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Abstract The Final Year Project (FYP) is one of the most important courses for every undergraduate student, and the effective operation of the FYPs in higher education still faces challenges, such as uneven resource distribution and limited efficiency. This study reports a mixed-methods approach to study the impact of a student-centered FYP allocation mechanism on student performance. This research aims to investigate how aligning students’ FYP choices with their interests can inspire motivation and enhance academic performance. More importantly, this mechanism improves students’ academic resilience, enabling them to navigate unexpected contextual factors. The study’s findings take into account various aspects, including student satisfaction with the allocation process, future improvement methods, and the relationship between interest and context. The outcomes observed in this study support our hypotheses, indicating the improvements in students’ academic performance as well as the pass and completion rates. Moreover, this research contributes to ‘resilience theory’ by exploring students’ adaptability to contextual changes and their enhancement of academic resilience. This study proposes recommendations for cultivating a dynamic student-centered classroom environment. Future work could pay attention to addressing the limitations of this study, exploring other factors influencing FYP allocation, and integrating more quantitative measures for a comprehensive assessment of its impact.

Abstract Background Frailty reduction and reversal have been addressed successfully among older populations within community settings. However, these findings may not be applicable to residential care settings, largely due to the complex and multidimensional nature of the condition. Relatively, few attempts at frailty prevention exist in residential settings. This review aims to identify and describe best practice models of care for addressing frailty among older populations in residential care settings. This research also sets out to explore the impact of multidisciplinary health service delivery models on health outcomes such as mortality, hospitalisations, quality of life, falls and frailty. Methods A scoping review of the literature was conducted to address the project objectives. Reference lists of included studies, bibliographic databases and the grey literature were systematically searched for literature reporting multidisciplinary, multidimensional models of care for frailty. Results The scoping review found no interventions that met the inclusion criteria. Of the 704 articles screened, 664 were excluded as not relevant. Forty articles were fully assessed, and while no eligible studies were found, relevant data were extracted from 10 near-eligible studies that reported single disciplines or single dimensions rather than a model of care. The physical, nutritional, medicinal, social and cognitive aspects of the near eligible studies have been discussed as playing a key role in frailty reduction or prevention care models. Conclusion This review has identified a paucity of interventions for addressing and reducing frailty in residential care settings. High-quality studies investigating novel models of care for addressing frailty in residential care facilities are required to address this knowledge gap. Similarly, there is a need to develop and validate appropriate screening and assessment tools for frailty in residential care populations. Health service providers and policy-makers should also increase their awareness of frailty as a dynamic and reversible condition. While age is a non-modifiable predictor of frailty, addressing modifiable factors through comprehensive care models may help manage and prevent the physical, social and financial impacts of frailty in the ageing population.

Abstract The 2021 Pacific Northwest heatwave was so extreme as to challenge conventional statistical and climate-model-based approaches to extreme weather attribution. However, state-of-the-art operational weather prediction systems are demonstrably able to simulate the detailed physics of the heatwave. Here, we leverage these systems to show that human influence on the climate made this event at least 8 [2–50] times more likely. At the current rate of global warming, the likelihood of such an event is doubling every 20 [10–50] years. Given the multi-decade lower-bound return-time implied by the length of the historical record, this rate of change in likelihood is highly relevant for decision makers. Further, forecast-based attribution can synthesise the conditional event-specific storyline and unconditional event-class probabilistic approaches to attribution. If developed as a routine service in forecasting centres, it could provide reliable estimates of human influence on extreme weather risk, which is critical to supporting effective adaptation planning.

Abstract Cultivated meat production requires bioprocess optimization to achieve cell densities that are multiple orders of magnitude higher compared to conventional cell culture techniques. These processes must maximize resource efficiency and cost-effectiveness by attaining high cell growth productivity per unit of medium. Microcarriers, or carriers, are compatible with large-scale bioreactor use, and offer a large surface-area-to-volume ratio for the adhesion and proliferation of anchorage-dependent animal cells. An ongoing challenge persists in the efficient retrieval of cells from the carriers, with conflicting reports on the effectiveness of trypsinization and the need for additional optimization measures such as carrier sieving. To surmount this issue, edible carriers have been proposed, offering the advantage of integration into the final food product while providing opportunities for texture, flavor, and nutritional incorporation. Recently, a proof of concept (POC) utilizing inactivated mycelium biomass derived from edible filamentous fungus demonstrated its potential as a support structure for myoblasts. However, this POC relied on a model mammalian cell line combination with a single mycelium species, limiting realistic applicability to cultivated meat production. This study aims to advance the POC. We found that the species of fungi composing the carriers impacts C2C12 myoblast cell attachment—with carriers derived from Aspergillus oryzae promoting the best proliferation. C2C12 myoblasts effectively differentiated on mycelium carriers when induced in myogenic differentiation media. Mycelium carriers also supported proliferation and differentiation of bovine satellite cells. These findings demonstrate the potential of edible mycelium carrier technology to be readily adapted in product development within the cultivated meat industry.

