Posttransplant Lymphoproliferative Disease Following Pancreas Transplantation: A 40 Year Single-Center Experience.

BACKGROUND: Chronic immunosuppression following pancreas transplantation carries significant risk, including posttransplant lymphoproliferative disease (PTLD). We sought to define the incidence, risk factors, and long-term outcomes of PTLD following pancreas transplantation at a single center. METHODS: All adult pancreas transplants between February 1, 1983 and December 31, 2023 at the University of Minnesota were reviewed, including pancreas transplant alone (PTA), simultaneous pancreas-kidney transplants (SPK), and pancreas after kidney transplants (PAK). RESULTS: Among 2353 transplants, 110 cases of PTLD were identified, with an overall incidence of 4.8%. 17.3% were diagnosed within 1 year of transplant, 32.7% were diagnosed within 5 years, and 74 (67.3%) were diagnosed after 5 years. The overall 30-year incidence of PTLD did not differ by transplant type-7.4% for PTA, 14.2% for SPK, and 19.4% for PAK (p = 0.3). In multivariable analyses, older age and Epstein-Barr virus seronegativity were risk factors for PTLD, and PTLD was a risk factor for patient death. PTLD-specific mortality was 32.7%, although recipients with PTLD had similar median posttransplant survival compared to those without PTLD (14.9 year vs. 15.6 year, p = 0.9). CONCLUSIONS: PTLD following pancreas transplantation is associated with significant mortality. Although the incidence of PTLD has decreased over time, a high index of suspicion for PTLD following PTx should remain in EBV-negative recipients.

LINC01432 binds to CELF2 in newly diagnosed multiple myeloma promoting short progression-free survival to standard therapy.

Multiple Myeloma (MM) is a highly prevalent and incurable form of cancer that arises from malignant plasma cells, with over 35,000 new cases diagnosed annually in the United States. While there are a growing number of approved therapies, MM remains incurable and nearly all patients will relapse and exhaust all available treatment options. Mechanisms for disease progression are unclear and in particular, little is known regarding the role of long non-coding RNAs (lncRNA) in mediating disease progression and response to treatment. In this study, we used transcriptome sequencing to compare newly diagnosed MM patients who had short progression-free survival (PFS) to standard first-line treatment (PFS < 24 months) to patients who had prolonged PFS (PFS > 24 months). We identified 157 differentially upregulated lncRNAs with short PFS and focused our efforts on characterizing the most upregulated lncRNA, LINC01432. We investigated LINC01432 overexpression and CRISPR/Cas9 knockdown in MM cell lines to show that LINC01432 overexpression significantly increases cell viability and reduces apoptosis, while knockdown significantly reduces viability and increases apoptosis, supporting the clinical relevance of this lncRNA. Next, we used individual-nucleotide resolution cross-linking immunoprecipitation with RT-qPCR to show that LINC01432 directly interacts with the RNA binding protein, CELF2. Lastly, we showed that LINC01432-targeted locked nucleic acid antisense oligonucleotides reduce viability and increases apoptosis. In summary, this fundamental study identified lncRNAs associated with short PFS to standard NDMM treatment and further characterized LINC01432, which inhibits apoptosis.

Language matters for biodiversity.

Language is central to the way people learn about the natural world. A salient concern of the biodiversity conservation arena has been to understand how language can be employed by scientists to communicate knowledge to nonexpert audiences and build ecological literacy. The use of analogy and narrative by scientists are prominent techniques. In this article, we consider how these two modes of language-based reasoning extend into ordinary conversational language use by the public, specifically when articulating everyday understanding and experiences of biodiversity. Drawing on a process of public engagement in a UK woodland environment, a typological framework based on principles of analogical and narrative reasoning is developed to characterize the precise character of processes of everyday biodiversity sense making. The implications of the framework are discussed in the context of future biodiversity research, particularly its participatory and educational dimensions.

Nature-based social prescribing programmes: opportunities, challenges, and facilitators for implementation.

BACKGROUND: Evidence on the health benefits of spending time in nature has highlighted the importance of provision of blue and green spaces where people live. The potential for health benefits offered by nature exposure, however, extends beyond health promotion to health treatment. Social prescribing links people with health or social care needs to community-based, non-clinical health and social care interventions to improve health and wellbeing. Nature-based social prescribing (NBSP) is a variant that uses the health-promoting benefits of activities carried out in natural environments, such as gardening and walking. Much current NBSP practice has been developed in the UK, and there is increasing global interest in its implementation. This requires interventions to be adapted for different contexts, considering the needs of populations and the structure of healthcare systems. METHODS: This paper presents results from an expert group participatory workshop involving 29 practitioners, researchers, and policymakers from the UK and Germany's health and environmental sectors. Using the UK and Germany, two countries with different healthcare systems and in different developmental stages of NBSP practice, as case studies, we analysed opportunities, challenges, and facilitators for the development and implementation of NBSP. RESULTS: We identified five overarching themes for developing, implementing, and evaluating NBSP: Capacity Building; Accessibility and Acceptability; Networks and Collaborations; Standardised Implementation and Evaluation; and Sustainability. We also discuss key strengths, weaknesses, opportunities, and threats for each overarching theme to understand how they could be developed to support NBSP implementation. CONCLUSIONS: NBSP could offer significant public health benefits using available blue and green spaces. We offer guidance on how NBSP implementation, from wider policy support to the design and evaluation of individual programmes, could be adapted to different contexts. This research could help inform the development and evaluation of NBSP programmes to support planetary health from local and global scales.

Cellular states are coupled to genomic and viral heterogeneity in HPV-related oropharyngeal carcinoma.

Head and neck squamous cell carcinoma (HNSCC) includes a subset of cancers driven by human papillomavirus (HPV). Here we use single-cell RNA-seq to profile both HPV-positive and HPV-negative oropharyngeal tumors, uncovering a high level of cellular diversity within and between tumors. First, we detect diverse chromosomal aberrations within individual tumors, suggesting genomic instability and enabling the identification of malignant cells even at pathologically negative margins. Second, we uncover diversity with respect to HNSCC subtypes and other cellular states such as the cell cycle, senescence and epithelial-mesenchymal transitions. Third, we find heterogeneity in viral gene expression within HPV-positive tumors. HPV expression is lost or repressed in a subset of cells, which are associated with a decrease in HPV-associated cell cycle phenotypes, decreased response to treatment, increased invasion and poor prognosis. These findings suggest that HPV expression diversity must be considered during diagnosis and treatment of HPV-positive tumors, with important prognostic ramifications.

Nature, smells, and human wellbeing.

The link between nature and human wellbeing is well established. However, few studies go beyond considering the visual and auditory underpinnings of this relationship, even though engaging with nature is a multisensory experience. While research linking smell to wellbeing exists, it focuses predominantly on smells as a source of nuisance/offence. Smells clearly have a prominent influence, but a significant knowledge gap remains in the nexus of nature, smell, and wellbeing. Here, we examine how smells experienced in woodlands contribute to wellbeing across four seasons. We show that smells are associated with multiple wellbeing domains, both positively and negatively. They are linked to memories, and specific ecological characteristics and processes over space/time. By making the link between the spatiotemporal variability in biodiversity and wellbeing explicit, we unearth a new line of enquiry. Overall, the multisensory experience must be considered by researchers, practitioners, policy-makers and planners looking to improve wellbeing through nature.

Staffing Up and Sustaining the Public Health Workforce.

OBJECTIVES: Estimate the number of full-time equivalents (FTEs) needed to fully implement Foundational Public Health Services (FPHS) at the state and local levels in the United States. METHODS: Current and full implementation cost estimation data from 168 local health departments (LHDs), as well as data from the Association of State and Territorial Health Officials and the National Association of County and City Health Officials, were utilized to estimate current and "full implementation" staffing modes to estimate the workforce gap. RESULTS: The US state and local governmental public health workforce needs at least 80 000 additional FTEs to deliver core FPHS in a post-COVID-19 landscape. LHDs require approximately 54 000 more FTEs, and states health agency central offices require approximately 26 000 more. CONCLUSIONS: Governmental public health needs tens of thousands of more FTEs, on top of replacements for those leaving or retiring, to fully implement core FPHS. IMPLICATIONS FOR POLICY AND PRACTICE: Transitioning a COVID-related surge in staffing to a permanent workforce requires substantial and sustained investment from federal and state governments to deliver even the bare minimum of public health services.

Drought Tolerance Strategies and Autophagy in Resilient Wheat Genotypes.

