Julkaisuarkisto

We introduce REACTOR, a computational tool designed to detect differential activity of transcriptional regulators and their target genes (regulons) in single-cell RNA-sequencing data. It expands the currently available framework for regulon analysis by introducing a robust statistical test to detect differential regulon activity between conditions, such as disease versus control, with multiple replicates. By contrasting different conditions, REACTOR enables identification of key condition- and cell type-specific regulons. To demonstrate the use of REACTOR, we illustrate its performance in a publicly available COVID-19 dataset.

According to activity-rotation relations, rapid rotators are expected to show high levels of magnetic activity. However, recent studies with TESS have found ultra-fast-rotating (UFR) M dwarfs with periods  d displaying low levels of flaring activity. There have been efforts to explore their magnetic field strengths through spectropolarimetric measurements and to assess the potential for binarity. However, neither could fully explain the lack of observed flaring activity despite their rapid rotation. Another avenue for investigation is to measure their coronal emission for signs of supersaturation: an underluminosity in X-rays observed for some rapidly rotating FGK stars. Therefore, in this study, we utilize X-ray observations from Swift and XMM–Newton of 10 M dwarf ultra-fast rotators with P < 1 d to determine their X-ray luminosities. Overall, we do not find evidence for supersaturation amongst our UFR M dwarf stars, instead determining them to be at the saturated level, or perhaps even enhanced. Therefore, supersaturation seems not to be the main driver behind the reduced level of flaring activity observed in these stars, and the mystery behind the magnetic activity of UFR low-mass stars remains. Additionally, we provide an updated analysis on the long-term variability within our sample using TESS light curves taken during Cycles 5 and 7. We identify 352 optical flares from our sample with energies between 1.2 × 10³¹ and 8.7 × 10³⁴ erg. We determine flare rates for each TESS cycle, compare them, identifying variations across a 7-yr timespan and attribute this to potential activity cycles.

We investigate the non-Gaussian features in the distribution of the matter power spectrum multipoles. Using the COVMOS method, we generated 100 000 mock realisations of dark matter density fields in both real and redshift space across multiple redshifts and cosmological models. We derived an analytical framework linking the non-Gaussianity of the power spectrum distribution to higher-order statistics of the density field, including the trispectrum and pentaspectrum. We explored the effect of redshift-space distortions, the geometry of the survey, the Fourier binning, the integral constraint, and the shot noise on the skewness of the distribution of the power spectrum measurements. Our results demonstrate that the likelihood of the estimated matter power spectrum significantly deviates from a Gaussian assumption on non-linear scales, particularly at low redshift. This departure is primarily driven by the pentaspectrum contribution, which dominates over the trispectrum at intermediate scales. We also examined the impact of the finiteness of the survey geometry in the context of the Euclid mission, and we find that both the shape of the survey and the integral constraint amplify the skewness.

Background: Emerging evidence suggests that antiviral treatment targeting human cytomegalovirus (HCMV) may improve outcomes in patients with glioblastoma (GBM). In this study, we analyzed serological data from the placebo-controlled VIGAS1 trial (Eudra number 2006-002022-29), which assessed the effect of valganciclovir (VGCV) on GBM progression in 42 patients, for impact of VGCV in preventing HCMV reactivation.

Methods: VIGAS1 patients had undergone radical surgery and were randomized to receive either VGCV (n = 22) or placebo (n = 20) alongside standard radiochemotherapy. Blood was prospectively collected at baseline and 3-, 12- and 24-week follow-up visits. GBM cell lines and a cytomegalovirus-infected murine brain cancer model were used to validate the clinical findings.

Results: Over the 24-week study period, we found that HCMV reactivation, as inferred from IgM seropositivity, occurred in 58.3% of patients in the placebo group, whereas this was completely prevented in the VGCV-treated group except for one patient with no treatment compliance (p = 0.0005). HCMV reactivation was linked to early recurrence. IgG-positive patients treated with VGCV showed a significantly longer time to progression (TTP) than those receiving placebo (6.7 vs. 3.7 months, p = 0.0408). We found a significant association between higher steroid doses and enhanced reactivation in the placebo group. In vitro and murine studies confirmed that corticosteroids, combined with radiation therapy, enhanced cytomegalovirus reactivation, which was mitigated by antiviral treatment.

Conclusions: These findings suggest that preventing HCMV reactivation with antiviral therapy may improve patient outcomes, especially in HCMV-seropositive GBM patients, and further support the hypothesis that HCMV is a tumor-promoting virus.

Purpose: To evaluate the diagnostic validity of PD identification in a national health registry requiring neurologist-confirmed diagnoses.
Patients and Methods: We analyzed the Turku PD Cohort including 1626 patients diagnosed with PD between 2006 and 2020 in specialist care. Patients were identified based on ≥ 2 entries of ICD-10 code G20. Diagnoses were re-evaluated through detailed chart review after a median follow-up of approximately 10 years. Two movement disorder specialists independently classified final diagnoses based on clinical records, imaging, and treatment data. Linkage to the Finnish Register of the Entitlements to Reimbursement of Pharmaceutical Expenses identified patients granted reimbursement for antiparkinsonian medications under ICD-10 code G20. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using the final clinical diagnosis as the reference.
Results: Of the 1626 patients, 1550 (95.3%) had received reimbursement for PD medications. After long-term follow-up, 1314 were confirmed as PD and 236 reclassified to alternative diagnoses. Registry identification showed high sensitivity (98.2%) and PPV (84.8%). Only 24 confirmed PD cases (1.8%) were not captured. Diagnostic revisions most commonly reflected atypical or secondary parkinsonian syndromes. Specificity was lower (18.1%), reflecting diagnostic evolution during follow-up rather than systematic miscoding. The median delay between diagnosis and registry entry was 24 days.
Conclusion: A national health registry requiring neurologist-confirmed diagnoses enables highly sensitive PD case identification with good PPV for epidemiological research. However, diagnostic evolution in early parkinsonism limits specificity in cross-sectional register data. Registry studies should therefore apply follow-up exclusion algorithms for alternative parkinsonian diagnoses.