ObjectivesRapid diameter growth is a criterion for ascending thoracic aortic aneurysm repair; however, there are sparse data on aneurysm elongation rate. The purpose of this study was to assess aortic elongation rates in nonsyndromic, nonsurgical aneurysms to understand length dynamics and correlate with aortic diameter over time.MethodsPatients with

BackgroundAdoptive transfer of T cells is a burgeoning cancer therapeutic approach. However, the fate of the cells, once transferred, is most often unknown. We describe the first clinical experience with a non-invasive biomarker to assay the apoptotic cell fraction (ACF) after cell therapy infusion, tested in the setting of head and neck squamous cell carcinoma (HNSCC). A patient with HNSCC received autologous tumor-infiltrating lymphocytes (TILs) labeled with a perfluorocarbon (PFC) nanoemulsion cell tracer. Nanoemulsion, released from apoptotic cells, clears through the reticuloendothelial system, particularly the Kupffer cells of the liver, and fluorine-19 (19F) magnetic resonance spectroscopy (MRS) of the liver was used to non-invasively infer the ACF.MethodsAutologous TILs were isolated from a patient in their late 50s with relapsed, refractory human papillomavirus-mediated squamous cell carcinoma of the right tonsil, metastatic to the lung. A lung metastasis was resected for T cell harvest and expansion using a rapid expansion protocol. The expanded TILs were intracellularly labeled with PFC nanoemulsion tracer by coincubation in the final 24 hours of culture, followed by a wash step. At 22 days after intravenous infusion of TILs, quantitative single-voxel liver 19F MRS was performed in vivo using a 3T MRI system. From these data, we model the apparent ACF of the initial cell inoculant.ResultsWe show that it is feasible to PFC-label ~70×1010 TILs (F-TILs) in a single batch in a clinical cell processing facility, while maintaining >90% cell viability and standard flow cytometry-based release criteria for phenotype and function. Based on quantitative in vivo 19F MRS measurements in the liver, we estimate that ~30% cell equivalents of adoptively transferred F-TILs have become apoptotic by 22 days post-transfer.ConclusionsSurvival of the primary cell therapy product is likely to vary per patient. A non-invasive assay of ACF over time could potentially provide insight into the mechanisms of response and non-response, informing future clinical studies. This information may be useful to developers of cytotherapies and clinicians as it opens an avenue to quantify cellular product survival and engraftment.

Electrically conductive biomaterials direct cell behavior by capitalizing on the effect of bioelectricity in tissue homeostasis and healing. Many studies have leveraged conductive biomaterials to influence cells and improve tissue healing, even in the absence of external stimulation. However, most studies using electroactive materials neglect characterizing how the inclusion of conductive additives affects the material's mechanical properties, and the interplay between substrate electrical and mechanical properties on cell behavior is poorly understood. Furthermore, mechanisms dictating how electrically conductive materials affect cell behavior in the absence of external stimulation are not explicit. In this study, we developed a mechanically and electrically tunable conductive hydrogel using agarose and the conductive polymer PEDOT:PSS. Under certain conditions, we observed that the hydrogel physical and electrical properties were decoupled. We then seeded human mesenchymal stromal cells (MSCs) onto the hydrogels and observed enhanced adhesion and spreading of MSCs on conductive substrates, regardless of the hydrogel mechanical properties, and despite the gels having no cell-binding sites. To explain this observation, we measured protein interaction with the gels and found that charged proteins adsorbed significantly more to conductive hydrogels. These data demonstrate that conductivity promotes cell adhesion, likely by facilitating increased adsorption of proteins associated with cell binding, providing a better understanding of the mechanism of action of electrically conductive materials.

