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Unravelling early myocardial changes in rheumatoid arthritis by cardiovascular magnetic resonance: insights from the UK biobank
No full textCOVID-19 exposure risks and protective measures in East London’s healthcare and academic sectors: Insights and applications of GloBody technology for infectious disease monitoring
No full textPost-streptococcal Autoimmunity and Its Relevance to Epstein-Barr virus as the Potential Cause of Multiple Sclerosis.
No full textCladribine tablets in Relapsing-Remitting Multiple Sclerosis preferentially target B-cells
No full textSleep disturbance as a transdiagnostic marker of children's mental health difficulties: A network analysis of item‐level associations between different types of sleep problems and different behavioural and emotional symptoms
No full textSpatial patterning of fibroblast TGFβ signaling underlies treatment resistance in rheumatoid arthritis.
No full textTreatment-refractory rheumatoid arthritis (RA) is a major unmet need, and the underlying mechanisms are poorly understood. To identify molecular determinants of refractory RA, we performed spatial transcriptomic profiling on synovial tissue biopsy samples taken 6 months before and after treatment. In the baseline biopsy samples of non-remitting patients, we identified increased fibrogenic signaling within vascular tissue niches, marked by high fibroblast COMP expression. We uncovered a role of endothelial-derived Notch signaling as an upstream regulator of fibroblast transforming growth factor beta (TGFβ) signaling via its opposing ability to induce TGFβ isoform expression while suppressing TGFβ receptors, generating a proximal-to-distal gradient of TGFβ sensitivity that can be altered with disruption of steady-state Notch signaling. In posttreatment biopsy samples, we observed significant immune depletion with expansion of fibrogenic niches, a process that can be reversed by inhibition of Notch and TGFβ signaling in RA patient-derived organoids. Collectively, our data implicate targeting of TGFβ signaling to prevent exuberant synovial tissue fibrosis as a potential therapeutic strategy for refractory RA
Investigating the Efficacy and Efficiency of Rechargeable Layered Double Hydroxides for Dental Applications
No full textLayered Double Hydroxides (LDHs) are inorganic lamellar structures that can act as systems for absorbing and releasing anions repeatedly. Their biocompatibility, anion exchange capacity and compositional tunability make them promising candidates for controlled and sustained delivery of cariostatic ions, particularly in orthodontic patients. Given the ongoing challenge of preventing dental caries, especially for patients wearing orthodontic brackets, it is essential to have innovative materials like LDHs for sustained anti-caries ions delivery. This study explores LDHs for sustained release of fluoride and monoflurophosphate ions. The latter offers dual delivery of fluoride and phosphate, which is regulated by the local concentration of alkaline phosphatase enzyme in the oral environment, to enhance remineralisation. Two LDH types (2:1 ZnAl and MgAl) were synthesised and charged with 0.012 M sodium fluoride (NaF) or sodium monofluorophosphate (MFP). LDHs were characterised before and after anion intercalation using X-Ray Diffraction, Fourier Transform Infrared Spectroscopy and electron microscopy. Ion release was evaluated over three charging/release cycles in deionised water using fluoride Ion Selective Electrodes (ISEs) for fluoride, and Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) for phosphate and cations (Zn, Mg and Al). Results showed sustained fluoride release, with MgAl-LDH releasing more anions than ZnAl- LDH. NaF-charged LDHs released more fluoride, while MFP-charged LDHs additionally released phosphate. Cation release was higher in MFP-charged LDHs. Charged LDHs were incorporated into light-curable adhesive resin (AR) and tested for fluoride release over 10 days using fluoride ISEs. Degree of conversion (DC), water uptake, desorption and solubility were also assessed. LDH incorporation did not affect DC and enabled sustained fluoride release above recommended caries-prevention levels. AR-containing-LDH showed more water uptake (~13%) and desorption than control samples (without LDH, ~10%), however, all samples demonstrated low solubility. These findings underscore LDHs as versatile nanocrystals for developing multifunctional dental materials, offering sustained cariostatic effects for caries prevention
Improved stage-specific survival in screen-detected breast cancer in Denmark: a cohort study.
Full text linkBACKGROUND: This study examined whether breast cancer survival improvements with screening are explained solely by detection at early stages and whether mortality can be predicted using stage and diagnosis date alone. METHODS: We compared stage-specific net survival between never-screened, symptomatic ever-screened (past attenders and interval cancers), and screen-detected breast cancer cases in Denmark using individual-level electronic health records from January 1, 2010 to December 31, 2022. Lifetables were generated from women without breast cancer, separately for never-screened and ever-screened women. Age-specific all-cause mortality rates were used to calculate excess mortality in women with breast cancer, which was then transformed into net survival. RESULTS: Of 817 128 women, 32 827 had breast cancer, with 8% presenting as stage III or IV. Survival differences between symptomatic and screen-detected cases were minimal for stages I-III but reached 40% at stage IV, with 5-year net survival for stage IV screen-detected women (74.7%) resembling stage IIIc symptomatic survival in never-screened women (72.6%). Survival from stage IV breast cancer was strongly associated with treatment, with median survival (years) of 4.4-6.0 with surgery, 1.6-2.2 with nonsurgical treatment, and 0.03-0.13 with no treatment; 67% of screen-detected patients received surgery (compared with 23% of never-screened and 27% of symptomatic ever-screened). CONCLUSIONS: Greater survival in screen-detected stage IV cases suggests that breast cancer screening may not have come too late and deserves to be investigated further. Predicting breast cancer mortality using stage at diagnosis and stage-specific survival (without differentiating by route to diagnosis) will underestimate the impact of breast screening on mortality