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BACKGROUND: Active surveillance (AS) is recommended for low-risk and some intermediate-risk prostate cancer. Uptake and practice of AS vary significantly across different settings, as does the experience of surveillance-from which tests are offered, and to the levels of psychological support. OBJECTIVE: To explore the current best practice and determine the most important research priorities in AS for prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: A formal consensus process was followed, with an international expert panel of purposively sampled participants across a range of health care professionals and researchers, and those with lived experience of prostate cancer. Statements regarding the practice of AS and potential research priorities spanning the patient journey from surveillance to initiating treatment were developed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Panel members scored each statement on a Likert scale. The group median score and measure of consensus were presented to participants prior to discussion and rescoring at panel meetings. Current best practice and future research priorities were identified, agreed upon, and finally ranked by panel members. RESULTS AND LIMITATIONS: There was consensus agreement that best practice includes the use of high-quality magnetic resonance imaging (MRI), which allows digital rectal examination (DRE) to be omitted, that repeat standard biopsy can be omitted when MRI and prostate-specific antigen (PSA) kinetics are stable, and that changes in PSA or DRE should prompt MRI ± biopsy rather than immediate active treatment. The highest ranked research priority was a dynamic, risk-adjusted AS approach, reducing testing for those at the least risk of progression. Improving the tests used in surveillance, ensuring equity of access and experience across different patients and settings, and improving information and communication between and within clinicians and patients were also high priorities. Limitations include the use of a limited number of panel members for practical reasons. CONCLUSIONS: The current best practice in AS includes the use of high-quality MRI to avoid DRE and as the first assessment for changes in PSA, with omission of repeat standard biopsy when PSA and MRI are stable. Development of a robust, dynamic, risk-adapted approach to surveillance is the highest research priority in AS for prostate cancer. PATIENT SUMMARY: A diverse group of experts in active surveillance, including a broad range of health care professionals and researchers and those with lived experience of prostate cancer, agreed that best practice includes the use of high-quality magnetic resonance imaging, which can allow digital rectal examination and some biopsies to be omitted. The highest research priority in active surveillance research was identified as the development of a dynamic, risk-adjusted approach.

Purpose To critically synthesise qualitative research to understand experiences of supportive care in people affected by brain cancer and their informal caregivers. Methods A qualitative systematic review was conducted according to the Joanna Briggs methodology and has been reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Guidelines. Electronic databases were searched by an expert systematic review librarian for all qualitative studies irrespective of research design. All publications were double screened by two reviewers using a pre-determined exclusion and inclusion criteria. The review was managed using Covidence systematic review software. Methodological quality assessment and data extraction were performed. Qualitative findings accompanied by illustrative quotes from included studies were extracted and grouped into categories, which created the overall synthesised findings. Results A total of 33 studies were included which represented a total sample of 671 participants inclusive of 303 patients and 368 informal caregivers. There was a total of 220 individual findings included in this review, which were synthesised into two findings (1) caregivers and patients perceived supports which would have been helpful and (2) caregiver and patient experiences of unmet supportive care needs. Conclusion This review highlighted the suffering and distress caused by brain cancer and associated treatments. Both patients and their informal caregivers experienced disconnect from themselves in renegotiating roles, and a profound sense of loneliness as the physical deterioration of the disease progressed. Both patients and informal caregivers reported similar unmet needs within the current service provision for brain cancer. However, what is apparent is that current cancer services are provided solely for patients, with little or no consideration to the support needs of both the patient and their informal caregiver. Service re-design is needed to improve care coordination with individualised informational support, implementation of holistic needs assessments for both the patients and their caregivers, better community support provision, improved opportunities for emotional care with early referral for palliative care services. Implications for cancer survivors It is recommended that members of the multidisciplinary brain cancer team reflect on these findings to target holistic needs assessments and develop shared self-management care plans for both the patient and the informal caregiver.