Microgels are an emerging platform for in vitro models and guiding cell fate due to their inherent porosity and tunability. This work describes a light-based technique for rapidly annealing microgels across a range of diameters. Utilizing 8-arm poly(ethylene) glycol-vinyl sulfone, the number of arms available for crosslinking, functionalization, and annealing is stoichiometrically controlled. Small and large microgels are fabricated to explore how microgel diameter impacts void space and the role of porosity on cell spreading, cell aggregation, and macrophage polarization. Mesenchymal stromal cells spread rapidly in both formulations, yet the smaller microgels permit a higher cell density. When seeded with macrophages, the smaller microgels promote an M1 phenotype, while larger microgels promote an M2 phenotype. As another application, the inherent porosity of annealed microgels is leveraged to induce cell aggregation. Finally, the microgels are implanted to examine how different size microgels influence endogenous cell invasion and macrophage polarization. The use of ultraviolet light allows for microgels to be noninvasively injected into a desired mold or wound defect before annealing, and microgels of different properties combined to create a heterogeneous scaffold. This approach is clinically relevant given its tunability and fast annealing time.

Introduction Physical frailty is associated with increased mortality and poor quality of life (QoL) before and after liver transplantation (LT). Evidence is lacking on how to tailor exercise and behavioural techniques in this patient population.Methods and analysis Home-based EXercise and motivAtional programme before and after Liver Transplantation (EXALT) is a phase 2b, open-label, two-centre randomised controlled clinical trial designed to investigate whether a remotely monitored ‘home-based exercise and theory-based motivation support programme (HBEP)’ before and after LT improves QoL in LT recipients. Adult patients awaiting a primary LT will be assessed for eligibility at two LT centres (Birmingham, Royal Free London). Participants will be randomly assigned (1:1) to receive either an HBEP while on the LT waiting list through to 24 weeks after LT (Intervention) or a patient exercise advice leaflet (Control). Using a standard method of difference in means (two-sided significance level 0.05; power 0.90) and accounting for a 35% attrition/withdrawal rate, a minimum of 133 patients will be randomised to each treatment group. The primary outcome measure will be assessed using intention-to-treat analysis of the difference in the Physical Component Score of Short form-36 version 2.0 health-related QoL questionnaire between the groups at 24 weeks post-LT.Ethics and dissemination The protocol was approved by the South Central-Hampshire A National Research Ethics Committee. Recruitment into the EXALT trial started in May 2022 and is due to end in June 2024, with 217/266 patients randomised to date. The intervention follow-up is due to finish in May 2026. The findings of this trial will be disseminated through peer-reviewed publications, conferences and social media.Trial registration number ISRCTN13476586.

Objective Digital interventions can be effective in preventing and treating common mental health conditions among university students. Incorporating student experiences and perspectives in the design and implementation of these programmes may improve uptake and engagement. This qualitative study explored university students’ perspectives of a low-intensity video-based mental health intervention, their recommendations for implementing the programme in university settings, and their views and recommendations to address barriers to engagement. Methods Participants (N = 115) were students (mean = 20.63 years, SD = 2.10) with elevated distress from 31 Australian universities drawn from a randomised controlled trial of the Uni Virtual Clinic-Lite (UVC-Lite). Data from students randomised to the intervention condition were collected via semi-structured interviews (n = 12) and open-ended questions during post-intervention surveys (n = 103). Data were analysed using content analysis. Results Participants generally reported positive views of the intervention, and most felt it should be offered to students as a universal intervention. Multiple methods of disseminating the intervention were suggested, including through university counselling, official platforms (e.g. student support services) and informal channels (e.g. word-of-mouth promotion). Difficulty integrating the programme into everyday life, pre-existing beliefs about mental health and technology-related factors were highlighted as barriers to engagement. Conclusion A low-intensity video-based mental health intervention was generally considered to be acceptable and appropriate for students with mild to moderate distress. Participants provided several suggestions to encourage uptake of the intervention and possible pathways to disseminate the intervention to students. The effectiveness of these should be examined in future trials.

