Introduction: Toward an Engaged Feminist Heritage Praxis

We advocate a feminist approach to archaeological heritage work in order to transform heritage practice and the production of archaeological knowledge. We use an engaged feminist standpoint and situate intersubjectivity and intersectionality as critical components of this practice. An engaged feminist approach to heritage work allows the discipline to consider women’s, men’s, and gender non-conforming persons’ positions in the field, to reveal their contributions, to develop critical pedagogical approaches, and to rethink forms of representation. Throughout, we emphasize the intellectual labor of women of color, queer and gender non-conforming persons, and early white feminists in archaeology

A cross comparison of technologies for the detection of microRNAs in FFPE samples from hepatoblastoma patients

MicroRNAs (miRNAs) are small non-coding RNA that regulate gene expression. Profiling miRNA patterns has provided insight into cancer. Formalin fixed paraffin embedded (FFPE) tissue is a major source of biological material, including miRNAs, in cancer research. However, analysing FFPE material can be challenging for researchers due to sample degradation and nucleic acid crosslinking. It is therefore valuable to characterise and document the quality of data that can be obtained from FPPE samples. In this study we compared the detection level of microRNAs between three independent platforms, next generation sequencing, microarray and NanoString, using FFPE samples from hepatoblastoma patients. Between 228 and 345 miRNAs were identified using the next generation sequencing platform, 79 to 125 miRNAs were identified with microarray and NanoString identified the most (135 to 411) miRNAs. Technical reproducibility was very high between the platforms. There were significant shared detection levels between the platforms, and a weak positive correlation was observed in the relative abundance level of commonly detected miRNAs between the platforms. This work highlights the advantages and disadvantages of the three miRNA detection platforms through performance comparisons. This will inform and aid the design of future studies aiming to quantify miRNA expression, and can be used as a guideline for selection of an appropriate platform

A cross comparison of technologies for the detection of microRNAs in FFPE samples from hepatoblastoma patients

MicroRNAs (miRNAs) are small non-coding RNA that regulate gene expression. Profiling miRNA patterns has provided insight into cancer. Formalin fixed paraffin embedded (FFPE) tissue is a major source of biological material, including miRNAs, in cancer research. However, analysing FFPE material can be challenging for researchers due to sample degradation and nucleic acid crosslinking. It is therefore valuable to characterise and document the quality of data that can be obtained from FPPE samples. In this study we compared the detection level of microRNAs between three independent platforms, next generation sequencing, microarray and NanoString, using FFPE samples from hepatoblastoma patients. Between 228 and 345 miRNAs were identified using the next generation sequencing platform, 79 to 125 miRNAs were identified with microarray and NanoString identified the most (135 to 411) miRNAs. Technical reproducibility was very high between the platforms. There were significant shared detection levels between the platforms, and a weak positive correlation was observed in the relative abundance level of commonly detected miRNAs between the platforms. This work highlights the advantages and disadvantages of the three miRNA detection platforms through performance comparisons. This will inform and aid the design of future studies aiming to quantify miRNA expression, and can be used as a guideline for selection of an appropriate platform

An epigenetic signature of advanced colorectal cancer metastasis

Summary: Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. The majority of CRC deaths are caused by tumor metastasis, even following treatment. There is strong evidence for epigenetic changes, such as DNA methylation, accompanying CRC metastasis and poorer patient survival. Earlier detection and a better understanding of molecular drivers for CRC metastasis are of critical clinical importance. Here, we identify a signature of advanced CRC metastasis by performing whole genome-scale DNA methylation and full transcriptome analyses of paired primary cancers and liver metastases from CRC patients. We observed striking methylation differences between primary and metastatic pairs. A subset of loci showed coordinated methylation-expression changes, suggesting these are potentially epigenetic drivers that control the expression of critical genes in the metastatic cascade. The identification of CRC epigenomic markers of metastasis has the potential to enable better outcome prediction and lead to the discovery of new therapeutic targets

