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These effects remained after controlling for demographics, isolation, and depression. Conclusion Sleep disturbance partially mediates the relationship between loneliness and self-reported health over 8 years. These findings are not attributable to isolation or depression. Further research is necessary to develop and assess a more comprehensive model of how loneliness shapes health. This study indicates that targeting sleep disturbance may mitigate the health risks of loneliness in older Americans.Introduction The US FDA receives more than 2 million postmarket reports each year. Safety Evaluators (SEs) review these reports, as well as external information, to identify potential safety signals. With the increasing number of reports and the size of external information, more efficient solutions for data integration and decision making are needed. Objectives The aim of this study was to develop an interactive decision support application for drug safety surveillance that integrates and visualizes information from postmarket reports, product labels, and biomedical literature. Methods We conducted multiple meetings with a group of seven SEs at the FDA to collect the requirements for the Information Visualization Platform (InfoViP). Using infographic design principles, we implemented the InfoViP prototype version as a modern web application using the integrated information collected from the FDA Adverse Event Reporting System, the DailyMed repository, and PubMed. The same group of SEs evaluated the InfoViP pe sources for their case series analyses.Introduction The term progressive fibrosing interstitial lung disease (ILD) describes patients with fibrotic ILDs who, irrespective of the aetiology of the disease, show a progressive course of their disease despite current available (and non-licensed) treatment. Besides in idiopathic pulmonary fibrosis, little is known about management and the burden of patients with fibrotic ILD, particularly those with a progressive behaviour. Methods Using the Delphi method, 40 European experts in ILD management delivered information on management of (progressive) fibrosing ILD and on the impact of the disease on patients' quality of life (QoL) and healthcare resource utilisation (HCRU). Annual costs were calculated for progressive and non-/slow-progressive fibrosing ILD for diagnosis, follow-up management, exacerbation management, and end-of-life care based on the survey data. Results Physicians reported that progression in fibrosing ILD worsens QoL in both patients and their caregivers. Progression of fibrosing ILD was associated with a greater use of HCRU for follow-up visits and maintenance treatment compared with the non-/slow progression. Protein Tyrosine Kinase inhibitor The number of patients who suffered at least one acute exacerbation was reported to be more than three times higher in progressive fibrosing ILD patients than in patients with non-/slow-progressive fibrosing ILD. On average, annual estimated costs of progressive fibrosing ILD per patient were 1.8 times higher than those of the non-/slow-progressive form of the disease. Conclusions Progression in fibrosing ILD causes a significant impact on QoL and HCRU and costs. These survey data underline the need for safe and effective therapies to slow the disease progression.Epigenetic processes are essential for normal development and the maintenance of tissue-specific gene expression in mammals. Changes in gene expression and malignant cellular transformation can result from disruption of epigenetic mechanisms, and global disruption in the epigenetic landscape is a key feature of cancer. The study of epigenetics in cancer has revealed that human cancer cells harbor both genetic alterations and epigenetic abnormalities that interplay at all stages of cancer development. Unlike genetic mutations, epigenetic aberrations are potentially reversible through epigenetic therapy, providing a therapeutically relevant treatment option. Histone methyltransferase inhibitors are emerging as an epigenetic therapy approach with great promise in the field of clinical oncology. The recent accelerated approval of the enhancer of zeste homolog 2 (EZH2; also known as histone-lysine N-methyltransferase EZH2) inhibitor tazemetostat for metastatic or locally advanced epithelioid sarcoma marks the first approval of such a compound for the treatment of cancer. Many other histone methyltransferase inhibitors are currently in development, some of which are being tested in clinical studies. This review focuses on histone methyltransferase inhibitors, highlighting their potential in the treatment of cancer. We also discuss the role for such epigenetic drugs in overcoming epigenetically driven drug resistance mechanisms, and their value in combination with other therapeutic approaches such as immunotherapy.Introduction Etrolizumab is a next-generation anti-integrin with dual action that targets two pathways of inflammation in the gut. A robust phase 3 clinical program in ulcerative colitis (UC) and Crohn's disease is ongoing and will evaluate the efficacy and safety of etrolizumab in well-defined patient populations in rigorous trials that include direct head-to-head comparisons against approved anti-tumor necrosis factor alpha agents (anti-TNF). The etrolizumab phase 3 clinical program consists of six randomized controlled trials (RCTs; UC HIBISCUS I and II, GARDENIA, LAUREL, HICKORY; Crohn's disease BERGAMOT) and two open-label extension trials (OLEs; UC COTTONWOOD; Crohn's disease JUNIPER) evaluating patients with moderately to severely active UC or Crohn's disease. Methods In the UC RCTs, patients are randomly assigned according to each protocol to receive etrolizumab, adalimumab, infliximab, or placebo. In BERGAMOT, patients are randomly assigned to receive