Exploring assisted dying policies for mature minors: A cross jurisdiction comparison of the Netherlands, Belgium & Canada.

Medical Assistance in Dying (MAID) was decriminalized in Canada in 2016 for individuals 18 years or older who met eligibility criteria. Currently, individuals younger than 18 years are legally permitted to access an assisted death in the Netherlands and Belgium, but not in Canada. To-date, no work has compared factors shaping the policy processes and outcomes in these three countries.

N-glycosylation by Mgat5 imposes a targetable constraint on immune-mediated tumor clearance.

The regulated glycosylation of the proteome has widespread effects on biological processes that cancer cells can exploit. Expression of N-acetylglucosaminyltransferase V (encoded by Mgat5 or GnT-V), which catalyzes the addition of β1,6-linked N-acetylglucosamine to form complex N-glycans, has been linked to tumor growth and metastasis across tumor types. Using a panel of murine pancreatic ductal adenocarcinoma (PDAC) clonal cell lines that recapitulate the immune heterogeneity of PDAC, we found that Mgat5 is required for tumor growth in vivo but not in vitro.

A Systematic Review of Validated Measures of U.S.-Based Bystander Intervention-Related Constructs.

This review aimed to identify U.S.-based, construct-validated measures of bystander intervention.

Children as an afterthought during COVID-19: defining a child-inclusive ethical framework for pandemic policymaking.

Background: Following the SARS pandemic, jurisdictions around the world began developing ethical resource allocation frameworks for future pandemics-one such framework was developed by Thompson and colleagues. While this framework offers a solid backbone upon which decision-makers can rest assured that their work is driven by rigorous ethical processes and principles, it fails to take into account the nuanced experiences and interests of children and youth (i.e.

Re-examining medical assistance in dying for mature minors in Canada: Reflections for health leaders.

In Canada, Medical Assistance in Dying (MAiD) is legal for many Canadians based on several criteria, though minors who are deemed sufficiently capable to make medical decisions (i.e. mature minors) remain ineligible.

Can Social Media Be Used as a Community-Building and Support Tool among Jewish Women Impacted by Breast and Ovarian Cancer? An Evidence-Based Observational Report.

About 1 in 40 Ashkenazi Jewish women carry a deleterious mutation in genes, predisposing them to hereditary breast/ovarian cancer (HBOC). Thus, efforts to prevent and control HBOC in the US must include sufficient outreach and education campaigns within and across the Jewish community. Social media (SM) is utilized in public health campaigns focused on cancer, but very little is known about the efficacy of those efforts when directed toward Jewish women at risk for ("previvors") and affected by ("survivors") HBOC.

The Unspeakable Nature of Death & Dying During Childhood: A Silenced Phenomenon in Pediatric Care.

In pediatric settings, the concept of hope is frequently positioned as a fundamental aspect of care and at odds with the possibility and proximity of death. This arguably fosters silence about death and dying in childhood despite evidence indicating the benefits of open communication at the end of life. In this paper, we describe the unspeakable nature of death and dying in childhood, including its conceptual and clinical causes and dimensions, its persistence, and the associated challenges for children and youth facing critical illnesses, their families, and society.

Glutamine deprivation triggers NAGK-dependent hexosamine salvage.

Tumors frequently exhibit aberrant glycosylation, which can impact cancer progression and therapeutic responses. The hexosamine biosynthesis pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a major substrate for glycosylation in the cell. Prior studies have identified the HBP as a promising therapeutic target in pancreatic ductal adenocarcinoma (PDA).

The Ethics of Adultcentrism in the Context of COVID-19: Whose Voice Matters?

Adultcentrism is an inherent feature of the social fabrics comprising most resource-rich countries in the twenty-first century that undermines the capacities, value, and voices of young people in various ways. In the context of COVID-19, we are confronted with the question of whose voice matters and must ask: is adultcentrism ethically permissible during a pandemic? This Critical Controversy examines this question in relation to evolving concepts of childhood, children's rights, and the capacities of young people, to highlight areas of tension, future research, and potential for critical dialogue.

Pancreatic cancers suppress negative feedback of glucose transport to reprogram chromatin for metastasis.

Although metastasis is the most common cause of cancer deaths, metastasis-intrinsic dependencies remain largely uncharacterized. We previously reported that metastatic pancreatic cancers were dependent on the glucose-metabolizing enzyme phosphogluconate dehydrogenase (PGD). Surprisingly, PGD catalysis was constitutively elevated without activating mutations, suggesting a non-genetic basis for enhanced activity.

