| 1. |
- Kang, E. Y., et al.
(författare)
-
MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma
- 2022
-
Ingår i: Virchows Archiv. - : Springer Science and Business Media LLC. - 0945-6317 .- 1432-2307. ; 480, s. 855-871
-
Tidskriftsartikel (refereegranskat)abstract
- Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naive HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naive tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naive HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36-0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.
|
|
| 2. |
- Al Kharusi, S., et al.
(författare)
-
SNEWS 2.0 : a next-generation supernova early warning system for multi-messenger astronomy
- 2021
-
Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 23:3
-
Forskningsöversikt (refereegranskat)abstract
- The next core-collapse supernova in the Milky Way or its satellites will represent a once-in-a-generation opportunity to obtain detailed information about the explosion of a star and provide significant scientific insight for a variety of fields because of the extreme conditions found within. Supernovae in our galaxy are not only rare on a human timescale but also happen at unscheduled times, so it is crucial to be ready and use all available instruments to capture all possible information from the event. The first indication of a potential stellar explosion will be the arrival of a bright burst of neutrinos. Its observation by multiple detectors worldwide can provide an early warning for the subsequent electromagnetic fireworks, as well as signal to other detectors with significant backgrounds so they can store their recent data. The supernova early warning system (SNEWS) has been operating as a simple coincidence between neutrino experiments in automated mode since 2005. In the current era of multi-messenger astronomy there are new opportunities for SNEWS to optimize sensitivity to science from the next galactic supernova beyond the simple early alert. This document is the product of a workshop in June 2019 towards design of SNEWS 2.0, an upgraded SNEWS with enhanced capabilities exploiting the unique advantages of prompt neutrino detection to maximize the science gained from such a valuable event.
|
|
| 3. |
|
|
| 4. |
- Zurcher, N. R., et al.
(författare)
-
C-11 PBR28 MR-PET imaging reveals lower regional brain expression of translocator protein (TSPO) in young adult males with autism spectrum disorder
- 2021
-
Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578.
-
Tidskriftsartikel (refereegranskat)abstract
- Mechanisms of neuroimmune and mitochondrial dysfunction have been repeatedly implicated in autism spectrum disorder (ASD). To examine these mechanisms in ASD individuals, we measured the in vivo expression of the 18 kDa translocator protein (TSPO), an activated glial marker expressed on mitochondrial membranes. Participants underwent scanning on a simultaneous magnetic resonance-positron emission tomography (MR-PET) scanner with the second-generation TSPO radiotracer [C-11]PBR28. By comparing TSPO in 15 young adult males with ASD with 18 age- and sex-matched controls, we showed that individuals with ASD exhibited lower regional TSPO expression in several brain regions, including the bilateral insular cortex, bilateral precuneus/posterior cingulate cortex, and bilateral temporal, angular, and supramarginal gyri, which have previously been implicated in autism in functional MR imaging studies. No brain region exhibited higher regional TSPO expression in the ASD group compared with the control group. A subset of participants underwent a second MR-PET scan after a median interscan interval of 3.6 months, and we determined that TSPO expression over this period of time was stable and replicable. Furthermore, voxelwise analysis confirmed lower regional TSPO expression in ASD at this later time point. Lower TSPO expression in ASD could reflect abnormalities in neuroimmune processes or mitochondrial dysfunction.
|
|
| 5. |
- Brusaferri, L., et al.
