Is COVID-19 Still a Threat? An Expert Opinion Review on the Continued Healthcare Burden in Immunocompromised Individuals

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact. The emergence of several variants during the pandemic has presented numerous challenges in preventing and managing this disease. The development of vaccines has played a pivotal role in controlling the pandemic, with a significant portion of the global population being vaccinated. This, along with the emergence of less virulent SARS-CoV-2 variants, has led to a reduction in the severity of COVID-19 outcomes for the overall population. Nevertheless, individuals with immunocompromising conditions continue to face challenges given their suboptimal response to vaccination and vulnerability to severe COVID-19. This expert review synthesizes recent published evidence regarding the economic and human impact of COVID-19 on such individuals. The literature suggests that rates of hospitalization, intensive care unit admission, and mechanical ventilation use were high during the pre-Omicron era, and remained high during Omicron and later, despite vaccination for this population. Moreover, studies indicated that these individuals experienced a negative impact on their mental health and health-related quality of life (HRQoL) compared to those without immunocompromising conditions, with elevated levels of anxiety, depression, and distress reported. Further, these individuals with immunocompromising conditions experienced substantial costs associated with COVID-19 and loss of income during the pandemic, though the evidence on the economic burden of COVID-19 in such individuals is limited. Generally, COVID-19 has increased healthcare resource use and costs, impaired mental health, and reduced HRQoL in those with varied immunocompromising conditions compared to both those without COVID-19 and the general population—underscoring the importance of continued real-world studies. Ongoing research is crucial to assess the ongoing burden of COVID-19 in vaccinated individuals with immunocompromising conditions who are still at risk of severe COVID-19 outcomes to ensure their needs are not disproportionately worse than the general population.</p

From stars and disks to planets:Reconstructing the formation of Solar Systems

Young stellar clusters are the laboratories to explore our understanding of how stars and their planets form and interact with their environment. Putting together clusters with different ages, we can witness the time evolution that brings us from the less evolved objects, to the precursors of our Solar System, tracking the processes for a large number of sources to investigate the underlying physics and statistics. Nevertheless, although young clusters are typically attributed a representative age and disk fraction and treated as a single entity, we are increasingly finding that this is often not the case: clusters are by far more diverse, and their substructures betray a variety of star formation histories, which are connected to the initial conditions of the protoplanetary disks and their final outcome as planets. The way disks get converted into planetary systems is also not smooth nor follows a single line. The interplay of different processes, together with the different initial conditions of disks, is expected to lead to various evolutionary pathways that may explain the diversity of extrasolar planetary systems. Finally, the planet-disk-star connection, where matter transport is driven through the disk and channelled onto the star, affects both planets sizes and locations as well as the properties of the stars. Here, I review the observational results and existing challenges in the field of star and planet formation, and how we can use an increasing body of data, with wavelength-, spatial- and time-resolution, to probe further into the evolution of young stars and disks

Disruptive Signification in a Hybrid Media Ecology:Civilisational Populism in Pakistan, Turkey and Indonesia

This paper employs the ontic/ontological distinction to explore the relationship between religion and populism in Pakistan, Turkey, and Indonesia within a hybrid media ecology. Building on recent discussions of nationalism and populism, the study investigates civilizational populism through the lens of the ontic/ontological distinction, which separates the ‘content’ and ‘form’ of populism. This framework is critical for understanding how populist movements utilize religion to construct notions of ‘the nation,’ ‘the people,’ and ‘civilization.’ The paper examines how Islamic and Islamist positions intertwine with populist narratives, deconstructing the concept of religious populism and exploring how hybrid media dynamics support these constructions. Drawing on 164 semi-structured interviews with populist supporters conducted ahead of the 2023/2024 elections, the study analyses how religious and ideological identifications shape populist narratives. Hybrid media ecology emerges as a vital factor in sustaining the ontic and ontological dimensions of religious populism, amplifying emotional attachments to ‘us’ while intensifying antagonisms toward the ‘Other.’ The findings reveal how social and legacy media interact to mediate these dynamics, reinforcing populist imaginaries.</p