FBXW7 Triggers Degradation of KMT2D to Favor Growth of Diffuse Large B-cell Lymphoma Cells.

Mature B-cell neoplasms are the fifth most common neoplasm. Due to significant heterogeneity at the clinical and genetic levels, current therapies for these cancers fail to provide long-term cures. The clinical success of proteasome inhibition for the treatment of multiple myeloma and B-cell lymphomas has made the ubiquitin pathway an important emerging therapeutic target.

Regulation of nuclear epigenome by mitochondrial DNA heteroplasmy.

Diseases associated with mitochondrial DNA (mtDNA) mutations are highly variable in phenotype, in large part because of differences in the percentage of normal and mutant mtDNAs (heteroplasmy) present within the cell. For example, increasing heteroplasmy levels of the mtDNA tRNA nucleotide (nt) 3243A > G mutation result successively in diabetes, neuromuscular degenerative disease, and perinatal lethality. These phenotypes are associated with differences in mitochondrial function and nuclear DNA (nDNA) gene expression, which are recapitulated in cybrid cell lines with different percentages of m.

ATP-citrate lyase multimerization is required for coenzyme-A substrate binding and catalysis.

ATP-citrate lyase (ACLY) is a major source of nucleocytosolic acetyl-CoA, a fundamental building block of carbon metabolism in eukaryotes. ACLY is aberrantly regulated in many cancers, cardiovascular disease, and metabolic disorders. However, the molecular mechanisms determining ACLY activity and function are unclear.

Acetyl-CoA Metabolism Supports Multistep Pancreatic Tumorigenesis.

Pancreatic ductal adenocarcinoma (PDA) has a poor prognosis, and new strategies for prevention and treatment are urgently needed. We previously reported that histone H4 acetylation is elevated in pancreatic acinar cells harboring mutations prior to the appearance of premalignant lesions. Because acetyl-CoA abundance regulates global histone acetylation, we hypothesized that altered acetyl-CoA metabolism might contribute to metabolic or epigenetic alterations that promote tumorigenesis.

Metabolic Signaling to the Nucleus in Cancer.

Nutrient-sensing mechanisms ensure that cellular activities are coordinated with nutrient availability. Recent work has established links between metabolite pools and protein post-translational modifications, as metabolites are substrates of enzymes that add or remove modifications such as acetylation, methylation, and glycosylation. Cancer cells undergo metabolic reprogramming and exhibit metabolic plasticity that allows them to survive and proliferate within the tumor microenvironment.

ATP-Citrate Lyase Controls a Glucose-to-Acetate Metabolic Switch.

Mechanisms of metabolic flexibility enable cells to survive under stressful conditions and can thwart therapeutic responses. Acetyl-coenzyme A (CoA) plays central roles in energy production, lipid metabolism, and epigenomic modifications. Here, we show that, upon genetic deletion of Acly, the gene coding for ATP-citrate lyase (ACLY), cells remain viable and proliferate, although at an impaired rate.

Targeting ACLY sensitizes castration-resistant prostate cancer cells to AR antagonism by impinging on an ACLY-AMPK-AR feedback mechanism.

The androgen receptor (AR) plays a central role in prostate tumor growth. Inappropriate reactivation of the AR after androgen deprivation therapy promotes development of incurable castration-resistant prostate cancer (CRPC). In this study, we provide evidence that metabolic features of prostate cancer cells can be exploited to sensitize CRPC cells to AR antagonism.

Comparative metabolomics reveals endogenous ligands of DAF-12, a nuclear hormone receptor, regulating C. elegans development and lifespan.

Small-molecule ligands of nuclear hormone receptors (NHRs) govern the transcriptional regulation of metazoan development, cell differentiation, and metabolism. However, the physiological ligands of many NHRs remain poorly characterized, primarily due to lack of robust analytical techniques. Using comparative metabolomics, we identified endogenous steroids that act as ligands of the C.

Targeted metabolomics reveals a male pheromone and sex-specific ascaroside biosynthesis in Caenorhabditis elegans.

In the model organism Caenorhabditis elegans, a class of small molecule signals called ascarosides regulate development, mating, and social behaviors. Ascaroside production has been studied in the predominant sex, the hermaphrodite, but not in males, which account for less than 1% of wild-type worms grown under typical laboratory conditions. Using HPLC-MS-based targeted metabolomics, we show that males also produce ascarosides and that their ascaroside profile differs markedly from that of hermaphrodites.