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Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy in need of new therapeutic options. Using unbiased analyses of super-enhancers (SEs) as sentinels of core genes involved in cell-specific function, here we uncover a druggable SE-mediated RNA-binding protein (RBP) cascade that supports PDAC growth through enhanced mRNA translation. This cascade is driven by a SE associated with the RBP heterogeneous nuclear ribonucleoprotein F, which stabilizes protein arginine methyltransferase 1 (PRMT1) to, in turn, control the translational mediator ubiquitin-associated protein 2-like. All three of these genes and the regulatory SE are essential for PDAC growth and coordinately regulated by the Myc oncogene. In line with this, modulation of the RBP network by PRMT1 inhibition reveals a unique vulnerability in Myc-high PDAC patient organoids and markedly reduces tumor growth in male mice. Our study highlights a functional link between epigenetic regulation and mRNA translation and identifies components that comprise unexpected therapeutic targets for PDAC.

Aims In schizophrenia, disorganisation and impoverished mental activity (as described in the classical descriptions by Kraepelin and Bleuler) together with impaired cognitive function, predict persisting functional impairment (Liddle, 2019). We propose that in schizophrenia, four ‘classical’ features (disorganisation, impoverished mental activity, cognitive dysfunction, and impaired role-functioning) arise from a shared pathophysiological process that increases risk of persisting functional impairment. We also propose that this shared process creates a risk of subsequent episodic reality distortion (delusions and hallucinations). In the current work, we investigate whether a single latent variable accounts for the shared variance in the four ‘classical’ features. We also investigate whether the severity of this latent variable based on assessment of long-standing classical symptoms predicts severity of current reality distortion. Methods We performed maximum likelihood factor analysis of disorganisation, impoverishment, cognition and role-function in three separate samples of patients (n = 54, n = 128, n = 64) with DSM diagnosed schizophrenia, schizo-affective disorder or bipolar disorder. In the first two samples, we quantified current disorganisation and impoverished mental activity using the Positive and Negative Syndrome Scale (PANSS). In the third, we scored persistent disorganisation and impoverished mental activity according to Symptoms & Signs of Psychosis Illness (SSPI) based on systematic examination of case records. We assessed cognition using the Digit Symbol Substitution Test (DSST) and role-function using the Social & Occupational functioning scale (in two studies) and the Personal & Social Performance scale (in one study). We quantified current reality distortion by summing SSPI scores for current delusions and hallucinations. Results In each of the three studies, a single latent variable accounted for more than 50% of variance. Loadings were similar whether current or persistent symptoms were used. The latent variable derived from persistent symptom scores correlated significantly with current reality distortion. Conclusion This series of studies provide further evidence that disorganisation, impoverished mental activity, cognitive impairment and impaired role function share substantial variance, consistent with the proposal that they reflect a core pathophysiological process underlying ‘classical’ schizophrenia. Furthermore, our findings are consistent with the hypothesis that over time, this pathophysiological process increases the risk of episodic reality distortion. However, these were all cross-sectional studies, and need to be confirmed using longitudinal data. Our findings have potential clinical and research implications including development of a custom-made clinical tool to quantify the core deficit as well as investigating targeted interventions employing medication or neuromodulation.

This article reconsiders the literature on civic nationalism and argues that, rather than representing an alternative to ethno-cultural nationalism, it is more accurate to think of the two terms at either end of a continuum. Whilst the fundamental British values (FBVs) are often interpreted through a cultural discourse, which serves to alienate and marginalise minoritised students and staff, this article demonstrates how teaching can avoid this framing and engage students with a civic discourse. Transcripts from secondary students' conversations about religious freedom illustrate that they are capable of balancing rights sensitively, of reaching pragmatic solutions and demonstrating sympathy for others. This demonstrates that the FBVs may create opportunities for developing an ethics of care within a deliberative democratic project.

