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The efficacy of anthracycline-based chemotherapeutics, which include doxorubicin and its structural relatives daunorubicin and idarubicin, remains almost unmatched in oncology, despite a side effect profile including cumulative dose-dependent cardiotoxicity, therapy-related malignancies and infertility. Detoxifying anthracyclines while preserving their anti-neoplastic effects is arguably a major unmet need in modern oncology, as cardiovascular complications that limit anti-cancer treatment are a leading cause of morbidity and mortality among the 17 million cancer survivors in the U.S. In this study, we examined different clinically relevant anthracycline drugs for a series of features including mode of action (chromatin and DNA damage), bio-distribution, anti-tumor efficacy and cardiotoxicity in pre-clinical models and patients. The different anthracycline drugs have surprisingly individual efficacy and toxicity profiles. In particular, aclarubicin stands out in pre-clinical models and clinical studies, as it potently kills cancer cells, lacks cardiotoxicity, and can be safely administered even after the maximum cumulative dose of either doxorubicin or idarubicin has been reached. Retrospective analysis of aclarubicin used as second-line treatment for relapsed/refractory AML patients showed survival effects similar to its use in first line, leading to a notable 23% increase in 5-year overall survival compared to other intensive chemotherapies. Considering individual anthracyclines as distinct entities unveils new treatment options, such as the identification of aclarubicin, which significantly improves the survival outcomes of AML patients while mitigating the treatment-limiting side-effects. Building upon these findings, an international multicenter Phase III prospective study is prepared, to integrate aclarubicin into the treatment of relapsed/refractory AML patients.

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African American mothers are unjustly burdened by both residential evictions and psychological distress. We quantified associations between trajectories of neighborhood evictions over time and the odds of moderate and serious psychological distress (MPD and SPD, respectively) during pregnancy among African American women. We linked publicly available data on neighborhood eviction filing and judgment rates to preconception and during-pregnancy addresses from the Life-course Influences on Fetal Environments (LIFE) Study (2009-2011; n = 808). Multinomial logistic regression-estimated odds of MPD and SPD during pregnancy that were associated with eviction filing and judgment rate trajectories incorporating preconception and during-pregnancy addresses (each categorized as low, medium, or high, with two 9-category trajectory measures). Psychological distress was measured with the Kessler Psychological Distress Scale (K6) (K6 scores 5-12 = MPD, and K6 scores ≥13 = SPD). MPD was reported in 60% of the sample and SPD in 8%. In adjusted models, higher neighborhood eviction filing and judgment rates, as compared with low/low rates, during the preconception and pregnancy periods were associated with 2- to 4-fold higher odds of both MPD and SPD during pregnancy among African American women. In future studies, researchers should identify mechanisms of these findings to inform timely community-based interventions and effective policy solutions to ensure the basic human right to housing for all. This article is part of a Special Collection on Mental Health.

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BACKGROUND: Housing instability is highly prevalent among intimate partner violence (IPV) survivors, and the coupling consequences of structural racism, sexism, classism, and the COVID-19 pandemic, may create more barriers to safe and adequate housing, specifically for Black women IPV survivors. In particular, the consequences of the COVID-19 pandemic had the potential to amplify disadvantages for Black women IPV survivors, yet very little research has acknowledged it. Therefore, the current study sought to assess the experiences of housing insecurity among Black women experiencing intimate partner violence (IPV) while navigating racism, sexism, and classism during the COVID-19 pandemic. METHODS: From January to April 2021, we conducted in-depth interviews with 50 Black women experiencing IPV in the United States. Guided by intersectionality, a hybrid thematic and interpretive phenomenological analytic approach was used to identify sociostructural factors shaping housing insecurity. RESULTS: Our findings demonstrate the various ways in which the COVID-19 pandemic shaped Black women IPV survivors' ability to obtain and sustain safe housing. We derived five themes to capture factors contributing to housing experiences: challenges with separate and unequal neighborhoods; pandemic-related economic inequalities; economic abuse limitations; and strategies to maintain housing. CONCLUSIONS: Obtaining and maintaining safe housing during the COVID-19 pandemic was difficult for Black women IPV survivors who were also navigating racism, sexism, and socioeconomic position. Interventions are needed to reduce the impact of these intersecting systems of oppression and power to facilitate the resources necessary for Black women IPV survivors to identify safe housing.