In this paper, we explore the concept of outdoor adventure in the context of mental health, proposing an ecological perspective to redefine adventure beyond its traditional associations with risk and physical challenge. We critically examine current frameworks and definitions of adventure, which often emphasise specific activities and natural environments yet overlook the individual’s experience and potential mental health benefits. From an ecological perspective, we emphasise the dynamic interplay between the individual, the activity, and the environment. This approach, grounded in ecological psychology, considers the multi-dimensional nature of adventure, including social, psychological, physical, and spiritual aspects. The paper challenges the traditional risk-focused view of adventure, advocating for a broader definition that includes diverse experiences and interactions, as well as the transformative potential of adventure in various environments, including urban settings. We highlight the changing demographics and motivations of adventure participants, moving away from the stereotypical young male risk-seeker, to more diverse and inclusive participant profiles. We argue that adventure facilitates the realisation of fundamental human affordances, often untapped in daily life, thereby enhancing mental health and wellbeing. This ecological perspective opens new avenues for understanding the role of adventure in mental health and wellbeing, offering a more comprehensive and inclusive approach to adventure activities as therapeutic interventions. This redefined understanding of adventure emphasises its potential as a powerful tool for enhancing human wellbeing, harmonising the relationship between people, tasks, and the environment, and offering profound implications for mental health contexts.

ABSTRACT Protein production strategies in bacteria are often limited due to the need for cell lysis and complicated purification schemes. To avoid these challenges, researchers have developed bacterial strains capable of secreting heterologous protein products outside the cell, but secretion titers often remain too low for commercial applicability. Improved understanding of the link between secretion system structure and its secretory abilities can help overcome the barrier to engineering higher secretion titers. Here, we investigated this link with the PrgI protein, the monomer of the secretory channel of the type 3 secretion system (T3SS) of Salmonella enterica. Despite detailed knowledge of the PrgI needle’s assembly and structure, little is known about how its structure influences its secretory capabilities. To study this, we recently constructed a comprehensive codon mutagenesis library of the PrgI protein utilizing a novel one-pot recombineering approach. We then screened this library for functional T3SS assembly and secretion titer by measuring the secretion of alkaline phosphatase using a high-throughput activity assay. This allowed us to construct a first-of-its-kind secretion fitness landscape to characterize the PrgI needle’s mutability at each position as well as the mutations which lead to enhanced T3SS secretion. We discovered new design rules for building a functional T3SS as well as identified hypersecreting mutants. This work can be used to increase understanding of the T3SS’s assembly and identify further targets for engineering. This work also provides a blueprint for future efforts to engineer other complex protein assemblies through the construction of fitness landscapes.IMPORTANCEProtein secretion offers a simplified alternative method for protein purification from bacterial hosts. However, the current state-of-the-art methods for protein secretion in bacteria are still hindered by low yields relative to traditional protein purification strategies. Engineers are now seeking strategies to enhance protein secretion titers from bacterial hosts, often through genetic manipulations. In this study, we demonstrate that protein engineering strategies focused on altering the secretion apparatus can be a fruitful avenue toward this goal. Specifically, this study focuses on how changes to the PrgI needle protein from the type 3 secretion system from Salmonella enterica can impact secretion titer. We demonstrate that this complex is amenable to comprehensive mutagenesis studies and that this can yield both PrgI variants with increased secretory capabilities and insight into the normal functioning of the type 3 secretion system.

In most patients with advanced prostate cancer treated with hormonal therapy, androgen independence eventually emerges, leading to death. Androgen receptor signalling remains an important prostate cancer driver, even in the advanced disease stage. MicroRNAs (miRs), non-coding RNAs that regulate gene expression by inhibiting translation and/or promoting degradation of target mRNAs, can act as tumour suppressors or “oncomiRs” and modulate tumour growth. Because of their stability in tissues and in circulation, and their specificity, microRNAs have emerged as potential biomarkers, as well as therapeutic targets in cancer. We identified miR-1271–5p as an androgen receptor modulatory microRNA and we show it can promote hormone sensitive prostate cancer cell growth. Inhibition or overexpression of miR-1271–5p levels affects prostate cancer cell growth, apoptosis and expression of both androgen receptor target genes and other genes that are likely direct targets, dependent on androgen receptor status, and tumour stage. We conclude that miR-1271–5p has the potential to drive progression of hormone-dependent disease and that the use of specific inhibitors of miR-1271–5p may have therapeutic potential in prostate cancer.

