University of Nottingham

Background: Major depressive disorder (MDD) is a leading cause of disability worldwide, yet antidepressant response remains highly variable, with many patients failing to achieve remission. Resting-state functional connectivity (RSFC) studies have linked MDD to large-scale brain network dysregulation, but methodological inconsistencies and limited focus on treatment response have hindered clinical translation. Methods: We conducted a resting-state fMRI study as part of an 8-week antidepressant trial on 86 patients with MDD and 93 healthy controls (HCs). Utilizing a seed-to-voxel approach based on prior studies of neural networks implicated in antidepressant response, we examined RSFC patterns associated with treatment outcomes. Additionally, we explored their relationships with cognitive function and depressive severity to elucidate neural mechanisms underlying treatment response. Results: Compared to the non-responder group, antidepressant responders exhibited significantly higher ROI-to-ROI FC between the posterior cingulate cortex (PCC) and subgenual anterior cingulate cortex (sgACC), with follow-up seed-to-voxel maps showing higher PCC couplings with the prefrontal cortex, thalamus, and amygdala. In responders, FC between the left amygdala and supramarginal gyrus, and between the ventromedial prefrontal cortex (VMPFC) and lateral occipital cortex, was negatively correlated with cognitive scores. Conversely, in the non-responder group, FC between the left subgenual anterior cingulate cortex (sgACC) and lateral occipital cortex was negatively correlated with digit span but positively with other tasks. FCs involving the amygdala, thalamus, and VMPFC were correlated with depression scale scores. Conclusions: Enhanced connectivity within networks related to emotion regulation, cognitive control, and attention in responders suggests neural mechanisms supporting improved emotional and cognitive flexibility.

In this chapter, we discuss an approach for crafting an artificial musician. At the centre of this is the understanding that music is an embodied process involving joint action and mutual perception. In contrast to many music-AI projects, we have designed and built a system from the bottom-up by focusing on musical togetherness and embedding the mutual perception of liveness and responsivity rather than symbolic representations of music such as midi-files, notation and audio. We view this from the perspective of creative artistic researchers, and therefore from an insider perspective. By developing an artificial musician that is co-creative and capable of ‘perceptual experience’ (Kirk, Zombies and us: understanding consciousness, Bloomsbury, London, 2017) we believe this approach is appropriate for a wide range of musical systems. The practice-based project at the centre of this paper is Solaris a jazz quartet in which three musicians are AI, trained with a dataset collected over two years, and only one musician (co-author Vear) is human. This ensemble has been performing since 2019 in various guises, mostly with compositions in the spirit of jazz and free improvisation. In the first section of this chapter, we outline the core perspectives that define our understanding of music-making, behavioural and embodied AI, AI as media, the nature of togetherness, and the importance of mutual perception of liveness and perceptual experience (Kirk, Zombies and us: understanding consciousness, Bloomsbury, London, 2017) from our musicking partners. These have been developed and tested through a process of practice-based methods, with the co-authors operating as practitioner-researchers in this process. From this, we present a list of guiding principles which we used to craft Solaris. Following this we discuss how we crafted Solaris through (a) a new dataset that captured certain physiological parameters from a series of professional jazz pianists; (b) a new approach to an AI-Factory built on models trained from the dataset, and (c) a digital score that represented the inner workings and experience of Solaris’ AI. We tested Solaris in several scenarios. The results obtained from the interaction of human musicians with Solaris are surprising, as they suggest that human musicians see Solaris as a competent jazz improviser who acts and responds in real time to the musical space. In the discussion section, we dig deeper into the implications of Solaris’ perceptual experience and playfully present a conceptualisation of Solaris as a sentient Creative-AI system. We propose a framework based on Charles Sanders Peirce’s concept of Synechism to understand sentience in the context of Creative-AI and from this insider perspective. The idea that AI should be understood as a form of mind, following the precepts of Peirce’s synechism, opens up new avenues for collaboration between humans and apparatus, breaking the Cartesian duality (spirit-matter) that has plagued us since Descartes (Hull, J Soc Comput 4(3), 193–204, 2023). What we experience when interacting with artificial media systems like Solaris is not just a cold, programmatic interaction with inert matter, there is the presence of a collaborative and creative spirit (Poltronieri and Vear, ISEA—Awaiting publication, 2024) that has perceptual experiences (Kirk, Zombies and us: understanding consciousness, Bloomsbury, London, 2017).

