| 1. |
- Rajewsky, N., et al.
(författare)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Tidskriftsartikel (refereegranskat)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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| 2. |
- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 3. |
- Pelletier, F., et al.
(författare)
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Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C
- 2021
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:2
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Tidskriftsartikel (refereegranskat)abstract
- Context: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. Objective: To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. Design: An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. Setting: This was a multicenter retrospective study using information collected from 3 predominant centers. Patients: A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. Main Outcome Measures: Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. Results: The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. Conclusions: Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder.
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| 6. |
- de Muynck, Ldan, et al.
(författare)
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Consensus Statement on the Use of Near-Infrared Fluorescence Imaging during Pancreatic Cancer Surgery Based on a Delphi Study: Surgeons' Perspectives on Current Use and Future Recommendations
- 2023
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Despite the potential of fluorescence imaging during pancreatic cancer surgery, more research is needed to facilitate the approval of tumor-targeted probes, standardize imaging techniques, and most importantly, gain trust from surgeons. Despite advancements in the development of novel probes, preclinical research settings do not always accurately represent the surgical setting. This first-of-its-kind Delphi consensus survey highlights current experiences and attitudes towards fluorescence imaging during pancreatic cancer surgery, specifically from surgeon's perspectives. The results from this consensus survey highlight potential new directions for future research, which could facilitate the standardized use of fluorescence imaging during pancreatic surgery. Indocyanine green (ICG) is one of the only clinically approved near-infrared (NIR) fluorophores used during fluorescence-guided surgery (FGS), but it lacks tumor specificity for pancreatic ductal adenocarcinoma (PDAC). Several tumor-targeted fluorescent probes have been evaluated in PDAC patients, yet no uniformity or consensus exists among the surgical community on the current and future needs of FGS during PDAC surgery. In this first-published consensus report on FGS for PDAC, expert opinions were gathered on current use and future recommendations from surgeons' perspectives. A Delphi survey was conducted among international FGS experts via Google Forms. Experts were asked to anonymously vote on 76 statements, with >= 70% agreement considered consensus and >= 80% participation/statement considered vote robustness. Consensus was reached for 61/76 statements. All statements were considered robust. All experts agreed that FGS is safe with few drawbacks during PDAC surgery, but that it should not yet be implemented routinely for tumor identification due to a lack of PDAC-specific NIR tracers and insufficient evidence proving FGS's benefit over standard methods. However, aside from tumor imaging, surgeons suggest they would benefit from visualizing vasculature and surrounding anatomy with ICG during PDAC surgery. Future research could also benefit from identifying neuroendocrine tumors. More research focusing on standardization and combining tumor identification and vital-structure imaging would greatly improve FGS's use during PDAC surgery.
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| 7. |
- Maricic, T, et al.
(författare)
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A direct RT-qPCR approach to test large numbers of individuals for SARS-CoV-2
- 2020
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 15:12, s. e0244824-
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Tidskriftsartikel (refereegranskat)abstract
- SARS-CoV-2 causes substantial morbidity and mortality in elderly and immunocompromised individuals, particularly in retirement homes, where transmission from asymptomatic staff and visitors may introduce the infection. Here we present a cheap and fast screening method based on direct RT-qPCR to detect SARS-CoV-2 in single or pooled gargle lavages (“mouthwashes”). This method detects individuals with large viral loads (Ct≤29) and we use it to test all staff at a nursing home daily over a period of three weeks in order to reduce the risk that the infection penetrates the facility. This or similar approaches can be implemented to protect hospitals, nursing homes and other institutions in this and future viral epidemics.
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| 8. |
- Nöthe, M., et al.
(författare)
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Prototype Open Event Reconstruction Pipeline for the Cherenkov Telescope Array
- 2022
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Ingår i: 37th International Cosmic Ray Conference (ICRC2021) - GAI - Gamma Ray Indirect. - Trieste, Italy : Sissa Medialab. - 1824-8039. ; 395
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Konferensbidrag (refereegranskat)abstract
- The Cherenkov Telescope Array (CTA) is the next-generation gamma-ray observatory currently under construction. It will improve over the current generation of imaging atmospheric Cherenkov telescopes (IACTs) by a factor of five to ten in sensitivity and it will be able to observe the whole sky from a combination of two sites: a northern site in La Palma, Spain, and a southern one in Paranal, Chile. CTA will also be the first open gamma-ray observatory. Accordingly, the data analysis pipeline is developed as open-source software. The event reconstruction pipeline accepts raw data of the telescopes and processes it to produce suitable input for the higher-level science tools. Its primary tasks include reconstructing the physical properties of each recorded shower and providing the corresponding instrument response functions. ctapipe is a framework providing algorithms and tools to facilitate raw data calibration, image extraction, image parameterization and event reconstruction. Its main focus is currently the analysis of simulated data but it has also been successfully applied for the analysis of data obtained with the first CTA prototype telescopes, such as the Large-Sized Telescope 1 (LST-1). pyirf is a library to calculate IACT instrument response functions, needed to obtain physics results like spectra and light curves, from the reconstructed event lists. Building on these two, protopipe is a prototype for the event reconstruction pipeline for CTA. Recent developments in these software packages will be presented. © Copyright owned by the author(s) under the terms of the Creative Commons.
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