Moyamoya disease (MMD) is a chronic, occlusive cerebrovasculopathy typified by progressive steno-occlusive disease of the intracranial internal carotid arteries (ICAs) and their proximal branches. Moyamoya syndrome (MMS) categorizes patients with characteristic MMD plus associated conditions. As such, the most usual presentations are those that occur with cerebral ischemia, specifically transient ischemic attack, acute ischemic stroke, and seizures. Hemorrhagic stroke, headaches, and migraines can also occur secondary to the compensatory growth of fragile collateral vessels propagated by chronic cerebral ischemia. While the pathophysiology of MMD is unknown, there remain numerous clinical associations including radiation therapy to the brain, inherited genetic syndromes, hematologic disorders, and autoimmune conditions. We describe the case of a 31-year-old woman who presented with recurrent ischemic cerebral infarcts secondary to rapidly progressive, bilateral MMD despite undergoing early unilateral surgical revascularization with direct arterial bypass. She had numerous metabolic conditions and rapidly decompensated, ultimately passing away despite intensive and aggressive interventions. The present case highlights that progression of moyamoya disease to bilateral involvement can occur very rapidly, within a mere 6 weeks, a phenomenon which has not been documented in the literature to our knowledge.

BackgroundNumerous studies have demonstrated the effectiveness of digital interventions for improving the mental health of university students. However, low rates of engagement with these interventions are an ongoing challenge and can compromise effectiveness. Brief, transdiagnostic, web-based video interventions are capable of targeting key mental health and related issues affecting university students and may be more engaging and accessible for this population. ObjectiveThis study used a 2-arm randomized controlled trial to evaluate the effectiveness of Uni Virtual Clinic-Lite (UVC-Lite), a fully automated, transdiagnostic, web-based video intervention, relative to an attention-control condition. The primary outcomes were symptoms of depression and generalized anxiety disorder. The secondary outcomes included psychological distress, social anxiety symptoms, body appreciation, quality of life, well-being, functioning, general self-efficacy, academic self-efficacy, and help seeking. Program use (intervention uptake and engagement) and satisfaction were also assessed. MethodsUniversity students (n=487) with mild to moderate symptoms of distress were recruited from universities across Australia and randomly allocated to receive access to the UVC-Lite intervention or an attention-control condition targeting general health for a period of 6 weeks. UVC-Lite includes 12 modules, each comprising a brief animated video and an accompanying exercise. Of the 12 modules, 7 also included a brief symptom screening quiz. Outcomes were assessed at baseline, postintervention, and 3- and 6-months postintervention. ResultsThe primary and secondary outcomes were analyzed on an intention-to-treat basis using mixed models repeated measures ANOVA. The intervention was not found to be effective relative to the control condition on any of the primary or secondary outcomes. While 67.9% (114/168) of participants accessed at least 1 module of the intervention, module completion was extremely low. Subgroup analyses among those who engaged with the program (completed at least 1 video) and those with higher baseline distress (Distress Questionnaire-5 score ≥15) did not reveal any differences between the conditions over time. However, uptake (accessing at least 1 video) and engagement (completing at least 1 video) were higher among those with higher baseline symptoms. Satisfaction with the intervention was high. ConclusionsThe UVC-Lite intervention was not effective relative to a control program, although it was associated with high satisfaction among students and was not associated with symptom deterioration. Given the challenges faced by universities in meeting demand for mental health services, flexible and accessible interventions such as UVC-Lite have the potential to assist students to manage symptoms of mental health problems. However, low uptake and engagement (particularly among students with lower levels of symptomatology) are significant challenges that require further attention. Future studies should examine the effectiveness of the intervention in a more highly symptomatic sample, as well as implementation pathways to optimize effective engagement with the intervention. Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12621000375853; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380146

