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An exploratory investigation into the experiences of community pharmacists when dealing with medicines shortages: interview study
Get PDFAcceptance and Commitment Therapy (ACT) for distress in university students with chronic physical health conditions::a single-arm feasibility study of an app-based intervention
No full textUniversity students living with chronic physical health conditions experience high levels of distress. However, limited research has investigated scalable psychological treatments to manage distress in this context. This study examined the feasibility and acceptability of an app based on Acceptance and Commitment Therapy (“ACT Companion”) for distressed students living with chronic physical health conditions. This was an online single-arm feasibility trial. Participants completed self-report measures at baseline, post-treatment and 1-month follow-up. A subsample of participants was also invited to an interview to discuss their experiences using the app. In terms of the primary feasibility parameters, 60 participants were recruited and 85% of these were retained at follow-up. However, the proportion of treatment completers was only 28.3%, which fell below the feasibility criterion for completion. Nonetheless, treatment satisfaction scores were comparable to previous trials of therapist-supported ACT for chronic pain. For the secondary feasibility outcomes, small to large effects were observed which, along with the 95% confidence intervals, suggest that the intervention may be associated with improvements in distress, wellbeing, life satisfaction, and psychological flexibility. The treatment package in its current form without any support appears not to be acceptable for this population. A fully powered trial may be feasible with adjustments to the treatment package, such as including some form of therapist support, to optimize engagement. Following further study, the ACT companion app may be a promising treatment to support the mental health of students with chronic physical health conditions in an accessible and scalable way
A Jagged1-regulated hybrid-EMT state identifies pancreatic cancer stem cells
Get PDFPancreatic ductal adenocarcinoma (PDAC) shows great cellular heterogeneity, with pronounced epithelial and mesenchymal cancer cell populations. We previously identified a PDAC subpopulation, marked by the tetraspanin CD9, which is capable of initiating PDAC and giving rise to PDAC heterogeneity. Here, we characterize a subset of CD9-high (CD9hi) tumor-initiating cells (TICs) with hybrid epithelial-mesenchymal transition (EMT) features, which show increased cancer stem cell properties, as evidenced by increased capacity to form organoids and generate epithelial and mesenchymal tumor cell progeny. Depletion of hybrid-EMT CD9hi cells leads to a gradual collapse of organoid formation and tumorigenic capability, suggesting that CD9hi TICs are required for long-term organoid formation and tumorigenicity. Hybrid- EMT CD9hi TICs upregulate the Notch ligand Jagged1, and Jag1 depletion or Notch inhibition impairs TIC self-renewal and PDAC cell differentiation. Conversely, Jag1 overexpression augments TIC self- renewal. Thus, Jagged1-mediated Notch signaling controls a hybrid-EMT state that is a defining feature of TICs in PDAC
Platelet-specific P2Y1 receptor deficient mice have suppressed pulmonary leukocyte recruitment in response to lipopolysaccharide
Get PDFA role for the P2Y1 receptor (P2Y1R) in platelet-driven inflammation has been established using a pharmacological approach, limited to an acute 4 hour time span. Nucleotide-structure P2Y1R antagonists have restricted experimental use due to inadequate pharmacokinetics, and an inability to decipher global versus cell specific effects in vivo. The creation of a conditional knock out (platelet) P2Y1R transgenic mouse model was designed to overcome these restrictions.A homozygous P2Y1 LoxP mouse colony was created using CRISPR/Cas9 technology, and crossed with a hemizygous P2Y1 LoxP with PF4-cre to provide offspring that are homozygous for P2Y1 LoxP flanked allele, and hemizygous for the PF4cre (platelet P2Y1-/-) and offspring homozygous for P2Y1 LoxP flanked allele, but non-carriers for PF4cre (control mice). Animals were intranasally administered LPS to induce pulmonary inflammation to assess the influence of phenotype on leukocyte recruitment.24 hours post intranasal LPS administration; pulmonary neutrophil and platelet recruitment were significantly suppressed, despite the fact that neutrophils retained the ability to migrate to fMLP ex vivo. Circulating platelet and leukocyte numbers were not different between control and platelet P2Y1-/- animals. Tail bleeding times revealed the platelet P2Y1-/- mice had a severe bleeding phenotype. The platelet specific P2Y1-/- mouse model confirms the importance of platelet P2Y1R in the regulation of inflammatory responses. A 60-70% inhibition of leukocyte recruitment over an extended time period was observed compared to previous pharmacological studies. Platelet P2Y1-/- mice will help further elucidate the mechanisms by which P2Y1R regulate platelet activation during inflammation. <br/
