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The mean level of urinary cadmium was 0.25 μg/g creatinine. There were significant inverse associations between smoking and total body, total hip, and trochanter BMD. The indirect effects via cadmium were estimated to be 43% of the total effects of smoking for whole body BMD, and even more for total hip and trochanter BMD. Smoking was also associated with higher risk of all fractures and major osteoporosis fractures. The indirect effects via cadmium were largest in non-vertebral osteoporosis fractures and hip fractures, constituting at least half of the total effects, in both the AFT and Aalen's model. The findings in this study provide evidence that cadmium exposure from tobacco smoke plays an important role in smoking-induced osteoporosis. This article is protected by copyright. All rights reserved. © 2020 American Society for Bone and Mineral Research.We read with great interest a recent editorial by Liang et al. on the management of COVID-19 in pregnancy. Their recommendations are clinically oriented and are likely to be useful to obstetricians and other healthcare professionals caring for such patients. However, we feel that development of evidence-based guidelines has been hindered by selective reporting of cases. We hereby would like to discuss a few additional points with regards to the challenges encountered while managing pregnant patients with COVID-19. This article is protected by copyright. All rights reserved.Inbreeding is a potent evolutionary force shaping the distribution of genetic variation within and among populations of plants and animals. Yet, our understanding of the forces shaping the expression and evolution of non-random mating in general, and inbreeding in particular, remains remarkably incomplete. Most research on plant mating systems focuses on self-fertilization and its consequences for automatic selection, inbreeding depression, purging, and reproductive assurance, whereas studies of animal mating systems have often assumed that inbreeding is rare, and that natural selection favors traits that promote outbreeding. Given that many sessile and sedentary marine invertebrates and marine macroalgae share key life-history features with seed plants (e.g., low mobility, modular construction, and the release of gametes into the environment), their mating systems may be similar. Here, we show that published estimates of inbreeding coefficients (FIS ) for sessile and sedentary marine organisms are similar and at least as high as noted in terrestrial seed plants. We also found that variation in FIS within invertebrates is related to the potential to self-fertilize, disperse, and choose mates. The similarity of FIS for these organismal groups suggests that inbreeding could play a larger role in the evolution of sessile and sedentary marine organisms than is currently recognized. Specifically, associations between traits of marine invertebrates and FIS suggest that inbreeding could drive evolutionary transitions between hermaphroditism and separate sexes, direct development and multiphasic life cycles, and external and internal fertilization. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Tertiary lymphoid structures (TLSs) provide an immunological antineoplastic effect. this website Recent evidences link a unique 12-chemokine (CCL2, -3, -4, -5, -8, -18, -19, -21, CXCL9, -10, -11, -13) signature status from tumor tissue and the TLS expression. However, the potential significance of 12-chemokine signature status for clinical use is unknown. We aimed to evaluate the association of 12-chemokine signature status with patient outcomes in colorectal cancer (CRC). We used integrated data of resected 975 CRC cases within three independent cohorts from France, Japan, and United States (GSE39582, KUMAMOTO from Kumamoto university hospital, and TCGA). The association of 12-chemokine signature status with clinicopathological features, patient outcome, TLS expression status, and key tumor molecular features was analyzed. Patients with low 12-chemokine signature status had a significant shorter relapse-free survival in discovery cohort (HR 1.61, 95% CI 1.11-2.39, P = 0.0123), which was confirmed in validation cohort (HR 3.31, 95% CI 1.33-10.08, P = 0.0087). High 12-chemokine signature status had significant associations with right-sided tumor, high tumor-localized TLS expression, BRAF mutant, CIMP-high status, and MSI-high status. Furthermore, RNA-seq based analysis showed that high 12-chemokine signature status was strongly associated with inflammation-related, immune cells-related, and apoptosis pathways (using Gene set enrichment analysis), and more tumor infiltrating immune cells, such as cytotoxic T lymphocytes and myeloid dendritic cells (using MCP-counter analysis). We investigated a promising effect of 12-chemokine signature status in CRC patients who underwent resection. Our data may be helpful in developing novel immunological treatment strategies for CRC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, that has no specific pharmacological treatments partially due to the unclear pathophysiological mechanisms. Regulators of G protein signaling (RGS) proteins are proteins that negatively regulate G protein-coupled receptor (GPCR) signaling. The member of R4/B subfamily are the smallest RGS proteins in size and RGS5 belongs to this family, which mediates pluripotent biological functions via canonical G-protein mediated pathways and non-GPCR pathways. Here, we combined genetic engineering rodent model and transcriptomics sequencing approach to investigate the role and regulatory mechanism of RGS5 in the development of NAFLD. APPROACH & RESULTS In this study, we found that RGS5 protects against NAFLD and NASH. Using RNA sequencing and an unbiased systematic investigative approach, we found that the activation of MAPK signaling cascades in response to metabolic challenge is negatively associated with hepatic RGS5 expression. Mechanistically, we