(1c) across and within eight high-income countries to best inform international benchmarking and policy recommendations. RESEARCH DESIGN AND METHODS Data were collected between 2013 and 2014 from 64,666 children with T1D who were amp;lt; 18 years of age across 528 centers in Germany, Austria, England, Wales, U.S., Sweden, Denmark, and Norway. We used fixed-and random-effects models adjusted for age, sex, diabetes duration, and minority status to describe differences between center means and to calculate the proportion of total variation in HbA(1c) levels that is attributable to between-center differences (intraclass correlation [ICC]). We also explored the association between within-center variation and childrens glycemic control. RESULTS Sweden had the lowest mean HbA(1c) (59mmol/mol [7.6%]) and together with Norway and Denmark showed the lowest between-center variations (ICC amp;lt;= 4%). Germany and Austria had the next lowest mean HbA(1c) (61-62 mmol/mol [7.7-7.8%]) but showed the largest center variations (ICC similar to 15%). Centers in England, Wales, and the U.S. showed low-to-moderate variation around high mean values. In pooled analysis, differences between counties remained significant after adjustment for children characteristics and center effects (P value amp;lt; 0.001). Across all countries, children attending centers with more variable glycemic results had higher HbA(1c) levels (5.6mmol/mol [0.5%] per 5mmol/mol [0.5%] increase in center SD of HbA(1c) values of all children attending a specific center). CONCLUSIONS A tsimilar average levels of HbA(1c), countries display different levels of center variation. The distribution of glycemic achievement within countries should be considered in developing informed policies that drive quality improvement.
33.	Dawed, Adem Y., et al. (författare) Variation in the plasma membrane monoamine transporter (PMAT) (encoded by SLC29A4) and organic cation transporter 1 (OCT1) (encoded by SLC22A1) and gastrointestinal intolerance to metformin in type 2 diabetes : An IMI direct study 2019 Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 42:6, s. 1027-1033 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE Gastrointestinal adverse effects occur in 20–30% of patients with metformin-treated type 2 diabetes, leading to premature discontinuation in 5–10% of the cases. Gastrointestinal intolerance may reflect localized high concentrations of metformin in the gut. We hypothesized that reduced transport of metformin via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe gastrointestinal adverse effects. RESEARCH DESIGN AND METHODS The study included 286 severe metformin-intolerant and 1,128 metformin-tolerant individuals from the IMI DIRECT (Innovative Medicines Initiative: DIabetes REsearCh on patient straTification) consortium. We assessed the association of patient characteristics, concomitant medication, and the burden of mutations in the SLC29A4 and SLC22A1 genes on odds of intolerance. RESULTS Women (P < 0.001) and older people (P < 0.001) were more likely to develop metformin intolerance. Concomitant use of transporter-inhibiting drugs increased the odds of intolerance (odds ratio [OR] 1.72, P < 0.001). In an adjusted logistic regression model, the G allele at rs3889348 (SLC29A4) was associated with gastrointestinal intolerance (OR 1.34, P = 0.005). rs3889348 is the top cis-expression quantitative trait locus for SLC29A4 in gut tissue where carriers of the G allele had reduced expression. Homozygous carriers of the G allele treated with transporter-inhibiting drugs had more than three times higher odds of intolerance compared with carriers of no G allele and not treated with inhibiting drugs (OR 3.23, P < 0.001). Use of a genetic risk score derived from rs3889348 and SLC22A1 variants found that the odds of intolerance were more than twice as high in individuals who carry three or more risk alleles compared with those carrying none (OR 2.15, P = 0.01). CONCLUSIONS These results suggest that intestinal metformin transporters and concomitant medications play an important role in the gastrointestinal adverse effects of metformin.