Multimodal treatment and tumour biology-driven long-term survival in PSC-associated hilar cholangiocarcinoma:A case report
Get PDFPrimary sclerosing cholangitis (PSC) is a recognised risk factor for hilar cholangiocarcinoma (hCCA). In selected patients, neoadjuvant chemoradiotherapy followed by liver transplantation provides the optimal chance of long-term survival. However, for the patient described in the present case report, at the time of the patient s treatment, the UK did not have an approved transplant programme for cholangiocarcinoma, and access to liver transplantation was limited, often necessitating upfront surgical resection despite its complexity and limited curative potential. The present study describes the case of a 52-year-old male patient with PSC who was diagnosed with hCCA and underwent an extended right hepatectomy. After 26 months, progressive liver dysfunction due to PSC-related cirrhosis prompted liver transplantation, which was approved following a lengthy appeals process. Over the following years, the patient developed metastases in the bowel, lungs and abdominal wall, all of which were successfully managed with surgical resections. He remained disease-free for 8 years following his initial diagnosis before developing intrahepatic recurrence. The tumour was HER2-positive, and the compassionate use of zanidatamab was initiated following progression on standard therapies. At the time of the writing of the present case report, the patient remained alive 101 months following this initial diagnosis. On the whole, the present case report highlights the potential impact of tumour biology and multimodal treatment in PSC-associated hCCA. The prolonged survival of the patient despite delayed transplant and metastatic recurrence suggests that PSC-related hCCA may follow a more indolent course compared to de novo cases. Future efforts are required to focus on tumour profiling and stratified therapeutic approaches to better guide treatment in this complex disease.</p
Associations between lifestyle factors and life quality in people living with psoriasis: results of the Asking People with Psoriasis about Lifestyle and Eating (APPLE) cross-sectional study
No full textPredicting restoration failures in primary and permanent teeth – A machine learning approach
Get PDFObjective: Machine learning (ML) predictive models promise to handle complex data and deliver accurate predictions in the medical field. The aim of this study was to develop ML predictive models for posterior dental restorations failures in both primary and permanent teeth. Methods: Data from two clinical datasets were used in this study, encompassing a Randomized Controlled Trial (RCT) for permanent teeth (CaCIA Trial) and a corresponding RCT for primary teeth (CARDEC 3). Models were developed using five different algorithms—Decision Tree, Random Forest, XGBoost, CatBoost and Neural Network—ensuring thorough cross-validation and calibration for predictive reliability. Clinical variables related to patients and teeth were considered as predictors. Model performances were assessed using accuracy, precision, recall, F1-score and ROC AUC, alongside SHAP plots for interpretability. Results: In the primary teeth dataset, all models demonstrated acceptable performance with AUC values around 0.67–0.75 and a balanced trade-off between precision and recall. In contrast, the models applied to permanent teeth yielded less predictive ability, with AUC values ranging from 0.53 to 0.62. Conclusion: Our results highlight how ML approaches effectively process intricate, multi-dimensional data related to restoration longevity, successfully integrating variables across patient characteristics, tooth properties, and diagnostic assessments within a unified analytical framework. Though promising as analytical tools, clinical implementation requires further validation with expanded, heterogeneous datasets to improve robustness and accuracy. Clinical significance: Machine-learning models that predict the risk of posterior restoration failure—using routinely collected patient, tooth, and diagnostic data—may help dentists tailor recall intervals, prioritize preventive or reparative care, and allocate chair time more efficiently.</p
A Dataset of Collections Dispersal Following Museum Closures in the UK During 2000–2025
Get PDFThis dataset details the closures of 479 museums in the UK between the 1st of January 2000 and the 31st of July 2025. The data records the reasons why museums closed, what happened to the collections, and the actors involved. We developed new taxonomies to code event and actor types; the objects are described using Wikidata items; and each museum is linked to its entry in the Mapping Museums database. The data was collected from a range of sources including historical documents, reports, news articles, and personal accounts. It can be integrated with a broader range of data relating to the UK’s changing cultural sector.</p
