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[Clinical characteristics of adolescents and young adults, and the relationship between neutrophil count/ratio and thrombosis in Japanese patients with polycythemia vera and essential thrombocythemia]
No full textThis review focuses on the findings of the JSH-MPN-R18 study, a retrospective analysis of 596 patients with polycythemia vera (PV) and 1,152 patients with of essential thrombocythemia (ET). Among the four sub-analyses conducted, one focused on adolescents and young adults (AYA population) with PV and ET, demonstrating that the characteristics of thrombotic events in young Japanese patients differ from those observed in Western populations. Specifically, the proportion of venous thrombosis among all thrombotic events was lower in the Japanese AYA population compared to their Western counterparts. Additionally, an analysis focusing on absolute neutrophil count and neutrophil ratio at diagnosis revealed their utility as predictors of thrombotic events, particularly in low-risk ET patients. These findings should contribute to the development of appropriate management strategies for young PV and ET patients in Japan, as well as to the enhancement of thrombotic risk stratification for PV and ET patients overall
Clonal evolution and therapy resistance in the era of precision cancer medicine : evolutionary trajectories in pediatric cancer
No full textPediatric cancers exhibit complex evolutionary dynamics driven by genetic instability, clonal selection, epigenetic reprogramming, and microenvironmental interactions. Tumor evolution is typically characterized by branching phylogenies, where subclones with unique genetic profiles emerge at different locations and time points. Partly as a result of this diversity, advanced cancers often develop resistance to multiple therapies, complicating treatment strategies. This review explores recurrent themes in clonal evolution across childhood cancers as well as evolution-inspired strategies to counter treatment resistance. A model of dynamic decision making is suggested to accommodate emerging methods for monitoring shifts in a cancer's clonal landscape and the widening repertoire of precision drugs. A larger drug toolbox will allow for more sophisticated evolutionary stratagems to cure or stabilize cancer, using methods such as adaptive therapy, extinction therapy, and reflexive control therapies. However, there are also inherent limits in predicting and controlling cancer evolution- emphasizing the need for early detection, particularly in the setting of predicting relapse, which disproportionately contributes to cancer related mortality in childhood. Understanding the evolutionary trajectories of pediatric cancers can inform more effective, personalized treatment protocols, ultimately enhancing survival rates and quality of life for young patients
Vetenskaplig akribi under tidspress – och andra utmaningar att hantera vid revideringen av en stor historisk ordbok
No full textThe first edition of the comprehensive diachronic-contemporary Swedish Academy Dictionary (SAOB) was completed in 2023 after more than 130 years of work. In 2024, a revision project was initiated with the aim of creating a more balanced dictionary by modernizing the content and addressing the major shortcomings. Tis paper discusses the revision process and the challenges encountered along the way, which are also relevant to other revision projects of large historical dictionaries of the SAOB type. Special attention is given to the dificulty of achieving precision and accuracy within tight time frames and to decision-making related to the combination of old and new parts within one and the same dictionary. The conclusion is that the workflow and review procedure need to be adjusted, and that clarity and transparency towards the user is crucial regarding both new and older versions of the lexicographic descriptions and the extent to which updating is carried out
Pseudomonas aeruginosa elastase down-regulates host inflammatory responses by degrading cytokines and chemokines : a non-healing wound perspective
No full textNon-healing venous leg ulcers are characterized by dysfunctional wound healing and frequently exhibit an absence of classical inflammatory signs, despite substantial bacterial loads of the Gram-negative pathogen Pseudomonas aeruginosa. To investigate this clinical observation, we used a porcine wound infection model and complementary in vitro cell and enzymatic activity assays. In vivo, P. aeruginosa infected wounds resulted in attenuated inflammatory responses compared to those infected with Staphylococcus aureus. Protease activity was elevated in P. aeruginosa-infected wounds relative to uninfected controls, while pro-inflammatory cytokine levels decreased over time. In vitro analyses employing cell cultures, wildtype and mutant strains, and clinical isolates from venous ulcers and blood, revealed that P. aeruginosa elastase (LasB) degrades a range of pro-inflammatory cytokines (G-CSF, GM-CSF, IFN-γ, IL-1ra, IL-6, IL-12p40, IL-23, TNF-α) and chemokines (Gro-α, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β) in the extracellular milieu, without impacting cell morphology, transcription factor activation, or subsequent intracellular cytokine production. Correspondingly, wound fluids from non-healing ulcers colonized/infected with P. aeruginosa degraded cytokines, whereas fluids from uninfected wounds did not. Collectively, our findings indicate that P. aeruginosa modulates host inflammation by degrading cytokines and chemokines
Search for Magnetic Monopole Pair Production in Ultraperipheral (Formula presented) Collisions at (Formula presented) with the ATLAS Detector at the LHC