Context: there is uncertainty regarding the most appropriate criteria for recruitment, monitoring, and reclassification in active surveillance (AS) protocols for localised prostate cancer (PCa). Objective: to perform a qualitative systematic review (SR) to issue recommendations regarding inclusion of intermediate-risk disease, biopsy characteristics at inclusion and monitoring, and repeat biopsy strategy. Evidence acquisition: a protocol-driven, Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-adhering SR incorporating AS protocols published from January 1990 to October 2020 was performed. The main outcomes were criteria for inclusion of intermediate-risk disease, monitoring, reclassification, and repeat biopsy strategies (per protocol and/or triggered). Clinical effectiveness data were not assessed. Evidence synthesis: of the 17 011 articles identified, 333 studies incorporating 375 AS protocols, recruiting 264 852 patients, were included. Only a minority of protocols included the use of magnetic resonance imaging (MRI) for recruitment (n = 17), follow-up (n = 47), and reclassification (n = 26). More than 50% of protocols included patients with intermediate or high-risk disease, whilst 44.1% of protocols excluded low-risk patients with more than three positive cores, and 39% of protocols excluded patients with core involvement (CI) >50% per core. Of the protocols, ?80% mandated a confirmatory transrectal ultrasound biopsy; 72% (n = 189) of protocols mandated per-protocol repeat biopsies, with 20% performing this annually and 25% every 2 yr. Only 27 protocols (10.3%) mandated triggered biopsies, with 74% of these protocols defining progression or changes on MRI as triggers for repeat biopsy. Conclusions: for AS protocols in which the use of MRI is not mandatory or absent, we recommend the following: (1) AS can be considered in patients with low-volume International Society of Urological Pathology (ISUP) grade 2 (three or fewer positive cores and cancer involvement ?50% CI per core) or another single element of intermediate-risk disease, and patients with ISUP 3 should be excluded; (2) per-protocol confirmatory prostate biopsies should be performed within 2 yr, and per-protocol surveillance repeat biopsies should be performed at least once every 3 yr for the first 10 yr; and (3) for patients with low-volume, low-risk disease at recruitment, if repeat systematic biopsies reveal more than three positive cores or maximum CI >50% per core, they should be monitored closely for evidence of adverse features (eg, upgrading); patients with ISUP 2 disease with increased core positivity and/or CI to similar thresholds should be reclassified. Patient summary: We examined the literature to issue new recommendations on active surveillance (AS) for managing localised prostate cancer. The recommendations include setting criteria for including men with more aggressive disease (intermediate-risk disease), setting thresholds for close monitoring of men with low-risk but more extensive disease, and determining when to perform repeat biopsies (within 2 yr and 3 yearly thereafter)., NA

Purpose The objective of this scoping review was to summarize systematically the available literature investigating the relationships between the coronavirus disease 2019 (COVID-19) pandemic and movement behaviors (physical activity, sedentary behavior, and sleep) of school-aged children (aged 5−11 years) and youth (aged 12−17 years) in the first year of the COVID-19 outbreak. Methods Searches for published literature were conducted across 6 databases on 2 separate search dates (November 25, 2020, and January 27, 2021). Results were screened and extracted by 2 reviewers (DCP and KR) independently, using Covidence. Basic numeric analysis and content analysis were undertaken to present thematically the findings of included studies according to the associated impact on each movement behavior. Results A total of 1486 records were extracted from database searches; of those, 150 met inclusion criteria and were included for analysis. Of 150 articles, 110 were empirical studies examining physical activity (n = 77), sedentary behavior/screen time (n = 58), and sleep (n = 55). Results consistently reported declines in physical-activity time, increases in screen time and total sedentary behavior, shifts to later bed and wake times, and increases in sleep duration. The reported impacts on movement behaviors were greater for youth than for children. Conclusion The COVID-19 pandemic is related to changes in the quantity and nature of physical activity, sedentary behavior, and sleep among children and youth. There is an urgent need for policy makers, practitioners, and researchers to develop solutions for attenuating adverse changes in physical activity and screen time among children and youth., Graphical Abstract Image, graphical abstract