This study explores indoor air pollutant (PM1, PM2.5 and NO2) concentrations over a 15-week period during the COVID-19 pandemic in a typical suburban household in Oxford, UK. A multi-room intensive monitoring study was conducted in a single dwelling using 10 air quality sensors measuring real-time pollutant concentrations at 10 second intervals to assess temporal and spatial variability in PM1, PM2.5 and NO2 concentrations, identify pollution-prone areas, and investigate the impact of residents' activities on indoor air quality. Significant spatial variations in PM concentrations were observed within the study dwelling, with highest hourly concentrations (769.0 & 300.9 μg m−3 for PM2.5, and PM1, respectively) observed in the upstairs study room, which had poor ventilation. Cooking activities were identified as a major contributor to indoor particulate pollution, with peak concentrations aligning with cooking events. Indoor NO2 levels were typically higher than outdoor levels, particularly in the kitchen where a gas-cooking appliance was used. There was no significant association observed between outdoor and indoor PM concentrations; however, a clear correlation was evident between kitchen PM emissions and indoor levels. Similarly, outdoor NO2 had a limited influence on indoor air quality compared to kitchen activities. Indoor sources were found to dominate for both PM and NO2, with higher Indoor/Outdoor (I/O) ratios observed in the upstairs bedroom and the kitchen. Overall, our findings highlight the contribution of indoor air pollutant sources and domestic activities to indoor air pollution exposure, notably during the COVID-19 pandemic when people were typically spending more time in domestic settings. Our novel findings, which suggest high levels of pollutant concentrations in upstairs (first floor) rooms, underscore the necessity for targeted interventions. These interventions include the implementation of source control measures, effective ventilation strategies and occupant education for behaviour change, all aimed at improving indoor air quality and promoting healthier living environments.

The emergence of zoonotic infections that can develop into pathogens of pandemic potential is a major concern for public health. The risks of emergence and transmission relate to multiple factors that range from land use to human–non-human animal contacts. Livestock agriculture plays a potentially significant role in those risks, shaping landscapes and providing hosts that can act as the source or amplifiers of emergent pathogens. The relative risks will be contingent upon the nature of those systems, with comparisons often made between intensive, indoor, biosecure systems and more extensive, outdoor, insecure systems. Microbiological, ecological and veterinary sciences provide useful entry points in specifying and modelling some of the relative risks. Yet, they often do so with little regard for social science inputs and by making assumptions about social and economic conditions. In this article, we respond to recent analyses of relative risks by raising the importance of social and economic drivers of risk. We chart social science insights and research that materially alter the zoonotic risks associated with livestock production. Our purpose is to emphasize the requirement for full appreciation of the social, economic and political components of zoonotic and pandemic risk.

BackgroundAs the number of cancer survivors increases, maintaining health-related quality of life in cancer survivorship is a priority. This necessitates accurate and reliable methods to assess how cancer survivors are feeling and functioning. Real-world digital measures derived from wearable sensors offer potential for monitoring well-being and physical function in cancer survivorship, but questions surrounding the clinical utility of these measures remain to be answered. ObjectiveIn this secondary analysis, we used 2 existing data sets to examine how measures of real-world physical behavior, captured with a wearable accelerometer, were related to aerobic fitness and self-reported well-being and physical function in a sample of individuals who had completed cancer treatment. MethodsOverall, 86 disease-free cancer survivors aged 21-85 years completed self-report assessments of well-being and physical function, as well as a submaximal exercise test that was used to estimate their aerobic fitness, quantified as predicted submaximal oxygen uptake (VO2). A thigh-worn accelerometer was used to monitor participants’ real-world physical behavior for 7 days. Accelerometry data were used to calculate average values of the following measures of physical behavior: sedentary time, step counts, time in light and moderate to vigorous physical activity, time and weighted median cadence in stepping bouts over 1 minute, and peak 30-second cadence. ResultsSpearman correlation analyses indicated that 6 (86%) of the 7 accelerometry-derived measures of real-world physical behavior were not significantly correlated with Functional Assessment of Cancer Therapy-General total well-being or linked Patient-Reported Outcomes Measurement Information System-Physical Function scores (Ps≥.08). In contrast, all but one of the physical behavior measures were significantly correlated with submaximal VO2 (Ps≤.03). Comparing these associations using likelihood ratio tests, we found that step counts, time in stepping bouts over 1 minute, and time in moderate to vigorous activity were more strongly associated with submaximal VO2 than with self-reported well-being or physical function (Ps≤.03). In contrast, cadence in stepping bouts over 1 minute and peak 30-second cadence were not more associated with submaximal VO2 than with the self-reported measures (Ps≥.08). ConclusionsIn a sample of disease-free cancer survivors, we found that several measures of real-world physical behavior were more associated with aerobic fitness than with self-reported well-being and physical function. These results highlight the possibility that in individuals who have completed cancer treatment, measures of real-world physical behavior may provide additional information compared with self-reported and performance measures. To advance the appropriate use of digital measures in oncology clinical research, further research evaluating the clinical utility of real-world physical behavior over time in large, representative samples of cancer survivors is warranted. Trial RegistrationClinicalTrials.gov NCT03781154; https://clinicaltrials.gov/ct2/show/NCT03781154

