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Early transcriptional states of spermatogonia and marker expressions in the prepubertal human testis following chemotherapy-induced depletion
No full textSTUDY QUESTION: Which spermatogonial differentiation states are present in prepubertal testes under normal conditions and following chemotherapy-induced depletion of spermatogonia in paediatric patients with cancer? SUMMARY ANSWER: Single-cell transcriptomic analysis reveals that only undifferentiated spermatogonia are present in prepubertal boys, while differentiated states emerge during puberty, with reduced protein expression of advanced spermatogonial markers observed in younger patients, those treated with alkylating agents, or those with a diminished spermatogonial pool. WHAT IS KNOWN ALREADY: Paediatric oncology treatments often involve gonadotoxic therapies that can impair spermatogonial stem cells, increasing the risk of subfertility. While five distinct spermatogonial subpopulations have been identified in adult testes via single-cell RNA sequencing, their presence in prepubertal testes of childhood cancer patients remains to be confirmed through marker protein expression. STUDY DESIGN, SIZE, DURATION: Gene expression profiles of spermatogonial subpopulations were investigated using single-cell RNA sequencing data from six testicular samples of healthy boys aged 0-17 years. Protein expression patterns were examined via immunofluorescence staining in 14 biobank control samples (median age: 4.9 years; range: 0.6-13.1 years) and in 31 prepubertal testicular tissue samples of paediatric patients with cancer (median age: 6.8 years; range: 0.7-13.1 years). PARTICIPANTS/MATERIALS, SETTING, METHODS: Gene expression profiles of UTF1 (states 0-1), ID4 (states 0-1), PIWIL4 (states 0-1), FGFR3 (states 0-2), and KIT (state 4), were analysed in testicular cells of paediatric origin obtained from our previously published open-access data source (GSE134144 and GSE120508). The protein expression of these spermatogonial subpopulation markers was evaluated by counting immunofluorescence-positive cells per analysed area. Marker expression was correlated with prior chemotherapy exposure and spermatogonia numbers. Exposure to alkylating agents was quantified as the cumulative cyclophosphamide equivalent dose (CED), and anthracycline exposure as the cumulative doxorubicin isoequivalent dose equivalents (DIE). A depleted spermatogonia pool was defined as having S/T Z-scores lower than -7 SD. MAIN RESULTS AND THE ROLE OF CHANCE: Transcriptomic analysis confirmed that germ cells in the prepubertal testis consist solely of undifferentiated spermatogonia. The expression of KIT protein, defining differentiated spermatogonia, was positively correlated with age (P < 0.001). A reduction in the number of spermatogonia expressing ID4 protein was associated with higher CED (P = 0.001), and spermatogonia expressing KIT protein with higher CED and DIE exposure (P = 0.005, and P = 0.035, respectively). A depleted spermatogonia pool (S/T Z-score <-7 SD) correlated with fewer spermatogonia expressing ID4 (P = 0.033), FGFR3 (P = 0.050), and KIT (P = 0.051) proteins. These results indicate that distinct protein expression patterns were observed following chemotherapy-induced reduction of the spermatogonial pool, with reduced expression of ID4, FGFR3, and KIT proteins. Numbers of spermatogonia positive for markers indicating more naïve, undifferentiated states, such as UTF1 and PIWIL4, did not correlate with spermatogonial pool reduction. LIMITATIONS, REASONS FOR CAUTION: The study population was heterogeneous in terms of age and treatment exposure. Moreover, the impact of specific cancer treatments could not be individually assessed. Limited tissue availability reduced the statistical power of the study, and repeated double or triple immunofluorescence staining could not be performed. As a result, the correlations between the expression of different spermatogonial markers can only be considered indicative trends. Child testicular control tissue samples were considered normal for inclusion if no testicular pathology was reported. However, detailed information on prior medical treatments or testicular volumes for the patients in this biobank was unavailable. WIDER IMPLICATIONS OF THE FINDINGS: Our observations suggest that alkylating agents have dose-dependent effects on all spermatogonial subpopulations. However, spermatogonial subtypes expressing the protein markers UTF1 and PIWIL4 were more resistant to chemotherapy-induced depletion of the spermatogonial pool, potentially representing true reserve stem cells. The identification of reserve stem cells could provide a valuable method for evaluating the fertility potential of testicular tissue collected for fertility preservation in prepubertal and peripubertal boys. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the Swedish Childhood Cancer Fund (PR2019-0123; PR2022-0115; TJ2020-0023) (J.-B.S.), Finnish Cancer Society (K.J.), Finnish Foundation for Paediatric Research (K.J.), Swedish Research Council (2018-03094; 2021-02107) (J.-B.S.), and Birgitta and Carl-Axel Rydbeck’s Research Grant for Paediatric Research (2020-00348; 2020-00335; 2021-00073; 2022-00317, 2024-00255) (J.-B.S., K.J.). Y.C. and Y.Y. received a scholarship from the Chinese Scholarship Council. J.S. was supported by a grant from Mary Béves Foundation for Childhood Cancer Research. H.B.O. was supported by the Sultan Qaboos University in Oman. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A
