Dietary fibres, including psyllium and inulin, are non-digestible carbohydrates found in fruits, vegetables and legumes (1) . An optimal intake of dietary fibre decreases the risk of type 2 diabetes, colon cancer and cardiovascular disease (2) , but only 5% of the UK adult population consumes the recommended dietary fibre intake of 30 g/d (3) . Optimal fibre intake is also thought to be important for patients. There is evidence from murine models that dietary fibre supplementation can improve tumour response and reduce normal tissue side effects caused by radiation in cancer patients (4) . Studying the effect of dietary fibres on healthy older people in detail is the first step to designing clinical trials in cancer patients. A within-subject, double-blinded study (n=40) was conducted on healthy older adults, over 60 years, to explore the response of the gut microbiota composition and activity to dietary fibre supplementation. Maltodextrin was given as placebo, with psyllium+inulin and inulin provided as diet interventions to be consumed for two weeks each, with a two-week washout period between treatments. Faecal samples for rRNA 16S sequencing, IgA and calprotectin analysis, as well as gut symptom and quality of life (QOL) questionnaires, were collected at the start and end of each intervention. The study was approved by the Human Studies Management Committee and Rowett Ethics committee. Participants self-assessed QoL remained stable during the study (Anova, p>0.05). However, all interventions reportedly caused flatulence (Friedman, p<0.05), with psyllium+inulin supplementation slightly increasing early satiation (p=0.04) and rumbling (p=0.02) when compared to maltodextrin. Participants average fibre intake was 23.8 g/day (SD=8.0) at baseline, and remained consistent during the study (Anova, p=0.0525). IgA showed no significant change between maltodextrin, psyllium+inulin and inulin supplementation (2431±5490 µg/ml, 2024±2633 µg/ml and 1614±1683 µg/ml, Anova, p=0.906). Calprotectin levels showed no significant change between maltodextrin, psyllium+inulin and inulin intake (41.30±56.13 mg/kg vs 28.06±32.29 mg/kg vs 27.60±33.97 mg/kg, Anova, p=0.529). However, the intake of psyllium+inulin significantly increased propionate concentration (3.17±1.68 MM vs 3.99±2.15 MM, t-test, p=0.023), and inulin supplementation significantly increased acetate (12.52±4.69 MM vs 14.45±5.58 MM, t-test, p=0.01) and propionate (3.27±1.38 MM vs 3.88±2.05 MM, t-test, p=0.007) concentrations. Metastats and LEfSE showed an increase in the genus Anaerostipes after psyllium+inulin supplementation, and an increase in the genera Anaerostipes and Bifidobacterium after inulin supplementation. Overall, the supplements were well tolerated, with no change in gut health markers IgA and calprotectin. Bifidobacteria are associated with increased apoptosis in cancer cells and reduced radiation-induced diarrhoea (5) , whereas lower abundance of Anaerostipes are reported in colorectal cancer patients (6) . As such, modifying the gut microbiota using dietary fibres to increase the abundance of Bifidobacteria and Anaerostipes could advance patient treatment.

INTRODUCTION:An increasing number of people are living beyond cancer with unmet health needs. The aim of this study was to co-design a digital intervention to improve health outcomes for people who have completed potentially curative treatment for cancer. METHODS:Two co-design workshops were held with patients, clinicians (including oncologists, general practitioners and nurses), digital/computing science experts and third-sector representatives. At workshop one, problems and gaps in care were identified and intervention ideas were generated. At workshop two, a prototype intervention was discussed and refined. RESULTS:The workshops were attended by 43 people in total: 26 at event one and 23 at event two (six attended both events). Patients valued relationship-based care and felt supported during hospital treatment. Patients 'fell off a cliff' after discharge, and there was consensus that more could be done in primary care to support those living beyond cancer. It was proposed that cancer reviews could be integrated into UK primary care chronic disease management activities. A digital form, the 'Structured Personalised Assessment for Reviews after Cancer' (SPARC) tool, was developed to support asynchronous consultations that would cover the breadth of problems and health promotion activities required for high-quality primary care for cancer. SPARC could also identify those without problems who do not require review. CONCLUSION:SPARC has been co-designed to support brief but comprehensive cancer review consultations between primary care clinicians and their patients. SPARC aligns with best practice guidelines. The next step is to evaluate SPARC with patients and in general practices. PATIENT AND PUBLIC CONTRIBUTION:Patient and stakeholder engagement was at the centre of this research study. Cancer organisations such as 'CLAN' cancer support, Prostate Cancer Scotland and Cancer Research UK helped us to engage with patients. The Aberdeen University Institute of Applied Health Science Patient Public Involvement group were also instrumental in sense-checking and improving the materials for the second workshop. We plan to involve our patient and carer partners in designing the next stages of our research (including study materials, processes and methods) so that they will be at the centre of evaluating the intervention that they have been instrumental in designing.