34.	Delfin, Carl, et al. (författare) A Federated Database for Obesity Research : An IMI-SOPHIA Study 2024 Ingår i: Life. - 0024-3019. ; 14:2 Tidskriftsartikel (refereegranskat)abstract Obesity is considered by many as a lifestyle choice rather than a chronic progressive disease. The Innovative Medicines Initiative (IMI) SOPHIA (Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy) project is part of a momentum shift aiming to provide better tools for the stratification of people with obesity according to disease risk and treatment response. One of the challenges to achieving these goals is that many clinical cohorts are siloed, limiting the potential of combined data for biomarker discovery. In SOPHIA, we have addressed this challenge by setting up a federated database building on open-source DataSHIELD technology. The database currently federates 16 cohorts that are accessible via a central gateway. The database is multi-modal, including research studies, clinical trials, and routine health data, and is accessed using the R statistical programming environment where statistical and machine learning analyses can be performed at a distance without any disclosure of patient-level data. We demonstrate the use of the database by providing a proof-of-concept analysis, performing a federated linear model of BMI and systolic blood pressure, pooling all data from 16 studies virtually without any analyst seeing individual patient-level data. This analysis provided similar point estimates compared to a meta-analysis of the 16 individual studies. Our approach provides a benchmark for reproducible, safe federated analyses across multiple study types provided by multiple stakeholders.
35.	Dours-Zimmermann, Maria T., et al. (författare) Versican V2 Assembles the Extracellular Matrix Surrounding the Nodes of Ranvier in the CNS 2009 Ingår i: The Journal of Neuroscience. - 1529-2401. ; 29:24, s. 7731-7742 Tidskriftsartikel (refereegranskat)abstract The CNS-restricted versican splice-variant V2 is a large chondroitin sulfate proteoglycan incorporated in the extracellular matrix surrounding myelinated fibers and particularly accumulating at nodes of Ranvier. In vitro, it is a potent inhibitor of axonal growth and therefore considered to participate in the reduction of structural plasticity connected to myelination. To study the role of versican V2 during postnatal development, we designed a novel isoform-specific gene inactivation approach circumventing early embryonic lethality of the complete knock-out and preventing compensation by the remaining versican splice variants. These mice are viable and fertile; however, they display major molecular alterations at the nodes of Ranvier. While the clustering of nodal sodium channels and paranodal structures appear in versican V2-deficient mice unaffected, the formation of the extracellular matrix surrounding the nodes is largely impaired. The conjoint loss of tenascin-R and phosphacan from the perinodal matrix provide strong evidence that versican V2, possibly controlled by a nodal receptor, organizes the extracellular matrix assembly in vivo.
36.	Holmberg, Carl Jacob, et al. (författare) The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study 2022 Ingår i: EUROPEAN JOURNAL OF CANCER. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 40:16 Tidskriftsartikel (refereegranskat)abstract Purpose: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. Methods: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. Results: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. Conclusion: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.
37.	Kim, Dae-Kyum, et al. (författare) EVpedia: A Community Web Portal for Extracellular Vesicles Research 2015 Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 31:6, s. 933-939 Tidskriftsartikel (refereegranskat)abstract Motivation: Extracellular vesicles (EVs) are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of the vesicular nomenclatures and components, online searches for EV-related publications and vesicular components are currently challenging. Results: We present an improved version of EVpedia, a public database for EVs research. This community web portal contains a database of publications and vesicular components, identification of orthologous vesicular components, bioinformatic tools and a personalized function. EVpedia includes 6879 publications, 172 080 vesicular components from 263 high-throughput datasets, and has been accessed more than 65 000 times from more than 750 cities. In addition, about 350 members from 73 international research groups have participated in developing EVpedia. This free web-based database might serve as a useful resource to stimulate the emerging field of EV research.
