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Background: Longitudinal Measurement Invariance (LMI) is critically important to evaluate changes in alcohol expectancies over time. However, past research has not explored the longitudinal properties of the Spanish Expectancy Questionnaire Short Form (EQ-SF).Objectives: To examine the reliability, sources of validity (structural, invariance across sex, and concurrent validity), and LMI of the Spanish EQ-SF among young adults who engage in binge drinking.Methods: Participants (n = 279; 48.4% female) completed the EQ-SF and, two months later, completed it again along with measures of alcohol use, drinking motives, and protective behavioral strategies (PBS). We performed confirmatory factor analysis for structural validity and measurement invariance analysis for longitudinal and sex stability.Results: The eight-factor intercorrelated model (i.e. social facilitation, fun, sexual disinhibition, tension reduction, antisocial effects, negative emotional states, negative physical effects, and cognitive impairments) provided the best fit (χ2(df) = 497.29(224), CFI = .962, RMSEA = .064, SRMR = .049). This model was invariant across sex and time. Reliability coefficients (Ordinal alpha) for each dimension were consistently strong at both time points (from .72 to .93 at T1 and .73 to .91 at T2). Positive alcohol expectancies at baseline were positively related to alcohol use and drinking motives and negatively related to PBS at follow-up, demonstrating predictive validity.Conclusion: Our results support the temporal invariance of the EQ-SF scores among Spanish young adults who engage in binge drinking. The evidence supports the suitability of this measure for accurately assessing changes in alcohol expectancies over time in interventions aimed at preventing binge drinking in young adults.

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AIMS: This study aimed to prospectively examine the explanatory value of the protection motivation theory (PMT) for the intention to use manner of drinking protective behavioral strategies (MD PBS) and to explore its invariance across genders. METHOD: A targeted sampling procedure was used to recruit 339 young adults in the community (Mage = 21.1; SD = 2.21; female = 50.7%) who completed baseline and 2-month follow-up measures of the PMT constructs and intentions to use each of the five MD PBS. RESULTS: Regression analyses revealed that the coping appraisal components (response efficacy and self-efficacy) had greater explanatory power for the intention to use MD PBS than the threat appraisal components (perceived vulnerability and perceived severity). Perceived vulnerability to alcohol consequences was not prospectively associated with any specific behavioral intention or with the total MD PBS score. In contrast, perceived severity was prospectively associated with the intention to use three out of five PBS and the total MD score. Regression coefficients revealed gender invariance for all six models. CONCLUSIONS: Our findings suggest that interventions aimed at encouraging young adults to use alcohol MD PBS would be most effective if they included components that enhance self-efficacy in using these strategies and emphasize their perceived usefulness in reducing alcohol-related consequences.

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BACKGROUND: Gender-specific interventions are crucial in addressing substance use disorders -particularly cannabis use disorder - as they allow for tailored therapeutic approaches and increase the likelihood of successful outcomes. However, differences in therapeutic processes and outcomes between males and females are often not observed, making the prognosis and development of such interventions more difficult. OBJECTIVE: This study aimed to examine the moderating role of sex in the relationship between treatment admission profile characterized by indicators of cannabis use and sociodemographic sources of gender inequality (e.g., employment status) and adherence and outcome at discharge. METHOD: A multicentric retrospective observational study was conducted with a sample of 3,814 outpatients diagnosed with cannabis use disorder. Electronic health records were used for data analysis. RESULTS: The interaction between sex and the number of children, as well as pre-treatment cannabis use, predicted lower treatment adherence, particularly among females. Additionally, the interaction between sex and the number of children predicted outcomes at discharge, with females showing a higher likelihood of dropout compared to males. DISCUSSION AND CONCLUSION: Enhanced comprehensive treatment with intensified contingency management programs should be prioritized for females (especially those with children) who have consumed cannabis in the month before treatment. Adopting a treatment policy framework incorporating sex/gender-sensitive therapist training and evaluative measures is essential for optimizing treatment outcomes for all patients.

