Background: Medulloblastoma (MB), the most common malignant pediatric brain tumor, is often incurable upon recurrence, largely driven by treatment-resistant quiescent cells. While quiescent SHH MB populations have been identified, the mechanisms driving their chemoresistance remain unclear. Here, we investigate the role of the cell cycle inhibitor p57 in inducing quiescence and show that dexamethasone, widely used in MB management, promotes p57-mediated quiescence, potentially reducing treatment efficacy. Methods: To assess p57’s role, we introduced a TMP-inducible p57 construct into Ptch1+/- SHH MB cells and treated them with vincristine. We also treated Ptch1+/- SHH MB cells with dexamethasone and quantified p57 levels and cell cycle states using high-throughput immunofluorescence imaging. Results: In culture, nuclear p57 was enriched in Sox2+ and Nestin+ stem-like SHH MB cells relative to rapidly-cycling Atoh1+ cells. Stabilizing p57 with TMP increased G0-phase cells six-fold, exhibiting survival to vincristine doses that caused complete cell death in controls. Dexamethasone treatment increased nuclear p57 by 40% and G0-phase cells by 15% in Ptch1+/- cells, while doubling G0-phase cells in Ptch1+/-;Trp53-/- cells. Conclusions: These findings suggest dexamethasone promotes p57-mediated quiescence, potentially contributing to chemoresistance in SHH MB. This raises critical concerns about the use of dexamethasone in MB treatment, as it may inadvertently enhance tumor recurrence.

The application of a tube combustion system (pyrolyzer) for the batch combustion of low carbon content environmental matrices, such as soil and sediment, for determining 14C specific activity is examined. The samples were combusted at 600°C, and the CO2 species produced were trapped in 3N NaOH, precipitated as BaCO3 by adding BaCl2, and subjected to acid-hydrolysis to transfer the CO2 species to the absorber-scintillator mixture for liquid scintillation counting (LSC). The method was validated by analyzing the samples by accelerator mass spectrometry (AMS) method. The minimum detectable activity (MDA) for the method, at 2σ confidence level, was 10 Bq kg–1C (4 pMC) for a counting time of 500 min and 7 Bq kg–1C (3 pMC) for 1000 min. The capability of the method to quantify a small excess of 14C specific activity (a few Bq kg–1C or pMC) in the environment of a nuclear facility, when compared to the ambient natural background level, was demonstrated by analyzing a total of 23 soil and 7 sediment samples from the vicinity of a pressurized heavy water reactor (PHWR) nuclear power plant (NPP) at Kaiga, India. The maximum excess 14C specific activity values recorded for soil and sediment matrices were 37 ± 7 Bq kg–1C and 11 ± 7 Bq kg–1C, respectively, confirming minimal radioecological impact of the operation of the NPP on the environment. The 14C specific activity ratio for the recently fallen leaf litter and the soil underneath at most of the sampling points in the vicinity of the NPP had a mean value of 1.03 with an associated standard deviation of 0.07. Statistical tests confirm that the mean values of the data set of 14C specific activity of leaf litter and underlying soil are not significantly different.

Glacier and snow melt are the primary sources of water for streams, and rivers in upper Indus region of the western Himalaya. However, the magnitude of runoff from this glacierized basin is expected to vary with the available energy in the catchment. Here, we used a physically based energy balance model to estimate the surface energy and surface mass balance (SMB) of the upper Chandra Basin glaciers for 7 hydrological years from 2015 to 2022. A strong seasonality is observed, with net radiation being the dominant energy flux in the summer, while latent and sensible heat flux dominated in the winter. The estimated mean annual SMB of the upper Chandra Basin glaciers is −0.51 ± 0.28 m w.e. a−1, with a cumulative SMB of −3.54 m w.e during 7 years from 2015 to 2022. We find that the geographical factors like aspect, slope, size and elevation of the glacier contribute towards the spatial variability of SMB within the study region. The findings reveal that a 42% increase in precipitation is necessary to counteract the additional mass loss resulting from a 1°C increase in air temperature for the upper Chandra Basin glaciers.

In a prospective, remote natural history study of 277 individuals with (60) and genetically at risk for (217) Parkinson’s disease (PD), we examined interest in the return of individual research results (IRRs) and compared characteristics of those who opted for versus against the return of IRRs. Most (n = 180, 65%) requested sharing of IRRs with either a primary care provider, neurologist, or themselves. Among individuals without PD, those who requested sharing of IRRs with a clinician reported more motor symptoms than those who did not request any sharing (mean (SD) 2.2 (4.0) versus 0.7 (1.5)). Participant interest in the return of IRRs is strong.