38.	Kjær, Kasper S., et al. (författare) Finding intersections between electronic excited state potential energy surfaces with simultaneous ultrafast X-ray scattering and spectroscopy 2019 Ingår i: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 10:22, s. 5749-5760 Tidskriftsartikel (refereegranskat)abstract Light-driven molecular reactions are dictated by the excited state potential energy landscape, depending critically on the location of conical intersections and intersystem crossing points between potential surfaces where non-adiabatic effects govern transition probabilities between distinct electronic states. While ultrafast studies have provided significant insight into electronic excited state reaction dynamics, experimental approaches for identifying and characterizing intersections and seams between electronic states remain highly system dependent. Here we show that for 3d transition metal systems simultaneously recorded X-ray diffuse scattering and X-ray emission spectroscopy at sub-70 femtosecond time-resolution provide a solid experimental foundation for determining the mechanistic details of excited state reactions. In modeling the mechanistic information retrieved from such experiments, it becomes possible to identify the dominant trajectory followed during the excited state cascade and to determine the relevant loci of intersections between states. We illustrate our approach by explicitly mapping parts of the potential energy landscape dictating the light driven low-to-high spin-state transition (spin crossover) of [Fe(2,2′-bipyridine)3]2+, where the strongly coupled nuclear and electronic dynamics have been a source of interest and controversy. We anticipate that simultaneous X-ray diffuse scattering and X-ray emission spectroscopy will provide a valuable approach for mapping the reactive trajectories of light-triggered molecular systems involving 3d transition metals.
39.	Kjær, Kasper S., et al. (författare) Solvent control of charge transfer excited state relaxation pathways in [Fe(2,2′-bipyridine)(CN)4]2- 2018 Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 20:6, s. 4238-4249 Tidskriftsartikel (refereegranskat)abstract The excited state dynamics of solvated [Fe(bpy)(CN)4]2-, where bpy = 2,2′-bipyridine, show significant sensitivity to the solvent Lewis acidity. Using a combination of optical absorption and X-ray emission transient spectroscopies, we have previously shown that the metal to ligand charge transfer (MLCT) excited state of [Fe(bpy)(CN)4]2- has a 19 picosecond lifetime and no discernable contribution from metal centered (MC) states in weak Lewis acid solvents, such as dimethyl sulfoxide and acetonitrile.1,2 In the present work, we use the same combination of spectroscopic techniques to measure the MLCT excited state relaxation dynamics of [Fe(bpy)(CN)4]2- in water, a strong Lewis acid solvent. The charge-transfer excited state is now found to decay in less than 100 femtoseconds, forming a quasi-stable metal centered excited state with a 13 picosecond lifetime. We find that this MC excited state has triplet (3MC) character, unlike other reported six-coordinate Fe(ii)-centered coordination compounds, which form MC quintet (5MC) states. The solvent dependent changes in excited state non-radiative relaxation for [Fe(bpy)(CN)4]2- allows us to infer the influence of the solvent on the electronic structure of the complex. Furthermore, the robust characterization of the dynamics and optical spectral signatures of the isolated 3MC intermediate provides a strong foundation for identifying 3MC intermediates in the electronic excited state relaxation mechanisms of similar Fe-centered systems being developed for solar applications.
40.	Kopp, Reinhard, et al. (författare) Multicenter Analysis of Endovascular Aortic Arch In Situ Stent-Graft Fenestrations for Aortic Arch Pathologies 2019 Ingår i: Annals of Vascular Surgery. - : Elsevier BV. - 0890-5096. ; 59, s. 36-47 Tidskriftsartikel (refereegranskat)abstract Background: In situ fenestration of aortic stent grafts for treatment of aortic arch aneurysms is a new option for endovascular aortic arch repair. So far, only few reports have shown perioperative and short-term results of in situ fenestrations for aortic arch diseases. We present the multicenter experience with the aortic arch in situ fenestration technique documented in the AARCHIF registry for treatment of aortic arch aneurysms or localized type A aortic dissections and analyzed perioperative outcome and midterm follow-up. Methods: Patients with aortic arch pathologies treated by aortic arch in situ fenestration with proximal stent graft landing in aortic arch Ishimura zones 0 and 1 were included in the registry. Stent-graft in situ fenestrations were created using needles or radiofrequency or laser catheters and completed by implantation of covered connecting stent grafts. Single in situ fenestrations for the left subclavian artery (LSA) were excluded. Results: Between 06/2009 and 03/2017, twenty-five patients were treated by in situ stent-graft fenestrations for aortic arch pathologies at 9 institutions in 7 different countries, 3 of them as bailout procedures for stent-graft malplacement. In situ fenestrations were performed for the brachiocephalic trunk (n = 20), the left common carotid artery (n = 21) and the LSA (n = 9). Technical success for intended in situ fenestrations was 94.0% (47/50), with additional supraaortic bypass procedures performed in 14 patients. Perioperative mortality occurred in 1 (4.0%) patient, treated as a bailout procedure and 3 (12.0%) perioperative strokes were observed. One proximal aortic stent-graft nonalignment and 4 type III endoleaks, 2 early and 2 late, required reeintervention. During follow-up (1–118 months), the diameter of aortic arch aneurysms decreased from 61.5 ± 4.1 mm to 48.4 ± 3.2 mm (P = 0.02) and, so far, 6 patients died from diseases unrelated to their aortic arch pathologies with a mean survival time of 79.5 months and 3 endovascular reinterventions for distal aortic expansion were performed. Cerebrovascular event (n = 4) was the most relevant prognostic factor for mortality during midterm follow-up (P = 0.003). Conclusions: The aortic arch in situ fenestration technique for endovascular aortic arch repair seems to be valuable treatment option for selected patients, although initial consideration of other treatment options is mandatory. Data about long-term durability are required.