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p53-mediated cell cycle arrest during DNA damage is dependent on the induction of p21 protein, encoded by the CDKN1A gene. p21 inhibits cyclin-dependent kinases required for cell cycle progression to guarantee accurate repair of DNA lesions. Hence, fine-tuning of p21 levels is crucial to preserve genomic stability. Currently, the multilayered regulation of p21 levels during DNA damage is not fully understood. Herein, we identify the human RNA binding motif protein 42 (RBM42) as a regulator of p21 levels during DNA damage. Genome-wide transcriptome and interactome analysis reveals that RBM42 alters the expression of p53-regulated genes during DNA damage. Specifically, we demonstrate that RBM42 facilitates CDKN1A splicing by counteracting the splicing inhibitory effect of RBM4 protein. Unexpectedly, we also show that RBM42, underpins translation of various splicing targets, including CDKN1A. Concordantly, transcriptome-wide mapping of RBM42-RNA interactions using eCLIP further substantiates the dual function of RBM42 in regulating splicing and translation of its target genes, including CDKN1A. Collectively, our data show that RBM42 couples splicing and translation machineries to fine-tune gene expression during DNA damage response.

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Dissolved organic matter (DOM) mediated indirect photodegradation can play an important role in the degradation of aquatic contaminants. Predicting the rate of this process requires knowledge of the photochemically produced reactive intermediates (PPRI) that react with the compound of interest, as well as the ability of individual DOM samples to produce PPRI. Key PPRI are typically identified using quencher studies, yet this approach often leads to results that are difficult to interpret. In this work, we analyze the indirect photodegradation of atorvastatin, carbamazepine, sulfadiazine, and benzotriazole using a diverse set of 48 waters from natural and engineered aquatic systems. We use this large data set to evaluate relationships between PPRI formation and indirect photodegradation rate constants, which are directly compared to results using standard quenching experiments. These data demonstrate that triplet state DOM (3DOM) and singlet oxygen (1O2) are critical PPRI for atorvastatin, carbamazepine, and sulfadiazine, while hydroxyl radical (˙OH) contributes to the indirect photodegradation of benzotriazole. We caution against relying on quenching studies because quenching of 3DOM limits the formation of 1O2 and all studied quenchers react with ˙OH. Furthermore, we show that DOM composition directly influences indirect photodegradation and that low molecular weight, microbial-like DOM is positively correlated with the indirect photodegradation rates of carbamazepine, sulfadiazine, and benzotriazole.

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OBJECTIVE: To assess the level of awareness and attitude of ENT surgeons towards dental implants and oral surgery procedures that involve the maxillary sinus. METHODS: A cross-sectional survey was conducted using a closed-ended questionnaire on 40 UK-based ENT surgeons. RESULTS: Within the study population, 45 per cent of ENT surgeons were not aware of sinus lift augmentation in implant dentistry. Only 25 per cent of respondents were aware of the two subtypes of sinus lift techniques. Thirty per cent of the respondents were aware of or had heard of benign positional paroxysmal vertigo following dental treatment. Fifty-two per cent of respondents came across a dental foreign body, most commonly a tooth that had been displaced into the maxillary sinus. It was also reported that 82.5 per cent of respondents had liaised with an oral surgeon for an oroantral communication problem or a dental infection. CONCLUSION: Dental awareness among ENT surgeons needs to be raised for optimum interdisciplinary communication and patient safety.

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Background: Alcohol use and the use of social media and other forms of digital communications is characteristic of young adults. The present study prospectively examined the relationship between social drinking motives and positive urgency and the engagement in regretted online social risk behaviors while drunk (having posted on social media, called or texted someone, or been visibly drunk in a photo) among a community sample of young adults. Methods: Using a targeted sampling procedure, we accessed a baseline sample of 360 young adults aged 18-25 years old from the community. Of these, 339 (mean age: 21.1 [SD = 2.21]; female = 50.7%) completed 2-month follow-up measures. Results: Social drinking motives and the tendency to act impulsively under conditions of positive affect (i.e. positive urgency) were measured at baseline, and frequency of regretted online social risk behaviors were measured at follow-up. Results showed that baseline social drinking motives were positively associated with all three regretted online social risk behaviors examined at follow-up. Higher baseline positive urgency scores were associated with a higher frequency of regretted posting on social media and calling or texting someone while drunk at follow-up. Conclusions: Our findings support the inclusion of positive urgency and social drinking motives as key components of preventive interventions aimed at reducing potential negative consequences of using social media and other forms of digital communications while under the effects of alcohol.