Background: We performed a network meta-analysis of randomized controlled trials to assess the comparative effectiveness of available pharmacological prophylaxis for migraines. Methods: We searched MEDLINE, EMBASE, Web of Science, Scopus, PsycINFO and Cochrane CENTRAL up to October 2023 for trials that: (1) enrolled adults diagnosed with chronic migraine, and (2) randomized them to any prophylactic medication vs. another medication or placebo. We performed a random-effects frequentist network meta-analysis for patient-important outcomes. Results: We included 193 randomized trials. Compared to placebo, CGRP monoclonal antibodies (mean difference [MD] -1.7, 95%CI: -1.1 to -2.2), injection of botulinum toxin (MD -1.8, 95%CI: -0.7 to -2.9), calcium channel blockers (MD -1.8, 95%CI: -0.5 to -3.0), beta-blockers (MD -1.4, 95%CI: -0.2 to -2.6), and anticonvulsants (MD -1.1, 95%CI: -0.4 to -1.8) were among the most effective treatments in reducing average number of headache days per months. Anticonvulsants (Risk Ratio [RR] 2.3, 95%CI: 1.8 to 3.0), calcium channel blockers (RR 1.8, 95% CI: 1.1 to 3.1), and tricyclic antidepressants (RR 2.3, 95% CI: 1.3 to 3.8) showed the highest risk of discontinuation due to adverse events. Conclusions: Our findings suggest that CGRP inhibitors, botulinum toxin, and beta-blockers may provide the greatest benefit, and tolerability, for reducing the frequency of migraine headaches.

Transcatheter closure has become a common treatment method for patent ductus arteriosus in premature infants at many centres; however, many remain uncertain about the ability to perform the procedure in the catheterisation laboratory for infants requiring high-frequency ventilation. This study presents our centre’s experience following the implementation of neonatal ventilatory guidelines, which resulted in 100% procedural success without any procedural or respiratory adverse events.

Legionellosis is a disease caused by the bacterium Legionella that most commonly presents as Legionnaires’ disease (LD), a severe form of pneumonia. From 2015 to 2019, an average of 438 LD cases per year were reported in Canada. However, it is believed that the actual number of cases is much higher, since LD may be underdiagnosed and underreported. The purpose of this study was to develop an estimate of the true incidence of illnesses, hospitalizations, and deaths associated with LD in Canada. Values were derived using a stochastic model, based on Canadian surveillance data from 2015 to 2019, which were scaled up to account for underdiagnosis and underreporting. Overall, there were an estimated 1,113 (90% CrI: 737–1,730) illnesses, 1,008 (90% CrI: 271–2,244) hospitalizations, and 34 (90% CrI: 4–86) deaths due to domestically acquired waterborne LD annually in Canada from 2015 to 2019. It was further estimated that only 36% of illnesses and 39% of hospitalizations and deaths were captured in surveillance, and that 22% of illnesses were caused by Legionella serogroups and species other than Legionella pneumophila serogroup 1 (non-Lp1). This study highlights the true burden and areas for improvement in Canada’s surveillance and detection of LD.

The Arcanum mission is a proposed L-class mother-daughter spacecraft configuration for the Neptunian system, the mass and volume of which have been maximised to highlight the wide-ranging science the next generation of launch vehicles will enable. The spacecraft is designed to address a long-neglected but high-value region of the outer Solar System, showing that current advances make such a mission more feasible than ever before. This paper adds to a series on Arcanum and specifically provides progress on the study of areas identified as critical weaknesses by the 2013–2022 decadal survey and areas relevant to the recently published Voyage 2050 recommendations to the European Space Agency (ESA).