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The lysine 4 of histone H3 (H3K4) can be methylated or acetylated into four states: H3K4me1, H3K4me2, H3K4me3, or H3K4ac. Unlike H3K4 methylation, the genome-wide distribution and functional roles of H3K4ac remain unclear. To understand the relationship of acetylation with methylation at H3K4 and to explore the roles of H3K4ac in the context of chromatin, we analyzed H3K4ac across the human genome and compared it with H3K4 methylation in K562 cells. H3K4ac was positively correlated with H3K4me1/2/3 in reciprocal analysis. A decrease in H3K4ac through the mutation of the histone acetyltransferase p300 reduced H3K4me1 and H3K4me3 at the H3K4ac peaks. H3K4ac was also impaired by H3K4me depletion in the histone methyltransferase MLL3/4-mutated cells. H3K4ac peaks were enriched at enhancers in addition to the transcription start sites (TSSs) of genes. H3K4ac of TSSs and enhancers was positively correlated with mRNA and eRNA transcription. A decrease in H3K4ac reduced H3K4me3 and H3K4me1 in TSSs and enhancers, respectively, and inhibited the eviction of histone H3 from them. The mRNA transcription of highly transcribed genes was affected by the reduced H3K4ac. Interestingly, H3K4ac played a redundant role with regard to H3K27ac in eRNA transcription. These results indicate that H3K4ac serves as a marker of both active TSSs and enhancers and plays a role in histone eviction and RNA transcription by leading to H3K4me1/3.

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Evidence suggests that being evicted harms health. Largely ignored in the existing literature is the possibility that evictions exert community-level health effects, affecting evicted individuals' social networks and shaping broader community conditions. In this narrative review, we summarize evidence and lay out a theoretical model for eviction as a community health exposure, mediated through four paths: 1) shifting ecologies of infectious disease and health behaviors, 2) disruption of neighborhood social cohesion, 3) strain on social networks, and 4) increasing salience of eviction risk. We describe methods for parsing eviction's individual and contextual effects and discuss implications for causal inference. We conclude by addressing eviction's potentially multilevel consequences for policy advocacy and cost-benefit analyses.

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This study aimed to understand the relationship between home eviction and child welfare system involvement at the county level. Using administrative data, we examined associations of home eviction and eviction filing rates with child abuse and neglect (CAN) reports and foster care entries. We found one additional eviction per 100 renter-occupied homes in a county was associated with a 1.3% increase in the rate of CAN reports and a 1.6% increase in foster care entries. The association between eviction and foster care entries was strongest among Hispanic children with an 8.1% increase. Assisting parents in providing stable housing may reduce the risk of child welfare system involvement, including out-of-home child placement. Primary and secondary prevention strategies could include housing assistance, increasing access to affordable and safe housing, as well as providing economic support for families (e.g., tax credits, childcare subsidies) that reduce parental financial burden to access stable housing.

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Millions of American renter households every year are threatened with eviction, an event associated with severe negative impacts on health and economic well-being. Yet we know little about the characteristics of individuals living in these households. Here, we link 38 million eviction court cases to US Census Bureau data to show that 7.6 million people, including 2.9 million children, faced the threat of eviction each year between 2007 and 2016. Overall, adult renters living with at least one child in their home were threatened with eviction at an annual rate of 10.4%, twice that of adults without children (5.0%). We demonstrate not only that the average evicted household includes one child, but that the most common age to experience eviction in America is during childhood. We also find that previous studies have underestimated racial disparities in eviction risk: Despite making up only 18.6% of all renters, Black Americans account for 51.1% of those affected by eviction filings and 43.4% of those evicted. Roughly one in five Black Americans living in a renter household is threatened with eviction annually, while one in ten is evicted. Black-White disparities persist across levels of income and vary by state. In providing the most comprehensive description to date of the population of US renters facing eviction, our study reveals a significant undercount of individuals impacted by eviction and motivates policies designed to stabilize housing for children and families.

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IMPORTANCE: Candida albicans lives as a commensal in most healthy humans but can cause superficial skin infections to life-threatening systemic infections. C. albicans also forms biofilms on biotic and abiotic surfaces. Biofilm cells are difficult to treat and highly resistant to antifungals. A specific set of genes is differentially regulated in biofilm cells as compared to free-floating planktonic cells of C. albicans. In this study, we addressed how a variant histone H3VCTG, a previously identified negative regulator of biofilm formation, modulates gene expression changes. By providing compelling evidence, we show that biased eviction of H3VCTG nucleosomes at the promoters of biofilm-relevant genes facilitates the accessibility of both transcription activators and repressors to modulate gene expression. Our study is a comprehensive investigation of genome-wide nucleosome occupancy in both planktonic and biofilm states, which reveals transition to an open chromatin landscape during biofilm mode of growth in C. albicans, a medically relevant pathogen.