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INTRODUCTION: Treatment retention and adherence are used as outcomes in numerous randomized clinical trials and observational studies conducted in the addiction field. Although usual criteria are 3/6 months of treatment retention or number of sessions attended, there is not a methodological support for conclusions using these criteria. This study analyzed the usefulness of retention and adherence to predict therapeutic success. METHODS: Retrospective observational study using real-world data from electronic health records of 11,907 patients in treatment diagnosed with cocaine, alcohol, cannabis and opiate use disorders or harmful use. RESULTS: Moderate effect size relations were found between the different type of clinical discharge and months in retention (η2  = 0.12) and proportion of attendance (η2  = 0.10). No relationship was found with the number of sessions attended. Using cut-off points (i.e., 3 or 6 months in treatment or attending 6 therapy sessions) worsens the ability to predict the type of discharge. DISCUSSIONS/CONCLUSION: Treatment retention and adherence are indicators moderately related to therapeutic success. Research using these indicators to assess the effectiveness of therapies should complement their results with other clinical indicators and quality of life measures.

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Previously, we showed that CDYL1 is recruited to DNA double-strand breaks (DSBs) to promote homologous recombination (HR) repair and foster transcriptional silencing. However, how CDYL1 elicits DSB-induced silencing is not fully understood. Here, we identify a CDYL1-dependent local decrease in the transcriptionally active marks histone lysine crotonylation (Kcr) and crotonylated lysine 9 of H3 (H3K9cr) at AsiSI-induced DSBs, which correlates with transcriptional silencing. Mechanistically, we reveal that CDYL1 crotonyl-CoA hydratase activity counteracts Kcr and H3K9cr at DSB sites, which triggers the eviction of the transcription elongation factor ENL and fosters transcriptional silencing. Furthermore, genetic inhibition of CDYL1 hydratase activity blocks the reduction in H3K9cr and alleviates DSB-induced silencing, whereas HR efficiency unexpectedly remains intact. Therefore, our results functionally uncouple the repair and silencing activity of CDYL1 at DSBs. In a broader context, we address a long-standing question concerning the functional relationship between HR repair and DSB-induced silencing, suggesting that they may occur independently.

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This systematic review identifies the psychological variables associated with the use of harm reduction strategies (HRS) among university students who use alcohol or cannabis. The reviewed studies are categorized according to the psychological variables studied and the different analytic approaches used (direct effects, mediation, and moderation). Among the empirical peer-reviewed studies identified (n = 76), most (94.7%) were cross-sectional studies conducted in the US (90.8%) with samples of alcohol-using university students (86.8%). Five categories were identified: mental health, motives/expectancies, personality, social cognition, and self-efficacy. The most studied constructs were motives, anxiety and depression, impulsivity, and social norms. Most studies conducted mediation or moderation analyses including psychological variables, HRS and alcohol outcomes. Social, enhancement and coping motives, impulsivity, and social norms of alcohol use were associated with lower use of HRS, which, in turn, was associated with a higher number of alcohol/cannabis outcomes. The results of moderation studies consistently suggest that HRS use was more protective for students with poor mental health, high impulsivity, and low self-regulation. The synthesis of evidence provided in this review could be useful for guiding future research and informing the design of interventions aimed at promoting the use of HRS among university students who use alcohol and/or cannabis.