PARSEC V2.0 : Rotating tracks and isochrones for seven additional metallicities in the range Z=0.0001-0.03
No full textPARSEC v2.0 rotating stellar tracks were previously presented for six metallicity values from subsolar to solar values, with initial rotation rates (ωi, defined as the ratio of the angular velocity and its critical value) spanning from the non-rotating case to very near the critical velocity (i.e. ωi = 0.99), and for initial masses covering the ∼0.7 M⊙ to 14 M⊙ interval. Furthermore, we provided the corresponding isochrones converted into several photometric systems for different inclination angles between the line-of-sight and the rotation axes, from 0° (pole-on) to 90° (equator-on). In this work, we expand this database with seven other metallicity sets, including five sets of low metallicity (Z = 0.0001 - 0.002) and two sets of super-solar values (up to Z = 0.03). We present the new stellar tracks, which comprise ∼3040 tracks in total (∼5500 including previous sets), along with the new corresponding rotating isochrones. We also introduce the possibility of creating isochrones by interpolation for values of rotating rates that were not available in the initial set of tracks. We compared a selection of our new models with rotating stellar tracks from the Geneva Stellar Evolution Code, and we assessed the quality of our new tracks by fitting the colour-magnitude diagram of the open cluster NGC 6067. We took advantage of the projected rotational velocity of member stars measured by Gaia to validate our results and examined the surface oxygen abundances in comparison with the observed data. All newly computed stellar tracks and isochrones can be retrieved via our dedicated web databases and interfaces
Paulinella acadia sp. nov., a New Photosynthetic Species Isolated From a Brackish Beach in British Columbia (Canada)
No full textPlastids in almost all photosynthetic lineages originated from a primary endosymbiosis between cyanobacteria and heterotrophic eukaryotes in an ancestor of Archaeplastida. Strikingly, this event was repeated about a billion years later in an ancestor of photosynthetic Paulinella. Due to the recent and independent occurrence of this second primary endosymbiosis, Paulinella amoebae serve as a remarkable model group for studying the origin of plastids. To date, three species of photosynthetic Paulinella have been described mainly from freshwater and marine environments. Here, we describe a fourth photosynthetic Paulinella species from a brackish beach near Vancouver (British Columbia, Canada) using morphological and molecular data that we named Paulinella acadia sp. nov. Although P. acadia sp. nov. appears similar to P. chromatophora under light microscopy, scanning electron microscopy and molecular phylogenetic analyses demonstrate its close relationship to P. longichromatophora. The discovery of P. acadia sp. nov. expands the diversity and ecological range within this group. Notably, it is the second photosynthetic Paulinella species found on a beach to be described, alongside its sister P. longichromatophora
Computerized chest radiograph analysis of air distribution after surfactant treatment of respiratory distress syndrome in extremely preterm infants
No full textThe early air distribution after surfactant instillation can have implications for the development of lung injury in extremely preterm newborns with respiratory distress syndrome (RDS). The objective of this study is to determine lung air distribution and focal heterogeneity after surfactant treatment of RDS, using computerized image analysis of chest radiographs (CXRs). This is a retrospective observational non-paired study where CXRs were assessed within 6 h after surfactant instillation in the surfactant-treated group [STG] (n = 52; median 24(+4); range 22(+0)-27(+5) weeks gestation) and at the same postnatal age in the pre-surfactant group [PSG] (n = 8; 25(+3); 23(+6)-26(+4)). Digital image analysis was performed by ImageJ of lung intercostal segments 2-7 bilaterally: mean pixel intensity (MPI) determines focal lung density and correlates negatively with lung aeration; focal heterogeneity in pixel intensity (FHPI) defines focal differences in aeration and correlates positively with overexpansion/atelectasis. MPI was higher in the left lung in STG than in PSG (p = 0.008). MPI was higher in the apical compared to the basal regions bilaterally, in both STG (right, p = 0.024; left, p = 0.015) and PSG (right, p = 0.047; left, p < 0.001). FHPI was higher on the right compared to the left 7th intercostal segment in STG (p = 0.006). FHPI of the right 7th segment was higher in STG than in PSG (p < 0.001). Conclusions: In this retrospective observational study of CXRs in extremely preterm infants, the right lungs were more aerated than the left lungs after surfactant, whereas the basal regions were more aerated than the apical regions regardless of surfactant treatment. We hypothesize that increased focal heterogeneity in these more aerated regions after surfactant may reflect overexpansion/atelectasis, which may be secondary to an inhomogeneous surfactant distribution, an observation that needs to be further validated in future studies
