Gradywollesen2090

Objective To examine the analytic approach of meta-analyses that include non-inferiority or equivalence (NI/EQ) trials. Study design and setting We used Scopus to identify meta-analyses including NI/EQ trials. We extracted data from the meta-analyses and their included RCTs. We used the RCT's NI/EQ margins to re-interpret the results of the meta-analyses, assessed for risk of biases unique to NI/EQ trials, and evaluated the consistency of the meta-analysis interpretation when using NI/EQ margins. Results We identified 38 unique meta-analyses including 515 RCTs, of which 125 (24.3%) were NI/EQ trials. Fourteen meta-analyses (36.8%) reported the study design of their included trials but only one (2.6%) interpreted their pooled estimates using NI/EQ margins and none assessed for risks of bias unique to NI/EQ trials. Nearly all NI/EQ trials (n=116, 92.8%) included in the meta-analyses reported NI/EQ margins. The meta-analyses of 30 outcomes were re-interpreted using the NI/EQ margins; re-interpretations conflicted with the conclusion of the meta-analyses in most cases (n=20, 66.7%). Conclusion Most meta-analyses including NI/EQ trials ignore trial design and do not assess risks of bias unique to NI/EQ studies. Meta-analyses addressing questions previously explored as NI/EQ should conduct a NI/EQ meta-analysis or use clear language when performing standard (i.e. superiority) meta-analyses.Catastrophic pandemics since the 17th century appear to have spurred innovative methods, concepts, and institutions in epidemiology•The plague, cholera, tuberculosis, influenza, and HIV/AIDS left a longstanding imprints on epidemiologic methods and concepts•Pandemics may generate an urgent need for methods that overcome the inadequacy of older methods•Covid-19 specific contribution could be a greater understanding of population thinking beyond academic and professional circlesObjectives The objectives of this study are to evaluate the relationship between authorship networking, socioeconomic factors, and scientific productivity across Latin America. Methods In a bibliometric analysis of cancer-related Latin-American publications, the relationship between authorship network indicators, sociodemographic factors, and number of peer-reviewed indexed publications per country was explored. A systematic review of the literature for cancer publications between 2000 and 2018 using the Scopus database limited to Latin-American authors was used for the construction of coauthorship and publication networks and their respective metrics. Sociodemographic variables including percentage of invested gross domestic product in research, population, and cancer incidence were also estimated. Multiple linear regression models were constructed to determine the relationship between productivity and the aforementioned variables. Results A total of 8,528 articles across nine countries were included. Brazil was the most productive nation with 41.8% of identified references followed by Mexico (16.6%) and Argentina (12.9%). Latin America experienced a 9% growth in number of publications across the studied time frame. After analyzing networking and sociodemographic variables, number of authors in a collaboration network and percentage of invested gross domestic product were associated with high productivity yielding a multiple regression model with an R2 value of 0.983. Conclusions This study indicates that extensive authorship networking and a high investment in research strongly predict cancer-related productivity.Objective The objective of the study was to measure if improving balance in known and observed confounders by propensity score (PS) matching yields different treatment effect estimates in randomized controlled trials (RCTs), thus indirectly measuring the influence of unknown confounders. Study design and setting This is an analysis of individual patient data of 26 large RCTs and comparison of agreement between PS-matched samples and the RCT results on one hand with the agreement between subsamples of RCTs (with sample sizes equal to the sample sizes of the PS-matched samples) and RCTs by Bland-Altman plots and corresponding intraclass correlation coefficients on the other. Results We included data on 213 outcomes from 37 treatment comparisons with 193,620 patients from 26 trials. Bland-Altman plots and intraclass correlation coefficients showed better agreement between PS-matched analysis and RCTs than between reduced RCTs and RCTs. Conclusion We found no indication for a detrimental influence of unknown confounders in PS-matched samples of RCTs.Objective To identify guidelines to assist systematic reviewers or clinical researchers in identifying sampling bias due to tumour heterogeneity (TH) in solid cancers assayed for somatic mutations. We assessed current reporting standards to determine the impact of TH on sample bias. Study design We conducted a systematic review searching 13 databases (Jan-2019) to identify guidelines. A post-hoc analysis was performed using 12 prostate tumour somatic mutation datasets from a previous systematic review to assess reporting on TH. Results Searches identified 2085 records. No formal guidelines were identified. Forty publications contained incidental recommendations across five major themes using multiple tumour samples (n=29), sample purity thresholds (n=14), using specific sequencing methods (n=8), using liquid biopsies (n=4), microdissection (n=4). In post-hoc analyses, 50% (6/12) clearly reported pathology methods. 42% (5/12) did not report pathology results. 42% (5/12) confirmed the pathology of the sample by direct diagnosis rather than inference. 42% (5/12) used multiple samples per patient. 