Publications by authors named "Amy Conway"

To examine plans for postpartum cannabis use among pregnant individuals who used cannabis during early pregnancy. Eighteen virtual focus groups were conducted from November 17, 2021, to December 17, 2021, with 23 Black and 30 White pregnant adults in Kaiser Permanente Northern California, who self-reported prenatal cannabis use during early pregnancy. Focus groups were recorded, transcribed, and analyzed using thematic analysis.

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Objective: This study aimed to assess agreement between self-report and urine toxicology measures assessing use of 2 illicit simulants (methamphetamine and cocaine) during early pregnancy.

Methods: This cross-sectional study of 203,053 pregnancies from 169,709 individuals receiving prenatal care at Kaiser Permanente Northern California between January 1, 2011, and December 31, 2019, assessed agreement ( κ , sensitivity, and specificity) between self-reported frequency and urine toxicology measures of methamphetamine and cocaine early in pregnancy.

Results: Prenatal use of the illicit stimulants was rare according to toxicology (n = 244 [0.

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Objective: To understand pregnant patients' reasons for prenatal cannabis use and perceptions of safety, desired and undesirable health care experiences, and desired information about prenatal cannabis use and secondarily to understand racial differences in these perceptions and preferences.

Methods: We conducted a qualitative study including 18 semi-structured, race-concordant virtual focus groups with pregnant individuals who self-reported cannabis use at prenatal care entry in a large integrated health care system in Northern California from November 2021 to December 2021. The focus groups included semi-structured questions that were recorded, transcribed, and coded by the research team.

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Objectives: The aims of the study are to identify patterns of early pregnancy substance use and to examine how these patterns relate to behavioral health conditions measured in early pregnancy.

Methods: We conducted a retrospective observational study (N= 265,274 pregnancies) screened for alcohol, cannabis, nicotine, pharmaceutical opioids, and stimulants during the first trimester via self-report and urine toxicology tests in Kaiser Permanente Northern California from January 1, 2012, to December 31, 2019. To identify patterns of prenatal substance use, we conducted latent class analysis.

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Introduction: Quantitative studies indicate that the COVID-19 pandemic has contributed to increased rates of prenatal cannabis use. However, little is known about how the pandemic has impacted cannabis use from the perspective of pregnant individuals themselves. Our objective was to characterize COVID-19-related changes in cannabis use among pregnant individuals who used cannabis during the pandemic.

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Transcription factors (TFs) are frequently mutated in cancer. Paediatric cancers exhibit few mutations genome-wide but frequently harbour sentinel mutations that affect TFs, which provides a context to precisely study the transcriptional circuits that support mutant TF-driven oncogenesis. A broadly relevant mechanism that has garnered intense focus involves the ability of mutant TFs to hijack wild-type lineage-specific TFs in self-reinforcing transcriptional circuits.

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Importance: As rates of prenatal cannabis use increase and cannabis legalization spreads across the US, studies are needed to understand the potential impacts of legalization from the perspectives of pregnant individuals who use cannabis.

Objective: To characterize pregnant individuals' perspectives on legalization of cannabis for adult use in California (effective in 2018) in relation to prenatal cannabis use behaviors and beliefs.

Design, Setting, And Participants: This qualitative study was conducted in Kaiser Permanente Northern California, a large health care system with universal screening for self-reported cannabis use at entrance to prenatal care.

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Importance: Prenatal cannabis use is associated with health risks for mothers and their children. Prior research suggests that rates of prenatal cannabis use in Northern California increased during the COVID-19 pandemic, but it is unknown whether increases varied with the local cannabis retail and policy environment.

Objective: To test whether pandemic-related increases in prenatal cannabis use were greater among pregnant individuals with greater retail availability of cannabis around their homes or among those living in jurisdictions that allowed storefront retailers.

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Unlabelled: Aberrant RAS/MAPK signaling is a common driver of oncogenesis that can be therapeutically targeted with clinically approved MEK inhibitors. Disease progression on single-agent MEK inhibitors is common, however, and combination therapies are typically required to achieve significant clinical benefit in advanced cancers. Here we focused on identifying MEK inhibitor-based combination therapies in neuroblastoma with mutations that activate the RAS/MAPK signaling pathway, which are rare at diagnosis but frequent in relapsed neuroblastoma.

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Unlabelled: Diffuse midline gliomas are uniformly fatal pediatric central nervous system cancers that are refractory to standard-of-care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape.

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Background And Aims: Cannabis use is increasingly common among pregnant individuals and might be a risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to test whether prenatal cannabis use is associated with increased risk of SARS-CoV-2 infection during pregnancy.

Design: This is a retrospective cohort study.

