| 1. |
- Egg, David, et al.
(författare)
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Therapeutic options for CTLA-4 insufficiency
- 2022
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Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 149:2, s. 736-746
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heterozygous germline mutations in cytotoxic T lymphocyte-associated antigen-4 (CTLA4) impair the immunomodulatory function of regulatory T cells. Affected individuals are prone to life-threatening autoimmune and lymphoproliferative complications. A number of therapeutic options are currently being used with variable effectiveness. Objective: Our aim was to characterize the responsiveness of patients with CTLA-4 insufficiency to specific therapies and provide recommendations for the diagnostic workup and therapy at an organ-specific level. Methods: Clinical features, laboratory findings, and response to treatment were reviewed retrospectively in an international cohort of 173 carriers of CTLA4 mutation. Patients were followed between 2014 and 2020 for a total of 2624 months from diagnosis. Clinical manifestations were grouped on the basis of organ-specific involvement. Medication use and response were recorded and evaluated. Results: Among the 173 CTLA4 mutation carriers, 123 (71%) had been treated for immune complications. Abatacept, rituximab, sirolimus, and corticosteroids ameliorated disease severity, especially in cases of cytopenias and lymphocytic organ infiltration of the gut, lungs, and central nervous system. Immunoglobulin replacement was effective in prevention of infection. Only 4 of 16 patients (25%) with cytopenia who underwent splenectomy had a sustained clinical response. Cure was achieved with stem cell transplantation in 13 of 18 patients (72%). As a result of the aforementioned methods, organ-specific treatment pathways were developed. Conclusion: Systemic immunosuppressants and abatacept may provide partial control but require ongoing administration. Allogeneic hematopoietic stem cell transplantation offers a possible cure for patients with CTLA-4 insufficiency.
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| 2. |
- Hon, Marc, et al.
(författare)
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A close-in giant planet escapes engulfment by its star
- 2023
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 618:7967, s. 917-920
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Tidskriftsartikel (refereegranskat)abstract
- When main-sequence stars expand into red giants, they are expected to engulf close-in planets(1-5). Until now, the absence of planets with short orbital periods around post-expansion, core-helium-burning red giants(6-8) has been interpreted as evidence that short-period planets around Sun-like stars do not survive the giant expansion phase of their host stars(9). Here we present the discovery that the giant planet 8 Ursae Minoris b(10) orbits a core-helium-burning red giant. At a distance of only 0.5 au from its host star, the planet would have been engulfed by its host star, which is predicted by standard single-star evolution to have previously expanded to a radius of 0.7 au. Given the brief lifetime of helium-burning giants, the nearly circular orbit of the planet is challenging to reconcile with scenarios in which the planet survives by having a distant orbit initially. Instead, the planet may have avoided engulfment through a stellar merger that either altered the evolution of the host star or produced 8 Ursae Minoris b as a second-generation planet(11). This system shows that core-helium-burning red giants can harbour close planets and provides evidence for the role of non-canonical stellar evolution in the extended survival of late-stage exoplanetary systems.
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| 3. |
- Kim, Ji-Hoon, et al.
(författare)
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A Pulse of Meteoric Subsurface Fluid Discharging Into the Chukchi Sea During the Early Holocene Thermal Maximum (EHTM)
- 2021
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Ingår i: Geochemistry Geophysics Geosystems. - 1525-2027. ; 22:8
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Tidskriftsartikel (refereegranskat)abstract
- The response of Arctic Ocean biogeochemistry to subsurface flow driven by permafrost thaw is poorly understood. We present dissolved chloride and water isotopic data from the Chukchi Sea Shelf sediments that reveal the presence of a meteoric subsurface flow enriched in cations with a radiogenic Sr fingerprint. This subsurface fluid is also enriched in dissolved inorganic carbon and methane that bear isotopic compositions indicative of a carbon reservoir modified by reactions in a closed system. Such fluid characteristics are in stark contrast with those from other sites in the Chukchi Sea where the pore water composition shows no sign of meteoric input, but reflect typical biogeochemical reactions associated with early diagenetic sequences in marine sediment. The most likely source of the observed subsurface flow at the Chukchi Sea Shelf is from the degradation of permafrost that had extended to the shelf region during the Last Glacial Maximum. Our data suggest that the permafrost-driven subsurface flow most likely took place during the 2-3 degrees C warming in the Early Holocene Thermal Maximum. This time scale is supported by numerical simulation of pore water profiles, which indicate that a minimum of several thousand years must have passed since the cessation of the subsurface methane-bearing fluid flow.
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| 4. |
- Kostka, Kristin, et al.
(författare)
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Unraveling COVID-19: A Large-Scale Characterization of 4.5 Million COVID-19 Cases Using CHARYBDIS.
- 2022
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Ingår i: Clinical epidemiology. - 1179-1349. ; 14, s. 369-384
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Tidskriftsartikel (refereegranskat)abstract
- Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD.We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services.We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed.We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.
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| 5. |
- Rae, Caroline D., et al.
(författare)
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Brain energy metabolism : A roadmap for future research
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Ingår i: Journal of Neurochemistry. - 0022-3042.
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Tidskriftsartikel (refereegranskat)abstract
- Although we have learned much about how the brain fuels its functions over the last decades, there remains much still to discover in an organ that is so complex. This article lays out major gaps in our knowledge of interrelationships between brain metabolism and brain function, including biochemical, cellular, and subcellular aspects of functional metabolism and its imaging in adult brain, as well as during development, aging, and disease. The focus is on unknowns in metabolism of major brain substrates and associated transporters, the roles of insulin and of lipid droplets, the emerging role of metabolism in microglia, mysteries about the major brain cofactor and signaling molecule NAD+, as well as unsolved problems underlying brain metabolism in pathologies such as traumatic brain injury, epilepsy, and metabolic downregulation during hibernation. It describes our current level of understanding of these facets of brain energy metabolism as well as a roadmap for future research.
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