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With the growth of community partnerships with housing providers to address social determinants of health, it may be time to rethink the term "landlord." The term, landlord, may be antiquated as it originated from medieval Europe in the 9th century, denotes rank, is male, and may create further divisions between tenants and landlords. In the US, many average Americans rent their property; as data from the Internal Revenue Service and the Rental Housing Finance Survey indicate nearly 10 million Americans reported rental income in 2020 and most of them own only 1-2 rental units. This commentary argues that the term "landlord" is no longer relevant, may be counterproductive to building a culture of health across stakeholder groups, and should be replaced. Some alternative terms are suggested, including "lessor" or "rental host." Accurate and neutral terms may be useful in engaging renters and property owners in addressing housing and homelessness issues in society.

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The COVID-19 pandemic spurred an economic downturn that may have eroded population mental health, especially for renters and homeowners who experienced financial hardship and were at risk of housing loss. Using household-level data from the Census Bureau's Household Pulse Survey (n = 805,223; August 2020-August 2021) and state-level data on eviction/foreclosure bans, we estimated linear probability models with two-way fixed effects to (1) examine links between COVID-related financial hardship and anxiety/depression and (2) assess whether state eviction/foreclosure bans buffered the detrimental mental health impacts of financial hardship. Findings show that individuals who reported difficulty paying for household expenses and keeping up with rent or mortgage had increased anxiety and depression risks but that state eviction/foreclosure bans weakened these associations. Our findings underscore the importance of state policies in protecting mental health and suggest that heterogeneity in state responses may have contributed to mental health inequities during the pandemic.

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The environment of an asthmatic patient can contain numerous sources of pollutants that degrade the quality of indoor air and have major repercussions on the occurrence and control of asthma. Assessment and improvement of the quality of indoor air should be assigned a major role in pneumology and allergology consultations. Characterization of an asthmatic's environment entails a search for biological pollutants with mite allergens, mildew, and allergens resulting from the proximity of pets. It is important to evaluate the chemical pollution represented by exposure to volatile organic compounds, which are increasingly present in our lodgings. Active or second-hand smoking must in all circumstances be sought out and quantified. Assessment of the environment is mediated by several methods, of which the application depends not only on the pollutant sought out, but also on enzyme-linked immunosorbent assay (ELISA), which has an essential role in quantification of biological pollutants. Attempts at expulsion of the different indoor environment pollutants is mediated by indoor environment advisors, whose efforts are aimed at obtaining reliable evaluation and control of indoor air. Implemented as a form of tertiary prevention, their methods are conducive to improved asthma control, in adults as well as children.

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We observed a zoo-housed group of cotton-top tamarins (Saguinus oedipus) before and after a bout of severe targeted aggression directed towards two of its members. The aggression was so severe and repeated that the zoo personnel was forced to remove the two victims and the main aggressor. In the tense period that preceded removal, the tamarins showed increased aggression, a steeper and linear dominance hierarchy, and reduced post-conflict reconciliation compared to the period following removal. In contrast, affiliative interactions such as grooming and peaceful food transfers did not differ in the two periods of observations. Patterns of reciprocity also remained stable. These results highlight the flexibility of tamarin social relationships and provide useful information for managing captive colonies and improving animal welfare.

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OBJECTIVE: Examine the association between historic residential redlining and present-day racial/ethnic composition of neighborhoods, racial/ethnic differences in social determinant of health domains, and risk of home evictions and food insecurity. RESEARCH DESIGN AND METHODS: We examined data on 12,334 (for eviction sample), and 8996 (for food insecurity sample), census tracts in 213 counties across 37 states in the USA with data on exposure to historic redlining. First, we examined relationships between Home Owners' Loan Corporation (HOLC) redlining grades (A="Best", B="Still Desirable", C="Definitely Declining", D="Hazardous") and present-day racial/ethnic composition and racial/ethnic differences in social determinant of health domains of neighborhoods. Second, we examined whether historic redlining is associated with present-day home eviction rates (measured across eviction filings rates, and eviction judgment rates for 12,334 census tracts in 2018) and food insecurity (measured across low supermarket access, low supermarket access and income, low supermarket access and low car ownership for 8996 census tracts in 2019). Multivariable regression models were adjusted for census tract population, urban/rural designation, and county level fixed effects. RESULTS: Relative to areas with a historic HOLC grading of "A (Best)", areas with a "D (Hazardous)" grading had a 2.59 (95%CI=1.99-3.19; p-value<0.01) higher rate of eviction filings, and a 1.03 (95%CI=0.80-1.27; p-value<0.01) higher rate of eviction judgments. Compared to areas with a historic HOLC grading of "A (Best)", areas rated with a "D (Hazardous)" had a 16.20 (95%CI=15.02-17.79; p-value<0.01) higher rate of food insecurity based on supermarket access and income, and a 6.15 (95%CI =5.53-6.76; p-value<0.01) higher rate of food insecurity based on supermarket access and car ownership. CONCLUSIONS: Historic residential redlining is significantly associated with present-day home evictions and food insecurity, highlighting persistent associations between structural racism and present-day social determinants of health.