41.	Kuhn, J, et al. (författare) Supramolecular Assembly of Aminoethylene-Lipopeptide PMO Conjugates into RNA Splice-Switching Nanomicelles 2019 Ingår i: ADVANCED FUNCTIONAL MATERIALS. - : Wiley. - 1616-301X .- 1616-3028. ; 29:48 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
42.	Kunnus, Kristjan, et al. (författare) Vibrational wavepacket dynamics in Fe carbene photosensitizer determined with femtosecond X-ray emission and scattering 2020 Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1 Tidskriftsartikel (refereegranskat)abstract The non-equilibrium dynamics of electrons and nuclei govern the function of photoactive materials. Disentangling these dynamics remains a critical goal for understanding photoactive materials. Here we investigate the photoinduced dynamics of the [Fe(bmip)2]2+ photosensitizer, where bmip = 2,6-bis(3-methyl-imidazole-1-ylidine)-pyridine, with simultaneous femtosecond-resolution Fe Kα and Kβ X-ray emission spectroscopy (XES) and X-ray solution scattering (XSS). This measurement shows temporal oscillations in the XES and XSS difference signals with the same 278 fs period oscillation. These oscillations originate from an Fe-ligand stretching vibrational wavepacket on a triplet metal-centered (3MC) excited state surface. This 3MC state is populated with a 110 fs time constant by 40% of the excited molecules while the rest relax to a 3MLCT excited state. The sensitivity of the Kα XES to molecular structure results from a 0.7% average Fe-ligand bond length shift between the 1 s and 2p core-ionized states surfaces.
43.	Linden, V, et al. (författare) High survival in adult patients with acute respiratory distress syndrome treated by extracorporeal membrane oxygenation, minimal sedation, and pressure supported ventilation 2000 Ingår i: Intensive care medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 26:11, s. 1630-1637 Tidskriftsartikel (refereegranskat)
44.	Linden, V, et al. (författare) Inter-hospital transportation of patients with severe acute respiratory failure on extracorporeal membrane oxygenation--national and international experience 2001 Ingår i: Intensive care medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 27:10, s. 1643-1648 Tidskriftsartikel (refereegranskat)
45.	Martrat, Griselda, et al. (författare) Exploring the link between MORF4L1 and risk of breast cancer 2011 Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 13:2 Tidskriftsartikel (refereegranskat)abstract Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to g-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, P-trend = 0.45 and 0.05, P-2df = 0.51 and 0.14, respectively; and rs10519219, P-trend = 0.92 and 0.72, P-2df = 0.76 and 0.07, respectively. Conclusions: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.