This research investigates the MIMO antenna by using the Theory of Characteristics Mode (TCM) where 10 modes are subjected in designing. Also, 5 modes are the significant mode and 2 modes correspond to non-significant which defines the operating bandwidth and notched bands. The proposed 2 × 2 MIMO antenna configuration is designed for wideband applications with a size of 0.44 × 0.68 mm2. The two isolated 12-sided polygons radiating patches placed adjacent to each other share a common ground which is printed on an FR4 substrate. The measured impedance bandwidth covers bandwidth 3.11–11.98 GHz with two bands rejecting capability: Wireless Local Area Network (WLAN) and Downlink-Uplink Satellite (DUS) system. These two interfering bands are mitigated by etching a C-type slot on the radiating patch and an inverted U-type slot in the microstrip feed. The simulated and measured results are also compared in the far-field region (Normalized Radiation Efficiency (NRE), Peak Gain (PG), and 2-D/3-D radiation pattern). Proposed MIMO antenna also offers good diversity performance with ECC2×2 < 0.00001, DG2×2 > 9.999 dB, TARC2×2 < −15.0 dB, CCL2×2 < 0.001 b/s/Hz and MEG2×2 ≅ −3.0 dB.

This research reports a four-port multiple-input-multiple-output (MIMO) antenna designed for 5G-NR band applications including n77: 3.30–4.20 GHz, n78: 3.30–3.80 GHz, and n79: 4.40–5.00 GHz. The proposed design is analyzed in two parts, one single-element asymmetrical fed Calendula flower-shaped antenna and the other four-port modified MIMO antenna with the connected ground. The evolution of the MIMO antenna is studied based on the characteristics and optimized single-element antenna. The measured 5G-NR bandwidth offers a very high matching of impedance for MIMO configuration and higher isolation in the same band. The MIMO antenna offers an average peak gain of 3.51 dBi with a radiation efficiency of more than 90%. The radiation patterns plotted at 3.51, 4.00, 4.50, and 5.00 GHz match with almost omni-directional and dipole patterns in H- and E-radiating planes respectively. The MIMO antenna also records good diversity performance (ECC, DG, CCL, MEG, and TARC) in n77, n78, and n79 5G bands.

Existence of genetic divergence, appropriate characterization of breeding lines for economically important traits and determining parents with favourable alleles is the crux of crop genetic improvement programmes. This study is the first report of unravelling genetics and potential of petaloid-type cytoplasmic male sterile (pt-CMS) lines in carrot. Ten pt-CMS lines were crossed with 10 inbreds in line × tester mating fashion to generate 100 testcross progenies. Nutritional profiling of the 100 testcrosses progenies along with 20 parental types was carried out for two consecutive years for eight important traits to identify superior combiners. The pooled analysis revealed that the carotenoid content in root is under the genetic control of major genes (oligogenic). The pooled analysis revealed less than unity value of σ2A/D and σgca2/σsca2 for majority of the traits depicting preponderance of non-additive gene effects. The pt-CMS lines KT-28A, Kt-62A, KT-80A and KT-95A were identified as good combiners for carotenoids. The cross combination, KT-98A × KS-50 identified as the best heterotic combiner for CUPRAC and FRAP content over the years. Similarly, the combinations, KT-62A × KS-21, KT-80A × New Kuroda and KT-62A × KS-59 were found promising across the years for developing nutritionally rich F1 hybrids. The interaction analysis among the different antioxidant traits and plant pigments unveiled the scope of simultaneous improvement.

The current study was undertaken to identify the sources of tolerance to bruchid in cowpea, by screening a set of germplasm accessions as a source for natural resistance. A total of 103 diverse accessions of cowpea were evaluated for resistance to Callosobruchus maculatus Fab. under no-choice artificial infestation conditions. Significant differences among the cowpea accessions were observed for oviposition, adult emergence, exit holes and per cent seed weight loss (PSWL) caused by the bruchid infestation. The accessions showed variation in physical seed parameters viz., colour, shape, testa texture, length, width and seed hardness. Among the seed biochemical parameters studied, per cent sugar content ranged from 0.322 (IC330950) to 1.493 (IC249137), and per cent phenol content ranged from 0.0326 (EC390261) to 1.081 (EC528423). Correlation studies indicated that PSWL had significant positive correlation (r = 0.335) with exit holes, oviposition (r = 0.219), adult emergence (r = 0.534) and seed roundness (r = 0.219). Adult emergence had a significant negative correlation with seed hardness (r = −0.332). Correlation with biochemical parameters indicated that PSWL had a significant positive correlation (r = 0.231) with sugar content and a significant negative correlation with phenol content (r = −0.219). None of the accessions were found to be immune to bruchid infestation. However, out of studied accessions, EC528425 and EC528387 were identified as resistant based on PSWL and moderately resistant based on adult emergence. These resistance sources of cowpea germplasm can be used as potential donors for development of bruchid tolerant/resistant cultivars.