Collaborative group assignments in undergraduate education are important for promoting skill development and preparation for the workplace; however, they are subject to the challenges associated with group dynamics. This research sought to determine the effectiveness of a Group Work Contract to facilitate professional behaviours and positive experiences amongst fourth year nutritional science students (n=144) while working collaboratively to complete a Group Literature Critique Assignment designed to promote scientific literacy and critical thinking skills. Changes in students' attitudes and approaches to group work were assessed before and after completion of the contract and the assignment via two online surveys (Pre- and Post-Group Work Surveys). Completion of the Group Work Contract improved group dynamics including i) frequency of communication, ii) distribution of effort between group members, iii) mutual reliability, iv) respectfulness and inclusivity. Students also reported fewer group problems and an improved ability to work collaboratively in problem solving (P<0.05). Importantly, students reported reduced feelings of anxiety related to group learning and perceptions of achieving a better outcome versus working alone and learning more as a result of working in a group (P<0.05). Additionally, students reported an improvement in their job readiness perceptions with respect to the development of their scientific literacy and critical thinking skills as a result of completing the Group Literature Critique Assignment (P<0.05). Collectively, this data demonstrates that structuring the group work process through the implementation of a Group Work Contract can support the development of positive and effective group dynamics resulting in reduced student anxiety about collaborative learning and perception of a better overall outcome.

Group work (GW) in undergraduate education facilitates the development of communication and collaborative skills. However, dysfunctional and inequitable group dynamics can have adverse effects, leading to increased anxiety. This research sought to determine the effectiveness of a Group Work Contract to facilitate the GW process in the face-to-face (n=168) and online (n=105) formats of a third year nutritional science course. Changes in students' attitudes and approaches to GW were assessed before (semester week 4) and after (semester week 12) completion of the contract and assignment via online surveys. The results in both course formats were similar, wherein the Group Work Contract reduced student anxiety and improved group dynamics and communication between group members, resulting in an improved learning experience overall. Further, the preferred methods of GW online communication utilized social networking platforms. This data demonstrates the benefits of formally structuring the GW process to optimize the student learning experience.

The pleiotropic actions of the Farnesoid X Receptor (FXR) are required for gut health, and reciprocally, reduced intestinal FXR signaling is seen in inflammatory bowel diseases (IBDs). Here, we show that activation of FXR selectively in the intestine is protective in inflammation-driven models of IBD. Prophylactic activation of FXR restored homeostatic levels of pro-inflammatory cytokines, most notably IL17. Importantly, these changes were attributed to FXR regulation of innate lymphoid cells (ILCs), with both the inflammation-driven increases in ILCs, and ILC3s in particular, and the induction of Il17a and Il17f  in ILC3s blocked by FXR activation. Moreover, a population of ILC precursor-like cells increased with treatment, implicating FXR in the maturation/differentiation of ILC precursors. These findings identify FXR as an intrinsic regulator of intestinal ILCs and a potential therapeutic target in inflammatory intestinal diseases.

In this paper, we argue that Indigenous data sovereignty (IDS) is vital for addressing threats to ecosystems, as well as for Indigenous Peoples re-establishing and maintaining sovereignty over their territories. Indigenous knowledge-holders face pressure from non-Indigenous scientists to collaborate to address environmental problems, while the open data movement is pressuring them to make their data public. We examine the role of IDS in the context of cumulative effects and climate change that threaten salmon-bearing ecosystems in British Columbia, guided by content from an online workshop in June 2022 and attended exclusively by a Tier-1 audience (First Nations knowledge-holders and/or technical staff working for Nations). Attention to data is required for fruitful collaborations between Indigenous communities and non-Indigenous researchers to address the impacts of climate change and the cumulative effects affecting salmon-bearing watersheds in BC. In addition, we provide steps that Indigenous governments can take to assert sovereignty over data, recommendations that external researchers can use to ensure they respect IDS, and questions that external researchers and Indigenous partners can discuss to guide decision-making about data management. Finally, we reflect on what we learned during the process of co-creating materials.

We present cosmological constraints from the analysis of angular power spectra of cosmic shear maps based on data from the first three years of observations by the Dark Energy Survey (DES Y3). Our measurements are based on the pseudo-Cℓ method and complement the analysis of the two-point correlation functions in real space, as the two estimators are known to compress and select Gaussian information in different ways, due to scale cuts. They may also be differently affected by systematic effects and theoretical uncertainties, making this analysis an important cross-check. Using the same fiducial Lambda cold dark matter model as in the DES Y3 real-space analysis, we find S8 ≡σ8 √Ωm/0.3 = 0.793-0.025+0.038 , which further improves to S8 = 0.784±0.026 when including shear ratios. This result is within expected statistical fluctuations from the real-space constraint, and in agreement with DES Y3 analyses of non-Gaussian statistics, but favours a slightly higher value of S8 , which reduces the tension with the Planck 2018 constraints from 2.3σ in the real space analysis to 1.5σ here. We explore less conservative intrinsic alignments models than the one adopted in our fiducial analysis, finding no clear preference for a more complex model. We also include small scales, using an increased Fourier mode cut-off up to kmax = 5 h Mpc-1 , which allows to constrain baryonic feedback while leaving cosmological constraints essentially unchanged. Finally, we present an approximate reconstruction of the linear matter power spectrum at present time, found to be about 20 per cent lower than predicted by Planck 2018, as reflected by the lo wer S8 value.

Background & aimsMitochondrial dysfunction disrupts the synthesis and secretion of digestive enzymes in pancreatic acinar cells and plays a primary role in the etiology of exocrine pancreas disorders. However, the transcriptional mechanisms that regulate mitochondrial function to support acinar cell physiology are poorly understood. Here, we aim to elucidate the function of estrogen-related receptor γ (ERRγ) in pancreatic acinar cell mitochondrial homeostasis and energy production.MethodsTwo models of ERRγ inhibition, GSK5182-treated wild-type mice and ERRγ conditional knock-out (cKO) mice, were established to investigate ERRγ function in the exocrine pancreas. To identify the functional role of ERRγ in pancreatic acinar cells, we performed histologic and transcriptome analysis with the pancreas isolated from ERRγ cKO mice. To determine the relevance of these findings for human disease, we analyzed transcriptome data from multiple independent human cohorts and conducted genetic association studies for ESRRG variants in 2 distinct human pancreatitis cohorts.ResultsBlocking ERRγ function in mice by genetic deletion or inverse agonist treatment results in striking pancreatitis-like phenotypes accompanied by inflammation, fibrosis, and cell death. Mechanistically, loss of ERRγ in primary acini abrogates messenger RNA expression and protein levels of mitochondrial oxidative phosphorylation complex genes, resulting in defective acinar cell energetics. Mitochondrial dysfunction due to ERRγ deletion further triggers autophagy dysfunction, endoplasmic reticulum stress, and production of reactive oxygen species, ultimately leading to cell death. Interestingly, ERRγ-deficient acinar cells that escape cell death acquire ductal cell characteristics, indicating a role for ERRγ in acinar-to-ductal metaplasia. Consistent with our findings in ERRγ cKO mice, ERRγ expression was significantly reduced in patients with chronic pancreatitis compared with normal subjects. Furthermore, candidate locus region genetic association studies revealed multiple single nucleotide variants for ERRγ that are associated with chronic pancreatitis.ConclusionsCollectively, our findings highlight an essential role for ERRγ in maintaining the transcriptional program that supports acinar cell mitochondrial function and organellar homeostasis and provide a novel molecular link between ERRγ and exocrine pancreas disorders.

For individuals with autism spectrum disorder (ASD) daily living skills (DLS) fall below chronological age and have been linked to factors such as language. Given the impact of DLS on daily life, it is critical to gain a comprehensive understanding of DLS profiles in children to guide effective treatment. Using a large dataset from the Autism Speaks Autism Treatment Network, the current study sought to: (1) examine whether there are subgroups of children with ASD defined by both their Vineland-II DLS scores and language abilities; and (2) explore the relationship between internalizing and externalizing symptoms on subgroups using the Child Behavior Checklist. A five-cluster solution was found, but one group was subsequently dropped. Four clusters were examined: "Low Language-Low DLS" (n = 143); "Low-Language High DLS" (n = 170); "High Language-Low DLS" (n = 189); and "High Language-High DLS" (n = 203). The "High Language-Low DLS" group had significantly higher internalizing and externalizing symptoms as compared to the other groups. The results highlight the importance of targeting DLS in school-age children with ASD, especially for those with comorbid internalizing and externalizing symptom to ensure that the gap between age and functional DLS does not continue to widen.

In a fourth year undergraduate nutritional toxicology course that included an instructional emphasis on scientific literature critique activities and assessments, we determined the change in students' (n=144) scientific literacy (SL) skills. The change in students' perceived and practical SL skills were determined by the completion of two surveys, administered at the start and end of the semester. Additionally, we conducted a follow-up SL survey at the end of the subsequent academic semester (i.e., four months later) to determine if students retained any improvements in their SL skills. Over the semester, students showed improvements in their perceived capabilities of all SL skill parameters assessed (P<0.05); however, the most significant gains were apparent in the areas of i) knowledge application (specifically identifying novel problems or research questions and using new information to address unfamiliar problems or knowledge gaps), and ii) knowledge translation and communication (translating complex information from the scientific literature into clear and understandable terms). There was no change in students TOSLS score between the start and end of the semester (P>0.05). In the follow-up SL survey students showed further improvements in their perceptions of the SL skills for 7 of the 10 parameters assessed compared to the end of the previous semester (P<0.05), however, there remained no change in their practical SL skills assessed using TOSLS. Collectively, this data demonstrates that students' perceptions of their SL capabilities may not align with their practical capabilities.