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INTRODUCTION: Although protective behavioural strategies (PBS) have shown to be effective in minimising alcohol-related negative consequences, research on the explanatory factors of their use is very scarce. Perceived efficacy has been demonstrated to be one of the most relevant explanatory factors in the use of health-related protective behaviours. The present study prospectively examines the relationship between the perceived efficacy of PBS in reducing alcohol-related negative consequences and the use of PBS in a community-based sample of young adults. In addition, the moderating role of drinking motives in this relationship is also examined. METHODS: Prospective design with a baseline assessment and a 2-month follow up. Using a targeted sampling procedure, 339 young adults were recruited from the community [mean age: 21.1 (SD = 2.21); female = 50.7%] and completed questionnaires to measure perceived efficacy of PBS and drinking motives at baseline and PBS use at follow up. RESULTS: Perceived efficacy of PBS at baseline was positively associated with PBS use at follow up, and these relationships were weaker as social, enhancement and coping motives scores increased. DISCUSSION AND CONCLUSIONS: Our findings support the need to include the perceived efficacy of PBS to reduce alcohol-related negative consequences in future interventions aimed at promoting PBS use. Moreover, these interventions should be personalised according to the initial levels of participants' drinking motives, incorporating elements that allow for neutralising their negative effects on PBS use (e.g. training in coping skills for those with strong coping motives).

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The emergence of new primate-specific genes is an essential factor in human and primate brain development and functioning. POU2F1/Oct-1 is a transcription regulator in higher eukaryotes which is involved in the regulation of development, differentiation, stress response, and other processes. We have demonstrated that the Tigger2 transposon insertion into the POU2F1 gene which occurred in the primate lineage led to the formation of an additional exon (designated the Z-exon). Z-exon-containing primate-specific Oct-1Z transcript includes a short upstream ORF (uORF) located at its 5'-end and the main ORF encoding the Oct-1Z protein isoform (Pou2F1 isoform 3, P14859-3), which differs from other Oct-1 isoforms by its N-terminal peptide. The Oct-1Z-encoding transcript is expressed mainly in human brain cortex. Under normal conditions, the translation of the ORF coding for the Oct-1Z isoform is repressed by uORF. Under various stress conditions, uORF enables a strong increase in the translation of the Oct-1Z-encoding ORF. Increased Oct-1Z expression levels in differentiating human neuroblasts activate genes controlling stress response, neural cell differentiation, brain formation, and organogenesis. We have shown that the Oct-1Z isoform of the POU2F1/Oct-1 transcription factor is an example of a primate-specific genomic element contributing to brain development and cellular stress defense.

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OBJECTIVE: Although previous studies have shown that protective behavioral strategies (PBS) predict alcohol use and its related consequences in college students, it is not known whether a broader population of young adults also benefit from PBS use. We longitudinally examined the relationship between PBS use and alcohol-related outcomes in a community sample of young adults composed of college students and noncollege individuals. METHOD: Targeted sampling was used to access 339 young adults in the community (mean age = 21.1 [SD = 2.21], 50.7% female; 59.0% college students) who completed baseline and 2-month follow-up measures. Three types of PBS were examined: manner of drinking, stopping/limiting drinking, and serious harm reduction. Regression analyses were conducted to test the predictive utility of PBS use on alcohol-related consequences, frequency and quantity of alcohol used, and binge drinking. RESULTS: Manner of drinking strategies were the strongest predictors of decreased alcohol consumption and alcohol-related negative consequences. Baseline manner of drinking scores were negatively associated with quantity of alcohol used, binge drinking, and alcohol-related consequences at follow-up. Serious harm reduction was longitudinally related to a lower frequency of alcohol consumption, stopping/limiting drinking was not associated with any outcome, and total PBS score was associated with all study outcomes. CONCLUSIONS: Our findings could benefit health promotion by informing the design of preventive interventions for reducing alcohol use and attendant health-related negative consequences in the young adult community. These results may also be of value in extending the applicability of PBS findings to a broader alcohol-using population of young adults beyond those exclusively composed of college students.