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BACKGROUND: Eviction during pregnancy has been shown to be associated with adverse birth outcomes. A safety net program focused on covering the costs of rent during pregnancy may aid in preventing adverse complications. OBJECTIVE: This study aimed to evaluate the cost-effectiveness of a program covering the cost of rent to prevent eviction during pregnancy. STUDY DESIGN: A cost-effectiveness model using TreeAge software was designed to evaluate the cost, effectiveness, and incremental cost-effectiveness ratio associated with eviction compared to no eviction during pregnancy. The cost of eviction from a societal perspective was compared to the annual cost of housing in the no eviction group, which was estimated by the median contract rent in the United States from 2021 national census data. Birth outcomes included preterm birth, neonatal death, and major neurodevelopmental delay. Probabilities and costs were derived from the literature. The cost-effectiveness threshold was set at $100,000/QALY. We performed univariable and multivariable sensitivity analyses to assess the robustness of the results. RESULTS: In our theoretical cohort of 30,000 pregnant individuals aged 15 to 44 years facing eviction annually, the no eviction during pregnancy strategy was associated with 1427 fewer preterm births, 47 fewer neonatal deaths, and 44 fewer cases of neurodevelopmental delay compared to eviction. At the median cost of rent in the United States, the no eviction strategy was associated with increased quality-adjusted life-years and decreased costs. Therefore, the no eviction strategy was the dominant strategy. In univariate sensitivity analysis varying the cost of housing, no eviction remained the cost-effective strategy and was cost-saving when rent was below $1016 per month. CONCLUSION: The no eviction strategy is cost-effective and reduces cases of preterm birth, neonatal death, and neurodevelopmental delay. When rent is below the median of $1016 per month, no eviction is the cost-saving strategy. These findings suggest that policies supporting social programmatic implementation for rent coverage for pregnant people at risk of eviction have the potential to be highly beneficial in reducing costs and disparities in perinatal outcomes.

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OBJECTIVE: Evictions are important social and behavioral determinants of health. Evictions are associated with a cascade of negative events that can lead to unemployment, housing insecurity/homelessness, long-term poverty, and mental health problems. In this study, we developed a natural language processing system to automatically detect eviction status from electronic health record (EHR) notes. MATERIALS AND METHODS: We first defined eviction status (eviction presence and eviction period) and then annotated eviction status in 5000 EHR notes from the Veterans Health Administration (VHA). We developed a novel model, KIRESH, that has shown to substantially outperform other state-of-the-art models such as fine-tuning pretrained language models like BioBERT and Bio_ClinicalBERT. Moreover, we designed a novel prompt to further improve the model performance by using the intrinsic connection between the 2 subtasks of eviction presence and period prediction. Finally, we used the Temperature Scaling-based Calibration on our KIRESH-Prompt method to avoid overconfidence issues arising from the imbalance dataset. RESULTS: KIRESH-Prompt substantially outperformed strong baseline models including fine-tuning the Bio_ClinicalBERT model to achieve 0.74672 MCC, 0.71153 Macro-F1, and 0.83396 Micro-F1 in predicting eviction period and 0.66827 MCC, 0.62734 Macro-F1, and 0.7863 Micro-F1 in predicting eviction presence. We also conducted additional experiments on a benchmark social determinants of health (SBDH) dataset to demonstrate the generalizability of our methods. CONCLUSION AND FUTURE WORK: KIRESH-Prompt has substantially improved eviction status classification. We plan to deploy KIRESH-Prompt to the VHA EHRs as an eviction surveillance system to help address the US Veterans' housing insecurity.

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Histone modifications regulate chromatin remodeling and gene expression in development and diseases. DOT1L, the sole histone H3K79 methyltransferase, is essential for embryonic development. Here, we report that DOT1L regulates male fertility in mouse. DOT1L associates with MLLT10 in testis. DOT1L and MLLT10 localize to the sex chromatin in meiotic and post-meiotic germ cells in an inter-dependent manner. Loss of either DOT1L or MLLT10 leads to reduced testis weight, decreased sperm count and male subfertility. H3K79me2 is abundant in elongating spermatids, which undergo the dramatic histone-to-protamine transition. Both DOT1L and MLLT10 are essential for H3K79me2 modification in germ cells. Strikingly, histones are substantially retained in epididymal sperm from either DOT1L- or MLLT10-deficient mice. These results demonstrate that H3K79 methylation promotes histone replacement during spermiogenesis.