Estimation of Residual Gastric Content After 3 or 4 h Fasting for Breast Milk in Infants : A Pilot Study With Randomization
No full textCPAP treatment adherence and head extension therapy by cervical collar in Obstructive sleep apnea
No full textBackground: Obstructive Sleep Apnea (OSA) causes repeated airway blockages during sleep, leading to low oxygen levels, poor sleep quality, and increased risk of cardiovascular disease and type 2 diabetes. Treatments such as mandibular advancement devices (MAD) or CPAP (Continuous Positive Airway Pressure), require high adherence, which is often lacking. As a result, many patients remain untreated, underscoring the need for new therapeutic alternatives. Aims and Methods: Paper I: A randomised controlled study investigated the effect of telemedicine (TM) compared with standard clinic visits (SC) on adherence to CPAP treatment after 6 months. It also examined the impact of other factors, including CPAP side effects, on treatment adherence in 217 patients with OSA. Paper II: A randomised, open, parallel-group intervention study evaluated the effect of head extension using a cervical collar on the respiratory events index [(REI) i.e. apnea-hypopnea index (AHI)] in 100 patients with moderate OSA. The lifestyle intervention group (LS) received life-style advice only, while the cervical collar group (CC/LS) received both lifestyle advice and treatment with an adjustable cervical collar to promote head extension during sleep. Assessments, including questionnaires and polygraphy, were performed at baseline and after 6 ± 2 weeks. Paper III: A qualitative study explored and highlighted patients’ experiences of cervical collar treatment for OSA in seven patients from the intervention group (CC/LS) of the previous randomised controlled trial (Paper II). Qualitative content analysis was performed in accordance with the method of Graneheim and Lundman. Results and conclusions: There were no differences in CPAP adherence between the TM and SC groups after 6 months, suggesting that TM does not improve adherence to CPAP treatment over this period. Factors negatively affecting CPAP adherence included smoking and side effects such as dry throat, increased awakenings, and difficulty exhaling. The patient group (CC/LS) showed a greater reduction in REI compared with the LS group. The reduction in REI was particularly pronounced in the supine position. Thus, a cervical collar may be a viable second-line treatment option for OSA, especially in cases of positional OSA. Patients found the cervical collar improved sleep and daytime alertness but noted it was bulky and required adjustment. Despite challenges, it is viewed as helpful and should be more widely available.Tidpunkt för disputation korrigerad.</p
Meritocratic Municipalities? : Promotions in Sweden’s Local Government Bureaucracy
No full textThe meritocratic principle—that public personnel should be selected based on competence rather than political loyalty, personal connections, or ascriptive characteristics—is a foundational normative benchmark in democratic governance. It is closely tied to efficiency, impartiality, and upholding legitimacy in democratic systems. While the macro-level benefits of institutionalized meritocracy are well-documented, we know less about how the principle functions in practice, particularly when it comes to internal career advancements. This dissertation addresses this gap by analyzing whether promotions in Sweden’s local government bureaucracy reflect adherence to the meritocratic principle. Using individual-level administrative data, it examines the promotion outcomes of three groups—former political candidates, women, and immigrants—whose career advancement may be influenced by non-merit factors. Each essay investigates whether political connections, gender, or immigrant background affects promotion probabilities once a rich set of individual merit indicators is held constant. Sweden’s local government bureaucracy offers a substantively important and analytically valuable setting for studying meritocracy in practice. Local governments play a central role in the Swedish welfare state and operate under strong normative expectations of impartial, competence-based staffing. At the same time, local staffing practices are lightly regulated, making adherence to meritocracy dependent on the practical exercise of discretion in personell decisions rather than on formal institutional safeguards. The results show that former political candidates are more likely to be promoted than their colleagues, but this advantage is not driven