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Abstract Preserving organs at subzero temperatures with halted metabolic activity holds the potential to prolong preservation and expand the donor organ pool for transplant. Our group recently introduced partial freezing, a novel approach in high-subzero storage at -15 °C, enabling 5-day storage of rodent livers through precise control over ice nucleation and unfrozen fraction. However, increased vascular resistance and tissue edema suggested a need for improvements to extend viable preservation. Here, we describe an optimized partial freezing protocol with key optimizations, including an increased concentration of polyethylene glycol (PEG) to enhance membrane stability while minimizing shear stress during cryoprotectant unloading with an acclimation period and a maintained osmotic balance through an increase in bovine serum albumin (BSA). These approaches ensured the viability during preservation and recovery processes, promoting liver function and ensuring optimal preservation. This was evidenced by increased oxygen consumption, decreased vascular resistance, and edema. Ultimately, we show that using the optimized protocol, livers can be stored for 10 days with comparable vascular resistance and lactate levels to 5 days, outperforming the viability of time-matched static cold stored (SCS) livers as the current gold standard. This study represents a significant advancement in expanding organ availability through prolonged preservation, thereby revolutionizing transplant medicine.

Abstract The organization of DNA into nucleosomes is a ubiquitous and ancestral feature that was once thought to be exclusive to the eukaryotic domain of life. Intriguingly, several representatives of the Nucleocytoplasmic Large DNA Viruses (NCLDV) encode histone-like proteins that in Melbournevirus were shown to form nucleosome-like particles. Medusavirus medusae (MM), a distantly related giant virus, encodes all four core histone proteins and, unique amongst most giant viruses, a putative acidic protein with two domains resembling eukaryotic linker histone H1. Here, we report the structure of nucleosomes assembled with MM histones and highlight similarities and differences with eukaryotic and Melbournevirus nucleosomes. Our structure provides insight into how variations in histone tail and loop lengths are accommodated within the context of the nucleosome. We show that MM-histones assemble into tri-nucleosome arrays, and that the putative linker histone H1 does not function in chromatin compaction. These findings expand our limited understanding of chromatin organization by virus-encoded histones.

Abstract Introduction Veterans residing in Northern Ireland (NI) likely experience higher levels of co-occurring lifetime trauma exposure and associated co-occurring mental health symptoms, due to the Troubles. As NI veterans have been subject to little exploration it is difficult to know how to support them. This exploratory study explored the co-occurrence of mental health symptoms as a function of co-occurring traumatic experiences. Methods Two latent class analyses (LCA) were conducted on NI veteran data (n = 609). One LCA factored endorsements of 16-lifetime traumatic events, with a separate LCA exploring the co-occurrence of symptoms across six mental health domains. Mental health symptom classes were considered as a function of trauma classes, military-specific variables, gender and age. Results Three trauma classes were identified: High Multi Trauma (10.84%); High Combat/Conflict (47.62%); Moderate Combat Conflict (41.54%), and three mental health symptom classes: High Co-occurring Mental Health (19.38%); High Depression Moderate Anxiety/Alcohol (24.63%); Moderate Alcohol/Normative (55.99%). Significant predictors of High Co-occurring Mental Health class membership were UDR service, ‘Worst’ military trauma and High Multi Trauma class membership. Both combat classes had a negative relationship with the High Co-occurring Mental Health. Predictors of the High Depression Moderate Anxiety/Alcohol class were High Multi Trauma class membership and UDR service, with Age and Moderate Combat Class membership having a negative relationship. Discussion NI veterans could be labelled as ‘traumatised’ due to high levels of combat/conflict exposure, yet the two combat classes seemed unrelated to membership of poorer mental health classes. UDR membership indicated that living in one’s theatre of war could have mental health implications. It was concerning that 45% experienced some co-occurring mental health symptoms with 19% experiencing the poorest symptoms. Hazardous alcohol use appeared unrelated to poor mental health. Further research is needed, utilising robust methods. No clinical inferences are to be made from this exploratory study.

Abstract Background Veteran residents in Northern Ireland (NI) are an under-researched population. Little is known about their experiences of trauma and mental health management. The overall mental well-being of veterans living in NI may be poorer than other veteran populations, due to the challenges presented by the unique landscape. Understanding their experiences is crucial for providing appropriate, targeted support. Method Six male veterans, who had received a mental health diagnosis, living in NI and all aged > 40 years participated. Semi-structured interviews, using open-ended questions, were conducted over the telephone. Interpretative phenomenological analysis was used to explore their experiences. Results Two experiential themes were identified each containing three experiential statements. Statements for ‘an extreme lack of’ included: lack of mental health literacy/awareness; lack of expectations of official support; lack of a sense of perceived appreciation. Statements for ‘an extreme abundance of’ included: exacerbated exposure to a range of extreme environments; high levels of ruled-based living; high levels of engaging with informal/local level support. Conclusions Several experiential statements aligned with existing literature, including having poor mental health literacy and problem recognition, and heavily utilising social support versus formal help-seeking. Some novel findings included bouncing between extreme positive and negative environments which could be as detrimental to mental health as experiencing conflict trauma. Heavy alcohol use was just another rule soldiers followed. Positive help-seeking experiences failed to improve poor opinions of support organisations. Finally, poor self-perceptions connected to military status are pertinent in NI, which seems to fuel self-marginalisation and distrust. A combination of factors likely contributes to many veterans living in NI having poorer mental well-being. Novel findings would benefit from further exploration as understanding how NI veterans interpret their experiences is key to providing adequate healthcare.