found that the 64-181aa fragment of RGS5 directly interacts with TGF-β-activated kinase 1 (TAK1) via the 1 -300aa fragment and inhibits TAK1 phosphorylation and the subsequent JNK/p38 pathways activation. CONCLUSION In hepatocytes, RGS5 is an essential molecule that protects against the progression of NAFLD. RGS5 directly binds to TAK1, preventing its hyperphosphorylation and the activation of the downstream JNK/p38 signaling cascade. RGS5 is a promising target molecule for fine-tuning the activity of TAK1 and for the treatment of NAFLD. This article is protected by copyright. All rights reserved.Limited data are available pertaining to life history and population connectivity of the data deficient southern stingray (Hypanus americanus, Hildebrand & Schroeder, 1928). In order to determine potential vulnerabilities of their populations, this study aimed to analyze their movement patterns and genetic variability. A population of southern stingrays encompassing nine sites around Cape Eleuthera, The Bahamas has been monitored using mark-recapture, spanning a 2.5 year period. Out of 200 individual stingrays, more than a third were encountered again. The home range of the females appears to be very restricted, which supports the notion of high site residency. As resident populations of stingrays could suffer from a lack of population connectivity and be predestined for genetic isolation and local extirpation, this study further investigated the genetic connectivity of four sample sites in the central and western Bahamas. A haplotype analysis from the mitochondrial D-loop region showed no distinct population structure strictly correlated to sample site. These findings were complemented by five microsatellite loci that revealed high degrees in genotypic variability and little population differentiation. The results suggest gene flow mediated by both males and females. This article is protected by copyright. All rights reserved.Accumulated evidence revealed that aberrant CpG island hypermethylation plays an important role in carcinogenesis which can serve as a promising target for molecular detection in body fluids. Despite a myriad of attempts to diagnose ovarian cancer (OC) at an early stage, this clinical aim remains a major challenge. To date, no single biomarker is able to accurately detect early OC in either tissue or body fluid. Aberrant DNA methylation patterns in circulating DNA provide highly specific cancer signals. In our study, we establish a novel panel of methylation-specific genes for the development of a TaqMan based qPCR assay to quantify methylation levels. We analyzed promoter methylation of homeobox A9 (HOXA9) and hypermethylated in cancer 1 (HIC1) quantitatively in 120 tissue samples and in 70 matched serum cell-free DNA (CFDNA) of cancerous and noncancerous samples by MethyLight assay. HOXA9 and HIC1 methylation occurred in 82.3 and 80.0% of OC tissue samples in singleplex assay, thereby confirming that methylation was highly cancer-specific. When either or both gene promoter showed methylation, the sensitivity was 88.2% with a specificity of 88.6% in tissue samples. The combined sensitivity for this novel marker panel in serum CFDNA was 88.9% (area under the curve [AUC] = 0.95). In contrast, no hypermethylation was observed in serum from matched cancer-free control women. Our results confirm the elevated performance of novel epigenetic marker panel (HOXA9 and HIC1) when analyzed in tissue and matched serum samples. Our findings reveal the potential of this biomarker panel as a suitable diagnostic serum biomarker for early screening of OC. © 2020 UICC.We noted the identification of further rat hepatitis E virus (HEV) cases in humans in Hong Kong (1). This emergence, infection of a Canadian UN worker in Africa (2) and serological evidence of exposure in German foresters (3) and hospitalized Vietnamese patients (4), raises the question of how widespread rat HEV infection is globally. This article is protected by copyright. All rights reserved.The evolving coronavirus disease 2019 (COVID-19) pandemic1 is certainly cause for concern. Proper communication and optimal decision-making is an ongoing challenge, as data evolve. The challenge is compounded, however, by exaggerated information. This can lead to inappropriate actions. It is important to differentiate promptly the true epidemic from an epidemic of false claims and potentially harmful actions. This article is protected by copyright. All rights reserved.We thank Dr. C. Adlhoch and Dr. SA Baylis for their comments on our study describing the impact of rat hepatitis E virus (Orthohepevirus C genotype 1 or HEV-C1) on human health in Hong Kong. We concur with them that HEV-C1 infection is currently a blind spot in hepatitis E diagnostic testing. As they point out, routinely used molecular assays for HEV diagnostics or blood donor screening would not be able to detect HEV-C1. This article is protected by copyright. All rights reserved.BACKGROUND Motor milestones in infancy are important developmental markers, not only for later motor skills but also for more widespread social, cognitive, and communication development. The aim of the current study was to investigate the relationships between fine and gross motor development in infants at 6 and 12 months of age and communication skills at 24 months of age. METHODS The Ages & Stages Questionnaire (ASQ-II) was used to measure gross motor, fine motor, and communication skills in a large population-based sample of 1,555 infants, recruited from well-baby clinics in five municipalities in South-Eastern Norway. Of these, 557 children had valid values of gross and fine motor scores at 6 and 12 months and for communication score at 24 months. The relationships between motor skills at 6 and 12 months and communication skills at 24 months were analysed using a linear regression analysis. RESULTS Gross motor skills at 6 months were positively associated with communication skills at 24 months (coefficients 0.