etrolizumab 105 mg, etrolizumab 210 mg, or placebients with varying treatment histories using an extensive repository of patient samples and data. Trial registration ClinicalTrials.gov HIBISCUS I (NCT02163759), HIBISCUS II (NCT02171429), GARDENIA (NCT02136069), LAUREL (NCT02165215), HICKORY (NCT02100696), COTTONWOOD (NCT02118584), BERGAMOT (NCT02394028), JUNIPER (NCT02403323).The Japanese encephalitis virus (JEV) is one of the vector borne causes of encephalitis found in southeastern Asia. This positive single-stranded RNA virus is a member of the Flaviviridae family, which notably includes dengue, tick-borne, West Nile, Zika as well as yellow fever, and transmits to humans by infected mosquitos. The main site of interactions for antibodies against this virus is the envelope protein domain III (ED3). link2 The present report investigates the time-dependent structural and conformational changes of JEV ED3 functional epitopes and escape mutants by computer simulations. The results indicate the presence of significant structural differences between the functional epitopes and the escape mutants. Mutation-induced structural/conformational instabilities of this type can decrease the antibody neutralization activity. Among the different escape mutants studied here, Ser40Lys/Asp41Arg appear to be most unstable, while Ser40Glu/Asp41Leu exhibit the lowest structural variations. The highest level of escape mutation observed in Ser40Lys is linked to the relatively higher values of root mean square deviation/fluctuation found in the molecular dynamics simulation of this protein. Secondary-structure deviations and depletion of H bonding are other contributing factors to the protein's increased instability. Overall, the proteins with residue 41 mutations are found to be structurally more ordered than those with residue 40 mutations. The detailed time-based structural assessment of the mutant epitopes described here may contribute to the development of novel vaccines and antiviral drugs necessary to defend against future outbreaks of JEV escape mutants.Background Preterm birth (PTB) is a major adverse pregnancy outcome and largely contributes to increasing neonatal and maternal mortality. link3 Genetic and environmental factors may play an important role in the development of PTB. Numerous studies have shown that immune genes related to the immune system, such as IL-6, IL-10, and TNFα, are associated with the occurrence of PTB. Objective We examined genetic associations between IL-6 rs1800796, IL-10 rs1800872, and TNFα rs1800630 polymorphisms and PTB in Korean women. Methods In this study, 115 PTB patients and 147 controls were analyzed. The genotyping of three SNPs was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results Our result showed that the rs1800872 polymorphism was significantly associated with the development of PTB in genotype frequency (odds ratio (OR) 1.71, 95% confidence interval (CI) 1.01-2.90, p = 0.046). We also found a significant association in an analysis of combined genotypes (rs1800796 CC, rs1800872 CA, and rs1800630 CA) (OR 7.43, 95% CI 2.06-26.84, p = 0.001). In a correlation analysis, rs1800630 A allele was significantly related with the increased birth weight (g) within PTB patients (p = 0.005). Conclusion Our results imply possible relationships between the rs1800796, rs1800872, and rs1800630 polymorphisms and the development of PTB.Background The apparent disconnection between biological complexity and both genome size (C-value) and gene number (G-value) is one of the long-standing biological puzzles. Gene-dense genomic sequences in prokaryotes or simple eukaryotes are highly constrained during selection, whereas gene-sparse genomic sequences in higher eukaryotes have low selection constraints. This review discusses the correlations of the C-value and G-value with genome architecture, polyploidy, repeatomes, introns, cell economy and phenomes. Discussion Eukaryotic chromosomes carry an assortment of various repeated DNA sequences (repeatomes). Expansion of copies of repeatomes together with polyploidization or whole-genome duplication (WGD) are major players in genome size (C-value) bloating, but genomes are equipped with counterbalancing systems such as diploidization, illegitimate recombination, and nonhomologous end joining (NHEJ) after double-strand breaks (DSBs). The lack of these efficient purging systems allowed the accumulation have been constructed. However, basic questions have not yet been fully resolved. Why have some species retained small genomes yet some closely related species have large genomes? Random genetic drift and mutational pressure might have affected for genome size in the limited population size during evolution; thus, genome size may be quasiadaptable rather than the best adaptive trait.Background Fertility is the most important economic trait in sows, as it is critical for profitability. Considerable phenotypic variation in litter size exists in Large White sows. However, relatively little is known about the underlying molecular and genetic bases. Objective An experiment was conducted to screen key genes that affect the fecundity of pigs during the luteal (L) and follicular phases (F) of the estrous cycle. Methods Eight sows (n = 4 for high fertility sows and n = 4 for low fertility sows) were sacrificed on day 14 (day 1 = first day of estrus) after estrus in the L phase. Another eight sows were slaughtered on day 20 of the estrous cycle in the F phase. Sixteen ovarian tissue samples were collected at the different sacrifice time points. Total RNA extracted was used to construct the library and then sequence on an Illumina HiSeq X10 system. Differentially expressed genes (DEGs) between high and low fertility in Large White sows were identified, and their potential biological functions were analyzed using bioinformatics analysis.