Abstract Screening liters of blood (i.e., apheresis) represents a generalized approach to promote the reliable access to circulating tumor cell clusters (CTCCs), which are known to be highly metastasis‐competent, yet ultrarare. However, no existing CTCC sorting technology has demonstrated high throughput, high yield, low shear stress, and minimal blood dilution simultaneously as required in apheresis. Here, a label‐free method is introduced termed Precision Apheresis for Non‐invasive Debulking of cell Aggregates (PANDA) to continuously isolate CTCCs from undiluted blood to clean buffer through size sorting, processing 1.4 billion cells per second. The cell focusing is optimized within whole blood leveraging secondary transverse flow and margination. The PANDA chip recovers >90% of spiked ≈24 rare HeLa cell clusters from 100 mL undiluted blood samples (equivalent to ≈500 billion blood cells) at 1 L h−1 throughput, with ≤20s device residence time, ≤15 Pa shear stress, and >99.9% return of blood components. The technology lays the groundwork for future routine isolation to increase the recovery of these ultrarare yet clinically significant tumor cell populations from large volumes of blood to advance cancer research, early detection, and treatment.

Background: The challenges presented by coronavirus disease 2019 (COVID-19) in higher education pressured learners and instructors to incorporate online emergent learning which presented several well-being and academic challenges to students. Objective: The purpose of this study is to examine the impact of studying online to students' well-being. Methods: A mixed methods approach was followed for this study. Eighty students completed an online survey that measured their stress level of studying online, and 13 semistructured interviews were conducted at Queen's University Belfast. Results: Findings suggest that online learning under such circumstances increased students' level of stress due to a number of perceived factors. Our findings also reveal the journey of student adjustment to online learning, reflecting the flexibility of blended learning as a long-term pedagogical strategy in universities, necessary for University's survival. Conclusion: As demonstrated in this study, after the initial difficulties of moving to online learning which had negative impacts on students learning and well-being, students subsequently adjusted to the online learning environment documenting students' adaptability to a new learning environment and highlighting student resilience.

Abstract Vascularized composite allotransplantations are complex procedures with substantial functional impact on patients. Extended preservation of VCAs is of major importance in advancing this field. It would result in improved donor-recipient matching as well as the potential for ex vivo manipulation with gene and cell therapies. Moreover, it would make logistically feasible immune tolerance induction protocols through mixed chimerism. Supercooling techniques have shown promising results in multi-day liver preservation. It consists of reaching sub-zero temperatures while preventing ice formation within the graft by using various cryoprotective agents. By drastically decreasing the cell metabolism and need for oxygen and nutrients, supercooling allows extended preservation and recovery with lower ischemia–reperfusion injuries. This study is the first to demonstrate the supercooling of a large animal model of VCA. Porcine hindlimbs underwent 48 h of preservation at − 5 °C followed by recovery and normothermic machine perfusion assessment, with no issues in ice formation and favorable levels of injury markers. Our findings provide valuable preliminary results, suggesting a promising future for extended VCA preservation.

Abstract Brief pulses of electric field (electroporation) and/or tensile stress (mechanoporation) have been used to reversibly permeabilize the plasma membrane of mammalian cells and deliver materials to the cytosol. However, electroporation can be harmful to cells, while efficient mechanoporation strategies have not been scalable due to the use of narrow constrictions or needles which are susceptible to clogging. Here we report a high throughput approach to mechanoporation in which the plasma membrane is stretched and reversibly permeabilized by viscoelastic fluid forces within a microfluidic chip without surface contact. Biomolecules are delivered directly to the cytosol within seconds at a throughput exceeding 250 million cells per minute. Viscoelastic mechanoporation is compatible with a variety of biomolecules including proteins, RNA, and CRISPR-Cas9 ribonucleoprotein complexes, as well as a range of cell types including HEK293T cells and primary T cells. Altogether, viscoelastic mechanoporation appears feasible for contact-free permeabilization and delivery of biomolecules to mammalian cells ex vivo.

This case study describes the novel development and demonstration of commercial, green, bio-based products using a peatland based recirculating integrated multi-trophic aquaculture (IMTA) system in the Irish Midlands. This site enables the transition from traditional peat harvesting for energy generation towards alternative sustainable employment. The system effectively addresses sustainable in-land freshwater aquaculture development. It also demonstrates value-chain products at scale for new feeds arising from the fish waste-stream by exploiting cascades from the fish culture waste-stream (bio-fertiliser) for cultivating duckweed and macroalgae. These plants can then be bio-refined and valorised to produce new products. The system also provides a circular demonstrator site that will facilitate industry and entrepreneurs to develop and test new innovations and ideas. By providing this open-access site to support companies in testing, financial constraints such as access to specialist equipment and technical expertise will be off-set thus enabling entrepreneurs and industry to develop new commercial products at scale. Additionally, the outputs from this system will help address and inform several United Nations sustainable development goals.

Although whistleblowing is thought to represent an effective mechanism for detecting and uncovering doping in sport, it has yet to become a widely adopted practice. Understanding the factors that encourage or discourage whistleblowing is of vital importance for the promotion of this practice and the development of pedagogical material to enhance the likelihood of whistleblowing. The current study employed a qualitative methodology to explore the personal and organisational factors that underpin intentions to blow the whistle or that may lead to engagement in whistleblowing behaviours in sport. Thirty-three competitive athletes across a range of sports took part in a semi-structured interview which sought to explore what they would do should they encounter a doping scenario. Content analysis revealed that whistleblowing is a dynamic process characterised by the interaction of a range of personal and organisational factors in determining the intention to report PED use. These factors included moral reasoning, a desire to keep the matter “in-house”, perceived personal costs, institutional attitudes to doping, and social support. Analysis revealed a number of “intervening events”, including a perceived lack of organisational protection (e.g., ethical leadership) within some sporting sub-cultures, which present an important obstacle to whistleblowing. The intention to report doping was underpinned by a “fairness-loyalty trade-off” which involved athletes choosing to adhere to either fairness norms (which relate to a sense that all people and groups are treated equally) or loyalty norms (which reflect preferential treatment towards an in-group) when deciding whether they would blow the whistle. The promotion of fairness norms that emphasise a group's collective interests might encourage athletes to view whistleblowing as a means of increasing group cohesiveness and effectiveness and thereby increase the likelihood of this practice.

Background: Liver donation after cardiac death (DCD) makes up a small percentage of the organs used in transplantation and poses a higher risk of graft loss compared to donation after brain death (DBD); this is a result of ischemia reperfusion for which the exact injury mechanisms are currently not fully understood. However, reperfusion injury has been shown to lead to necrosis as well as apoptosis through oxidative stress and mitochondrial dysfunction. In this work, we propose that use of the pro-survival, anti-apoptotic CEPT cocktail in post-ischemia normothermic machine perfusion (NMP) may improve recovery in rat livers subjected to extended durations of warm ischemia. Materials and Methods: Livers procured from male Lewis rats were subjected to 90 min of warm ischemia, followed by 6 h of NMP where they were treated either with the survival-enhancing anti-apoptotic cocktail (CEPT), the vehicle (DMSO) or the base media with no additives. Results: The CEPT-treated group exhibited lower expression of hepatic injury biomarkers, and improvement in a range of hepatocellular symptoms associated with the hepatic parenchyma, biliary epithelium and the sinusoidal endothelium, including recovery of bile secretion and lowered vascular resistance. Conclusions: This study's findings suggest apoptosis plays a more significant role in ischemia-reperfusion injury than previously understood, and provide useful insight for further investigation of the specific underlying mechanisms and development of novel treatment methods.

Abstract Lymphoma is one of the most common cancers in adolescents and young adults, but historically, this population has had lower clinical trial enrollment and improvements in overall survival as compared to other age populations. There are multiple challenges that are unique to this population that have affected drug development and clinical trial enrollment. Our panel of experts have identified barriers, and in this review, we discuss current methods to address these barriers as well as potential solutions moving forward.

This paper explores the problem of automated robot program generation from limited historical data when neither accurate geometric environmental models nor online vision feedback are available. The Program Reuse Framework (PRF) is developed, which uses expert-defined motion classes, a novel data structure introduced in this work, to learn affordances, workspaces, and skills from historical data. Historical data comprise raw robot joint trajectories and descriptions of the robot task being completed. Given new tasks, motion classes are then used again to formulate an optimization problem capable of generating new open-loop, skill-based programs to complete the tasks. To cope with a lack of geometric models, a technique to learn safe workspaces from demonstrations is developed, allowing the risk of new programs to be estimated before execution. A new learnable motion primitive for redundant manipulators is introduced, called a redundancy dynamical movement primitive, which enables new end-effector goals to be reached while mimicking the whole-arm behavior of a demonstration. A mobile manipulator part transportation task is used throughout to illustrate each step of the framework.