T cell receptor (TCR) T cell therapies target tumor antigens in a human leukocyte antigen (HLA)-restricted manner. Biomarker-defined therapies require validation of assays suitable for determination of patient eligibility. For clinical trials evaluating TCR T cell therapies targeting melanoma-associated antigen A4 (MAGE-A4), screening in studies NCT02636855 and NCT04044768 assesses patient eligibility based on: (1) high-resolution HLA typing and (2) tumor MAGE-A4 testing via an immunohistochemical assay in HLA-eligible patients. The HLA/MAGE-A4 assays validation, biomarker data, and their relationship to covariates (demographics, cancer type, histopathology, tissue location) are reported here. HLA-A∗02 eligibility was 44.8% (2,959/6,606) in patients from 43 sites across North America and Europe. While HLA-A∗02:01 was the most frequent HLA-A∗02 allele, others (A∗02:02, A∗02:03, A∗02:06) considerably increased HLA eligibility in Hispanic, Black, and Asian populations. Overall, MAGE-A4 prevalence based on clinical trial enrollment was 26% (447/1,750) across 10 solid tumor types, and was highest in synovial sarcoma (70%) and lowest in gastric cancer (9%). The covariates were generally not associated with MAGE-A4 expression, except for patient age in ovarian cancer and histology in non-small cell lung cancer. This report shows the eligibility rate from biomarker screening for TCR T cell therapies and provides epidemiological data for future clinical development of MAGE-A4-targeted therapies.

Microplastics (MPs) are an everyday part of life, and are now ubiquitous in the environment. Crucially, MPs have not just been found within the environment, but also within human bodies, including the blood. We aimed to provide novel information on the range of MP polymer types present, as well as their size and shape characteristics, in human whole blood from 20 healthy volunteers. Twenty-four polymer types were identified from 18 out of 20 (90 %) donors and quantified in blood, with the majority observed for the first time. Using an LOQ approach, five polymer types met the threshold with a lower mean ± SD of 2466 ± 4174 MP/L. The concentrations of plastics analysed in blood samples ranged from 1.84 − 4.65 μg/mL. Polyethylene (32 %), ethylene propylene diene (14 %), and ethylene–vinyl-acetate/alcohol (12 %) fragments were the most abundant. MP particles that were identified within the blood samples had a mean particle length of 127.99 ± 293.26 µm (7–3000 µm), and a mean particle width of 57.88 ± 88.89 µm (5–800 µm). The MPs were predominantly categorised as fragments (88 %) and were white/clear (79 %). A variety of plastic additive chemicals were identified including endocrine disrupting-classed phthalates. The procedural blank samples comprised 7 polymer types, that were distinct from those identified in blood, mainly resin (25 %), polyethylene terephthalate (17 %), and polystyrene (17 %) with a mean ± SD of 4.80 ± 5.59 MP/L. This study adds to the growing evidence that MPs are taken up into the human body and are transported via the bloodstream. The shape and sizes of the particles raise important questions with respect to their presence and associated hazards in terms of potential detrimental impacts such as vascular inflammation, build up within major organs, and changes to either immune cell response, or haemostasis and thrombosis.

Objective Using digital systems to support the management and delivery of social care is a priority for UK governments. This study explored progress towards, and experiences of, digitalisation in the homecare sector and providers’ views on contributing client data to a national policy/research dataset. Methods Over 150 UK homecare providers completed an on-line survey (October–December 2022). The survey was hosted on Qualtrics and comprised fixed- and free-text response questions. The recruited sample aligned with the profile of UK homecare providers in terms of use of digital systems, organisation type and size. Results Almost all respondents (95.5%) were using digital systems, in part or exclusively, to support care delivery. However, many (42.7%) reported a desire to further digitalise or a dissatisfaction with existing systems. Findings highlight the time and work involved in choosing a a software system, with the decision regarded as relatively high risk. Over 50 different software systems were being used across the sample. Most respondents (72.5%) supported the creation of a national dataset on homecare users. However, support and recompense are likely to needed to secure buy-in from what is a predominantly private sector context. Conclusions Findings suggest a complex and changing situation, with numerous different digital systems being used and the sector at different stages of digitalisation. The high-pressure, low margin context of UK homecare appeared to be exerting an influence on progress towards digitalisation. Evaluations of government strategies to stimulate and support digitalisation in this diverse and predominantly private sector context will be valuable.