Development of an FKBP12-recruiting chemical-induced proximity DNA-encoded library and its application to discover an autophagy potentiator

Chemical inducers of proximity (CIPs) are molecules that recruit one protein to another and introduce new functionalities toward modulating protein states and activities. While CIP-mediated recruitment of E3 ligases is widely exploited for the development of degraders, other therapeutic modalities remain underexplored. We describe a non-degrader CIP-DNA-encoded library (CIP-DEL) that recruits FKBP12 to target proteins using non-traditional acyclic structures, with an emphasis on introducing stereochemically diverse and rigid connectors to attach the combinatorial library. We deployed this strategy to modulate ATG16L1 T300A, which confers genetic susceptibility to Crohn's disease (CD), and identified a compound that stabilizes the variant protein against caspase-3 (Casp3) cleavage in a FKBP12-independent manner. We demonstrate in cellular models that this compound potentiates autophagy, and reverses the xenophagy defects as well as increased cytokine secretion characteristic of ATG16L1 T300A. This study provides a platform to access unexplored chemical space for CIP design to develop therapeutic modalities guided by human genetics.</p

DEM modelling of highly porous soft rocks

A novel bond damage model is proposed to better replicate the behaviour of highly porous soft-rocks. The contact model employs an exponential damage law to describe the permanent deformation developing at the microscale. To i) reach a high porosity initial state, ii) reproduce complex contact configuration of irregular grains and iii) consider the physical existence of fractured bond fragments, a far-field interaction is introduced in this model, enabling non overlapping particles to transmit forces. The model performance is validated by replicating the behaviour of Maastricht calcarenite. Finally, a 3D coupled DEM (Discrete Element Method) - FDM (Finite Difference Method) modelling is employed to simulate the penetration of a cone-end shaped pile in calcarenite. The good agreement between the experimental and numerical results suggests that the proposed model has the potential to reveal microscopic mechanism of soft-rock / structure interaction

Space for Imagination?:Exploring the challenges of implementing art-based, metacognitive approaches for supporting imagination as a route to agency

This paper explores the implementation and evaluation of Imagination Agents, a mixed-methods case study, with young people aged 12–13, funded by a Royal Society of Arts Catalyst Award. The project was grounded in a flexible theory that imagination enables the necessary originality for creativity, enabling learners to construct personal understandings of their own learning which equate to metacognition, with this enabling the self-awareness and confidence for personal and, in turn, social/democratic agency. Life in a posthuman world necessitates the creation of new understandings, which can be produced through the application of imagination and agency, towards the conceptualisation and facilitation of positive change. Supporting learners to develop imagination and understand it metacognitively could result in personal agency which better equips them as participants within and activators of healthy environments. Based on Burns' (2024) models of cognitive/metacognitive imagination, we tried to support imagination and agency through a focus on the local environment. Implementation of the pedagogy and evaluation was very challenging in the school context. There was little space for imagination and agency. In conclusion, we consider how we might create such a space

Protein families secreted by nematodes to modulate host immunity

Parasitic nematodes release a wide variety of immunomodulatory proteins, which allow them to escape the host’s immune-mediated killing or ejection mechanisms. This immunomodulation is mediated by nematode excretory/secretory (E/S) products, which contain multiple families of immunomodulatory proteins. Many of these families are conserved across different parasitic nematodes, while others are apparently unique to specific species. While some E/S products interact with host proteins, others have evolved to target host lipids, glycans, and metabolites. In this review, we will focus on three families of immunomodulatory proteins, which are particularly expanded in intestinal nematodes: the venom allergen-like proteins, the apyrases, and the complement control protein domain-containing proteins. These families of proteins suppress host immune responses, and evidence is gathering that these could be effective vaccine antigens against these intractable parasites