Pneumococcal pneumonia trends in adults hospitalised with community-acquired pneumonia over 10 years (2013-2023) and the role of serotype 3

Background With higher valency pneumococcal vaccines on the horizon and new adult immunisation strategies under discussion, we aimed to evaluate the contribution of individual pneumococcal serotypes to the burden of pneumococcal community-acquired pneumonia (CAP). Over 10 years, trends in pneumococcal pneumonia epidemiology in adults hospitalised with CAP were assessed. The risk factors and severity associated with serotype 3 were examined.Methods We conducted a prospective cohort study of adults hospitalised with CAP between September 2013 and May 2023. Pneumococcal serotypes were identified using a serotype-specific 24-valent urinary-antigen assay. Trends in the proportion of CAP due to pneumococcus and causative serotypes were compared prepandemic and postpandemic. Risk factors and severity of serotype 3 pneumonia were compared with other serotypes using logistic regression.Results Of 5186 patients with CAP, 2193 (42.2%) had pneumococcal pneumonia. The proportion of CAP due to pneumococcus increased across all ages between 2013 and 2023 (36.4%–66.9%, p<0.001). The proportion due to serotype 3 increased significantly from 13.4% (2013) to 48.8% (2023). Serotype 3 pneumonia in adults was associated with older age (p<0.001), male sex (adjusted OR (aOR) 2.22, 95% CI 1.64 to 3.01) and chronic renal disease (aOR 1.81, 95% CI 1.09 to 3.02). Serotype 3 pneumonia was not observed to be associated with severity, critical care requirement, mortality or readmission.Interpretation Serotype 3 is the predominant serotype in adult pneumococcal CAP and has been increasing despite a mature infant pneumococcal immunisation programme, consistent with a lack of herd protection for this serotype

Fucoxanthin mitigates mercury-induced mitochondrial toxicity in the human ovarian granulosa cell line

Mercury (Hg) is known to be a hazardous toxin with a significant negative impact on female reproduction through mechanisms that remain unclear. The carotenoid fucoxanthin (FX) is an antioxidant with several positive effects on human health. This study aimed to examine the potential protective role of FX in reducing the Hg-induced bioenergetic disturbances in a human ovarian granulosa cell line model. (methods briefly) Hg was found to reduce the viability of granulosa cells in a concentration-dependent manner, with an estimated 72-hour EC50 of 10 µM. In contrast, FX (10 and 20 µM) improved cell viability. Hg (1 and 10 µM) significantly reduced cellular ATP levels, mitochondrial membrane potential, oxygen consumption rates, and lactate production. Additionally, Hg impaired the activities and kinetics of mitochondrial complexes I and III and reduced the expression of mitochondrial genes ND1, ND5, cytochrome B, cytochrome C oxidase, and ATP synthase subunits 6 and 8. According to tests on mitochondrial membranes, Hg increased membrane fluidity by reducing saturated fatty acid levels and increasing those of unsaturated fatty acids. Hg also promoted mitochondrial swelling and enhanced the inner mitochondrial membrane permeability to hydrogen and potassium ions. FX (10 µM) was shown to mitigate the negative effects of Hg on the viability of treated granulosa cells, bioenergetics parameters, and mitochondrial membrane integrity in a concentration-dependent manner. Based on these findings, bioenergetic disruption may be a key underlying cause of Hg-induced ovarian dysfunction. Furthermore, FX may have a potential therapeutic role in treating ovarian disorders caused by Hg-induced disruption of granulosa cell bioenergetics

Researching the everyday educational lives of low-income families: the importance of researcher and participant contexts

This paper highlights the importance of considering both researcher and participant contexts when exploring everyday educational lives. It emerges during a period of increasing and sustained social inequality in England, and against a backdrop of increasingly tight research timeframes and resources in higher education. Drawing on a project engaging low-income families in Greater London, the paper takes the everyday as its conceptual focus and questions how we can be critically attentive to everyday educational lives if we struggle to access and develop research relationships with particular social groups. We offer empirical insight into the hesitancies towards, and avoidances of, research participation that centre around knowledge, fear, and trust, and which are heightened concerns where aspects of family life, parenting, and children come to the fore. The paper considers how these can be mitigated in an academic environment where limited time and resourcing shape possibilities of research engagements and offers practical moves linked to research relationships, relevance and presence for how researchers can address these challenges to enable research to be more inclusive