Mesenchymal stem cells (MSCs) are extensively used in tissue regenerative procedures. One source of MSCs is the periodontal ligament (PDL) of teeth. Isolation of MSCs from extracted teeth is reasonably simple, being less invasive and presenting fewer ethical concerns than does the harvesting of MSC’s from other sites. The objectives of this study were to isolate and characterize the PDL stem cells (PDLSC) from healthy adults’ extracted teeth and then to characterize them by comparing them with bone-marrow derived MSCs (BMMSC). Methods The PDL tissue was scraped from the roots of freshly extracted teeth to enzymatically digest using collagenase. The cells were sub-cultured. Flow-cytometric analysis for the MSC surface-markers CD105, CD73, CD166, CD90, CD34, CD45 and HLA-DR was performed. To confirm the phenotype, total RNA was extracted to synthesize cDNA and which was then subjected to RT-PCR. The gene-expression for Oct4A, Sox2, NANOG and GAPDH was determined by gel-electrophoresis. To assess their multilineage potential, cells were cultured with osteogenic, chondrogenic and adipogenic medium and then stained by Alizarin-red, Alcian-blue and Oil-Red-O respectively. MSCs from the bone-marrow were processed similarly to serve as controls. Results The cells isolated from extracted teeth expanded successfully. On flow-cytometric analysis, the cells were positive for CD73, CD90, CD105, CD166 and negative for CD34, CD45 and HLA-DR. The PDLSCs expressed Oct4A, Sox2, and NANOG mRNA with GAPDH expression. Cells cultured in the osteogenic, chondrogenic and adipogenic media stained positive for Alizarin-red, Alcian-blue and Oil- Red-O respectively. The surface marker expression and the trilineage differentiation characteristics were comparable to those of the BMMSCs. Conclusions The periodontal ligament tissue of extracted teeth is a potential source of therapeutically useful MSCs. Harvesting them is not invasive and are a promising source of MSC as the PDLSCs showed characteristics similar to those of the highly regarded MSC’s derived from bone-marrow.

Epstein-Barr virus (EBV) is associated with a diverse range of tumors of both lymphoid and epithelial origin. Similar to other herpesviruses, EBV displays a bipartite life cycle consisting of latent and lytic phases. Current dogma indicates that the latent genes are key drivers in the pathogenesis of EBV-associated cancers, while the lytic genes are primarily responsible for viral transmission. In recent years, evidence has emerged to show that the EBV lytic phase also plays an important role in EBV tumorigenesis, and the expression of EBV lytic genes is frequently detected in tumor tissues and cell lines. The advent of next generation sequencing has allowed the comprehensive profiling of EBV gene expression, and this has revealed the consistent expression of several lytic genes across various types of EBV-associated cancers. In this review, we provide an overview of the functional implications of EBV lytic gene expression to the oncogenic process and discuss possible avenues for future investigations.

Interplay between EBV infection and acquired genetic alterations during nasopharyngeal carcinoma (NPC) development remains vague. Here we report a comprehensive genomic analysis of 70 NPCs, combining whole-genome sequencing (WGS) of microdissected tumor cells with EBV oncogene expression to reveal multiple aspects of cellular-viral co-operation in tumorigenesis. Genomic aberrations along with EBV-encoded LMP1 expression underpin constitutive NF-κB activation in 90% of NPCs. A similar spectrum of somatic aberrations and viral gene expression undermine innate immunity in 79% of cases and adaptive immunity in 47% of cases; mechanisms by which NPC may evade immune surveillance despite its pro-inflammatory phenotype. Additionally, genomic changes impairing TGFBR2 promote oncogenesis and stabilize EBV infection in tumor cells. Fine-mapping of CDKN2A/CDKN2B deletion breakpoints reveals homozygous MTAP deletions in 32-34% of NPCs that confer marked sensitivity to MAT2A inhibition. Our work concludes that NPC is a homogeneously NF-κB-driven and immune-protected, yet potentially druggable, cancer., The genomic characterisation of nasopharyngeal carcinoma (NPC) remains crucial. Here, the authors perform whole-genome sequencing for 70 NPCs with EBV gene expression, report the somatic alterations and EBV-mediated effects converging on NF-κB activation and immune escape and identify targetable homozygous MTAP deletions.