No full textThis Letter presents a search for highly ionizing magnetic monopoles in (Formula presented) of ultraperipheral (Formula presented) collision data at (Formula presented) collected by the ATLAS detector at the LHC. A new methodology that exploits the properties of clusters of hits reconstructed in the innermost silicon detector layers is introduced to study highly ionizing particles in heavy-ion data. No significant excess above the background, which is estimated using a data-driven technique, is observed. Using a nonperturbative semiclassical model, upper limits at 95% confidence level are set on the cross section for pair production of monopoles with a single Dirac magnetic charge in the mass range of 20-150 GeV. Depending on the model, monopoles with a single Dirac magnetic charge and mass below 80-120 GeV are excluded. © 2025 CERN, for the ATLAS Collaboration
Same data, different analysts: variation in effect sizes due to analytical decisions in ecology and evolutionary biology
No full textAlthough variation in effect sizes and predicted values among studies of similar phenomena is inevitable, such variation far exceeds what might be produced by sampling error alone. One possible explanation for variation among results is differences among researchers in the decisions they make regarding statistical analyses. A growing array of studies has explored this analytical variability in different fields and has found substantial variability among results despite analysts having the same data and research question. Many of these studies have been in the social sciences, but one small “many analyst” study found similar variability in ecology. We expanded the scope of this prior work by implementing a large-scale empirical exploration of the variation in effect sizes and model predictions generated by the analytical decisions of different researchers in ecology and evolutionary biology. We used two unpublished datasets, one from evolutionary ecology (blue tit, Cyanistes caeruleus, to compare sibling number and nestling growth) and one from conservation ecology (Eucalyptus, to compare grass cover and tree seedling recruitment). The project leaders recruited 174 analyst teams, comprising 246 analysts, to investigate the answers to prespecified research questions. Analyses conducted by these teams yielded 141 usable effects (compatible with our meta-analyses and with all necessary information provided) for the blue tit dataset, and 85 usable effects for the Eucalyptus dataset. We found substantial heterogeneity among results for both datasets, although the patterns of variation differed between them. For the blue tit analyses, the average effect was convincingly negative, with less growth for nestlings living with more siblings, but there was near continuous variation in effect size from large negative effects to effects near zero, and even effects crossing the traditional threshold of statistical significance in the opposite direction. In contrast, the average relationship between grass cover and Eucalyptus seedling number was only slightly negative and not convincingly different from zero, and most effects ranged from weakly negative to weakly positive, with about a third of effects crossing the traditional threshold of significance in one direction or the other. However, there were also several striking outliers in the Eucalyptus dataset, with effects far from zero. For both datasets, we found substantial variation in the variable selection and random effects structures among analyses, as well as in the ratings of the analytical methods by peer reviewers, but we found no strong relationship between any of these and deviation from the meta-analytic mean. In other words, analyses with results that were far from the mean were no more or less likely to have dissimilar variable sets, use random effects in their models, or receive poor peer reviews than those analyses that found results that were close to the mean. The existence of substantial variability among analysis outcomes raises important questions about how ecologists and evolutionary biologists should interpret published results, and how they should conduct analyses in the future. © The Author(s) 2025
Novel 1-(2-Aryl-2-adamantyl)piperazine Derivatives Exhibit In Vitro Anticancer Activity Across Various Human Cancer Cell Lines, with Selective Efficacy Against Melanoma
No full textBackground and Objectives: Cutaneous melanoma (CM) is widely regarded as the most aggressive form of skin cancer worldwide, showing a rising global incidence. It develops from the uncontrolled transformation of pigment-producing melanocytes. The aim of this study is to characterize the cytotoxic and anti-proliferative properties of two 1-(2-aryl-adamantyl)piperazine derivatives, 6 and 7, with a specific emphasis on their impact on melanoma cells. Both compounds are synthesized based on the adamantane core structure which increases drug-like properties of the lead compound phencyclidine I, without increasing toxicity. Materials and Methods: This study describes concentration-dependent effects on cell viability and clonogenicity. Results: SRB assays, clonogenic (long-term) assays, and scratch assays reveal a significant anticancer activity of these two agents at low μΜ levels with a selective activity against melanoma cells. Furthermore, Western blot experiments indicate that both 6 and 7 induce LC3 accumulation, procaspase 3 decrease, and PARP cleavage, suggesting the implication of multiple death pathways in their anticancer mechanism of action. Conclusions: This study sheds light on the in vitro anticancer potential of two novel 1-(2-aryl-2-adamantyl)piperazine derivatives. It highlights their differential activity against melanoma and emphasizes their potential as lead candidates for further therapeutic exploration