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This review discusses the potential of major histocompatibility complex (MHC) Class II constructs as stroke therapeutics. We focus on the delivery of MHC Class II construct, DRmQ, as a safe and effective treatment for ischemic stroke. DRmQ was observed to attenuate behavioral deficits and decrease microglia activation and proinflammatory cytokines, illustrating its ability to mitigate the secondary cell death following stroke. Similar anti-neuroinflammation treatments, such as transplantation of mesenchymal stem cells and mitochondrial transfers, are briefly discussed to provide further support that sequestration of inflammation stands as a robust therapeutic target for stroke.

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BACKGROUND: Relapse in drug use constitutes a research topic on addiction that is relevant for understanding both the addictive process and its clinical implications. The objective of this study was to explore if it is possible to identify patient profiles according to their performance on cognitive tasks whilst examining the relationship between such profiles and relapse. METHODS: The sample consisted of 222 patients with dependence on cocaine and / or alcohol, of which 86 % were men. Cognitive domains related to salience, decision- making, and emotional processing were measured. RESULTS: Latent class analysis revealed three patient profiles that differ in terms of performance on cognitive tasks. Two of these profiles are clearly differentiated in terms of their execution of the impulsive decision-making task. The third patient profile, unlike the latter two, is composed of patients with severe alterations in the three domains evaluated. Analysis revealed that patients in Profile 3 are those with the highest rates of relapse in cocaine (Profile 1 = 40.3 %; Profile 2 = 35.6 %; Profile 3 = 69.2 %; Chi2 = 9.169; p < .05) and cocaine and alcohol use (Profile 1 = 55.1 %; Profile 2 = 54.1 %; Profile 3 = 80 %; Chi2 = 6.698; p < .05). CONCLUSIONS: The results support the postulates of the I-RISA model. From a clinical perspective, these findings highlight the need for a comprehensive evaluation of the cognitive domains involved in addiction.

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Crystalline rocks can produce dangerous radiation levels on the basis of their content in radioisotopes. Here, we report radiological data from 10 metamorphic and igneous rock samples collected from the crystalline basement of the Peloritani Mountains (southern Italy). In order to evaluate the radiological properties of these rocks, the gamma radiation and the radon emanation have been measured. Moreover, since some of these rocks are employed as building materials, we assess the potential hazard for population connected to their use. Gamma spectroscopy was used to measure the 226Ra, 232Th and 40K activity concentration, whereas the radon emanation was investigated by using a RAD 7 detector. The results show 226Ra, 232Th and 40K activity concentration values ranging from (17 ± 4) to (56 ± 8) Bq kg-1, (14 ± 3) to (77 ± 14) Bq kg-1 and (167 ± 84) to (1760 ± 242) Bq kg-1, respectively. Values of the annual effective dose equivalent outdoor range from 0.035 to 0.152 mSv y-1, whereas the gamma index is in the range of 0.22-0.98. The 222Rn emanation coefficient and the 222Rn surface exhalation rate vary from (0.63 ± 0.3) to (8.27 ± 1.6)% and from (0.12 ± 0.03) to (2.75 ± 0.17) Bq m-2 h-1, respectively. The indoor radon derived from the building use of these rocks induces an approximate contribution to the annual effective dose ranging from 8 to 176 µSv y-1. All the obtained results suggest that the crystalline rocks from the Peloritani Mountains are not harmful for the residential population, even though they induce annual effective doses due to terrestrial gamma radiation above the worldwide average values. Moreover, their use as building materials does not produce significant health hazards connected to the indoor radon exposure.