46.	Oohashi, T, et al. (författare) Mouse ten-m/Odz is a new family of dimeric type II transmembrane proteins expressed in many tissues 1999 Ingår i: Journal of Cell Biology. - 0021-9525. ; 145:3, s. 563-577 Tidskriftsartikel (refereegranskat)abstract The Drosophila gene ten-m/odz is the only pair rule gene identified to date which is not a transcription factor. In an attempt to analyze the structure and the function of ten-m/odz in mouse, we isolated four murine ten-m cDNAs which code for proteins of 2,700-2, 800 amino acids. All four proteins (Ten-m1-4) lack signal peptides at the NH2 terminus, but contain a short hydrophobic domain characteristic of transmembrane proteins, 300-400 amino acids after the NH2 terminus. About 200 amino acids COOH-terminal to this hydrophobic region are eight consecutive EGF-like domains. Cell transfection, biochemical, and electronmicroscopic studies suggest that Ten-m1 is a dimeric type II transmembrane protein. Expression of fusion proteins composed of the NH2-terminal and hydrophobic domain of ten-m1 attached to the alkaline phosphatase reporter gene resulted in membrane-associated staining of the alkaline phosphatase. Electronmicroscopic and electrophoretic analysis of a secreted form of the extracellular domain of Ten-m1 showed that Ten-m1 is a disulfide-linked dimer and that the dimerization is mediated by EGF-like modules 2 and 5 which contain an odd number of cysteines. Northern blot and immunohistochemical analyses revealed widespread expression of mouse ten-m genes, with most prominent expression in brain. All four ten-m genes can be expressed in variously spliced mRNA isoforms. The extracellular domain of Ten-m1 fused to an alkaline phosphatase reporter bound to specific regions in many tissues which were partially overlapping with the Ten-m1 immunostaining. Far Western assays and electronmicroscopy demonstrated that Ten-m1 can bind to itself.
47.	Ostaszewski, Marek, et al. (författare) COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms 2021 Ingår i: Molecular Systems Biology. - : John Wiley & Sons. - 1744-4292 .- 1744-4292. ; 17:10 Tidskriftsartikel (refereegranskat)abstract We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.
48.	Reinhard, H, et al. (författare) Endothelial progenitor cells in long-standing asymptomatic type 1 diabetic patients with or without diabetic nephropathy 2011 Ingår i: Nephron. Clinical practice. - : S. Karger AG. - 1660-2110. ; 118:3, s. C309-C314 Tidskriftsartikel (refereegranskat)abstract A decrease in the number and dysfunction of endothelial progenitor cells (EPC) may increase the risk for progression of cardiovascular disease (CVD) in type 1 diabetic patients with diabetic nephropathy (DN). Our aim was to evaluate EPC numbers in asymptomatic CVD type 1 diabetic patients with or without DN and to study the effect of CVD and medication on EPC numbers. <i>Methods:</i> We examined EPC numbers in 37 type 1 diabetic patients with DN and 35 type 1 diabetic patients with long-standing normoalbuminuria. Patients were without symptoms of CVD and the prevalence of CVD was previously shown to be very low. EPC number was assessed in in vitro cultures by fluorescent staining of attached cells. <i>Results:</i> There was no difference in EPC numbers between patients with DN (mean ± SD 120 ± 49 cells/field) and normoalbuminuria (108 ± 41 cells/field; p = 0.25). Furthermore, EPC number was not associated with CVD (p > 0.05). Conventional risk factors were significantly higher in patients with DN and they received more CVD-preventive treatment. All patients receiving simvastatin or calcium-channel blockers had higher numbers of EPC compared to patients not treated with these drugs. <i>Conclusions:</i> Asymptomatic patients with DN had EPC numbers similar to normoalbuminuric patients, which was related to aggressive CVD intervention therapy. This may have contributed to the low prevalence of CVD.
49.	Reinhard, H, et al. (författare) Multifactorial treatment increases circulating endothelial progenitor cell number in type 2 diabetic patients 2007 Ingår i: DIABETOLOGIA. - 0012-186X. ; 50, s. S481-S481 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
50.	Reinhard, H, et al. (författare) Multifactorial treatment increases endothelial progenitor cells in patients with type 2 diabetes 2010 Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 53:10, s. 2129-2133 Tidskriftsartikel (refereegranskat)

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