Drought resiliency strategies combine developmental, physiological, cellular, and molecular mechanisms. Here, we compare drought responses in two resilient spring wheat (Triticum aestivum) genotypes: a well-studied drought-resilient Drysdale and a resilient genotype from the US Pacific North-West Hollis. While both genotypes utilize higher water use efficiency through the reduction of stomatal conductance, other mechanisms differ. First, Hollis deploys the drought escape mechanism to a greater extent than Drysdale by accelerating the flowering time and reducing root growth. Second, Drysdale uses physiological mechanisms such as non-photochemical quenching (NPQ) to dissipate the excess of harvested light energy and sustain higher Fv/Fm and ϕPSII, whereas Hollis maintains constant NPQ but lower Fv/Fm and ϕPSII values. Furthermore, more electron donors of the electron transport chain are in the oxidized state in Hollis than in Drysdale. Third, many ROS homeostasis parameters, including peroxisome abundance, transcription of peroxisome biogenesis genes PEX11 and CAT, catalase protein level, and enzymatic activity, are higher in Hollis than in Drysdale. Fourth, transcription of autophagy flux marker ATG8.4 is upregulated to a greater degree in Hollis than in Drysdale under drought, whereas relative ATG8 protein abundance under drought stress is lower in Hollis than in Drysdale. These data demonstrate the activation of autophagy in both genotypes and a greater autophagic flux in Hollis. In conclusion, wheat varieties utilize different drought tolerance mechanisms. Combining these mechanisms within one genotype offers a promising strategy to advance crop resiliency.

LINC00355 regulates p27KIP expression by binding to MENIN to induce proliferation in late-stage relapse breast cancer.

Late-stage relapse (LSR) in patients with breast cancer (BC) occurs more than five years and up to 10 years after initial treatment and has less than 30% 5-year relative survival rate. Long non-coding RNAs (lncRNAs) play important roles in BC yet have not been studied in LSR BC. Here, we identify 1127 lncRNAs differentially expressed in LSR BC via transcriptome sequencing and analysis of 72 early-stage and 24 LSR BC patient tumors. Decreasing expression of the most up-regulated lncRNA, LINC00355, in BC and MCF7 long-term estrogen deprived cell lines decreases cellular invasion and proliferation. Subsequent mechanistic studies show that LINC00355 binds to MENIN and changes occupancy at the CDKN1B promoter to decrease p27Kip. In summary, this is a key study discovering lncRNAs in LSR BC and LINC00355 association with epigenetic regulation and proliferation in BC.

Can biodiverse streetscapes mitigate the effects of noise and air pollution on human wellbeing?

Most of the global population are urban, with inhabitants exposed to raised levels of pollution. Pollutants negatively impact human wellbeing, and can alter the structure and diversity of ecosystems. Contrastingly, urban biodiversity can positively contribute to human wellbeing. We know little, however, about whether the negative impacts of pollution on wellbeing could be lessened for householders living on more biodiverse streets, as the complex interlinkages between pollution, biodiversity and wellbeing have rarely been examined. Here, we used structural equation modelling to simultaneously test whether biodiversity (actual and perceived) mediates the relationship between traffic-related pollution (noise, dB; nitrogen dioxide, NO2) or air pollution (PM2.5) and wellbeing (mental wellbeing, happiness). In summer 2019, we conducted questionnaires and biodiversity surveys, and collected noise and air pollution data, from households (n = 282) across the streetscapes of Leeds, UK. Biodiversity (actual or perceived) showed no mediating effects. However, increased flowering plant richness was positively associated with mental wellbeing. Traffic-related pollution negatively affected pollinator and flowering plant richness, but not wellbeing. This could be because householders are not exposed to high levels of noise or NO2 because they do not maintain front gardens on noisier streets. There was no measurable effect of air pollution on biodiversity or wellbeing. These findings shed light on the complex mechanisms through which biodiversity could improve human wellbeing. Enhancing the diversity of plant species in streetscapes would have a positive effect on wellbeing, further emphasising the important role that biodiverse urban streetscapes play in improving the liveability of cities.

New fossil discoveries illustrate the diversity of past terrestrial ecosystems in New Caledonia.