Purpose To critically appraise studies to identify experiences of unmet supportive care needs of individuals affected by testicular cancer. Methods A registered priori systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. CINAHL, PsycINFO, and MEDLINE were searched for quantitative, qualitative, and mixed methods studies using a wide range of search terms. All articles were double screened according to a pre-determined eligibility criterion. Reference lists of the final included studies were checked for further eligible studies. The review process was managed using Covidence systematic review software. Data from the studies were extracted, methodological quality appraisal conducted, and a narrative synthesis conducted. Results Of the 72 papers identified, 36 studies were included. In descending order of frequency of need, psychological needs were identified in 26/36, physical needs 18/36, interpersonal/intimacy needs 19/36, health system/information needs 11/36, cognitive needs 9/36, social needs 7/36, and of equal frequencies counts of 4/36 for family, practical, and patient-clinician information needs. Only one study explored spiritual needs and no daily living needs were identified. Conclusions The experience of needs varied in terms of frequency and distress which were commonly influenced by the age of the individual across the cancer care continuum persisting after 1-year post-treatment. Implications for Cancer Survivors When caring for individuals affected by testicular cancer, clinicians are encouraged to take a holistic lens to cancer care, particularly to explore issue or concerns that young men affected by testicular cancer might be embarrassed or reticent to discuss.

Purpose To critically synthesise evidence regarding the supportive care needs of those living with cancer during the COVID-19 pandemic. Methods An integrative systematic review followed a pre-registered protocol, reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) Guidelines. We searched three databases (CINAHL, MEDLINE, and APA PsycINFO) using keywords and included all qualitative, quantitative, and mixed methods studies irrespective of research design published between December 2019 and February 2022. All articles were double screened according to a pre-determined eligibility criterion with reference lists of the final included studies checked for further studies. The review process was managed using Covidence systematic review software. Data from the studies were extracted, methodological quality appraisal conducted, and a narrative synthesis conducted. Results Eighteen publications were included. The findings identified that individuals affected by cancer reported a range of physical, psychological, social, and health system unmet needs during the global pandemic. Unique to the pandemic itself, there was fear of the unknown of the longer-term impact that the pandemic would have on treatment outcomes, cancer care follow-up, and clinical service delays. Conclusion Many individuals living with cancer experienced unmet needs and distress throughout the different waves of the COVID-19 pandemic, irrespective of cancer type, stage, and demographic factors. Implications for Cancer Survivors We recommend clinicians use these findings to identify the individual person-centred needs to optimise recovery as we transition to the post-pandemic cancer care.

Homeobox genes are master regulators of morphogenesis and differentiation by acting at the top of genetic hierarchies and their deregulation is associated with a variety of human diseases. They usually contain a highly conserved sequence that codes for the homeodomain of the protein, a specialized motif with three α helices and an N-terminal arm that aids in DNA binding. However, one homeodomain protein, HOPX, is unique among its family members in that it lacks the capacity to bind DNA and instead functions by interacting with transcriptional regulators. HOPX plays crucial roles in organogenesis and is expressed in both embryonic and adult stem cells. Loss of HOPX expression is common in cancer, where it functions primarily as a tumor suppressor gene. In this review, we describe the function of HOPX in development and discuss its role in carcinogenesis.

We report here the application of silyl enol ether moieties as efficient alkene coupling partners within cobalt-mediated intramolecular Pauson-Khand reactions. This cyclization strategy delivers synthetically valuable oxygenated cyclopentenone products in yields of ≤93% from both ketone- and aldehyde-derived silyl enol ethers, incorporates both terminal and internal alkyne partners, and delivers a variety of decorated systems, including more complex tricyclic structures. Facile removal of the silyl protecting group reveals oxygenated sites for potential further elaboration.

Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we identify for the first time a role for monoamine oxidase A (MAOA) in NPC. MAOA is a mitochondrial enzyme that catalyzes oxidative deamination of neurotransmitters and dietary amines. Depending on the cancer type, MAOA can either have a tumour-promoting or tumour-suppressive role. We show that MAOA is down-regulated in primary NPC tissues and its down-regulation enhances the migration of NPC cells. In addition, we found that EBV infection can down-regulate MAOA expression in both pre-malignant and malignant nasopharyngeal epithelial (NPE) cells. We further demonstrate that MAOA is down-regulated as a result of IL-6/IL-6R/STAT3 signalling and epigenetic mechanisms, effects that might be attributed to EBV infection in NPE cells. Taken together, our data point to a central role for EBV in mediating the tumour suppressive effects of MAOA and that loss of MAOA could be an important step in the pathogenesis of NPC.

Little is known about the medical conditions and medication use of individuals who are homeless and have mental health problems. This study used secondary data (N = 933) from a mental health clinic serving homeless adults. Primary outcomes were the number and types of self-reported medical conditions and medications. About half (52.60%) of participants were taking one or more medications (mean = 1.67; SD = 2.30), most commonly antidepressants, antipsychotics, and anticonvulsants. Most frequently reported medical conditions were headaches/migraines, hypertension, and arthritis with a mean of 3.09 (SD = 2.74) conditions. Age and sex were significant predictors of the number of medical conditions. Age and the length of time homeless were significant predictors of the number of medications taken. Results suggest that those who are older and have been homeless longer appear to be increased risk for health problems and may need more medications to manage these conditions.

To identify the relationship between integrative oncology (IO) services on patients' physical and psychosocial outcomes and to explore the experiences of IO among patients, carers and healthcare professionals.This integrative review was reported according to PRISMA guidelines. A search architecture was developed using key words and the following databases were searched: Medline (OVID), EmCare for Nurses (OVID), PsycINFO (OVID); AMED (OVID), CINAHL (EBSCO), Pubmed, the Cochrane Library (CCRT and CDSR) controlled trials databases and ANZ CTR. All articles were assessed according to a pre-determined selection criterion. 426 articles were assessed and 18 were included (4 qualitative, 9 quantitative and 5 mixed methods).Patients reported a reduction in some cancer related symptoms and treatment related side effects. Positive psychosocial impacts were reported such as an increased ability to cope with their cancer diagnosis and treatment. The experiences of healthcare professionals highlighted the importance of a collaborative approach among the Multi-Disciplinary Team (MDT), ongoing education and research to ensure Complementary Integrative Therapies (CIT) were evidence-based.The provision of IO impacts positively on patients' self-reported physical and emotional wellbeing and quality of life at all stages of their cancer experience. Patients reported that IO supported their engagement in their own health and wellbeing by increasing feelings of control and empowerment. However, to successfully integrate CIT with conventional cancer treatments it is imperative that cancer centres adopt a collaborative and evidence-based informed approach to CIT.

Theoretical evaluations indicate the radiation weighting factor for thermal neutrons differs from the current International Commission on Radiological Protection (ICRP) recommended value of 2.5, which has radiation protection implications for high-energy radiotherapy, inside spacecraft, on the lunar or Martian surface, and in nuclear reactor workplaces. We examined the relative biological effectiveness (RBE) of DNA damage generated by thermal neutrons compared to gamma radiation. Whole blood was irradiated by 64 meV thermal neutrons from the National Research Universal reactor. DNA damage and erroneous DNA double-strand break repair was evaluated by dicentric chromosome assay (DCA) and cytokinesis-block micronucleus (CBMN) assay with low doses ranging 6–85 mGy. Linear dose responses were observed. Significant DNA aberration clustering was found indicative of high ionizing density radiation. When the dose contribution of both the 14N(n,p)14C and 1H(n,γ)2H capture reactions were considered, the DCA and the CBMN assays generated similar maximum RBE values of 11.3 ± 1.6 and 9.0 ± 1.1, respectively. Consequently, thermal neutron RBE is approximately four times higher than the current ICRP radiation weighting factor value of 2.5. This lends support to bimodal peaks in the quality factor for RBE neutron energy response, underlining the importance of radiological protection against thermal neutron exposures.