Background Numerous countries use the EXTEL HEMO-AUTO MC Quantitative Faecal Immunochemical Test (qFIT) to screen for faecal haemoglobin. We aimed to determine if bacterial 16S rRNA gene sequencing results (16S V1V2) from the leftover qFIT cassettes would be stable over time and comparable with larger volume faecal collection protocols. Methods Four qFIT probe samples were taken from each of the sixteen fresh healthy volunteer stool samples and 16S results were compared after 0, 4, 7 and 14 days, to provide a baseline control and mimic postage and sample processing conditions in cancer screening programmes. qFIT results were then compared to those of standard laboratory processing of larger whole-stool samples. DNA was extracted from 100 NHS surplus qFIT samples from symptomatic patients reporting rectal bleeding and quantified to assess suitability for 16S sequencing. Results Bacterial composition and diversity from healthy volunteer qFITs remained stable over 14 days with no differences compared to baseline (day 0) and larger stool control samples; at least 75% of the symptomatic qFITs yielded sufficient DNA for 16S sequencing. Conclusion qFIT samples were not significantly different to control samples and stable over 14 days, allowing them to be used for large-scale low-cost population-based intestinal microbiota studies. Clinical Trial Registration The study was registered on clinicaltrials.gov ([NCT06100549][1]). ### Competing Interest Statement AMJ holds a voluntary committee role with the Nutrition Society, Association for the study of Obesity and British Nutrition Foundation. AWW has received research funding from ZOE Ltd, and undertakes consultancy for EnteroBiotix Ltd. The other authors declare no conflict of interest. ### Funding Statement This work was funded by the NHS Grampian Endowment Fund. CRUK Scotland Centre funding enabled collaboration and research development (CTRQQR-2021\100006) and this project was supported by the RSE Research Workship grant 2399. MvdH is funded by a PhD studentship funded by the University of Aberdeen Development Trust and Friends of ANCHOR. AWW and the Rowett Institute receive core funding from the Scottish Governments Rural and Environment Science and Analytical Services Division (RESAS). AEKs Chair is funded by Friends of ANCHOR. FVNDs Chair is funded by Bowel Cancer UK-Royal College of Surgeons of Edinburgh. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The ethical committee of the Rowett Institute gave ethical approval for this work. The ethical committee of NHS Grampian Biorepository gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. The raw sequencing datasets used for this study have been deposited in the NCBI Short Read Archive, under accession number PRJNA1268008. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT06100549&atom=%2Fmedrxiv%2Fearly%2F2025%2F07%2F05%2F2025.07.04.25330898.atom

Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2

Ultrasound-mediated drug delivery is typically performed using transducers with center frequencies <= 1 MHz to promote acoustic cavitation. Such frequencies are not commonly used for diagnostic ultrasound due to limited spatial resolution. Therefore, delivery and monitoring of therapeutic ultrasound typically requires two transducers to enable both treatment and imaging. This study investigates the feasibility of using a single commercial ultrasound imaging transducer operating at 5 MHz for both drug delivery and real-time imaging. We compared a single-transducer system (STS) at 5 MHz with a conventional dual-transducer system (DTS) using a 1.1 MHz therapeutic transducer and an imaging probe. in vitro experiments demonstrated that the STS could achieve comparable extravasation depth and area as the DTS, with higher drug deposition observed at 5 MHz. Additionally, extravasation patterns were influenced by peak negative pressure (PNP) and duty cycle, with the narrower beam width at 5 MHz offering potential advantages for targeted drug delivery. in vivo experiments in a murine bladder cancer model confirmed the efficacy of the STS for real-time imaging and drug delivery, with cavitation dose correlating with drug deposition. The results suggest that a single-transducer approach may enhance the precision and efficiency of ultrasound-mediated drug delivery, potentially reducing system complexity and cost.

Electronic health records contain detailed information about the medical condition of patients, but they are difficult for patients to understand even if they have access to them. We explore whether ChatGPT (GPT 4) can help explain multidisciplinary team (MDT) reports to colorectal and prostate cancer patients. These reports are written in dense medical language and assume clinical knowledge, so they are a good test of the ability of ChatGPT to explain complex medical reports to patients. We asked clinicians and lay people (not patients) to review explanations and responses of ChatGPT. We also ran three focus groups (including cancer patients, caregivers, computer scientists, and clinicians) to discuss output of ChatGPT. Our studies highlighted issues with inaccurate information, inappropriate language, limited personalization, AI distrust, and challenges integrating large language models (LLMs) into clinical workflow. These issues will need to be resolved before LLMs can be used to explain complex personal medical information to patients.

Supplementary Table S1. dCK positivity of nuclei of xenograft tumour, stroma and vasculature.

Supplemental figures 1-5: S1 - Identification of MRE11 truncation by mass spectrometry and western blot quantification from Fig 1A. S2 - Western blots of protein levels after chloroquine treatment and densitometry of MRE11 levels after PAN and cycloheximide from Fig. 2C,D S3 - Additional cell death analysis by FACS and western blotting supportive of Figs 2 and 3A, S4 - quantification of western blots in Figure 5B, S5 - Additional western blots supportive of data in Figure 6, and data for generation and characterisation of stable cell lines, with further presentation clonogenic assays for cell lines used in Fig 6.

Radiosensitising effects of panobinostat under hypoxia. A) Effect of 24-hour 25 nM PAN or DMSO on radiosensitivity of RT112 cells under 2% O2 (hypoxia) and normoxia and exposure to irradiation under the same conditions. Normoxia data taken from (14).

PDF file - 287K, Supplementary Table 1. Target regions for Ku80 and RAD51 siRNA. Supplementary Figure 1. Western blots of Ku80 and RAD51 in RT112 stable shRNA clones. Supplementary Figure 2. Full length western blots.

Background: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology. Objective: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data. Design, setting, and participants: Data from 32 studies that includes 13,790 bladder cancer cases and 343, 502 controls of European ancestry were used for meta-analysis. Outcome measurements and statistical analyses: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. A polygenic risk score (PRS) was generated on the basis of known and novel susceptibility variants and tested for interaction with smoking. Results and limitations: Multiple novel bladder cancer susceptibility loci (6p.22.3, 7q36.3, 8q21.13, 9p21.3, 10q22.1, 19q13.33) as well as improved signals in three known regions (4p16.3, 5p15.33, 11p15.5) were identified, bringing the number of independent markers at genome-wide significance (p < 5 x 10-8) to 24. The 4p16.3 (FGFR3/TACC3) locus was associated with a stronger risk for women than for men (p-interaction = 0.002). Bladder cancer risk was increased by interactions between smoking status and genetic variants at 8p22 (NAT2; multiplicative p value for interaction [pM-I] = 0.004), 8q21.13 (PAG1; pM-I = 0.01), and 9p21.3 (LOC107987026/MTAP/CDKN2A; pM-I= 0.02). The PRS based on the 24 independent GWAS markers (odds ratio per standard deviation increase 1.49, 95% confidence interval 1.44-1.53), which also showed comparable results in two prospective cohorts (UK Biobank, PLCO trial), revealed an approximately fourfold difference in the lifetime risk of bladder cancer according to the PRS (e.g., 1st vs 10th decile) for both smokers and nonsmokers. Conclusions: We report novel loci associated with risk of bladder cancer that provide clues to its biological underpinnings. Using 24 independent markers, we constructed a PRS to stratify lifetime risk. The PRS combined with smoking history, and other estab-lished risk factors, has the potential to inform future screening efforts for bladder cancer. Patient summary: We identified new genetic markers that provide biological insights into the genetic causes of bladder cancer. These genetic risk factors combined with life-style risk factors, such as smoking, may inform future preventive and screening strate-gies for bladder cancer.Published by Elsevier B.V. on behalf of European Association of Urology.

