estimation accuracy. In addition, the uncertainty measures provided by our method correlate with estimation errors and produce reasonable confidence intervals; these results suggest potential application of the proposed uncertainty quantification method in brain studies. Characterizing functional brain connectivity using resting functional magnetic resonance imaging (fMRI) is challenging due to the relatively small Blood-Oxygen-Level Dependent contrast and low signal-to-noise ratio. Denoising using surface-based Laplace-Beltrami (LB) or volumetric Gaussian filtering tends to blur boundaries between different functional areas. To overcome this issue, a time-based Non-Local Means (tNLM) filtering method was previously developed to denoise fMRI data while preserving spatial structure. The kernel and parameters that define the tNLM filter need to be optimized for each application. Here we present a novel Global PDF-based tNLM filtering (GPDF) algorithm that uses a data-driven kernel function based on a Bayes factor to optimize filtering for spatial delineation of functional connectivity in resting fMRI data. We demonstrate its performance relative to Gaussian spatial filtering and the original tNLM filtering via simulations. We also compare the effects of GPDF filtering against LB filtering using individual in-vivo resting fMRI datasets. Our results show that LB filtering tends to blur signals across boundaries between adjacent functional regions. In contrast, GPDF filtering enables improved noise reduction without blurring adjacent functional regions. These results indicate that GPDF may be a useful preprocessing tool for analyses of brain connectivity and network topology in individual fMRI recordings. V.In this work, the new polysaccharide-platinum conjugates of 5-aminosalicylic acid modified lycium barbarum polysaccharide linking platinum compounds were designed in order to construct an anticancer metal drug delivery system. The multiple analysis methods were used to describe the chemical structure and physical properties of the polysaccharide-metal conjugates. The results showed that 5-aminosalicylic acid successfully acted as linker which was covalently bound between polysaccharide and platinum compound. The morphology and rheological properties of polysaccharide have been changed by the formation of conjugates, which exhibited certain inhibition specificity to A549 (human lung cancer cell line). The agarose gel electrophoresis and fluorescence microscopy results demonstrated that such conjugates promoted the unwinding of DNA and could significantly damage the nucleus of A549 cells. Cell cycle analyzing the Pt complex of conjugates could cause intracellular DNA damage and induced G2 phase arrest. GSK3685032 So, polysaccharide-platinum conjugates might find a range of applications, for example in metal anticancer drug delivery. Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania, which has very limited treatment options and affects poor and underdeveloped populations. The current treatment is plagued by many complications, such as high toxicity, high cost and resistance to parasites; therefore, novel therapeutic agents are urgently needed. Herein, the synthesis, characterization and in vitro leishmanicidal potential of new complexes with the general formula [RuCl3(TMP)(dppb)] (1), [PtCl(TMP)(PPh3)2]PF6 (2) and [Cu(CH3COO)2(TMP)2]·DMF (3) (dppb = 1,4-bis(diphenylphosphino)butane, PPH3 = triphenylphosphine and TMP = trimethoprim) were evaluated. The complexes were characterized by infrared, UV-vis, cyclic voltammetry, molar conductance measurements, elemental analysis and NMR experiments. Also, the geometry of (2) and (3) were determined by single crystal X-ray diffraction. Despite being less potent against promastigote L. amazonensis proliferation than amphotericin B reference drug (IC50 = 0.09 ± 0.02 μM), complex (2) (IC50 = 3.6 ± 1.5 μM) was several times less cytotoxic (CC50 = 17.8 μM, SI = 4.9) in comparison with amphotericin B (CC50 = 3.3 μM, SI = 36.6) and gentian violet control (CC50 = 0.8 μM). Additionally, complex (2) inhibited J774 macrophage infection and amastigote number by macrophages (IC50 = 6.6 and SI = 2.7). Outstandingly, complex (2) was shown to be a promising candidate for a new leishmanicidal therapeutic agent, considering its biological power combined with low toxicity. PURPOSE Adjuvant endocrine therapy (AET) significantly reduces the risk of breast cancer recurrence and mortality in women with hormone receptor (HR+) breast cancer. Despite the documented survival benefits with AET, non-adherence and non-persistence remains a significant problem. This systematic review of qualitative research aimed to synthesise breast cancer patients’ experiences of adherence and persistence to oral endocrine therapy. METHODS The ENTREQ guidelines were followed. A systematic search strategy was performed across eleven electronic databases (Embase, Cinahl, Pubmed, Psychinfo, Proquest, Lenus, Scopus, Web of Science, Rian.ie, EThOS e-theses online, DART Europe). Thomas and Harden’s three-stage approach to thematic analysis was undertaken on the findings of all included studies. Confidence in the findings were reviewed using GRADE-CERQual. RESULTS Twenty-four qualitative studies were included in the synthesis. Three analytic themes were identified (We don’t have an option; the side effects are worse than the disease; help us with information and support). Adherence was often driven by women feeling they had no option and a fear of cancer recurrence. Persistence was helped with support and information. Non-adherence and non-persistence were associated with debilitating side effects, inadequate information and lack of support. CONCLUSIONS Adherence and persistence to AET was often suboptimal among breast cancer patients. Women commonly felt isolated and neglected as a result of insufficient information and support from healthcare professionals. If women are to persist with AET, primary care providers should be aware of the facilitators and barriers to adherence, and they should be knowledgeable in symptom management strategies.