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Article Synopsis
  • Anti-GD2 antibody immunotherapy has improved outcomes for high-risk neuroblastoma in children, but nearly 50% of patients still relapse, highlighting a need to understand resistance mechanisms.
  • Research shows that lower GD2 expression is linked to a mesenchymal cell state in neuroblastoma, leading to decreased sensitivity to anti-GD2 therapy due to reduced expression of the enzyme ST8SIA1, which is crucial for GD2 synthesis.
  • Targeting the EZH2 enzyme with pharmacological inhibitors can restore GD2 expression and re-sensitize mesenchymal neuroblastoma cells to anti-GD2 therapy, suggesting a potential combined treatment strategy to improve patient outcomes.
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Importance: Rates of prenatal cannabis use are increasing alongside perceptions that cannabis is a harmless therapeutic for pregnancy-related ailments, while rates of prenatal use of alcohol and tobacco are decreasing. It is important to examine whether cannabis use during pregnancy is increasing similarly among patients with and patients without co-occurring substance use.

Objectives: To examine trends in cannabis polysubstance use during pregnancy and to test differences in cannabis use over time among pregnant individuals who use only cannabis vs those who use cannabis and other substances.

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Article Synopsis
  • Leukemic blasts are bad immune cells that are not working correctly and can cause leukemia, a type of blood cancer.
  • Researchers found that a protein called IRF2BP2 is really important for these bad cells to survive because it helps control inflammation in the body.
  • If they mess with IRF2BP2, the leukemia cells start to die because it causes inflammation that they can't handle.
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Cannabis use among individuals before and during pregnancy is increasing alongside the proliferation of new products with various modes of administration. Preconception cannabis use is a strong predictor of prenatal cannabis use. Yet little is known about how individuals administer cannabis during the preconception period, particularly in socioeconomically vulnerable populations.

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Article Synopsis
  • Gene expression regulation in neuroblastoma is primarily influenced by the histone acetyltransferase EP300, while CBP plays a minimal role, especially in high-risk cases.
  • A novel compound, JQAD1, was developed to target and degrade EP300, leading to decreased enhancer acetylation and increased apoptosis of neuroblastoma cells.
  • JQAD1 shows limited toxicity to normal cells and its effectiveness is dependent on the expression of cereblon (CRBN) in neuroblastoma cells.
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Improved control of Plasmodium vivax malaria can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of patients. We screened several compound libraries against P. vivax liver stages, including 1565 compounds against mature hypnozoites, resulting in one drug-like and several probe-like hits useful for investigating hypnozoite biology.

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CRISPR-Cas9-based genetic screens have successfully identified cell type-dependent liabilities in cancer, including acute myeloid leukemia (AML), a devastating hematologic malignancy with poor overall survival. Because most of these screens have been performed using established cell lines, evaluating the physiologic relevance of these targets is critical. We have established a CRISPR screening approach using orthotopic xenograft models to validate and prioritize AML-enriched dependencies , including in CRISPR-competent AML patient-derived xenograft (PDX) models tractable for genome editing.

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Article Synopsis
  • T-cell acute lymphoblastic leukemia (T-ALL) has limited treatment options, especially for patients with relapsed or refractory disease, prompting research into specific metabolic pathway dependencies for therapy development.
  • A CRISPR-Cas9 screen identified the one-carbon folate, purine, and pyrimidine pathways as crucial for T-ALL cell proliferation, with the use of an inhibitor, RZ-2994, showing differential sensitivity among T-ALL cell lines and inducing cell cycle arrest.
  • The research indicates that targeting SHMT1 and SHMT2 through RZ-2994 not only impairs growth and progression of T-ALL but also shows promise in overcoming drug resistance, emphasizing the need for further exploration of SH
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Fusion-transcription factors (fusion-TFs) represent a class of driver oncoproteins that are difficult to therapeutically target. Recently, protein degradation has emerged as a strategy to target these challenging oncoproteins. The mechanisms that regulate fusion-TF stability, however, are generally unknown.

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The core cohesin subunit STAG2 is recurrently mutated in Ewing sarcoma but its biological role is less clear. Here, we demonstrate that cohesin complexes containing STAG2 occupy enhancer and polycomb repressive complex (PRC2)-marked regulatory regions. Genetic suppression of STAG2 leads to a compensatory increase in cohesin-STAG1 complexes, but not in enhancer-rich regions, and results in reprogramming of cis-chromatin interactions.

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Article Synopsis
  • * The study identifies NXT1 as a selective and rapidly lethal target in neuroblastoma, showing that it forms a crucial component of mRNA export alongside NXF1.
  • * A novel mechanism of synthetic lethality is proposed between NXT1 and NXT2, suggesting a therapeutic strategy to selectively eliminate NXF1 in tumor cells while minimizing toxicity to normal cells.
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  • Cancer cells adapt to stress, creating weaknesses that can be targeted; a study found that VCP, a stress-related protein, is particularly vulnerable in acute myeloid leukemia (AML).
  • The research showed that AML is the most sensitive cancer type to VCP inhibition, validated through various models and techniques.
  • A new VCP inhibitor, CB-5339, was developed and shown to effectively work with DNA-damaging drugs like anthracyclines, supporting its potential for clinical testing in AML treatment.
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Objectives: The goal of this study was to evaluate the association between pregnancy intentions and substance use in early pregnancy among pregnant women receiving prenatal care in a large, integrated healthcare system.

Methods: The sample comprised 29,787 Kaiser Permanente Northern California pregnant women (12.1% aged <25, 36.

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