Supplementary Figure S1. Transfection efficiency of siRNA measured with fluorescence. 50 nM Block-iT fluorescent siRNA was transfected and cells fixed 6 h later.

Supplementary Figures 1-2 from MRE11 Expression Is Predictive of Cause-Specific Survival following Radical Radiotherapy for Muscle-Invasive Bladder Cancer

Supplementary Figure S3. Inverse correlation between S phase accumulation of cells and gemcitabine IC50. Cells were treated with 10 nM gemcitabine for 24 h, prior to fixation in 70% ethanol and staining with propidium iodide. The proportion of cells in S phase was calculated using ModFit LT (Verity Software House).

Days for RT112 xenografts to treble in volume and body weights and treatment of Ku80KD xenografts. A) Days for xenografts to treble in volume (PAN+IR vs IR, p=0.06). Skin overlying the xenograft developed ulceration in two mice treated with IR alone and four mice in the PAN+IR group, beyond the time to treble tumour volume; B) Body weight in mice carrying RT112 xenografts, vehicle (n=5), PAN (n=7), PAN+IR (n=6) or IR alone (n=6); C) Mouse body weights in mice carrying 30% KuKD xenografts for vehicle (n=4), PAN (n=6), PAN+IR (n=6) or IR alone (n=6); D) Ku80 knock-down cells express approximately 70% protein; E) Treatment of Ku80KD xenograft mice.

HDAC expression and cellular response to HDAC inhibition. A) qPCR of mRNA expression of HDAC 1-11 genes in normal human urothelial cells (NHU) and RT112, CAL29 and T24 bladder cancer cells. Relative gene expression was normalised to GAPDH levels (n=3); B) Effects of panobinostat on expression of selected HDAC proteins (n=2); C) Clonogenic assay representing cytotoxicity of mocetinostat in RT112, CAL29 and T24 bladder cancer cells, after 24 h incubation (n=3); D) Clonogenic assay representing cytotoxicity of TMP195 in RT112 cells, after 24 h incubation (n=3); E) Effect of panobinostat on acetylation levels of histone H3 lysine 18 (H3K18) at 0.5, 1, 2, 3 and 24 h incubation in RT112 cells (n=2); F) Quantification of western blots in Figure 6 (n=3 for MRE11, HDAC1 and NBS1, n=2 for HDAC2 and RAD51); G) HR assay results for TMP195 (n=3).

A) Assessment of acute large bowel damage. CD1-nude mice treated with mock treatment or PAN (10 mg/kg) +/-IR. Lesions were scored semi-quantitatively using a 0-5 scale where 0 is no lesion present to 5 where the entire organ was affected by the pathology. B) Assessment of damage to intestine and bladder at 12 weeks. P=lesion present; scoring is semi-quantitative. Cage 2 mouse 1 was culled 2 days after being irradiated in error without the collimator present and cage 2 mouse 5 became unwell 7.5 weeks post-treatment and was culled, but no histopathological effects of the treatment were observed in the bowel. Cage 4 mouse 4 developed moderate diffuse ulcerative colitis. Amyloid was present in the small intestine of animals from all groups including the control group and is considered a pre-existing spontaneous lesion not related to the experimental protocol. Lesions were scored semi-quantitatively using a 0-5 scale where 0 is no lesion present to 5 where the entire organ was affected by the pathology.