Spectral principal axis system (SPAS) and tuning of tensor-valued encoding for microscopic anisotropy and time-dependent diffusion in the rat brain
No full textTensor-valued encoding in diffusion MRI allows probing of microscopic anisotropy in tissue, however, time-dependent diffusion (TDD) can bias results unless b-tensors are carefully tuned to account for TDD. We propose two novel strategies for tuning b-tensors to enable accurate measurements without interference from TDD due to restricted diffusion. The first strategy involves identifying encoding tensor projections that yield equal mean diffusivities (MD), providing robust tuning across a wide range of diffusion spectra. The second strategy uses geometric averaging of signals, ensuring tuning regardless of the diffusion spectra. Importantly, the same encoding waveforms used for geometric averaging to probe microscopic anisotropy (µA) can also generate an independent contrast due to TDD. This is enabled by considering spectral anisotropy of encoding and defining the spectral principal axis system (SPAS), which unfolds TDD as an additional independent dimension in tensor-valued encoding. Projections of encoding waveforms along the SPAS axes allow for the simultaneous acquisition of independent contrasts due to both µA and TDD within a single multidimensional diffusion encoding protocol. Additionally, SPAS projections inherit useful properties from the reference tensor, such as optimized b-value, motion nulling, and minimal concomitant field effects. This framework is demonstrated through simulations of various restricted diffusion compartments. Experimental validation on perfusion-fixed and in vivo rat brains highlights the method’s potential for enhanced microstructural specificity. In addition to mapping MD, fractional anisotropy, and unbiased microscopic fractional anisotropy, we propose a model-free approach to independently map µA and TDD. This approach uses a minimal yet highly specific protocol, enabling the identification of distinct µA-TDD contrasts across different brain regions, including details in cortical gray matter, choroid plexus, dentate gyrus of the hippocampus, and white matter
Gathering the grassroots: farmer groups as vehicles for political mobilization of small-scale farmers in Uganda
No full textCollective action by small-scale farmers can contribute significantly toward rural development. One important aspect that remains relatively neglected, especially in research set in Africa, is the role of farmer collectives in political processes. We study the local-level dynamics of a farmer-based organization mobilizing for agroecology and food sovereignty in Uganda. Through qualitative, collaborative research we examine the origins, characteristics and challenges of eight farmer groups, with a particular interest in how collective action is sustained and political mobilization gets fostered among the grassroots. Compared to the traditional NGOs that dominate the civil society landscape, we argue that organizations structured upon farmer groups are conducive to building grassroots engagement. We especially highlight the role of reflexive experimentation with agricultural alternatives, and suggest that the emerging fabric of local farmer groups expands mobilization opportunities. However, groups also experience many challenges including problematic gender dynamics, and political mobilization cannot be expected to simply emerge from collective action. For fostering democratically governed agri-food systems, we identify three important forms of “literacy” that surrounding organizations can support farmer groups in building: institutional, agroecological, and political
Sectoral attribution of greenhouse gas and pollutant emissions using multi-species eddy covariance on a tall tower in Zurich, Switzerland
No full textEddy covariance measurement of species that are co-emitted with carbon dioxide (CO2), such as carbon monoxide (CO) and nitrogen oxides NO and NO2 (NOx), provides an opportunity to attribute a net flux to individual source or sink categories. We present eight months of continuous simultaneous measurements of fluxes (F) of CO2, CO, NOx, methane (CH4), and nitrous oxide (N2O) from a tall tower (112 m a.g.l.) in Zurich, Switzerland. Median daily fluxes of FCO2 were 1.47 times larger in the winter (November–March) as opposed to summer (August–October) months (10.9 vs. 7.4 µmol m−2 s−1); 1.08 times greater for FCO (30 vs. 28 nmol m−2 s−1); 1.08 times greater for FNOx (14 vs. 13 nmol m−2 s−1); 1.01 times greater for FCH4 (13.5 vs. 13.3 nmol m−2 s−1); and not statistically significantly different for FN2O. Flux ratios of FCO /FCO2 and FNOx /FCO2 are well characterised by inventory emission ratios of stationary combustion and road transport in cold months. In warm months both FCO /FCO2 and FNOx /FCO2 systematically exceed expected inventory ratios during the day, while no statistically significant seasonal difference is observed in FNOx /FCO, indicating biospheric photosynthetic activity. A linear mixing model is proposed and applied to attribute half-hourly FCO2, FCO, and FNOx to stationary combustion and road transport emission categories as well as determine the biospheric FCO2. Flux attribution is reasonable at certain times and from certain wind directions, but over-attributes CO and NOx fluxes to road traffic and CO2 fluxes to stationary combustion, and overestimates photosynthetic CO2 uptake