Introduction Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient’s quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients.Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut microbiome. Most cohorts studying the gut microbiota to date have been underpowered, examined single treatments and produced heterogeneous results. Lack of cross-treatment comparisons and well-powered independent replication cohorts hampers the ability to infer real-world utility of predictive signatures.IBD-RESPONSE will use multi-omic data to create a predictive tool for treatment response. Future patient benefit may include development of biomarker-based treatment stratification or manipulation of intestinal microbial targets. IBD-RESPONSE and downstream studies have the potential to improve quality of life, reduce patient risk and reduce expenditure on ineffective treatments.Methods and analysis This prospective, multicentre, observational study will identify and validate a predictive model for response to advanced IBD therapies, incorporating gut microbiome, metabolome, single-cell transcriptome, human genome, dietary and clinical data. 1325 participants commencing advanced therapies will be recruited from ~40 UK sites. Data will be collected at baseline, week 14 and week 54. The primary outcome is week 14 clinical response. Secondary outcomes include clinical remission, loss of response in week 14 responders, corticosteroid-free response/remission, time to treatment escalation and change in patient-reported outcome measures.Ethics and dissemination Ethical approval was obtained from the Wales Research Ethics Committee 5 (ref: 21/WA/0228). Recruitment is ongoing. Following study completion, results will be submitted for publication in peer-reviewed journals and presented at scientific meetings. Publications will be summarised at www.ibd-response.co.uk.Trial registration number ISRCTN96296121.

ABSTRACTCryptococcus neoformans causes lethal meningitis and accounts for approximately 10%–15% of AIDS-associated deaths worldwide. There are major gaps in our understanding of how this fungus invades the mammalian brain. To investigate the dynamics of C. neoformans tissue invasion, we mapped fungal localization and host cell interactions in infected brain, lung, and upper airways using mouse models of systemic and airway infection. To enable this, we developed an in situ imaging pipeline capable of measuring large volumes of tissue while preserving anatomical and cellular information by combining thick tissue sections, tissue clarification, and confocal imaging. We confirm high fungal burden in mouse upper airway after nasal inoculation. Yeast in turbinates were frequently titan cells, with faster kinetics than reported in mouse lungs. Importantly, we observed one instance of fungal cells enmeshed in lamina propria of the upper airways, suggesting penetration of airway mucosa as a possible route of tissue invasion and dissemination to the bloodstream. We extend previous literature positing bloodstream dissemination of C. neoformans, by finding viable fungi in the bloodstream of mice a few days after intranasal infection. As early as 24 h post systemic infection, the majority of C. neoformans cells traversed the blood-brain barrier, and were engulfed or in close proximity to microglia. Our work presents a new method for investigating microbial invasion, establishes that C. neoformans can breach multiple tissue barriers within the first days of infection, and demonstrates microglia as the first cells responding to C. neoformans invasion of the brain.IMPORTANCECryptococcal meningitis causes 10%–15% of AIDS-associated deaths globally. Still, brain-specific immunity to cryptococci is a conundrum. By employing innovative imaging, this study reveals what occurs during the first days of infection in brain and in airways. We found that titan cells predominate in upper airways and that cryptococci breach the upper airway mucosa, which implies that, at least in mice, the upper airways are a site for fungal dissemination. This would signify that mucosal immunity of the upper airway needs to be better understood. Importantly, we also show that microglia, the brain-resident macrophages, are the first responders to infection, and microglia clusters are formed surrounding cryptococci. This study opens the field to detailed molecular investigations on airway immune response, how fungus traverses the blood-brain barrier, how microglia respond to infection, and ultimately how microglia monitor the blood-brain barrier to preserve brain function.

