| 11. |
- Allesøe, Rosa Lundbye, et al.
(författare)
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Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
- 2023
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408
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Tidskriftsartikel (refereegranskat)abstract
- The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
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| 12. |
- Beck, Lisa J., et al.
(författare)
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Differing Mechanisms of New Particle Formation at Two Arctic Sites
- 2021
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 48:4
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Tidskriftsartikel (refereegranskat)abstract
- New particle formation in the Arctic atmosphere is an important source of aerosol particles. Understanding the processes of Arctic secondary aerosol formation is crucial due to their significant impact on cloud properties and therefore Arctic amplification. We observed the molecular formation of new particles from low-volatility vapors at two Arctic sites with differing surroundings. In Svalbard, sulfuric acid (SA) and methane sulfonic acid (MSA) contribute to the formation of secondary aerosol and to some extent to cloud condensation nuclei (CCN). This occurs via ion-induced nucleation of SA and NH3 and subsequent growth by mainly SA and MSA condensation during springtime and highly oxygenated organic molecules during summertime. By contrast, in an ice-covered region around Villum, we observed new particle formation driven by iodic acid but its concentration was insufficient to grow nucleated particles to CCN sizes. Our results provide new insight about sources and precursors of Arctic secondary aerosol particles.
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| 13. |
- Bejanyan, Nelli, et al.
(författare)
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Myeloablative Conditioning for Allogeneic Transplantation Results in Superior Disease-Free Survival for Acute Myelogenous Leukemia and Myelodysplastic Syndromes with Low/Intermediate but not High Disease Risk Index : A Center for International Blood and Marrow Transplant Research Study
- 2021
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Ingår i: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 27:1, s. 68.e1-68.e9
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Tidskriftsartikel (refereegranskat)abstract
- Compared with reduced-intensity conditioning (RIC), myeloablative conditioning (MAC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, disease-specific risk factors in AML/MDS can further inform when MAC and RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the Disease Risk Index (DRI) in 4387 adults (age 40 to 65 years) to identify the impact of conditioning intensity. In the low/ intermediate-risk DRI cohort, RIC was associated with lower nonrelapse mortality (NRM) (hazard ratio [HR],.74; 95% confidence interval [CI],.62 to.88; P <.001) but significantly greater relapse risk (HR, 1.54; 95% CI, 1.35 to 1.76; P <.001) and thus inferior disease-free survival (DFS) (HR, 1.19; 95% CI, 1.07 to 1.33; P =.001). In the high/ very high-risk DRI cohort, RIC was associated with marginally lower NRM (HR,.83; 95% CI,.68 to 1.00; P =.051) and significantly higher relapse risk (HR, 1.23; 95% CI, 1.08 to 1.41; P =.002), leading to similar DFS using either RIC or MAC. These data support MAC over RIC as the preferred conditioning intensity for patients with AML/MDS with low/intermediate-risk DRI, but with a similar benefit as RIC in high/very high-risk DRI. Novel MAC regimens with less toxicity could benefit all patients, but more potent antineoplastic approaches are needed for the high/ very-high risk DRI group.
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| 14. |
- Bruze, Magnus, et al.
(författare)
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Increased rates of fragrance allergy in fibromyalgia individuals tested with the Swedish baseline patch test series
- 2023
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 0926-9959 .- 1468-3083. ; 37:1, s. 104-113
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Tidskriftsartikel (refereegranskat)abstract
- Background: Contact allergy can manifest in a variety of ways clinically. Systemic contact allergy may occasionally present with pain in muscles and joints. Fibromyalgia is a chronic rheumatic disease characterized by pain and with virtually unknown aetiology. Objectives: The aim of this study was to investigate the contact allergy rates to the sensitizers in a baseline series and compare with corresponding rates in dermatitis patients and the general population. Methods: Patch testing with the Swedish baseline series was performed in 120 individuals with fibromyalgia. Fisher's exact test was used for pair-wise comparisons of contact allergy rates between the fibromyalgia group and two control groups, dermatitis patients and individuals in the general population. Results: Contact allergy was significantly more common in the fibromyalgia group compared to the general population concerning nickel and the fragrance markers Myroxolon pereirae and fragrance mix I. There were fewer allergic reactions to preservatives in the fibromyalgia group compared with the dermatitis group. Conclusions: Myroxolon pereirae and fragrance mix I represent besides fragrance allergy also allergy to flavouring substances which indicate that oral exposure to flavouring substances and hygiene products might be important for sensitization and possibly elicitation of systemic contact allergy symptoms in fibromyalgia individuals.