New Caledonia was, until recently, considered an old continental island harbouring a rich biota with outstanding Gondwanan relicts. However, deep marine sedimentation and tectonic evidence suggest complete submergence of the island during the latest Cretaceous to the Paleocene. Molecular phylogenies provide evidence for some deeply-diverging clades that may predate the Eocene and abundant post-Oligocene colonisation events. Extinction and colonization biases, as well as survival of some groups in refuges on neighbouring paleo-islands, may have obscured biogeographic trends over long time scales. Fossil data are therefore crucial for understanding the history of the New Caledonian biota, but occurrences are sparse and have received only limited attention. Here we describe five exceptional fossil assemblages that provide important new insights into New Caledonia's terrestrial paleobiota from three key time intervals: prior to the submersion of the island, following re-emergence, and prior to Pleistocene climatic shifts. These will be of major importance for elucidating changes in New Caledonia's floristic composition over time.

Bird diversity and psychological wellbeing: A comparison of green and coastal blue space in a neotropical city.

Accelerating rates of urbanisation are contributing to biodiversity declines worldwide. However, urban green (e.g. parks) and blue spaces (e.g. coast) provide important habitat for species. Emerging evidence also shows that green and blue spaces can benefit human psychological wellbeing, although few studies originate from the Global South and it is unclear whether more biodiverse spaces offer greater wellbeing gains. We examine how bird diversity (abundance, species richness, Shannon diversity, and community composition) in green and coastal blue space in Georgetown, Guyana, is associated with people's wellbeing (positive and negative affect, anxiety) in situ, using point counts and questionnaires. Bird community composition differed between green and coastal sites, and diversity was significantly higher in green sites. Positive affect and anxiety did not differ between green and coastal sites, but negative affect was higher in coastal sites. Mixed-effect models showed no associations between biodiversity and wellbeing, implying other features are contributing to people's positive wellbeing. Despite no association between biodiversity and wellbeing, both green and coastal blue sites are important for wellbeing and supporting different bird communities. City planning authorities and public health professionals should ensure these social and environmental needs are met in developing cities in the Global South.

Voices on diversity: Making the scientific community more inclusive.

As part of our commitment to amplifying the voices of underrepresented scientists, we are publishing the insights and experiences of a panel of underrepresented scientists. In this piece, they discuss ways to make science more inclusive-from key points they wish their colleagues understood to actions those in the scientific community can take. These are the personal opinions of the authors and may not reflect the views of their institutions.

Voices on diversity: support systems that work.

As part of our commitment to amplifying the voices of underrepresented scientists, we are publishing the insights and experiences of a panel of underrepresented scientists. In this segment, we asked about support systems-the types of support that are most helpful (and less helpful), how to find a supportive network, and how institutions can better support underrepresented scientists. These are the personal opinions of the authors and may not reflect the views of their institutions.

Voices on diversity: recruiting underrepresented scientists.

As part of our commitment to amplifying the voices of underrepresented scientists, we are publishing the insights and experiences of a panel of underrepresented scientists. In this piece, they discuss strategies to recruit underrepresented minority students to universities and careers in science. These are the personal opinions of the authors and may not reflect the views of their institutions.

Voices on diversity: confronting racial bias.

As part of our commitment to amplifying the voices of underrepresented scientists, we are publishing the insights and experiences of a panel of underrepresented scientists. Here, they discuss the impact of racial bias and share strategies for addressing it. These are the personal opinions of the authors and may not reflect the views of their institutions.

Voices on Diversity: Creating a Sense of Belonging.

As part of our commitment to amplifying the voices of underrepresented scientists, we are publishing the insights and experiences of a panel of underrepresented scientists. Here they tell us about behaviors that can lead underrepresented scientists to feel that they do not belong and what the scientific community can do to provide better support. These are the personal opinions of the authors and may not reflect the views of their institutions.

A global horizon scan of the future impacts of robotics and autonomous systems on urban ecosystems.

Technology is transforming societies worldwide. A major innovation is the emergence of robotics and autonomous systems (RAS), which have the potential to revolutionize cities for both people and nature. Nonetheless, the opportunities and challenges associated with RAS for urban ecosystems have yet to be considered systematically. Here, we report the findings of an online horizon scan involving 170 expert participants from 35 countries. We conclude that RAS are likely to transform land use, transport systems and human-nature interactions. The prioritized opportunities were primarily centred on the deployment of RAS for the monitoring and management of biodiversity and ecosystems. Fewer challenges were prioritized. Those that were emphasized concerns surrounding waste from unrecovered RAS, and the quality and interpretation of RAS-collected data. Although the future impacts of RAS for urban ecosystems are difficult to predict, examining potentially important developments early is essential if we are to avoid detrimental consequences but fully realize the benefits.