Serrated polyps have been recognised in the last decade as important premalignant lesions accounting for between 15% and 30% of colorectal cancers. There is therefore a clinical need for guidance on ...how to manage these lesions; however, the evidence base is limited. A working group was commission by the British Society of Gastroenterology (BSG) Endoscopy section to review the available evidence and develop a position statement to provide clinical guidance until the evidence becomes available to support a formal guideline. The scope of the position statement was wide-ranging and included: evidence that serrated lesions have premalignant potential; detection and resection of serrated lesions; surveillance strategies after detection of serrated lesions; special situations-serrated polyposis syndrome (including surgery) and serrated lesions in colitis; education, audit and benchmarks and research questions. Statements on these issues were proposed where the evidence was deemed sufficient, and re-evaluated modified via a Delphi process until >80% agreement was reached. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool was used to assess the strength of evidence and strength of recommendation for finalised statements.
: we suggest that until further evidence on the efficacy or otherwise of surveillance are published, patients with sessile serrated lesions (SSLs) that appear associated with a higher risk of future neoplasia or colorectal cancer (SSLs ≥10 mm or serrated lesions harbouring dysplasia including traditional serrated adenomas) should be offered a one-off colonoscopic surveillance examination at 3 years (
).
Background
In the general population, individuals with minoritized sexual orientation and gender identity have a higher burden of chronic health conditions than heterosexual individuals. However, the ...extent to which sexual orientation is associated with excess burden of chronic conditions in adolescent and young adult cancer survivors (AYACS) is unknown.
Methods
Lesbian, gay, and bisexual (LGB) AYACSs, LGB individuals without a history of cancer, and heterosexual AYACSs were identified by self‐reported data from the cross‐sectional National Health Interview Survey (2013–2020). Socioeconomic factors and the prevalence of chronic health conditions were compared between groups using χ2 tests. Logistic regression methods were used to determine the odds of chronic conditions by socioeconomic factors within and between survivor and comparison groups.
Results
One hundred seventy LGB cancer survivors, 1700 LGB individuals without a history of cancer, and 1700 heterosexual cancer survivors were included. Compared with heterosexual survivors, LGB survivors were less likely to be married (p = .001) and more likely to have never been married (p < .001). LGB survivors were more likely to have incomes between 100% and 200% of the federal poverty level than LGB individuals without a history of cancer (p = .012) and heterosexual survivors (p = .021) and were less likely to report incomes >200% the federal poverty level. LGB survivors had higher odds of chronic health conditions than LGB individuals without a history of cancer (odds ratio, 2.45; p < .001) and heterosexual survivors (odds ratio, 2.16; p = .003).
Conclusions
LGB AYACSs are at increased risk of having chronic health conditions compared with both LGB individuals without a history of cancer and heterosexual AYACSs.
Adolescent and young adult cancer survivors with minoritized sexual orientations face an elevated risk of chronic health conditions compared with both sexual minority individuals without a history of cancer and heterosexual adolescent and young adult cancer survivors. To reduce health outcome disparities, addressing individual‐level barriers to care and implementing system‐wide strategies are essential for improving the well‐being of this population.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Survivors of adolescent and young adult (AYA) cancer experience significant psychological distress and encounter barriers to accessing mental health care. Few studies have investigated racial/ethnic ...disparities in psychological health outcomes among AYA survivors, and none have compared outcomes within a racially minoritized population.
National Health Interview Survey data (2010-2018) were analyzed that identified non-Hispanic Black (hereafter, Black) survivors of AYA cancer and age- and sex-matched Black noncancer controls. Sociodemographic factors, chronic health conditions, modifiable behaviors (smoking and alcohol use), and psychological outcomes were assessed with χ
tests. Logistic regression models, adjusted for survey weights, were used to evaluate the odds of psychological distress by cancer status after adjusting for covariates. Interactions between variables and cancer status were investigated.
The study included 334 Black survivors of AYA cancer and 3340 Black controls. Compared to controls, survivors were more likely to report moderate/severe distress (odds ratio OR, 1.64; p < .001), use mental health care (OR, 1.53; p = .027), report an inability to afford mental health care (OR, 3.82; p < .001), and use medication for anxiety and/or depression (OR, 2.16; p = .001). Forty-one percent of survivors reported moderate/severe distress, and only 15% used mental health care. Among survivors, ages 18-39 years (vs. 40-64 years) and current smoking (vs. never smoking) were associated with the presence of moderate/severe distress. Among survivors with distress, high poverty status was associated with reduced utilization of mental health care.
A cancer diagnosis for a Black AYA is associated with greater psychological distress within an already vulnerable population.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Purpose
Survivors of adolescent and young adult (AYA) cancer experience psychological distress and insufficient access to mental health care. Few studies have investigated racial/ethnic disparities ...in psychological health outcomes in this population. This study compared psychological distress, mental health care use, and inability to afford mental health care between Hispanic/Latino survivors of AYA cancer and Hispanic/Latino controls.
Methods
The National Health Interview Survey data (2010–2018) were analyzed to identify Hispanic/Latino survivors of AYA cancer and Hispanic/Latino age‐ and sex‐matched non‐cancer controls. Sociodemographic, chronic health, modifiable factors, and psychological outcomes were compared using chi‐square tests. Logistic regression models with survey weights were used to assess the log‐odds of psychological distress in relation to covariates, along with the cancer group. Interactions were evaluated between each variable and cancer group.
Results
The study included 370 Hispanic/Latino survivors of AYA cancer (mean time since diagnosis = 12.34 years) and 3700 Hispanic/Latino controls. Compared to controls, survivors were more likely to report moderate/severe distress (OR = 2.23, p < 0.001), use of mental health care (OR = 2.11, p < 0.001) and inability to afford mental health care (OR = 3.05, p < 0.001). Forty‐one percent of survivors reported moderate/severe distress and only 16% utilized mental health care. Among survivors, having more than two chronic health conditions and public insurance (compared to private insurance) were associated with the presence of moderate/severe distress. Among survivors experiencing moderate/severe distress, lack of insurance was associated with decreased utilization of mental health care.