Background: Childhood trauma impacts brain development, increasing vulnerability to Major Depressive Disorder (MDD). The frontal-limbic network, essential for emotion regulation and stress response, is frequently implicated in MDD pathophysiology. This study examined whether childhood trauma is associated with alterations in resting-state functional connectivity (FC) within brain networks involved in emotion regulation in individuals with MDD and healthy controls (HCs). Methods: A cross-sectional study was conducted with 76 patients with MDD and 97 HCs (aged 19–64 years). Resting-state FC was assessed among 24 predefined regions of interest (ROIs) within brain networks associated within the fronto-limbic circuit. Childhood trauma was quantified using the Childhood Trauma Questionnaire (CTQ). ROI-to-ROI FC and global/regional brain network properties were evaluated. Results: The MDD group demonstrated significant reductions in frontal-limbic FC (e.g., left dorsolateral prefrontal cortex [dlPFC]–left hippocampus, left dlPFC–right pregenual anterior cingulate cortex [ACC], right pregenual ACC–right subgenual ACC). Brain network properties analysis revealed a negative correlation between global efficiency and emotional neglect severity, as well as positive correlations between local efficiency/clustering efficiency and total CTQ scores. Specifically, in the MDD group, the clustering coefficient in the ventromedial prefrontal cortex (vmPFC) was positively associated with emotional neglect, whereas in the HC group, total CTQ scores were positively correlated with the nodal degree of the right subgenual ACC. Conclusion: Childhood trauma is associated with significant alterations in resting-state FC and brain network properties within the frontal-limbic network in individuals with MDD. These findings highlight a potential neural pathway through which early adversity contributes to MDD pathophysiology.

This chapter provides a detailed account of African domestic poultry genetic resources, their diversity, and unique features. It aims to bring together information to provide a comprehensive picture of the topic. Section 7.1 introduces African poultry genetic resources, their importance, and previous interventions conducted to better utilize this important resource. Section 7.2 deals with the origin of poultry genetic resources and their dispersal into Africa. The introduction of domesticated chickens into Africa is not well documented. Although indigenous birds have several adaptive traits and associated genes that are important in the tropics, the real value of indigenous chicken breeds is often underestimated. They have a poor appearance, relatively low productivity, and are consequently considered to have low value compared to their improved commercial counterparts. Chicken genetic resources are endangered and underconserved. However, there has been recent emphasis on local chicken breed development and conservation, which has gained attention. The section demonstrates how chickens have become a key part of the African poultry production system and how they can remain vital and instrumental, considering the current climate change. Sections 7.3, 7.4, 7.5 and 7.6 describe the available chicken and duck resources in different parts of Africa and outline their unique features and population estimates. Considering the population size of these genetic resources, conservation efforts to support their utilization are addressed in Sect. 7.8. Furthermore, the importance of conserving poultry genetic resources using germplasm cryobanking (cryoconservation) is described. Section 7.10 describes genetic improvement attempts in Africa involving indigenous chicken populations. The information appears to be limited to a few examples, as not many improvement programs are ongoing, and information on some programs is not available. Section 7.11 describes the major constraints of poultry production in Africa, followed by the economic contributions in Sect. 7.12. The last chapter implies the way forward in the utilization of poultry genetic resources in Africa.

The COVID-19 pandemic demonstrated the lethal potential of emerging zoonotic viruses, particularly coronaviruses. While global attention has largely centered on SARS-CoV-2, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) remains an overlooked yet credible pandemic threat. The objective of this commentary is to spotlight the virological, epidemiological, and evolutionary features of MERS-CoV and its potential to trigger the next coronavirus pandemic. MERS-CoV, characterized by its high case fatality rate (~ 34%) and persistent circulation in dromedary camels, continues to cause sporadic outbreaks with limited human-to-human transmission. However, the inherent mutability of RNA viruses raises concerns that adaptive mutations could enhance MERS-CoV’s transmissibility, potentially transforming it into a highly contagious human pathogen. This commentary revisits the virology, epidemiology, and zoonotic dynamics of MERS-CoV, highlighting the risks posed by viral evolution, the ongoing “slow burn” of zoonotic spillovers, and the dangers of post-pandemic complacency. We argue for renewed investment in surveillance, vaccine development, and proactive public health measures, grounded in a One Health approach. Vigilant monitoring of MERS-CoV and other emerging pathogens is essential to prevent future pandemics and to avoid being caught off guard once again.