Children’s independent mobility (IM) is associated with a range of benefits and understanding the factors that influence IM can support creation of effective interventions. The review (Prospero CRD42016042174) systematically summarized the available literature for social-ecological correlates of children’s IM in school-aged children and youth (aged 5–17 years). In this case, 53 studies were included and evaluated six individual, 15 interpersonal, 12 social environment, and 19 built environment- level variables. Most studies originated from Australia (n = 15) and Canada (n = 8) with most published in 2011 or later (n = 48). Variables that were consistently (positively and/or negatively) associated with children’s IM were age, ethnicity/race, child’s perceived competence, ownership of a house/access to house keys, having siblings, parents’ attitude toward IM and perception of child’s confidence, children’s interest in environment and activities, parents’ concern around traffic, housing/residential density, length of residency in one’s home, distance to destinations, and proximity to green space. Given the inter-related social-ecological correlates identified, intervention to promote children’s IM will likely need a multi-level and multi-sectoral approach. However, focus areas of building children’s skills and confidence, helping parents gain confidence in their children’s abilities, assuaging parental traffic concerns, and building environments with shorter distances to destinations of interest for children should be prioritized.

Extracellular ATP in the tumor microenvironment exhibits either pro- or antitumor effect via interaction with P2Y receptors, but the intracellular signaling and functional roles of P2Y receptors in oral squamous cell carcinoma (OSCC) are unclear. We aimed to study the effect of ATP on OSCC cell lines and the potential mechanisms involved. Through GEPIA dataset analysis, high expression levels of mRNA encoding P2Y receptors, the ATP-induced G protein-coupled receptors, were associated with better overall patient survival in head and neck squamous cell carcinoma. qPCR analysis showed that the poorly differentiated OSCC SAS cell line, had higher P2RY1 expression level compared to the well-differentiated H103 and H376 cell lines. Western blotting and flow cytometry analyses revealed that ATP phosphorylated ERK and elevated intracellular calcium signaling in all tested cell lines. A significant S-phase cell cycle arrest was observed in SAS, and preincubation with the MEK inhibitor PD0325901 reversed the ATP-induced S-phase arrest. We further demonstrated that ATP induced a slight reduction in cell count and colony formation yet significant apoptosis in SAS. Overall, we postulate that the ATP-induced S-phase arrest effect in SAS cells may be regulated through P2Y receptor-mediated ERK signaling, thus suggesting a potential antitumor effect of ATP via interaction with its distinct profile of P2Y receptors.

The dairy sector in Ireland is in potential conflict with environmental regulations due to the abolition of European Union dairy quotas and domestic agricultural expansion policy. The ‘Dairy Carbon Navigator’ aims to help Irish farmers reduce the carbon footprint of their milk and enhance economic viability by suggesting actions that could be taken to reduce carbon footprint. The tool is a national solution to Ireland’s contribution to the global problem of climate change and food production. It was designed to drive a decrease in net global greenhouse gas (GHG) emissions per unit milk produced but may conflict with legislation and policy designed to reduce total national emissions. The aim of this work was to assess the feasibility of taking a systems thinking approach to identify areas of policy conflict, using carbon footprint reduction on Irish dairy farms as a case study. This was done by developing a causal loop diagram (CLD), which reflected a typical Irish dairy farm. The causal loop diagram was used to show the direction of change in farm level impact caused by implementing the Dairy Carbon Navigator recommendations. This was used to identify potential conflicts between farm management changes and the achievement of the EU Effort Sharing Decision (regulating GHG emissions), National Emissions Ceiling Directive (regulating some GHG emissions and acidification) and the Water Framework and Nitrates Directives (regulating eutrophication). It was found that extending the grazing season would increase absolute greenhouse gas emissions and absolute eutrophication but decrease carbon footprint. Increasing total herd intake per unit milk would also increase absolute impact. However, across all recommendations, reductions in carbon footprint, acidification and eutrophication per unit milk solids was predicted, due to increased efficiency. These results reflected the rising emissions detailed in the most recent national inventory report and reported decline in water quality, threatening the current overall good status of Irish waterbodies. The qualitative methods used to develop the CLD may introduce bias, but this was moderated by using workshops with interested parties. However, the main benefit of the approach was the identification of the differences between improving production efficiency (impact per unit output) and absolute mitigation of environmental impacts (decrease in national inventory). Systems thinking facilitates an interdisciplinary approach to policy evaluation from initiation to implementation, and highlights issues that may be overlooked when policy instruments are focused on a single factor.