Reprogramming roadmap reveals route to human induced trophoblast stem cells

The reprogramming of human somatic cells to primed or naive induced pluripotent stem cells recapitulates the stages of early embryonic development 1–6. The molecular mechanism that underpins these reprogramming processes remains largely unexplored, which impedes our understanding and limits rational improvements to reprogramming protocols. Here, to address these issues, we reconstruct molecular reprogramming trajectories of human dermal fibroblasts using single-cell transcriptomics. This revealed that reprogramming into primed and naive pluripotency follows diverging and distinct trajectories. Moreover, genome-wide analyses of accessible chromatin showed key changes in the regulatory elements of core pluripotency genes, and orchestrated global changes in chromatin accessibility over time. Integrated analysis of these datasets revealed a role for transcription factors associated with the trophectoderm lineage, and the existence of a subpopulation of cells that enter a trophectoderm-like state during reprogramming. Furthermore, this trophectoderm-like state could be captured, which enabled the derivation of induced trophoblast stem cells. Induced trophoblast stem cells are molecularly and functionally similar to trophoblast stem cells derived from human blastocysts or first-trimester placentas 7. Our results provide a high-resolution roadmap for the transcription-factor-mediated reprogramming of human somatic cells, indicate a role for the trophectoderm-lineage-specific regulatory program during this process, and facilitate the direct reprogramming of somatic cells into induced trophoblast stem cells. </p

Severe neurological outcomes after very early bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD)

© 2020, The Author(s).To test the association between bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD) and long-term clinical outcome and to identify risk factors for severe outcomes, a dataset comprising 504 patients from the international registry study ARegPKD was analyzed for characteristics and complications of patients with very early (≤ 3 months; VEBNE) and early (4–15 months; EBNE) bilateral nephrectomies. Patients with very early dialysis (VED, onset ≤ 3 months) without bilateral nephrectomies and patients with total kidney volumes (TKV) comparable to VEBNE infants served as additional control groups. We identified 19 children with VEBNE, 9 with EBNE, 12 with VED and 11 in the TKV control group. VEBNE patients suffered more frequently from severe neurological complications in comparison to all control patients. Very early bilateral nephrectomies and documentation of severe hypotensive episodes were independent risk factors for severe neurological complications. Bilateral nephrectomies within the first 3 months of life are associated with a risk of severe neurological complications later in life. Our data support a very cautious indication of very early bilateral nephrectomies in ARPKD, especially in patients with residual kidney function, and emphasize the importance of avoiding severe hypotensive episodes in this at-risk cohort

Risk Factors for Early Dialysis Dependency in Autosomal Recessive Polycystic Kidney Disease

© 2018 Elsevier Inc.Objective: To identify prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with autosomal recessive polycystic kidney disease (ARPKD) as a basis for parental counseling after prenatal and perinatal diagnosis. Study design: A dataset comprising 385 patients from the ARegPKD international registry study was analyzed for potential risk markers for dialysis during the first year of life. Results: Thirty-six out of 385 children (9.4%) commenced dialysis in the first year of life. According to multivariable Cox regression analysis, the presence of oligohydramnios or anhydramnios, prenatal kidney enlargement, a low Apgar score, and the need for postnatal breathing support were independently associated with an increased hazard ratio for requiring dialysis within the first year of life. The increased risk associated with Apgar score and perinatal assisted breathing was time-dependent and vanished after 5 and 8 months of life, respectively. The predicted probabilities for early dialysis varied from 1.5% (95% CI, 0.5%-4.1%) for patients with ARPKD with no prenatal sonographic abnormalities to 32.3% (95% CI, 22.2%-44.5%) in cases of documented oligohydramnios or anhydramnios, renal cysts, and enlarged kidneys. Conclusions: This study, which identified risk factors associated with onset of dialysis in ARPKD in the first year of life, may be helpful in prenatal parental counseling in cases of suspected ARPKD