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| 15. |
- De Rezende, Susanna F., et al.
(författare)
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Automating algebraic proof systems is NP-hard
- 2021
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Ingår i: STOC 2021 - Proceedings of the 53rd Annual ACM SIGACT Symposium on Theory of Computing. - New York, NY, USA : ACM. - 0737-8017. - 9781450380539 ; , s. 209-222
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Konferensbidrag (refereegranskat)abstract
- We show that algebraic proofs are hard to find: Given an unsatisfiable CNF formula F, it is NP-hard to find a refutation of F in the Nullstellensatz, Polynomial Calculus, or Sherali-Adams proof systems in time polynomial in the size of the shortest such refutation. Our work extends, and gives a simplified proof of, the recent breakthrough of Atserias and Müller (JACM 2020) that established an analogous result for Resolution.
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| 16. |
- De Rezende, Susanna F., et al.
(författare)
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KRW composition theorems via lifting
- 2020
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Ingår i: Proceedings - 2020 IEEE 61st Annual Symposium on Foundations of Computer Science, FOCS 2020. - 0272-5428. - 9781728196213 - 9781728196220 ; 2020-November, s. 43-49
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Konferensbidrag (refereegranskat)abstract
- One of the major open problems in complexity theory is proving super-logarithmic lower bounds on the depth of circuits (i.e., mathrm{P} nsubseteq text{NC}{1}). Karchmer, Raz, and Wigderson [13] suggested to approach this problem by proving that depth complexity behaves'as expected' with respect to the composition of functions f diamond g. They showed that the validity of this conjecture would imply that mathrm{P} nsubseteq text{NC}{1}. Several works have made progress toward resolving this conjecture by proving special cases. In particular, these works proved the KRW conjecture for every outer function, but only for few inner functions. Thus, it is an important challenge to prove the KRW conjecture for a wider range of inner functions. In this work, we extend significantly the range of inner functions that can be handled. First, we consider the monotone version of the KRW conjecture. We prove it for every monotone inner function whose depth complexity can be lower bounded via a query-to-communication lifting theorem. This allows us to handle several new and well-studied functions such as the s-t-connectivity, clique, and generation functions. In order to carry this progress back to the non-monotone setting, we introduce a new notion of semi-monotone composition, which combines the non-monotone complexity of the outer function with the monotone complexity of the inner function. In this setting, we prove the KRW conjecture for a similar selection of inner functions, but only for a specific choice of the outer function f.
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| 17. |
- De Rezende, Susanna F., et al.
(författare)
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Nullstellensatz Size-Degree Trade-offs from Reversible Pebbling
- 2021
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Ingår i: Computational Complexity. - : Springer Science and Business Media LLC. - 1016-3328 .- 1420-8954. ; 30:1
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Tidskriftsartikel (refereegranskat)abstract
- We establish an exactly tight relation between reversiblepebblings of graphs and Nullstellensatz refutations of pebbling formulas,showing that a graph G can be reversibly pebbled in time t and space s if and only if there is a Nullstellensatz refutation of the pebbling formulaover G in size t + 1 and degree s (independently of the field in whichthe Nullstellensatz refutation is made). We use this correspondenceto prove a number of strong size-degree trade-offs for Nullstellensatz,which to the best of our knowledge are the first such results for thisproof system.
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| 18. |
- De Rezende, Susanna, et al.
(författare)
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Lifting with simple gadgets and applications to circuit and proof complexity
- 2020
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Ingår i: Proceedings - 2020 IEEE 61st Annual Symposium on Foundations of Computer Science, FOCS 2020. - 0272-5428. - 9781728196213 - 9781728196220 ; 2020-November, s. 24-30
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Konferensbidrag (refereegranskat)abstract
- We significantly strengthen and generalize the theorem lifting Nullstellensatz degree to monotone span program size by Pitassi and Robere (2018) so that it works for any gadget with high enough rank, in particular, for useful gadgets such as equality and greater-than. We apply our generalized theorem to solve three open problems: •We present the first result that demonstrates a separation in proof power for cutting planes with unbounded versus polynomially bounded coefficients. Specifically, we exhibit CNF formulas that can be refuted in quadratic length and constant line space in cutting planes with unbounded coefficients, but for which there are no refutations in subexponential length and subpolynomial line space if coefficients are restricted to be of polynomial magnitude. •We give the first explicit separation between monotone Boolean formulas and monotone real formulas. Specifically, we give an explicit family of functions that can be computed with monotone real formulas of nearly linear size but require monotone Boolean formulas of exponential size. Previously only a non-explicit separation was known. •We give the strongest separation to-date between monotone Boolean formulas and monotone Boolean circuits. Namely, we show that the classical GEN problem, which has polynomial-size monotone Boolean circuits, requires monotone Boolean formulas of size 2{Omega(n text{polylog}(n))}. An important technical ingredient, which may be of independent interest, is that we show that the Nullstellensatz degree of refuting the pebbling formula over a DAG G over any field coincides exactly with the reversible pebbling price of G. In particular, this implies that the standard decision tree complexity and the parity decision tree complexity of the corresponding falsified clause search problem are equal. This is an extended abstract. The full version of the paper is available at https://arxiv.org/abs/2001.02144.