The excited states of N=44 ^{74}Zn were investigated via γ-ray spectroscopy following ^{74}Cu β decay. By exploiting γ-γ angular correlation analysis, the 2_{2}^{+}, 3_{1}^{+}, 0_{2}^{+}, and 2_{3}^{+} states in ^{74}Zn were firmly established. The γ-ray branching and E2/M1 mixing ratios for transitions deexciting the 2_{2}^{+}, 3_{1}^{+}, and 2_{3}^{+} states were measured, allowing for the extraction of relative B(E2) values. In particular, the 2_{3}^{+}→0_{2}^{+} and 2_{3}^{+}→4_{1}^{+} transitions were observed for the first time. The results show excellent agreement with new microscopic large-scale shell-model calculations, and are discussed in terms of underlying shapes, as well as the role of neutron excitations across the N=40 gap. Enhanced axial shape asymmetry (triaxiality) is suggested to characterize ^{74}Zn in its ground state. Furthermore, an excited K=0 band with a significantly larger softness in its shape is identified. A shore of the N=40 "island of inversion" appears to manifest above Z=26, previously thought as its northern limit in the chart of the nuclides.

BackgroundExtremely preterm (EPT) birth has been related to dysregulation of stress responses and behavioral/learning problems at school age. Early adverse experiences can blunt HPA axis reactivity. We hypothesized that an attenuated cortisol awakening response would be associated with developmental and behavioral problems at school age in EPT children.MethodsThis secondary analysis of a sub-cohort of the SUPPORT study included children born between 24 and 27 weeks, evaluated at 6-7 years with a neurodevelopmental battery and cortisol measures. Differences were tested between EPT and a term-born group. Relationships of cortisol awakening response to test scores were analyzed.ResultsCortisol was measured in 110 EPT and 29 term-born 6-7 year olds. Unadjusted WISC-IV and NEPSY-II scores were significantly worse among EPT children only. Conners Parent Rating Scale behavior scores were significantly worse among EPT children. After adjusting for covariates, blunted cortisol awakening responses were found to be associated with poorer scores on memory tests and greater problems with inattention for the EPT group (p

Significant progress has been made in designing bone materials capable of directing endogenous cells to promote vascularized bone regeneration. However, current strategies lack regulation of the specific endogenous cell populations for vascularized bone regeneration, thus leading to adverse tissue formation and decreased regenerative efficiency. Here, we engineered a biomaterial to regulate endogenous cell adhesion and promote vascularized bone regeneration. The biomaterial works by presenting two synthetic ligands, LLP2A and LXW7, explicitly targeting integrins α4β1 and αvβ3, respectively, expressed on the surfaces of the cells related to bone formation and vascularization, such as mesenchymal stem cells (MSCs), osteoblasts, endothelial progenitor cells (EPCs), and endothelial cells (ECs). In vitro, the LLP2A/LXW7 modified biomaterial improved the adhesion of MSCs, osteoblasts, EPCs, and ECs via integrin α4β1 and αvβ3, respectively. In an adult rat calvarial bone defect model, the LLP2A/LXW7 modified biomaterial enhanced bone formation and vascularization by synergistically regulating endogenous cells with osteogenic and angiogenic potentials, such as DLX5+ cells, osteocalcin+ cells, CD34+/CD45- cells and CD31+ cells. In a fetal sheep spinal bone defect model, the LLP2A/LXW7 modified biomaterial augmented bone formation and vascularization without any adverse effects. This innovative biomaterial offers an off-the-shelf, easy-to-use, and biologically safe product suitable for vascularized bone regeneration in both fetal and adult disease environments.

Sweetpotatoes are a major crop in California, ranking sixth in value among organic commodities in the state. In recent years, there has been growing consumer interest in diverse specialty varieties, particularly purple types and those associated with Asian American and Pacific Islander (AAPI) communities, some of which are currently imported into the state. In this study, we screened 45 diverse sweetpotato varieties and breeding lines under California organic conditions in a preliminary characterization of their agronomic performance. We then conducted culinary evaluations with a tasting panel of students primarily identifying as Asian/Asian American to determine the preference for each type in terms of flavor and culinary appeal. Our results indicated that major tradeoffs exist among existing germplasm, with no variety or line excelling across all agronomic and culinary traits. These results suggest that sweetpotato breeding could be an effective mechanism to combine superior agronomic traits of major commercial classes with the high culinary quality of diverse materials that are not adapted to California organic production. These results provide a strong justification for the value of sweetpotato breeding to ultimately promote a more profitable, sustainable, and just food system in the region.