by alignment with the ruling party, which is reassuring from the perspective of politicization. The findings also reveal a substantial promotion disadvantage for women that persists after accounting for merit, family situation, and policy sector, suggesting discrimination and a deviation from the meritocratic principle. For immigrants, the disadvantage for the whole group of first- and second-generation immigrants is modest, but a pronounced gap emerges for first-generation immigrants without Swedish upper-secondary education, raising concerns about exclusionary norms or bias in the recognition of credentials. Taken together, the findings do not support an unequivocally positive assessment of internal promotions in Sweden’s local government bureaucracy. While the absence of partisan favoritism is encouraging, the disadvantages faced by women and by a specific subgroup of immigrants indicate that problematic personell practices may allow non-merit factors to influence advancement. More broadly, the results underscore that different forms of non-meritocratic selection can coexist within the same institutional setting, and that meritocracy must be evaluated not only in relation to formal procedures but also in terms of how merit is defined, assessed, and applied in practice
Soluble cerebral Aβ protofibrils link Aβ plaque pathology to changes in CSF Aβ42/Aβ40 ratios, neurofilament light and tau in Alzheimer’s disease model micece
No full textThe Aβ42/Aβ40 ratio in the cerebrospinal fluid (CSF) and the concentrations of neurofilament light (NfL) and total tau (t-tau) are changed in the early stages of Alzheimer’s disease (AD), but their neurobiological correlates are not entirely understood. Here, we used 5xFAD transgenic mice to investigate the associations between these CSF biomarkers and measures of cerebral Aβ, including Aβ42/Aβ40 ratios in plaques, insoluble fibrillar deposits and soluble protofibrils. A high Aβ42/Aβ40 ratio in soluble protofibrils was the strongest independent predictor of low CSF Aβ42/Aβ40 ratios and high CSF NfL and t-tau concentrations when compared to Aβ42/Aβ40 ratios in plaques and insoluble fibrillar deposits. Furthermore, the Aβ42/Aβ40 ratio in soluble protofibrils fully mediated the associations between the corresponding ratio in plaques and all the investigated CSF biomarkers. In AppNL-G-F/NL-G-F knock-in mice, protofibrils fully mediated the association between plaques and the CSF Aβ42/Aβ40 ratio. Together, the results suggest that the Aβ42/Aβ40 ratio in CSF might better reflect brain levels of soluble Aβ protofibrils than insoluble Aβ fibrils in plaques in AD. Furthermore, elevated concentrations of NfL and t-tau in CSF might be triggered by increased brain levels of soluble Aβ protofibrils
Influence of redeposited tungsten and EUROFER97 layers on deuterium retention in plasma-facing materials
No full textRetention of hydrogen isotopes in plasma-facing materials is a key challenge for safety and fuel efficiency of nuclear fusion reactors. In realistic reactor environments, simultaneous processes, such as erosion, redeposition, implantation and outgassing, can alter surface compositions and may affect hydrogen isotope retention. In this study, we investigate how thin redeposited layers of tungsten and EUROFER97 influence retention and release of previously implanted deuterium. Using a combination of Elastic Recoil Detection Analysis and Rutherford Backscattering Spectrometry, we quantify deuterium retention during in-situ annealing up to 600 °C. Comparisons between coated and uncoated samples show that redeposited tungsten can act as partial diffusion barrier, preventing deuterium from outgassing. In contrast, redeposited EUROFER97 layers show no such effect and appear virtually transparent to deuterium diffusion. These findings emphasize the critical role of redeposited layers on fuel retention and have implications for wall lifetime estimates and fuel inventory control in fusion devices
Between consensus and contention : Economic defence, industry interests, and the funding of metal stockpiling in Sweden, 1973–1987
No full textThe turmoil of conflict and international crisis affects government as well as business interests. This article investigates how government–business relationships developed to tackle the potential problems of so-called peacetime crises that could adversely affect the country's steel and metal industries if the imports of alloy metals were disrupted in Sweden during the 1970s and 1980s. Based on extensive archival material and using an Advocacy Coalition Framework, we examine how this problem was negotiated between key stakeholders in Sweden during the period 1973–1987. We conclude that while the corporatist arrangements for negotiation were designed to build consensus, the state and business interests ultimately came into disagreement with each other. These results reflect recent research which emphasise that the relations between the state defence actors and business interests have been characterised by antagonism and contentions to a much larger degree than has been assumed in previous research