Notes

Emblematic Convergence or perhaps Divergence? Producing A feeling of (the Rhetorical) Feels of a University-Wide Organizational Change.
PHGDH inhibitors administered as single-agent therapy to NOG mice harboring patient-derived MYCN-amplified neuroblastoma xenografts slowed tumor growth. However, combining a PHGDH inhibitor with the standard-of-care chemotherapy drug, cisplatin, revealed antagonism of chemotherapy efficacy in vivo. Emergence of chemotherapy resistance was confirmed in the genetic PHGDH knockout model in vitro. Altogether, PHGDH knockout or inhibition by small molecules consistently slows proliferation, but stops short of killing the cells, which then establish resistance to classical chemotherapy. Although PHGDH inhibition with small molecules has produced encouraging results in other preclinical cancer models, this approach has limited attractiveness for patients with neuroblastoma.Intratumor heterogeneity of colorectal cancers (CRCs) is manifested both at the genomic and epigenomic levels. Early genetic aberrations in carcinogenesis are clonal and present throughout the tumors, but less is known about the heterogeneity of the epigenetic CpG island methylator phenotype (CIMP). CIMP characterizes a subgroup of CRCs thought to originate from specific precursor lesions, and it is defined by widespread DNA methylation within promoter regions. In this work, we investigated CIMP in two to four multiregional samples from 30 primary tumors (n = 86 samples) using the consensus Weisenberger gene panel (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1). Twenty-nine of 30 tumors (97%) showed concordant CIMP status in all samples, and percent methylated reference (PMR) values of all five markers had higher intertumor than intratumor variation (P value = 1.5e-09). However, a third of the CIMP+ tumors exhibited discrepancies in methylation status in at least one of the five gene markers. To conclude, CIMP status was consistent within primary CRCs, and it is likely a clonal phenotype. However, spatial discordances of the individual genes suggest that large-scale analysis of multiregional samples could be of interest for identifying CIMP markers that are robust to intratumor heterogeneity.
Millions of people worldwide experience severe trauma in their lifetime. Trauma has immediate and long-term effects on emotional wellbeing. Moreover, the experiences of one generation may influence subsequent generations via social and biological pathways. Poor mental health and emotion dysregulation associated with trauma may affect parenting behaviours, which may have long-lasting effects on children's development.

We use longitudinal data from a unique sample of 732 caregivers of children aged 6-36months living in extremely poor rural households in Rwanda to examine associations of caregiver lifetime trauma, recent daily hardships, mental health, and emotion dysregulation with parenting behaviours reflecting parental acceptance and rejection of their offspring.

Cumulative trauma exposure (β=.234, p<.001) and recent daily hardships (β=.323, p<.001) are associated with higher levels of internalising symptoms. Trauma (β=.257, p<.001) and daily hardships (β=.323, p < 0.001) are also associateer trauma on mental health and child wellbeing.
Caregiver internalising and PTSD symptoms are important mechanisms through which caregiver trauma and hardship affect parenting behaviours. Emotion dysregulation is a shared mechanism linking caregivers' mental health problems with parenting behaviours that reflect acceptance and rejection of the child. Emotion regulation is indicated as a key target for prevention of adverse effects of caregiver trauma on mental health and child wellbeing.
Populations experiencing homelessness have high rates of tobacco use and experience substantial barriers to cessation. Tobacco-caused conditions are among the leading causes of morbidity and mortality among people experiencing homelessness, highlighting an urgent need for interventions to reduce the burden of tobacco use in this population.

To assess whether interventions designed to improve access to tobacco cessation interventions for adults experiencing homelessness lead to increased numbers engaging in or receiving treatment, and whether interventions designed to help adults experiencing homelessness to quit tobacco lead to increased tobacco abstinence. To also assess whether tobacco cessation interventions for adults experiencing homelessness affect substance use and mental health.

We searched the Cochrane Tobacco Addiction Group Specialized Register, MEDLINE, Embase and PsycINFO for studies using the terms un-housed*, homeless*, housing instability, smoking cessation, tobacco use disorder, smokeleining participants for long-term follow-up of at least six months. Studies should also explore interventions that increase access to cessation services, and address the social and environmental influences of tobacco use among people experiencing homelessness. Finally, studies should explore the impact of tobacco cessation on mental health and substance-use outcomes.
This study investigates obesity and comorbidity in Black and White women with early breast cancer (stages I-III) and their potential impact on treatment decisions for patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) tumors.

In this retrospective chart review, comparisons of frequencies for Black and White patients were calculated with the Fisher exact test. Log binomial regression was used to estimate prevalence ratios (PRs) with 95% confidence intervals for total and individual comorbidities, and multivariable modeling was used to estimate PRs adjusted for age and body mass index (BMI).

In a sample of 548 patients, 26% were Black, and 74% were White. Sixty-two percent of Black patients and 32% of White patients were obese (BMI ≥ 30 kg/m
; P < .0001). Seventy-five percent of Black patients and 87% of White patients had HR+ tumors (P = .001). Significant intergroup differences were seen for 2 or more total comorbidities (62% of Blacks vs 47% of ies, and it highlights the prevalence of competing risks that may complicate outcomes in breast cancer.We present demographic, clinical, laboratory characteristics and outcomes of the patients with solid malignancies and novel coronavirus disease (COVID-19) collected from the National COVID-19 Registry of Turkey. A total of 1523 patients with a current or past diagnosis of solid tumors and diagnosed with COVID-19 (confirmed with PCR) between 11 March and 20 May 2020 were included. The primary outcome was 30-day mortality. Median age was 61 (range 18-94), and 752 (49%) were male. The most common types of cancers were breast (19.8%), prostate (10.9%) and colorectal cancer (10.8%). 65% of the patients had at least one comorbidity. SR-18292 At least one COVID-19-directed therapy was given in 73% of the patients.. Hospitalization rate of the patients was 56.6% and intensive care unit admission rate was 11.4%. Seventy-seven (5.1%) patients died within 30 days of diagnosis. The first multivariate model which included only the demographic and clinical characteristics showed older age, male gender and presence of diabetes and receipt of cytotoxic therapy to be associated with increased 30-day mortality, while breast and prostate cancer diagnoses were associated with lower 30-day mortality.
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