Recent evidence indicates that social anxiety disorders are increasing alongside a growing sense of disconnection from communities. However, anxiety disorders are often overlooked or perceived as 'less serious' mental health issues. Consequently, young people may avoid formal psychological interventions or discussions with family members for fear of being misunderstood, increasingly turning instead to online spaces for support. This study aimed to explore how adolescents (aged 12-18) use Reddit to share their experiences of anxiety. A total of 105 posts, made between January 2021 and January 2022, were thematically analysed. Three themes were identified: Perceived barriers in seeking mental health support; Reddit as a last resort: motivators leading to anonymous posts; and 'Remember you are not alone': empathy and support through distance. The findings highlight adolescents' fear of stigma and rejection, as well as limited access to appropriate mental health services. For many, online help-seeking provided opportunities to share distress, seek advice, and connect with empathetic peers. Understanding social media's role in adolescents' emotional regulation, identity, and peer support can inform empathetic, tailored care. Encouraging open dialogue about online experiences supports safe coping and strengthens therapeutic relationships. Professionals should help adolescents build digital literacy and consider the potential therapeutic value of weak online ties, while research on practicalities, safeguarding, and outcomes is needed before implementation.

This paper simulates biofuel production from algae (Chlorella) in wastewater. It analyzes the effects of three factorssunlight intensity, photosynthesis time, and nitrogen concentration in wastewateron algal biomass and biodiesel yield. Additionally, the research establishes and applies mathematical models to the analysis of two different places, where the results show that in Shaanxi Province and Qinghai Province, the biodiesel yield per cubic meter of wastewater is 23.5 g/m and 8.9 g/m respectively. The biofuel yield of the system is 10% of the algal biomass. Furthermore, the paper concludes that the system's energy consumption mainly lies in the hydrogenation treatment section. The total energy consumption for producing 1 kg biodiesel is 937 MJ (blue H2), 855 MJ (grey H2) and 981 MJ (green H2) respectively. The carbon emissions for producing 1kg biodiesel is -2.2 kg CO2(blue H2), 25.9 kg CO2(grey H2) and -17.8 kg CO2(green H2) respectively.

Objective To assess the relationship between cam morphology and the development of radiographic hip osteoarthritis (RHOA), overall and in subgroups based on age, biological sex and body mass index (BMI). Methods Hips with no RHOA at baseline and with available follow-up during 4–8 years were selected from the Worldwide Collaboration on Osteoarthritis PrediCtion for the Hip (World COACH) consortium. Alpha angles were uniformly measured on anteroposterior radiographs, with a threshold of 60 ° used to define cam morphology. Incident RHOA was defined as the transition from an RHOA-free state at baseline to definite diagnosis of RHOA at follow-up. The association between baseline cam morphology and the development of RHOA was assessed using a three-level mixed-effects logistic regression model, accounting for hip side, individual and cohort-level variation. Results A total of 23 886 hips were included (mean age: 62.2±8.4 years; 70.6% female; BMI: 27.4±4.5; mean time to follow-up: 6.1±3.0 years). Cam morphology was associated with RHOA (OR: 1.87, 95% CI 1.36 to 2.59), as was a greater alpha angle (OR 1.02, 95% CI 1.01 to 1.03 for every degree increase). The overall relative risk of developing RHOA in hips with cam morphology was 1.62 (95%CI 1.26 to 2.07), greatest for those aged 51–60 years (2.15, 95% CI 1.55 to 2.98) and higher in males (2.50, 95% CI 1.67 to 3.73), compared with females (1.75,95% CI 1.24 to 2.48). Conclusion Hips with cam morphology have higher odds of developing RHOA within 4–8 years compared with hips without cam morphology. The relative risk was highest in subgroups of participants aged 51–60 years and in males, making cam morphology a potential target for primary or secondary prevention of RHOA.