Soil organic carbon (SOC) sequestration across agroecosystems worldwide can contribute to mitigate the effects of climate change by reducing levels of atmospheric CO2. Stabilisation of organic carbon (OC) in the fine soil fraction (< 20 µm) is considered an important long-term store of SOC, and the saturation deficit (difference between measured OC and estimated maximum OC in the fine fraction) is frequently used to assess SOC sequestration potential following the linear regression equation developed by Hassink (1997). However, this approach is often taken without any assessment of the fit of the equation to the soils being studied. The statistical limitations of linear regression have previously been noted, giving rise to the proposed use of boundary line (BL) analysis and quantile regression (QR) to provide more robust estimates of maximum SOC stabilisation. The objectives of this work were to assess the suitability of the Hassink (1997) equation to estimate maximum fine-fraction OC in UK grassland soils of varying sward ages and to evaluate the linear regression, boundary line and quantile regression methods to estimate maximum fine-fraction OC. A chronosequence of 10 grasslands was sampled, in order to assess the relationship between sward age (time since the last reseeding event) and the measured and predicted maximum fine-fraction OC. Significantly different regression equations show that the Hassink (1997) equation does not accurately reflect maximum fine-fraction OC in UK grasslands when determined using the proportion of the fine soil fraction (< 20 µm, %) and measured fine-fraction OC (g C per kg soil). The QR estimate of maximum SOC stabilisation was almost double that of the linear regression and BL analysis (0.89 ± 0.074, 0.43 ± 0.017 and 0.57 ± 0.052 g C per kg soil, respectively). Sward age had an inconsistent effect on the measured variables and potential maximum fine-fraction OC. Fine-fraction OC across the grasslands made up 4.5 % to 55.9 % of total SOC, implying that there may be either high potential for additional C sequestration in the fine fraction of these soils or that protection in aggregates is predominant in these grassland soils. This work highlights the need to ensure that methods used to predict maximum fine-fraction OC reflect the soil in situ, resulting in more accurate assessments of carbon sequestration potential.

Many of the characteristics ascribed to cancer-associated fibroblasts (CAFs) are shared by activated, autophagic and senescent fibroblasts. Whilst most oral squamous cell carcinomas (OSCCs) are genetically unstable (GU-OSCC), genetically stable variants (GS-OSCC) have been described and, notably, CAF activation (myofibroblast differentiation) and senescence are characteristics particularly associated with GU-OSCCs. However, it is not known whether autophagy is disrupted in these cells or whether autophagy regulates the development of the myofibroblast and senescent phenotypes. In this study, we show that senescent CAFs from GU-OSCCs contained more autophagosomes than normal human oral fibroblasts (NHOFs) and CAFs from GS-OSCCs possibly due to autophagic impairment. Further, we show that deregulation of autophagy in normal fibroblasts, either by inhibition with autophagy inhibitor, SAR405, or activation with TGF-β1, induced fibroblast activation and senescence: In response to TGF-β1, autophagy was induced prior to the development of the activated and senescent phenotypes. Lastly, we show that both SAR405- and TGF-β1-treated NHOFs enhance OSCC cell migration but only TGF-β1-treated cells increase OSCC invasion through Matrigel, indicating that TGF-β1 has additional effects that are independent of fibroblast activation/senescence. These results suggest a functional role for autophagy in the development of myofibroblast and CAF phenotypes.