58% (7/12) reported on tumour purity (range 10% to 100%). Conclusions As precision medicine progresses to the clinic, guidelines are required to help evidence-based decision makers understand how TH may impact sample bias. Authors need to clearly report pathology methods and results, tumour purity methods and results.Lung cancer is the leading cause of cancer death in the world. Natural product deguelin and its truncated analogs have been reported to be potential therapeutic agents for lung cancer. In order to improve the potency, a novel truncated deguelin derivative (4) possessing nitric oxide (NO) donor was designed and synthesized. The biological evaluation showed that hybrid 4 exerted potent activity with an IC50 value of 0.41 μM in H1299 cells. Mechanism studies showed that it arrested the cell cycle at G2/M phase and suppressed Hsp90 function. In addition, hybrid 4 demonstrated potent inhibitory activity on the migration and invasion of lung cancer cells. Together, the promising results warrant further development of hybrid 4 as a potential anticancer agent for the treatment of lung cancer.The plants of genus Toona are well known for diverse limonoid secondary metabolites, while polyacetylenes are rarely found from Toona species. In this work, six new polyacetylenes toonasindiynes A-F (1-6) and six known analogues (7-12) were isolated from the root bark of Toona sinensis. Their structures and absolute configurations were elucidated by HRESIMS, 1D and 2D NMR spectroscopic analysis, modified Mosher's method, and biosynthetic consideration. These polyacetylenes share the same 4,6-diyne moiety with different side chain length and different oxidation degree. Bioactivity screening revealed the cytotoxic activity of 3, 5, 9, and 11 against U2OS cells, and the inhibitory effects on nitric oxide (NO) production of 1, 2, 5, 8, 9, and 11 in lipopolysaccharide-induced RAW 264.7 cells.The chemical investigation of the flowers and twigs of Calliandra calothyrsus (Fabaceae) led to the isolation of three new oleanane-type triterpenoid saponins, named calothyrsusosides AC (13). Their structures were established by direct interpretation of their spectral data, mainly HRESIMS, 1D NMR and 2D NMR (1H, 1H NMR DOSY, 13C NMR, COSY, HSQC, HMBC, HSQC-TOCSY and NOESY) and by comparison with literature data. Compounds 1 and 2 were tested for their antiproliferative activity against two digestive carcinoma human cell lines Hep3B (hepatocellular carcinoma) and Caco-2 (epithelial colorectal adenocarcinoma). Both compounds exhibited an antiproliferative activity against the Hep3B cell line, with IC50 values of 6.0 and 6.5 μM, respectively, while no effect was detected against the epithelial colorectal adenocarcinoma Caco-2 (CC50 > 25 μM).Two novel quinolone alkaloids (1 and 2) and two novel indole alkaloids (5 and 8), together with eleven known analogues, were isolated from the nearly ripe fruits of Evodia rutaecarpa. Their structures were determined by extensive spectroscopic data, including NMR, HRESIMS, and ECD. selleck inhibitor Additionally, the anti-tumor, hypoglycemic, and anti-bacterial activities of the isolated alkaloids were evaluated in vitro. Compound 5 as a new alkaloid displayed moderate inhibitory effect against four human cancer cell lines (MCF-7 IC50 = 30.7 μM, Hepg-2 IC50 = 65.2 μM, A549 IC50 = 39.1 μM, and SHSY-5Y IC50 = 24.7 μM), α-glucosidase (IC50 = 23.9 μM) and PTP1B (IC50 = 75.8 μM). Compound 11 showed better inhibitory effect against PTP1B (IC50 = 16.2 μM) compared with that of the positive control. Compounds 5, 13, and 14 showed moderate inhibitory effects against Bacillus cereus with MIC values of 50, 25, and 10 μM, respectively.In the last decade, the advances in the molecular analyses and sequencing techniques allowed researchers to study developmental dysplasia of the hip (DDH) more thoroughly. Certain chromosomes, genes, loci and polymorphisms are being associated with variable severity of this disorder. The wide range of signs and symptoms is dependent either on isolated or systemic manifestation. Phenotypes of isolated cases range from only a mild ligamental laxity, through subluxation, to a complete dislocation of the femoral head. Systemic manifestation is connected to various forms of skeletal dysplasia and other malformations characterized by significant genetic aberrations. To reveal the background of DDH heredity, multiple studies focused on large sample sizes with an emphasis on the correlation between genotype, phenotype and continuous clinical examination. Etiological risk factors that have been observed and documented in patients include genetic, environmental, and mechanical factors, which significantly contribute to the familial or nonfamilial occurrence and phenotypic variability of this disorder. Still, the multifactorial etiology and pathogenesis of DDH are not yet sufficiently clarified, explained, or understood. Formation of connective tissue, osteogenesis, chondrogenesis, and all other affected pathways and variations in the function of their individual elements contribute to the creation of the pathology in a developing human body. This review article presents an up-to-date list of known DDH associated genes, their products, and functional characteristics.Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among reproductive-age women. The circRNA-miRNA axis functions in various diseases progression have been partially revealed in the past two decades. However, little is known about the role of the circRNA-miRNA axis in PCOS progression. MicroRNA miR-760, which is characterized by tissue-specific, has been studied in several cancers. Firstly, we found that miR-760 expression was decreased in PCOS tissues insulin treated GCs, KGN and SVOG cells. Secondly, The CCK-8 and apoptosis experiment results suggested that downregulated miR-760 promoted cell proliferation ability and suppressed apoptosis activity in KGN and SVOG cells. Then, the bioinformatic analysis result indicated that circPUM1 was a potential sponge to miR-760. By performing AGO2-RIP, RNA pull-down, Luciferase reporter, and qRT-PCR experiments, we demonstrated that circPUM1 acted as a molecular sponge to miR-760, and decreased miR-760 expression. Moreover, it was found that the promotive effect of circPUM1 was mediated by regulating miR-760.