Other '68s: Lineages and Legacies of May ’68

May ’68 has inspired cultural, social and political movements across the world but has been used also to criticise them. This book interrogates the consideration of the revolts in France as the pinnacle or even paradigm of a particular avatar in a revolutionary lineage that would include the liminal moments of 1789 and 1917. But it also engages in a mapping of the synchronous but not necessarily aligned rebellious events and purported legacies that orbited around that momentous year in the West and its internal periphery, on the other side of the Iron Curtain and in the strategic centre of the Global South constituted by Latin America in the 1960s. The collection combines fresher perspectives with more established scholarship in history, philosophy, critical theory, literary studies, psychoanalysis and visual culture through which the contributors deconstruct the rich and paradoxical conditions, development and vestiges, as creative as well as troubling, of an iconic moment of the twentieth century

Interplay between genetics and epigenetics in lung fibrosis

Lung fibrosis, including idiopathic pulmonary fibrosis (IPF), is a complex and devastating disease characterised by the progressive scarring of lung tissue leading to compromised respiratory function. Aberrantly activated fibroblasts deposit extracellular matrix components into the surrounding lung tissue, impairing lung function and capacity for gas exchange. Both genetic and epigenetic factors have been found to play a role in the pathogenesis of lung fibrosis, with emerging evidence highlighting the interplay between these two regulatory mechanisms. This review provides an overview of the current understanding of the interplay between genetics and epigenetics in lung fibrosis. We discuss the genetic variants associated with susceptibility to lung fibrosis and explore how epigenetic modifications such as DNA methylation, histone modifications, and non-coding RNA expression contribute to disease. Insights from genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS) are integrated to explore the molecular mechanisms underlying lung fibrosis pathogenesis. We also discuss the potential clinical implications of genetics and epigenetics in lung fibrosis, including the development of novel therapeutic targets. Overall, this review highlights the importance of considering both genetic and epigenetic factors in the understanding and management of lung fibrosis

SLC1A5 is a key regulator of glutamine metabolism and a prognostic marker for aggressive luminal breast cancer

Cancer cells exhibit altered metabolism, often relying on glutamine (Gln) for growth. Breast cancer (BC) is a heterogeneous disease with varying clinical outcomes. We investigated the role of the amino acid transporter SLC1A5 (ASCT2) and its association with BC subtypes and patient outcomes. In large BC cohorts, SLC1A5 mRNA (n = 9488) and SLC1A5 protein (n = 1274) levels were assessed and correlated their expression with clinicopathological features, molecular subtypes, and patient outcomes. In vitro SLC1A5 knockdown and inhibition studies in luminal BC cell lines (ZR-75-1 and HCC1500) were used to further explore the role of SLC1A5 in Gln metabolism. Statistical analysis was performed using chi-squared tests, ANOVA, Spearman’s correlation, Kaplan–Meier analysis, and Cox regression. SLC1A5 mRNA and SLC1A5 protein expression were strongly correlated in luminal B, HER2 + and triple-negative BC (TNBC). Both high SLC1A5 mRNA and SLC1A5 protein expression were associated with larger tumour size, higher grade, and positive axillary lymph node metastases (P < 0.01). Importantly, high SLC1A5 expression correlated with poor BC-specific survival specifically in the highly proliferative luminal subtype (P < 0.001). Furthermore, SLC1A5 knockdown by siRNA or GPNA inhibition significantly reduced cell proliferation and glutamine uptake in ZR-75-1 cells. Our findings suggest SLC1A5 plays a key role in the aggressive luminal BC subtype and represents a potential therapeutic target. Further research is needed to explore SLC1A5 function in luminal BC and its association with Gln metabolism pathways

Prospects of a statistical detection of the 21-cm forest and its potential to constrain the thermal state of the neutral IGM during reionization

⁠The 21-cm forest signal is a promising probe of the Epoch of Reionization complementary to other 21-cm line observables and Ly α forest signal. Prospects of detecting it have significantly improved in the last decade thanks to the disco very of more than 30 radio-loud quasars at these redshifts, upgrades to telescope facilities, and the notion that neutral hydrogen islands persist down to z ≲ 5 . 5. We forward-model the 21-cm forest signal using seminumerical simulations and incorporate various instrumental features to explore the potential of detecting the 21-cm forest at z = 6, both directly and statistically, with the currently available (uGMRT) and forthcoming (SKA1-low) observatories. We show that it is possible to detect the 1D power spectrum of the 21-cm forest spectrum, especially at large scales of k ≲ 8 . 5 MHz −1 with the 500 hr of the uGMRT time and k ≲ 32 . 4 MHz −1 with the SKA1-low over 50 hr if the intergalactic medium (IGM) is 25 per cent neutral and these neutral hydrogen regions have a spin temperature of ≲ 30 K. On the other hand, we infer that a null-detection of the signal with such observations of 10 radio-loud sources at z ≈ 6 can be translated into constraints on the thermal and ionization state of the IGM which are tighter than the currently available measurements. Moreover, a null-detection of the 1D 21-cm forest power spectrum with only 50 hr of the uGMRT observations of 10 radio-loud sources can already be competitive with the Ly α forest and 21-cm tomographic observations in disfavouring models of significantly neutral and cold IGM at z = 6

StomaGAN: Improving image-based analysis of stomata through Generative Adversarial Networks

Stomata regulate gas exchange between plants and the atmosphere, but analysing their morphology is challenging due to anatomical variability and artifacts during image acquisition. Deep learning (DL) can address these challenges but often requires large and diverse datasets, which are costly and error prone to produce. Generative adversarial networks (GANs) offer a solution by generating artificial data via unsupervised learning. However, GANs often suffer from problems including mode collapse, vanishing gradients, and network failure, particularly with small datasets. Here, we present StomaGAN, a deep convolutional GAN (DCGAN) with tailored modifications to address common GAN issues. We collected 559 stomatal impressions of field, or faba bean (Vicia faba) consisting of ~3,000 stoma, 80% of which were used to train StomaGAN. Evaluation metrics, including generator and discriminator loss progression and a mean Fréchet Inception Distance (FID) score of 61.4 across eight experimental runs confirms successful training. To validate StomaGAN, we generated artificial images to train a deep convolutional neural network (DCNN) based on the DeepLabV3 framework for stomata detection from real, unseen images. The DCNN achieved a mean Interception over Union (IoU) of 0.95 on artificial training images and a 0.91 on real, unseen, images across varying magnifications. Our results demonstrate that StomaGAN effectively generates high-quality synthetic datasets, enabling reliable stomatal detection and enhancing phenotypic analysis. This approach reduces the need for extensive manual data collection and simplifies complex morphological assessments

Waterborne debris impact forces on wall structures: Elastic analytical model integrating the effects of the structural mass

To evaluate the structural safety against waterborne debris impacts, the impact loads are usually computed with analytical models such as those proposed by ASCE/SEI 7–22. These models often assume a massless structure to simplify the analytical formulations, which can be an oversimplifying and inaccurate assumption in cases where the structure is heavier and more flexible than the debris. To address this problem, we aim to define the domain in which the existing models are inaccurate and to propose a new analytical model to accurately compute the debris impact forces through comprehensive finite element simulations and analytical modelling. We defined such a domain in the design space of structure-to-debris mass and stiffness ratios and assessed which are the most accurate analytical models to compute debris impact forces across this space. Our proposed model significantly improves upon the overestimating results of the ASCE/SEI 7–22 model when both stiffness and mass are important in determining the impact forces