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| 19. |
- Forsgård, Richard A., 1987-, et al.
(författare)
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Limosilactobacillus reuteri DSM 17938 supplementation and SARS-CoV-2 specific antibody response in healthy adults : a randomized, triple-blinded, placebo-controlled trial
- 2023
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Ingår i: Gut microbes. - : Taylor & Francis. - 1949-0976 .- 1949-0984. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Studies have shown that probiotics can decrease the symptoms of respiratory tract infections as well as increase antibody responses following certain vaccinations. We examined the effect of probiotic supplementation on anti-SARS-CoV-2 specific antibody responses upon SARS-CoV-2 infection as well as after COVID-19 vaccination. In this randomized, triple-blinded, placebo-controlled intervention study with a parallel design, 159 healthy adults without prior SARS-CoV-2 infection or COVID-19 vaccination and any known risk factors for severe COVID-19 were randomly allocated into two study arms. The active treatment arm consumed a probiotic product containing a minimum of 1 × 108 colony-forming units of Limosilactobacillus reuteri DSM 17938 + 10 μg vitamin D3 twice daily for 6 months. The placebo arm consumed identical tablets containing only 10 μg vitamin D3. Anti-SARS-CoV-2 specific antibodies and virus neutralizing antibody titers were analyzed from blood samples collected at baseline, after 3 months, and after 6 months. Differences in serum antibody titers between the two study arms were tested with independent t-test using log-transformed values. In the intention-to-treat (ITT) analysis, SARS-CoV-2 infected individuals in the active treatment arm (n = 6) tended to have higher serum anti-spike IgG (609 [168-1480] BAU/ml vs 111 [36.1-1210] BAU/ml, p = 0.080) and anti-receptor binding domain (RBD) IgG (928 [212-3449] BAU/ml vs (83.7 [22.8-2094] BAU/ml, p = 0.066) levels than individuals in the placebo arm (n = 6). Considering individuals who were fully vaccinated with mRNA-based COVID-19 vaccines, the active treatment arm (n = 10) exhibited significantly higher serum levels of anti-RBD IgA (135 [32.9-976] BAU/ml vs 61.3 [26.7-97.1] BAU/ml, p = 0.036) than the placebo arm (n = 7) >28 days postvaccination. Supplementation with specific probiotics might improve the long-term efficacy of mRNA-based COVID-19 vaccines via enhanced IgA response.
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| 20. |
- Goobar, Ariel, 1962-, et al.
(författare)
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Uncovering a population of gravitational lens galaxies with magnified standard candle SN Zwicky
- 2023
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Ingår i: Nature Astronomy. - 2397-3366. ; 7:9, s. 1098-1107
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Tidskriftsartikel (refereegranskat)abstract
- Detecting gravitationally lensed supernovae is among the biggest challenges in astronomy. It involves a combination of two very rare phenomena: catching the transient signal of a stellar explosion in a distant galaxy and observing it through a nearly perfectly aligned foreground galaxy that deflects light towards the observer. Here we describe how high-cadence optical observations with the Zwicky Transient Facility, with its unparalleled large field of view, led to the detection of a multiply imaged type Ia supernova, SN Zwicky, also known as SN 2022qmx. Magnified nearly 25-fold, the system was found thanks to the standard candle nature of type Ia supernovae. High-spatial-resolution imaging with the Keck telescope resolved four images of the supernova with very small angular separation, corresponding to an Einstein radius of only θE = 0.167″ and almost identical arrival times. The small θE and faintness of the lensing galaxy are very unusual, highlighting the importance of supernovae to fully characterize the properties of galaxy-scale gravitational lenses, including the impact of galaxy substructures.
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