Microplastics (MPs) are found in all environments, within the human food chain, and have been recently detected in several human tissues. The objective herein was to undertake an analysis of MP contamination in human urine samples, from healthy individuals and participants with endometriosis, with respect to their presence, levels, and the characteristics of any particles identified. A total of 38 human urine samples and 15 procedural blanks were analysed. MPs were characterised using μFTIR spectroscopy (size limitation of 5 μm) and SEM-EDX. In total, 123 MP particles consisting of 22 MP polymer types were identified within 17/29 of the healthy donor (10 mL) urine samples, compared with 232 MP particles of differing 16 MP polymer types in 12/19 urine samples from participants with endometriosis. Healthy donors presented an unadjusted average of 2589 ± 2931 MP/L and participants with endometriosis presented 4724 ± 9710 MP/L. Polyethylene (PE)(27%), polystyrene (PS)(16%), resin and polypropylene (PP)(both 12%) polymer types were most abundant in healthy donor samples, compared with polytetrafluoroethylene (PTFE) (59%), and PE (16%) in samples from endometriosis participants. The MP levels within healthy and endometriosis participant samples were not significantly different. However, the predominant polymer types varied, and the MPs from the metal catheter-derived endometriosis participant samples and healthy donors were significantly smaller than those observed in the procedural blanks. The procedural blank samples comprised 62 MP particles of 10 MP polymer types, mainly PP (27%), PE (21%), and PS (15%) with a mean ± SD of 17 ± 18, highlighting the unavoidable contamination inherent in measurement of MPs from donors. This is the first evidence of MP contamination in human urine with polymer characterisation and accounting for procedural blanks. These results support the phenomenon of transport of MPs within humans, specifically to the bladder, and their characterisation of types, shapes and size ranges identified therein.

Decades of work have elucidated cytokine signalling and transcriptional pathways that control T cell differentiation and have led the way to targeted biologic therapies that are effective in a range of autoimmune, allergic and inflammatory diseases. Recent evidence indicates that obesity and metabolic disease can also influence the immune system1-7, although the mechanisms and effects on immunotherapy outcomes remain largely unknown. Here, using two models of atopic dermatitis, we show that lean and obese mice mount markedly different immune responses. Obesity converted the classical type 2 T helper (TH2)-predominant disease associated with atopic dermatitis to a more severe disease with prominent TH17 inflammation. We also observed divergent responses to biologic therapies targeting TH2 cytokines, which robustly protected lean mice but exacerbated disease in obese mice. Single-cell RNA sequencing coupled with genome-wide binding analyses revealed decreased activity of nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) in TH2 cells from obese mice relative to lean mice. Conditional ablation of PPARγ in T cells revealed that PPARγ is required to focus the in vivo TH response towards a TH2-predominant state and prevent aberrant non-TH2 inflammation. Treatment of obese mice with a small-molecule PPARγ agonist limited development of TH17 pathology and unlocked therapeutic responsiveness to targeted anti-TH2 biologic therapies. These studies reveal the effects of obesity on immunological disease and suggest a precision medicine approach to target the immune dysregulation caused by obesity.

Aims: With up to 40% of patients having patellofemoral joint osteoarthritis (PFJ OA), the two arthroplasty options are to replace solely the patellofemoral joint via patellofemoral arthroplasty (PFA), or the entire knee via total knee arthroplasty (TKA). The aim of this study was to assess postoperative success of second-generation PFAs compared to TKAs for patients treated for PFJ OA using patient-reported outcome measures (PROMs) and domains deemed important by patients following a patient and public involvement meeting. Methods: MEDLINE, EMBASE via OVID, CINAHL, and EBSCO were searched from inception to January 2022. Any study addressing surgical treatment of primary patellofemoral joint OA using second generation PFA and TKA in patients aged above 18 years with follow-up data of 30 days were included. Studies relating to OA secondary to trauma were excluded. ROB-2 and ROBINS-I bias tools were used. Results: A total of nine studies were included, made up of four randomized controlled trials (domain 1) and five cohort studies (domain 2). PROMs and knee function specific scores developed for reporting TKA were unable to detect any difference between PFA and TKA. There was no significant difference in complications between PFA and TKA. PFAs were found to have a better postoperative range of motion. Conclusion: TKA and PFA are both viable options for patients with primary PFJ OA. Over time, we have seen an emphasis on patient satisfaction and better quality of life. Recommending sacrificing healthy medial and lateral compartments to treat patellofemoral joint arthritis should be given further thought. Cite this article: Bone Jt Open 2023;4(12):948–956.