Cell-free microRNAs in body fluids have emerged as promising biomarker candidates in neurodegenerative diseases. While several studies have identified dysregulated miRNAs in sporadic Parkinson’s disease, it remains unclear whether distinguishable alterations of cell-free miRNAs occur in genetic forms of the disease, such as those associated with the LRRK2 G2019S mutation. In this proof-of-concept study, we used a human induced pluripotent stem cell-derived dopaminergic neuron model to investigate whether the LRRK2 G2019S mutation induces detectable changes in the intra- and extracellular miRNAome, and whether miRNA signatures identified in vitro can be validated in patient-derived cerebrospinal fluid. We differentiated dopaminergic neurons from induced pluripotent stem cells carrying the LRRK2 G2019S mutation and an isogenic gene-corrected control. Extracellular vesicles were isolated from the culture medium and used as a source of cell-free miRNA. Next, small RNA libraries were generated and analyzed. Differentially expressed microRNAs were validated in an independent batch using RT-qPCR. We further quantified candidate microRNAs in cerebrospinal fluid samples from five LRRK2 G2019S patients and matching healthy controls. The patient cohort included the fibroblast donor from whom the stem cells were originally derived. We successfully isolated extracellular vesicles from induced pluripotent stem cell-derived human dopaminergic neurons. We identified a distinct set of differentially expressed miRNAs in cellular and cell-free RNA, among which let-7g-5p and miR-21-5p were consistently upregulated and validated across independent replicates. These alterations were reflected in the cerebrospinal fluid of the original donor and partially reproduced in additional LRRK2 patients, supporting the concept of patient-specific signatures. A strong correlation between intra- and extracellular miRNA expression was observed. Our findings demonstrate that induced pluripotent stem cell-derived dopaminergic neurons can serve as a model to identify individualized, cell-free microRNA signatures associated with the LRRK2 G2019S mutation. The dysregulated miRNAs detected in vitro were mirrored in patient cerebrospinal fluid, supporting their potential as accessible molecular readouts. These results lay the groundwork for personalized biomarker strategies in genetic forms of Parkinson’s disease and warrant further validation in larger patient cohorts.

Ethiopia faces challenges of food insecurity, malnutrition, and biodiversity loss. The predominantly rural population relies on staple cereals, leading to deficiencies in essential micronutrients. Ethiopia’s Eastern Afromontane biodiversity hotspot hosts a variety of wild edible fruits (WEFs) that could help alleviate these deficiencies. However, WEFs are stigmatised as “food-for-the-poor” and remain underutilised partly due to limited data on their nutritional value. This study is the first to systematically assess the elemental composition of 23 wild and four cultivated fruit species from Oromia and Southern Nations Nationalities and Peoples (SNNP) regions of Ethiopia. Using inductively coupled plasma mass spectrometry, we found several WEFs to be rich in Ca, Fe, Mg, and Se, often surpassing levels in cultivated fruits. A 100 g serving of these fresh fruits could provide up to 40% of recommended nutrient intakes for adolescent boys. Analysis of soil samples collected from fruit harvesting sites revealed significant correlations between soil and fruit elemental concentrations for several minerals, highlighting the importance of soil properties in determining the nutritional quality of WEFs. Species distribution modelling for 11 selected WEF species identified suitable habitats across southern Ethiopia, with significant spatial variation, suggesting opportunities for targeted promotion and conservation. Integrating WEFs into diets and agroforestry systems could enhance nutrition and biodiversity. Further research on bioavailability, domestication, and policy engagement is recommended.

The RNA modification N ⁶ -methyladenosine (m ⁶ A) plays a key role in RNA processing. It is catalysed by the RNA methyltransferase complex (MTC) which includes METTL3, METTL14 and CBLL1. Recently, a METTL3 inhibitor demonstrated promising preclinical results in several cancer types, yet the therapeutic potential of targeting m ⁶ A in breast cancer (BCa) remains poorly understood. Utilising a large BCa cohort, we identified that increased METTL14 and CBLL1 expression was associated with a more favourable prognosis, whereas increased METTL3 expression was associated with poorer patient outcomes in Triple Negative BCa (TNBC). Using siRNA depletion, we identified distinct METTL3, METTL14 and CBLL1 regulated gene networks in BCa cell lines. METTL3 inhibition reduced proliferation and invasion of BCa cell lines and induced an immune activation transcriptional signature. These results provide insight into the clinical functions of METTL3, METTL14 and CBLL1 in BCa and support the therapeutic potential of targeting METTL3 in BCa, particularly in TNBC.

