Measuring and reporting treatment adherence:what can we learn by comparing two respiratory conditions?

Medication non-adherence, defined as any deviation from the regimen recommended by their healthcare provider, can increase morbidity, mortality and side effects, while reducing effectiveness. Through studying two respiratory conditions, asthma and tuberculosis (TB), we thoroughly review the current understanding of the measurement and reporting of medication adherence. In this paper, we identify major methodological issues in the standard ways that adherence has been conceptualised, defined and studied in asthma and TB. Between and within the two diseases there are substantial variations in adherence reporting, linked to differences in dosing intervals and treatment duration. Critically, the communicable nature of TB has resulted in dose-by-dose monitoring becoming a recommended treatment standard. Through the lens of these similarities and contrasts, we highlight contemporary shortcomings in the generalised conceptualisation of medication adherence. Furthermore, we outline elements in which knowledge could be directly transferred from one condition to the other, such as the application of large-scale cost-effective monitoring methods in TB to resource-poor settings in asthma. To develop a more robust evidence-based approach, we recommend the use of standard taxonomies detailed in the ABC taxonomy when measuring and discussing adherence. Regimen and intervention development and use should be based on sufficient evidence of the commonality and type of adherence behaviours displayed by patients with the relevant condition. A systematic approach to the measurement and reporting of adherence could improve the value and generalisability of research across all health conditions.status: publishe

Biological activity of synthesized 5-{1-[(4-chlorophenyl)sulfonyl]piperidin-4- yl}-2-mercapto-1,3,4-oxadiazole derivatives demonstrated by in silico and BSA binding studies

We synthesized a series of compounds bearing pharmacologically important 1,3,4-oxadiazole and piperidine moieties. Spectral data analysis by 1 H-NMR, 13C-NMR, IR and EI-MS was used to elucidate the structures of the synthesized molecules. Docking studies explained the different types of interaction of the compounds with amino acids, while bovine serum albumin (BSA) binding interactions showed their pharmacological effectiveness. Antibacterial screening of these compounds demonstrated moderate to strong activity against Salmonella typhi and Bacillus subtilis but only weak to moderate activity against the other three bacterial strains tested. Seven compounds were the most active members as acetyl cholinesterase inhibitors. All the compounds presented displayed strong inhibitory activity against urease. Compounds 7l, 7m, 7n, 7o, 7p, 7r, 7u, 7v, 7x and 7v were highly active, with respective IC50 values of 2.14±0.003, 0.63±0.001, 2.17±0.006, 1.13±0.003, 1.21±0.005, 6.28±0.003, 2.39±0.005, 2.15±0.002, 2.26±0.003 and 2.14±0.002 µM, compared to thiourea, used as the reference standard (IC50 = 21.25±0.15 µM). These new urease inhibitors could replace existing drugs after their evaluation in comprehensive in vivo studies

The Investigation of the Chemical Composition and Applicability of Gold Nanoparticles Synthesized with Amygdalus communis (Almond) Leaf Aqueous Extract as Antimicrobial and Anticancer Agents

The current work’s main objective was to determine the chemical composition of Amygdalus communis (AC) leaf extract and examine the antibacterial and cytotoxic properties of biosynthesized gold nanoparticles (AuNPs). The chemical composition of AC leaf extract was determined using LC-ESI/MS/MS to detect compounds that may be responsible for the reducing, stabilizing, and capping steps in the synthesis of nanoparticles and their biological activities. The AC-AuNPs were spherical, with a particle size lower than 100 nm and a face-centered cubic structure. The EDX spectrum confirmed the formation of AuNPs and a negative zeta potential value (−27.7 mV) suggested their physicochemical stability. The in vitro cytotoxic efficacy of the AC-AuNPs against colorectal adenocarcinoma (Caco-2), glioma (U118), and ovarian (Skov-3) cancer cell lines and human dermal fibroblasts (HDFs) was evaluated by MTT assay. CaCo-2 cell proliferation was effectively inhibited by the AC-AuNPs at concentrations between 25 and 100 g mL−1. The AC-AuNPs exerted preeminent antimicrobial activity against Bacillus subtilis with an MIC of 0.02 μg/mL, whilst good activity was shown against Staphylococcus aureus bacteria and Candida albicans yeast with an MIC of 0.12 μg/mL. Ultimately, the results support the high antibacterial and anticancer potential of biosynthesized AuNPs from AC leaf extract

Green synthesis of silver nanoparticles mediated Diospyros kaki L. (Persimmon): determination of chemical composition and evaluation of their antimicrobials and anticancer activities

The eco-friendly synthesis of metallic nanoparticles (MNPs) using biological materials is an encouraging and innovativeness approach to nanotechnology. Among other synthesizing methods, biological methods are chosen because of their high efficiency and purity in many aspects. In this work, using the aqueous extract obtained from the green leaves of the D. kaki L. (DK); silver nanoparticles were synthesized in a short time and simply with an eco-friendly approach. The properties of the synthesized silver nanoparticles (AgNPs) were characterized using various techniques and measurements. In the characterization data of AgNPs, Maximum absorbance at 453.34 nm wavelengths, the average size distribution of 27.12 nm, the surface charge of −22.4 mV, and spherical appearance were observed. LC-ESI-MS/MS analysis was used to assess the compound composition of D. kaki leaf extract. The chemical profiling of the crude extract of D. kaki leaves revealed the presence of a variety of phytochemicals, predominantly phenolics, resulting in the identification of five major high-feature compounds: two major phenolic acids (Chlorogenic acid and Cynarin), and tree flavonol glucosides (hyperoside, quercetin-3-glucoside, and quercetin-3- D-xyloside). The components with the highest concentrations were cynarin, chlorogenic acid, quercetin-3- D-xyloside, hyperoside, and quercetin-3-glucoside, respectively. Antimicrobial results were determined by a MIC assay. The biosynthesized AgNPs exhibited strong antibacterial activity against the human and food pathogen Gram (+ and −) bacteria and good antifungal activity against pathogenic yeast. It was determined that 0.03–0.050 μg/mL concentrations ranges of DK-AgNPs were growth suppressive concentrations on all pathogen microorganisms. The MTT technique was used to study the cytotoxic effects of produced AgNPs on cancer cell lines (Glioblastoma (U118), Human Colorectal Adenocarcinoma (Caco-2), Human Ovarian Sarcoma (Skov-3) cancer cell lines, and Human Dermal Fibroblast (HDF) healthy cell line). It has been observed that they have a suppressive effect on the proliferation of cancerous cell lines. After 48 h of treatment with Ag-NPs, the DK-AgNPs were found to be extremely cytotoxic to the CaCo-2 cell line, inhibiting cell viability by up to 59.49% at a concentration of 50 g mL−1. It was found that the viability was inversely related to the DK-AgNP concentration. The biosynthesized AgNPs had dose-dependent anticancer efficacy. Because of the high concentration of bioactive chemicals in Diospyros kaki, it may be employed as a biological resource in medicinal applications. DK-AgNPs were shown to be an effective antibacterial agent as well as a prospective anticancer agent. The results provide a potential approach for the biogenic production of DK-AgNPs utilizing D. kaki aqueous leaf extract

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment