Citations

AbstractThe Baby‐Friendly Hospital Initiative is a global health promotion intervention that outlines the Ten Steps hospitals should implement to support newborns' breastfeeding. This US‐based study aimed to determine which hospital characteristics and community factors are associated with hospitals' attainment of Baby‐Friendly designation. We used a cross‐sectional design and used 2018 data from the Baby‐Friendly, USA Inc. designation program merged with the American Hospital Association annual survey data set. Multilevel logistic regression analysis was used to assess hospital characteristics of interest among the sample consisting of 312 Baby‐Friendly hospitals and 1449 non‐Baby‐Friendly. Our results show that Baby‐Friendly hospitals are more likely to be government nonfederal hospitals, in the Midwest or South regions, serve communities with higher birth totals, and reside in competitive markets. Based on the results of this study, hospitals should seek further and examine their community's characteristics and structures to identify opportunities and encourage the attainment of improved breastfeeding initiatives such as Baby‐Friendly designation.

In part one of this two-part paper, we present eight principles that we believe must be considered for more effective treatment of the currently incurable cancers. These are addressed by multidrug adjunctive cancer treatment (MDACT), which uses multiple repurposed non-oncology drugs, not primarily to kill malignant cells, but rather to reduce the malignant cells’ growth drives. Previous multidrug regimens have used MDACT principles, e.g., the CUSP9v3 glioblastoma treatment. MDACT is an amalgam of (1) the principle that to be effective in stopping a chain of events leading to an undesired outcome, one must break more than one link; (2) the principle of Palmer et al. of achieving fractional cancer cell killing via multiple drugs with independent mechanisms of action; (3) the principle of shaping versus decisive operations, both being required for successful cancer treatment; (4) an idea adapted from Chow et al., of using multiple cytotoxic medicines at low doses; (5) the idea behind CUSP9v3, using many non-oncology CNS-penetrant drugs from general medical practice, repurposed to block tumor survival paths; (6) the concept from chess that every move creates weaknesses and strengths; (7) the principle of mass—by adding force to a given effort, the chances of achieving the goal increase; and (8) the principle of blocking parallel signaling pathways. Part two gives an example MDACT regimen, gMDACT, which uses six repurposed drugs—celecoxib, dapsone, disulfiram, itraconazole, pyrimethamine, and telmisartan—to interfere with growth-driving elements common to cholangiocarcinoma, colon adenocarcinoma, glioblastoma, and non-small-cell lung cancer. gMDACT is another example of—not a replacement for—previous multidrug regimens already in clinical use, such as CUSP9v3. MDACT regimens are designed as adjuvants to be used with cytotoxic drugs.

Measles is an RNA virus infectious disease mainly seen in children. Despite the availability of an effective vaccine against measles, it remains a health issue in children. Although it is a self-limiting disease, it becomes severe in undernourished and immune-compromised individuals. Measles infection is associated with secondary infections by opportunistic bacteria due to the immunosuppressive effects of the measles virus. Recent reports highlight that measles infection erases the already existing immune memory of various pathogens. This review covers the incidence, pathogenesis, measles variants, clinical presentations, secondary infections, elimination of measles virus on a global scale, and especially the immune responses related to measles infection.

Abstract Background The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. Methods We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2– or 3–degree-of-freedom joint test. A set-based score test was applied for rare genetic variants. Results The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2–degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P < 1.2 × 10−4). Conclusion Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.

Abstract Background: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer. Methods: Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (>28 g/day) with light-to-moderate drinkers (1–28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models. Results: For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 > 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose–response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11; 95% confidence interval (CI), 1.06–1.17; OR for AA genotype = 1.22; 95% CI, 1.14–1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif. Conclusions: Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region. Impact: The study identifies multifaceted evidence of a possible functional effect for rs1318920.

miRNAs biomarkers are emerging as an essential part of clinical oncology. Their oncogenic and tumour suppressor properties playing a role in malignancy has generated interest in their potential for use in disease prognosis. While several studies on miRNA have been carried out across the globe, evaluating the clinical implications of miRNAs in cancer diagnosis and prognosis research has currently not been attempted. A study delineating the area of miRNA research, including the topics presently being focused on, the seminal papers in this field, and the direction of research interest, does not exist. This study aims to conduct a large-scale, global data analysis and bibliometric profiling analysis of studies to evaluate the research output of clinical implications of miRNAs in cancer diagnosis and prognosis listed in the SCOPUS database. A systematic search strategy was followed to identify and extract all relevant studies, subsequently analysed to generate a bibliometric map. SPSS software (version 27) was used to calculate bibliometric indicators or parameters for analysis, such as year and country of affiliation with leading authors, journals, and institutions. It is also used to analyse annual research outputs, including total citations and the number of times it has been cited with productive nations and H-index. The number of global research articles retrieved for miRNA-Cancer research over the study period 2003 to 2019 was 18,636. Between 2012 and 2019, the growth rate of global publications is six times (n = 15,959; 90.71 percent articles) that of 2003 to 2011. (2704; 9.29 per cent articles). China published the most publications in the field of miRNA in cancer (n = 7782; 41%), while the United States had the most citations (n = 327,538; 48%) during the time span. Of these journals, Oncotarget has the highest percentage of article publications. The journal Cancer Research had the most citations (n = 41,876), with 6.20 per cent (n = 41,876). This study revealed a wide variety of journals in which miRNA-Cancer research are published; these bibliometric parameters exhibit crucial clinical information on performance assessment of research productivity and quality of research output. Therefore, this study provides a helpful reference for clinical oncologists, cancer scientists, policy decision-makers and clinical data researchers.

Abstract Background Observational studies have shown higher folate consumption to be associated with lower risk of colorectal cancer (CRC). Understanding whether and how genetic risk factors interact with folate could further elucidate the underlying mechanism. Aggregating functionally relevant genetic variants in set-based variant testing has higher power to detect gene-environment (GxE) interactions and may provide information on the underlying biological pathway. Objective We investigated interactions between folate consumption and predicted gene expression on colorectal cancer risk across the genome. Methods We used variant weights from the PrediXcan models of colon tissue-specific gene expression as a priori variant information for a set-based GxE approach. We harmonized total folate intake (mcg/day) based on dietary intake and supplemental use across cohort and case-control studies and calculated sex and study specific quantiles. Analyses were performed using a mixed effects score tests for interactions between folate and genetically predicted expression of 4,839 genes with available genetically predicted expression. We meta-analyzed results across 23 studies for a total of 13,498 cases with colorectal tumors and 13,918 controls of European ancestry. Results We found suggestive evidence of interaction with folate intake for genes including glutathione S-Transferase Alpha 1 (GSTA1; p=4.3E-4), Tonsuko Like, DNA Repair Protein (TONSL; p=4.3E-4), and Aspartylglucosaminidase (AGA: p=4.5E-4). Glutathione is an antioxidant, preventing cellular damage and is a downstream metabolite of homocysteine and metabolized by GSTA1. TONSL is part of a complex that functions in the recovery of double strand breaks and AGA plays a role in lysosomal breakdown of glycoprotein. Conclusion We identified three genes involved in preventing or repairing DNA damage that may interact with folate consumption to alter CRC risk.

In the last few decades, carcinogenesis has been extensively explored and substantial research has identified immunogenic involvement in various types of cancers. As a result, immune checkpoint blockers and other immune-based therapies were developed as novel immunotherapeutic strategies. However, despite being a promising therapeutic option, immunotherapy has significant constraints such as a high cost of treatment, unpredictable toxicity, and clinical outcomes. miRNAs are non-coding, small RNAs actively involved in modulating the immune system’s multiple signalling pathways by binding to the 3′-UTR of target genes. miRNAs possess a unique advantage in modulating multiple targets of either the same or different signalling pathways. Therefore, miRNA follows a ‘one drug multiple target’ hypothesis. Attempts are made to explore the therapeutic promise of miRNAs in cancer so that it can be transported from bench to bedside for successful immunotherapeutic results. Therefore, in the current manuscript, we discussed, in detail, the mechanism and role of miRNAs in different types of cancers relating to the immune system, its diagnostic and therapeutic aspect, the effect on immune escape, immune-checkpoint molecules, and the tumour microenvironment. We have also discussed the existing limitations, clinical success and the prospective use of miRNAs in cancer.

Aim To provide a contemporary analysis of incidence trends of infective endocarditis (IE) with its changing epidemiology over the past two decades in Europe. Methods A systematic review was conducted at the Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus and Web of Science were searched for studies published between 1 January 2000 and 30 November 2020. All studies were independently reviewed by four referees and those that included a population-based incidence of IE in patients, irrespective of age, in Europe were included. Least squares regression was used to estimate pooled temporal trends in IE incidence. Results Of 9138 articles screened, 18 studies were included in the review. Elderly men predominated in all studies. IE incidence increased 4.1% per year (95% CI 1.8% to 6.4%) in the pooled regression analysis of eight studies that included comprehensive and consistent trends data. When trends data were weighted according to population size of individual countries, an increase in yearly incidence of 0.27 cases per 100 000 people was observed. Staphylococci and streptococci were the most common pathogens identified. The rate of surgical intervention ranged from 10.2% to 60.0%, and the rate of inpatient mortality ranged from 14.3% to 17.5%. In six studies that examined the rate of injection drug use, five of them reported a rate of less than 10%. Conclusion Based on findings from our systematic review, IE incidence in Europe has doubled over the past two decades in Europe. Multiple factors are likely responsible for this striking increase. Trial registeration number CRD42020191196.