Recombinant growth factors are used in tissue engineering to stimulate cell proliferation, migration, and differentiation. Conventional methods of growth factor delivery for therapeutic applications employ large amounts of these bioactive cues. Effective, localized growth factor release is essential to reduce the required dose and potential deleterious effects. The endogenous extracellular matrix (ECM) sequesters native growth factors through its negatively charged sulfated glycosaminoglycans. Mesenchymal stromal cells secrete an instructive extracellular matrix that can be tuned by varying culture and decellularization methods. In this study, mesenchymal stromal cell-secreted extracellular matrix was modified using λ-carrageenan as a macromolecular crowding (MMC) agent and decellularized with DNase as an alternative to previous decellularized extracellular matrices (dECM) to improve growth factor retention. Macromolecular crowding decellularized extracellular matrix contained 7.7-fold more sulfated glycosaminoglycans and 11.7-fold more total protein than decellularized extracellular matrix, with no significant difference in residual DNA. Endogenous BMP-2 was retained in macromolecular crowding decellularized extracellular matrix, whereas BMP-2 was not detected in other extracellular matrices. When implanted in a murine muscle pouch, we observed increased mineralized tissue formation with BMP-2-adsorbed macromolecular crowding decellularized extracellular matrix in vivo compared to conventional decellularized extracellular matrix. This study demonstrates the importance of decellularization method to retain endogenous sulfated glycosaminoglycans in decellularized extracellular matrix and highlights the utility of macromolecular crowding to upregulate sulfated glycosaminoglycan content. This platform has the potential to aid in the delivery of lower doses of BMP-2 or other heparin-binding growth factors in a tunable manner.

AbstractThe Paleoproterozoic Mârmorilik Formation in the Karrat basin of West Greenland hosts the Black Angel Zn–Pb deposit. Chlorine-rich scapolite, zones with vuggy porosity and quartz nodules in the ore-bearing marble are herein interpreted to represent metamorphosed, vanished, and replaced evaporites, respectively. Mineralization is closely associated with anhydrite with δ34S values (5.2–12.6‰) broadly comparable to published values for Paleoproterozoic seawater sulfate. Considering the fundamental attributes of the mineralization and host sequence, a Mississippi Valley-type (MVT) model is the most obvious explanation for mineralization. Overlying the ore-bearing sequence are organic-rich semipelites and massive calcitic marbles, which may have served as seals for hydrocarbon or reduced sulfur and acted as chemical traps for deposition of the sulfidic ore. The Mârmorilik Formation contained an interlayered sulfate-rich evaporite-carbonate sequence, a common setting for MVT deposits in the late Neoproterozoic and Phanerozoic, but unique among the few known MVT deposits in the Paleoproterozoic. This ca. 1915 Ma evaporite-carbonate platform is younger than sulfate evaporites deposited during and immediately after the ca. 2220–2060 Ma Lomagundi carbon isotope excursion and records a significant seawater sulfate level during a time interval when it was assumed that it had been too low to form extensive evaporite deposits. Therefore, MVT and clastic-dominated (CD) Zn–Pb deposits in the geological record might progressively fill the apparent gap in marine sulfate evaporites and provide unique insights into Proterozoic seawater sulfate level. Considering the sequence of tectonic events that affected the Karrat basin, the mineralization took place between Nagssugtoqidian collision (

There is an urgent need for countries to transition their national food and land-use systems toward food and nutritional security, climate stability, and environmental integrity. How can countries satisfy their demands while jointly delivering the required transformative change to achieve global sustainability targets? Here, we present a collaborative approach developed with the FABLE—Food, Agriculture, Biodiversity, Land, and Energy—Consortium to reconcile both global and national elements for developing national food and land-use system pathways. This approach includes three key features: (1) global targets, (2) country-driven multi-objective pathways, and (3) multiple iterations of pathway refinement informed by both national and international impacts. This approach strengthens policy coherence and highlights where greater national and international ambition is needed to achieve global goals (e.g., the SDGs). We discuss how this could be used to support future climate and biodiversity negotiations and what further developments would be needed.