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PURPOSE: Conjunctival nevi in young individuals can correspond to the entity named Inflammatory Juvenile Conjunctival Nevus (IJCN), presenting clinically as a rapid growth lesion, and showing at the histopathological study an inflammatory infiltrate surrounding the lesion. All these findings can suggest a diagnosis of malignancy. Due to a case of IJCN diagnosed in our Pathology department, we realized that this entity is rarely reported in the literature and histopathological diagnostic criteria are not well defined. The aim of our study is to compare the histopathological characteristics of conjunctival nevi in patients aged thirty years or less to those in patients above 30 years, looking for the findings described in IJCN. METHODS: All the excisional specimens of resected conjunctival nevus in a tertiary hospital from 2000 to 2018 were retrieved from the Pathology department archives. Demographic data were recorded, and histopathological variables (histological type of nevus, lymphocytic infiltration, eosinophilic infiltration, presence of lymphoid follicles, stromal nevomelanocytic component, intraepithelial nevomelanocytic component, epithelial inclusions, quantity of goblet cells in epithelial inclusions, cellular atypia, mitoses and maturation of the lesion) were evaluated by three independent observers. Statistical analysis was performed comparing the two age groups. RESULTS: The study determined a significant predominance of the lymphocytic and eosinophilic infiltration in the group of patients aged thirty years or less respect to the elderly group. The percentage of stromal component of the lesion is larger in patients over thirty years compared to the younger group. There was no correlation between epithelial inclusions, maturation or cytological atypia and age groups. CONCLUSION: We found some histopathological differences in conjunctival nevi related to young age, some of them coincident with the ones described in IJCN, which histopathologically could lead to a misleading diagnosis. However, we did not find significant differences related to age in many of the described histopathological findings described in IJCN. Larger series with a greater number of cases would be of interest to characterize more precisely this lesion.

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Drosophila sechellia is a dietary specialist fruit fly that evolved from a generalist ancestor to specialize on the toxic fruit of Morinda citrifolia This species pair has been the subject of numerous studies where the goal has largely been to determine the genetic basis of adaptations associated with host specialization. Because one of the most striking features of M. citrifolia fruit is the production of toxic volatile compounds that kill insects, most genomic studies in D. sechellia to date have focused on gene expression responses to the toxic compounds in its food. In this study, we aim to identify new genes important for host specialization by profiling gene expression response to 3,4-dihydroxyphenylalanine (L-DOPA). Recent work found it to be highly abundant in M. citrifolia, critical for reproductive success of D. sechellia, and supplementation of diet with the downstream pathway product dopamine can influence toxin resistance phenotypes in related species. Here we used a combination of functional genetics and genomics techniques to identify new genes that are important for D. sechellia ecological adaptation to this new niche. We show that L-DOPA exposure can affect toxin resistance phenotypes, identify genes with plastic responses to L-DOPA exposure, and functionally test an identified candidate gene. We found that knock-down of Esterase 6 (Est6) in a heterologous species alters toxin resistance suggesting Est6 may play an important role in D. sechellia host specialization.

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Cells have evolved DNA damage response (DDR) to repair DNA lesions and thus preserving genomic stability and impeding carcinogenesis. DNA damage induction is accompanied by transient transcription repression. Here, we describe a previously unrecognized role of chromodomain Y-like (CDYL1) protein in fortifying double-strand break (DSB)-induced transcription repression and repair. We showed that CDYL1 is rapidly recruited to damaged euchromatic regions in a poly (ADP-ribose) polymerase 1 (PARP1)-dependent, but ataxia telangiectasia mutated (ATM)-independent, manner. While the C-terminal region, containing the enoyl-CoA hydratase like (ECH) domain, of CDYL1 binds to poly (ADP-ribose) (PAR) moieties and mediates CDYL1 accumulation at DNA damage sites, the chromodomain and histone H3 trimethylated on lysine 9 (H3K9me3) mark are dispensable for its recruitment. Furthermore, CDYL1 promotes the recruitment of enhancer of zeste homolog 2 (EZH2), stimulates local increase of the repressive methyl mark H3K27me3, and promotes transcription silencing at DSB sites. In addition, following DNA damage induction, CDYL1 depletion causes persistent G2/M arrest and alters H2AX and replication protein A (RPA2) phosphorylation. Remarkably, the 'traffic-light reporter' system revealed that CDYL1 mainly promotes homology-directed repair (HDR) of DSBs in vivo. Consequently, CDYL1-knockout cells display synthetic lethality with the chemotherapeutic agent, cisplatin. Altogether, our findings identify CDYL1 as a new component of the DDR and suggest that the HDR-defective 'BRCAness' phenotype of CDYL1-deficient cells could be exploited for eradicating cancer cells harboring CDYL1 mutations.

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