Oxidative aging of asphalt binder, is a well-recognized and omnipresent phenomenon that leads to several distress types. As an effective way to tackle it, antioxidants have been introduced in asphalt binders. Although it is well documented that certain antioxidants are effective in preventing the deleterious impact of aging on the physical and mechanical properties of asphalt binders, an in-depth investigation of their impacts on meaningful viscoelastic parameters is yet missing. Therefore, this paper examines two promising antioxidants, namely kraft lignin and zinc diethyldithiocarbamate at two different contents of 3% and 5% binder enhancement, utilizing distress-related rheological indicators. Among others, master curves, the Glover-Rowe and ΔΤc parameters were extracted from Dynamic Shear Rheometer, supporting in general a softening effect for zinc and a stiffening effect for lignin. Ultimately, this work seeks to shed light on the functionality of these antioxidants at the virgin asphalt binder state as well as to comprehensively assess their efficiency after laboratory short- and long-term aging compared to their unmodified counterparts. As such, a Relative Aging Index is introduced to fairly compare the aging capacity of the two antioxidants in all blends. Additionally, the rheological investigation is contrasted with aging-related functional groups via Fourier-Transform Infrared spectroscopy, and the findings indicate that there is sufficient basis for supporting a satisfying correlation between the Glover-Rowe parameter and the carbonyl index. Overall, this study dives into a detailed analysis of the rheological behavior of antioxidant-enhanced binders and provides confidence for the application of zinc on a wide scale.

Objectives This study aimed to evaluate the feasibility of delivering a vocational rehabilitation intervention (Return to Work After Trauma—ROWTATE), remotely to individuals recovering from traumatic injuries. The primary objectives were to assess therapists’ training and competence, adapt the intervention and training for remote delivery and assess the feasibility and fidelity of remote delivery to inform a definitive randomised controlled trial. Design A mixed-methods feasibility study incorporating (1) telerehabilitation qualitative literature review, (2) qualitative interviews preintervention and postintervention with therapists and patients, (3) a team objective structured clinical examination to assess competency, (4) usefulness of training, attitudes towards (15-item Evidence-Based Practice Attitude Scale) and confidence in (4-item Evidence Based Practice Confidence Scale) evidence-based practice, intervention delivery confidence (8-bespoke questions) and intervention behaviour determinants (51-items Theoretical Domains Framework) and (5) single-arm intervention delivery feasibility study. Setting The study was conducted in two UK Major Trauma Centres. The intervention and training were adapted for remote delivery due to the COVID-19 pandemic. Participants Therapists: Seven occupational therapists (OTs) and clinical psychologists (CPs) were trained, and six participated in competency assessment. Seven OTs and CPs participated in preintervention interviews and surveys; six completed post-intervention interviews and four completed post-training surveys. Patients: 10 patients were enrolled in the single-arm feasibility study and 4 of these participated in postintervention qualitative interviews. Inclusion criteria included therapists involved in vocational rehabilitation delivery and patients admitted to major trauma centres. Exclusion criteria included participation in other vocational rehabilitation trials or those who had returned to work or education for at least 80% of preinjury hours. Intervention: The ROWTATE vocational rehabilitation intervention was delivered remotely by trained OTs and CPs. Training included competency assessments, mentoring and adaptation for telerehabilitation. The intervention was delivered over multiple sessions, with content tailored to individual patient needs. Results Therapists found the training useful, reported positive attitudes (Evidence-Based Practice Attitude Scale mean=2.9 (SD 0.9)) and high levels of confidence in delivering evidence-based practice (range 75%–100%) and the ROWTATE intervention (range 80%–100%). Intervention barriers identified pretraining became facilitators post-training. Half the therapists needed additional support post-training through mentoring or additional training. The intervention and training were successfully adapted for remote delivery. High levels of fidelity (intervention components delivered: OTs=84.5%, CPs=92.9%) and session attendance rates were found (median: OT=97%, CP=100%). Virtually all sessions were delivered remotely (OT=98%, CP=100%). The intervention was acceptable to patients and therapists; both considered face-to-face delivery where necessary was important. Conclusions The ROWTATE intervention was delivered remotely with high fidelity and attendance and was acceptable to patients and therapists. Definitive trial key changes include modifying therapist training, competency assessment, face-to-face intervention delivery where necessary and addressing lower fidelity intervention components. Trial registration number ISRCTN74668529.

The study of history is traditionally characterized by written assessments. And yet, more creative forms of assessment have the potential to empower students, develop new skills and exhibit ‘imaginative insight’. Such an approach is in line with the recommendations of the UK's Quality Assurance Agency for Higher Education, as reflected in its ‘Subject Benchmark Statement’ for the discipline of history. This Forum piece critically examines creative assessment in history using practitioner research. It examines the pivotal role creative assessment played in the design and redesign of two undergraduate modules. It then considers the student experience of undertaking creative assessment using qualitative and quantitative research data. The article concludes by advocating for greater creativity in assessment design.