(författare)
-
The pandemic brain: Neuroinflammation in non-infected individuals during the COVID-19 pandemic
- 2022
-
Ingår i: Brain, Behavior, and Immunity. - : Elsevier BV. - 0889-1591. ; 102, s. 89-97
-
Tidskriftsartikel (refereegranskat)abstract
- While COVID-19 research has seen an explosion in the literature, the impact of pandemic-related societal and lifestyle disruptions on brain health among the uninfected remains underexplored. However, a global increase in the prevalence of fatigue, brain fog, depression and other “sickness behavior”-like symptoms implicates a possible dysregulation in neuroimmune mechanisms even among those never infected by the virus. We compared fifty-seven ‘Pre-Pandemic’ and fifteen ‘Pandemic’ datasets from individuals originally enrolled as control subjects for various completed, or ongoing, research studies available in our records, with a confirmed negative test for SARS-CoV-2 antibodies. We used a combination of multimodal molecular brain imaging (simultaneous positron emission tomography / magnetic resonance spectroscopy), behavioral measurements, imaging transcriptomics and serum testing to uncover links between pandemic-related stressors and neuroinflammation. Healthy individuals examined after the enforcement of 2020 lockdown/stay-at-home measures demonstrated elevated brain levels of two independent neuroinflammatory markers (the 18 kDa translocator protein, TSPO, and myoinositol) compared to pre-lockdown subjects. The serum levels of two inflammatory markers (interleukin-16 and monocyte chemoattractant protein-1) were also elevated, although these effects did not reach statistical significance after correcting for multiple comparisons. Subjects endorsing higher symptom burden showed higher TSPO signal in the hippocampus (mood alteration, mental fatigue), intraparietal sulcus and precuneus (physical fatigue), compared to those reporting little/no symptoms. Post-lockdown TSPO signal changes were spatially aligned with the constitutive expression of several genes involved in immune/neuroimmune functions. This work implicates neuroimmune activation as a possible mechanism underlying the non-virally-mediated symptoms experienced by many during the COVID-19 pandemic. Future studies will be needed to corroborate and further interpret these preliminary findings. © 2022 Elsevier Inc.
|
|
| 6. |
- Baxter, Amanda L., et al.
(författare)
-
Collaborative experience between scientific software projects using Agile Scrum development
- 2022
-
Ingår i: Software, practice & experience. - : John Wiley & Sons. - 0038-0644 .- 1097-024X. ; 52:10, s. 2077-2096
-
Tidskriftsartikel (refereegranskat)abstract
- Developing sustainable software for the scientific community requires expertise in software engineering and domain science. This can be challenging due to the unique needs of scientific software, the insufficient resources for software engineering practices in the scientific community, and the complexity of developing for evolving scientific contexts. While open-source software can partially address these concerns, it can introduce complicating dependencies and delay development. These issues can be reduced if scientists and software developers collaborate. We present a case study wherein scientists from the SuperNova Early Warning System collaborated with software developers from the Scalable Cyberinfrastructure for Multi-Messenger Astrophysics project. The collaboration addressed the difficulties of open-source software development, but presented additional risks to each team. For the scientists, there was a concern of relying on external systems and lacking control in the development process. For the developers, there was a risk in supporting a user-group while maintaining core development. These issues were mitigated by creating a second Agile Scrum framework in parallel with the developers' ongoing Agile Scrum process. This Agile collaboration promoted communication, ensured that the scientists had an active role in development, and allowed the developers to evaluate and implement the scientists' software requirements. The collaboration provided benefits for each group: the scientists actuated their development by using an existing platform, and the developers utilized the scientists' use-case to improve their systems. This case study suggests that scientists and software developers can avoid scientific computing issues by collaborating and that Agile Scrum methods can address emergent concerns.
|
|
| 7. |
- von Arx, K., et al.
(författare)
-
Resonant inelastic x-ray scattering study of Ca3Ru2O7
- 2020
-
Ingår i: Physical Review B. - 2469-9969 .- 2469-9950. ; 102:23
-
Tidskriftsartikel (refereegranskat)abstract
- We present a combined oxygen K-edge x-ray absorption spectroscopy and resonant inelastic x-ray scattering (RIXS) study of the bilayer ruthenate Ca3Ru2O7. Our RIXS experiments on Ca3Ru2O7 were carried out on the overlapping planar and interplanar oxygen resonances, which are distinguishable from the apical one. Comparison to equivalent oxygen K-edge spectra recorded on band-Mott insulating Ca2RuO4 is made. In contrast to Ca2RuO4 spectra, which contain excitations linked to Mott physics, Ca3Ru2O7 spectra feature only intra-t(2g) ones that do not directly involve the Coulomb energy scale. As found in Ca2RuO4, we resolve two intra-t(2g) excitations in Ca3Ru2O7. Moreover, the lowest lying excitation in Ca3Ru2O7 shows a significant dispersion, revealing a collective character different from what is observed in Ca2RuO4. Theoretical modeling supports the interpretation of this lowest energy excitation in Ca3Ru2O7 as a magnetic transverse mode with multiparticle character, whereas the corresponding excitation in Ca2RuO4 is assigned to combined longitudinal and transverse spin modes. These fundamental differences are discussed in terms of the inequivalent magnetic ground-state manifestations in Ca2RuO4 and Ca3Ru2O7.
|
|