Conclusions
Having cancer as an AYA may exacerbate disparities in psychological health within the Hispanic/Latino population.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Purpose
There is a growing population of survivors of adolescent and young adult (AYA) cancers (age 15–39 years at diagnosis). Studies in AYA cancer survivors have identified racial and ethnic ...disparities in long-term outcomes. To understand the extent to which a cancer diagnosis exacerbates pre-existent health disparities within a minoritized population, comparisons should be made to those of the same race or ethnicity without a cancer history.
Methods
Self-reported data from the National Health Interview Survey (2009–2018) were used to identify Hispanic AYA cancer survivors and Hispanic age- and sex-matched controls. SES factors (marital status, income, education, insurance) and prevalence of chronic health conditions were compared between groups using chi-square tests. The log-odds of chronic conditions were modeled by survey-weighted logistic regression with relation to age at survey, sex, marital status, education, family income, and cancer group (control versus cancer), together with interactions between each variable and cancer group (survivors vs. controls).
Results
Five hundred thirty-nine survivors and 5390 controls were included. Compared with controls, survivors were less likely to be married and have family income > 45 K/year, and more likely to be insured and have completed some college. Survivors had higher odds than controls of chronic health conditions (odds ratio (OR): 7.39,
p
< 0.001 for at least 1 and OR: 4.78,
p
< 0.001 for 3 or more) including cardiovascular disease, diabetes, and hypertension. Female sex, higher educational attainment, and public insurance were each associated with increased odds of chronic conditions in Hispanic AYA survivors.
Conclusions
An AYA cancer diagnosis is associated with poor SES outcomes and increased odds of comorbidities within the Hispanic population.
Implications for Cancer Survivors
Cancer history can exacerbate underlying health disparities. Screening for chronic conditions is especially important in minoritized populations.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The US population of adolescent and young adult (age 15-39 years at diagnosis) cancer survivors is growing. Previous studies have identified racial and ethnic disparities in survival and health ...outcomes in racially minoritized survivors, including Black survivors, compared with White survivors. However, comparisons should be made between those of the same race or ethnicity with and without a history of AYA cancer to fully understand the association of a cancer diagnosis with socioeconomic status (SES) and health outcomes within a minoritized population.
Non-Hispanic Black AYA cancer survivors and non-Hispanic Black age- and sex-matched controls were identified from self-reported data from the National Health Interview Survey (2009-2018). SES factors and chronic health conditions prevalence were compared between survivors and controls using chi-square tests. Survey-weighted logistic regression models were used to determine odds of chronic conditions by SES factors within and between survivors and controls. Interactions between each variable and cancer group were assessed.
A total of 445 survivors and 4450 controls were included. Survivors were less likely than controls to be married, have family income >45K/year, have completed a bachelor's degree or higher, and have private insurance. Survivors had higher odds than controls of having at least one (odds ratio (OR): 7.02, p<0.001) and ≥3 (OR: 4.44, p<0.001) chronic conditions. Survivors had higher odds of each chronic condition assessed including cardiovascular disease, diabetes, and hypertension. Survivors had higher odds of having chronic health conditions compared with controls across all SES variables.
A cancer diagnosis during adolescence and young adulthood is associated with poor SES outcomes and increased odds of comorbidities within the Black population, thus further exacerbating existing disparities.
Black AYA cancer survivors have a very high risk of developing chronic health conditions after cancer treatment and interventions are needed to improve long-term health outcomes for this population.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Genetic studies of human evolution require high-quality contiguous ape genome assemblies that are not guided by the human reference. We coupled long-read sequence assembly and full-length ...complementary DNA sequencing with a multiplatform scaffolding approach to produce ab initio chimpanzee and orangutan genome assemblies. By comparing these with two long-read de novo human genome assemblies and a gorilla genome assembly, we characterized lineage-specific and shared great ape genetic variation ranging from single- to mega-base pair-sized variants. We identified ~17,000 fixed human-specific structural variants identifying genic and putative regulatory changes that have emerged in humans since divergence from nonhuman apes. Interestingly, these variants are enriched near genes that are down-regulated in human compared to chimpanzee cerebral organoids, particularly in cells analogous to radial glial neural progenitors.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
Pharmaceutical and agrochemical discovery programs are under considerable pressure to meet increasing global demand and thus require constant innovation. Classical hydrocarbon scaffolds have long ...assisted in bringing new molecules to the market place, but an obvious omission is that of the Platonic solid cubane. Eaton, however, suggested that this molecule has the potential to act as a benzene bioisostere. Herein, we report the validation of Eaton's hypothesis with cubane derivatives of five molecules that are used clinically or as agrochemicals. Two cubane analogues showed increased bioactivity compared to their benzene counterparts whereas two further analogues displayed equal bioactivity, and the fifth one demonstrated only partial efficacy. Ramifications from this study are best realized by reflecting on the number of bioactive molecules that contain a benzene ring. Substitution with the cubane scaffold where possible could revitalize these systems, and thus expedite much needed lead candidate identification.
Over 25 years ago, Eaton proposed that cubane could act as a benzene bioisostere. This hypothesis has now been confirmed with the synthesis and evaluation of cubane derivatives of five biologically important molecules: Two cubane analogues showed increased bioactivity compared to their benzene counterparts whereas two further analogues were of equal bioactivity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The reprogramming of human somatic cells to primed or naive induced pluripotent stem cells recapitulates the stages of early embryonic development
. 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
. 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.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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