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Cellular quiescence is an important physiological state both in unicellular and multicellular eukaryotes. Quiescent cells are halted for proliferation and stop the cell cycle at the G0 stage. Using fission yeast as a model organism, we have previously found that several subunits of a conserved chromatin remodeling complex, Ino80C (INOsitol requiring nucleosome remodeling factor), are required for survival in quiescence. Here, we demonstrate that Ino80C has a key function in the regulation of gene expression in G0 cells. We show that null mutants for two Ino80C subunits, Iec1 and Ies2, a putative subunit Arp42, a null mutant for the histone variant H2A.Z, and a null mutant for the Inositol kinase Asp1 have very similar phenotypes in quiescence. These mutants show reduced transcription genome-wide and specifically fail to activate 149 quiescence genes, of which many are localized to the subtelomeric regions. Using spike in normalized ChIP-seq experiments, we show that there is a global reduction of H2A.Z levels in quiescent wild-type cells but not in iec1∆ cells and that a subtelomeric chromosome boundary element is strongly affected by Ino80C. Based on these observations, we propose a model in which Ino80C is evicting H2A.Z from chromatin in quiescent cells, thereby inactivating the subtelomeric boundary element, leading to a reorganization of the chromosome structure and activation of genes required to survive in quiescence.

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Background: To investigate housing experiences during the COVID-19 pandemic among Black women experiencing intimate partner violence (IPV) who are also navigating racism, sexism, and classism. Methods: From January to April 2021, we conducted in-depth interviews with 50 Black women experiencing IPV in the United States. Guided by intersectionality, a hybrid thematic and interpretive phenomenological analytic approach was used to identify sociostructural factors shaping housing insecurity. Results: Our findings demonstrate the various ways in which the COVID-19 pandemic shaped Black women IPV survivors' ability to obtain and sustain safe housing. Five themes were derived to capture factors contributing to housing experiences: challenges with separate and unequal neighborhoods; pandemic-related economic inequalities; economic abuse limitations; mental toll of eviction; and strategies to maintain housing. Conclusions: Obtaining and maintaining safe housing during the COVID-19 pandemic was difficult for Black women IPV survivors who were also navigating racism, sexism, and socioeconomic position. Structural-level interventions are needed to reduce the impact of these intersecting systems of oppression and power in order to facilitate the resources necessary for Black women IPV survivors to identify safe housing.

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Studying ∼200,000 evictions filed against ∼300,000 Philadelphians from 2005 to 2021, we focus on the role of transit to court in preventing tenants from asserting their rights. In this period, nearly 40% of tenants facing eviction were ordered to leave their residences because they did not show up to contest cases against them and received a default judgment. Controlling for a variety of potential confounds at the tenant and landlord level, we find that residents of private tenancies with longer transit travel time to the courthouse were more likely to default. A 1-h increase in estimated travel time increases the probability of default by between 3.8% and 8.6% points across different model specifications. The effect holds after adjusting for direct distance to the court, unobserved landlord characteristics, and even baseline weekend travel time. However, it is absent in public housing evictions, where timing rules are significantly laxer, and during the COVID-19 pandemic, when tenants had the opportunity to be present virtually. We estimate that had all tenants been equally able to get to the court in 10 min, there would have been 4,000 to 9,000 fewer default evictions over the sample period. We replicate this commuting effect in another dataset of over 800,000 evictions from Harris County, Texas. These results open up a new way to study the physical determinants of access to justice, illustrating that the location and accessibility of a courthouse can affect individual case outcomes. We suggest that increased use of video technology in court may reduce barriers to justice.

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This study examined experiences with eviction, house foreclosures, and homelessness in a large U.S. city sample of adults with Coronavirus Disease-2019 (COVID-19). A total of 3595 adults with COVID-19 participated in an assessment of health and well-being after completing contact tracing activities. The sample had a 5.7% lifetime prevalence of eviction, 3.7% lifetime prevalence of house foreclosure, and 8.2% lifetime prevalence of homelessness. Relative importance analyses revealed drug use was the most important variable associated with any lifetime eviction, lifetime house foreclosure, lifetime homelessness, and being currently at-risk of eviction or recently evicted. Loneliness was also relatively strongly associated with any lifetime eviction or homelessness, while socioeconomic characteristics were the most importance variables associated with late mortgage payments in the past month. Treatment for addiction problems may be important for in the aftermath of the COVID-19 pandemic and adults with histories of housing instability may be particularly at risk.

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