Music training is related to late ERP modulation and enhanced performance during Simon task but not Stroop task.

Increasing evidence suggests that music training correlates with better performance in tasks measuring executive function components including inhibitory control, working memory and selective attention. The Stroop and Simon tasks measure responses to congruent and incongruent information reflecting cognitive conflict resolution. However, there are more reports of a music-training advantage in the Simon than the Stroop task. Reports indicate that these tasks may differ in the timing of conflict resolution: the Stroop task might involve early sensory stage conflict resolution, while the Simon task may do so at a later motor output planning stage. We hypothesize that musical experience relates to conflict resolution at the late motor output stage rather than the early sensory stage. Behavioral responses, and event-related potentials (ERP) were measured in participants with varying musical experience during these tasks. It was hypothesized that musical experience correlates with better performance in the Simon but not the Stroop task, reflected in ERP components in the later stage of motor output processing in the Simon task. Participants were classified into high- and low-music training groups based on the Goldsmith Musical Sophistication Index. Electrical brain activity was recorded while they completed visual Stroop and Simon tasks. The high-music training group outperformed the low-music training group on the Simon, but not the Stroop task. Mean amplitude difference (incongruent-congruent trials) was greater for the high-music training group at N100 for midline central (Cz) and posterior (Pz) sites in the Simon task and midline central (Cz) and frontal (Fz) sites in the Stroop task, and at N450 at Cz and Pz in the Simon task. N450 difference peaks occurred earlier in the high-music training group at Pz. Differences between the groups at N100 indicate that music training may be related to better sensory discrimination. These differences were not related to better behavioral performance. Differences in N450 responses between the groups, particularly in regions encompassing the motor and parietal cortices, suggest a role of music training in action selection during response conflict situations. Overall, this supports the hypothesis that music training selectively enhances cognitive conflict resolution during late motor output planning stages.

Pancreas preserving duodenectomy (PPrD).

BACKGROUND: Pancreaticoduodenectomy has been the standard of care for managing duodenal neoplasms, but recent studies show similar overall and disease-specific survival after pancreas-preserving duodenectomy (PPrD) with potentially less morbidity. METHODS: Retrospective cohort of all adult (age >18) patients who underwent PPrD with curative intent of a neoplasm in or invading into the duodenum at our institution from 2011 to 2022 (n â€‹= â€‹29), excluding tumors involving the Ampulla of Vater or the pancreas. Statistical analyses were performed using STATA. RESULTS: R0 resection was achieved in 93 â€‹% patients. Ten (34.4 â€‹%) experienced postoperative complications (13.7 â€‹% within Clavien-Dindo III-V). PPrD patients had lower rates of pancreatic leak, delayed gastric emptying, and deep surgical site infection. CONCLUSIONS: In this case series, we demonstrate PPrD is safe and effective, with a high rate of complete resection and lower complication rate than that seen in pancreaticoduodenectomy.

What have adolescents in Rio de Janeiro city, Brazil, done to reduce their community violence exposure? / O que os adolescentes do município do Rio de Janeiro, Brasil, têm feito para reduzir sua exposição à violência comunitária?

This study aims to identify the individual community strategies to avoid violence exposure most used by adolescents from public and private schools in the IX Administrative Region of Rio de Janeiro and investigate the profile of co-occurrence and its prevalence in specific population subgroups. This is a cross-sectional study with 693 individuals. A multidimensional questionnaire collected information regarding strategies to avoid community violence exposure and was self-completed in the classroom. The most used strategies were avoiding walking close to armed people (55.5%), avoiding walking alone (30.5%), and avoiding returning home at dawn (24.7%). Girls adopt more of all (concurrently) the four limiting behaviors to reduce their community violence exposure (53% vs. 32%). Notably, the adoption of such strategies differed by socioeconomic indicators and was higher among adolescents from lower-income households. These findings point to the high frequency of use of such strategies by adolescents, which may hinder and limit the full development of their social and cultural skills.

O objetivo do estudo é conhecer as estratégias individuais mais utilizadas por adolescentes de escolas públicas e privadas da IX Região Administrativa do município do Rio de Janeiro para evitar a exposição à violência comunitária, bem como investigar o perfil de coocorrência e sua prevalência em subgrupos populacionais específicos. Trata-se de um estudo seccional com 693 indivíduos. As informações referentes às estratégias para evitar a exposição à violência comunitária foram coletadas por meio de questionário multidimensional autopreenchido em sala de aula. As estratégias mais utilizadas foram: evitar passar onde há pessoas armadas (55,5%), evitar andar sozinho (30,5%) e evitar voltar para casa de madrugada (24,7%). Observou-se que as meninas adotam mais todos (concomitantemente) os quatro tipos de comportamento limitantes para reduzir sua exposição à violência comunitária (53% vs. 32%). Ressalta-se que a adoção de tais estratégias diferiu segundo os indicadores socioeconômicos, sendo maior entre os adolescentes oriundos de família de estratos de renda mais baixos. Tais achados chamam a atenção para a alta frequência de utilização de tais estratégias por adolescentes, o que pode cercear e limitar o pleno desenvolvimento de suas habilidades sociais e culturais.

O que os adolescentes do município do Rio de Janeiro, Brasil, têm feito para reduzir sua exposição à violência comunitária? / What have adolescents in Rio de Janeiro city, Brazil, done to reduce their community violence exposure?

Resumo O objetivo do estudo é conhecer as estratégias individuais mais utilizadas por adolescentes de escolas públicas e privadas da IX Região Administrativa do município do Rio de Janeiro para evitar a exposição à violência comunitária, bem como investigar o perfil de coocorrência e sua prevalência em subgrupos populacionais específicos. Trata-se de um estudo seccional com 693 indivíduos. As informações referentes às estratégias para evitar a exposição à violência comunitária foram coletadas por meio de questionário multidimensional autopreenchido em sala de aula. As estratégias mais utilizadas foram: evitar passar onde há pessoas armadas (55,5%), evitar andar sozinho (30,5%) e evitar voltar para casa de madrugada (24,7%). Observou-se que as meninas adotam mais todos (concomitantemente) os quatro tipos de comportamento limitantes para reduzir sua exposição à violência comunitária (53% vs. 32%). Ressalta-se que a adoção de tais estratégias diferiu segundo os indicadores socioeconômicos, sendo maior entre os adolescentes oriundos de família de estratos de renda mais baixos. Tais achados chamam a atenção para a alta frequência de utilização de tais estratégias por adolescentes, o que pode cercear e limitar o pleno desenvolvimento de suas habilidades sociais e culturais.

Abstract This study aims to identify the individual community strategies to avoid violence exposure most used by adolescents from public and private schools in the IX Administrative Region of Rio de Janeiro and investigate the profile of co-occurrence and its prevalence in specific population subgroups. This is a cross-sectional study with 693 individuals. A multidimensional questionnaire collected information regarding strategies to avoid community violence exposure and was self-completed in the classroom. The most used strategies were avoiding walking close to armed people (55.5%), avoiding walking alone (30.5%), and avoiding returning home at dawn (24.7%). Girls adopt more of all (concurrently) the four limiting behaviors to reduce their community violence exposure (53% vs. 32%). Notably, the adoption of such strategies differed by socioeconomic indicators and was higher among adolescents from lower-income households. These findings point to the high frequency of use of such strategies by adolescents, which may hinder and limit the full development of their social and cultural skills.

Well-dispersed titanium dioxide and silver nanoparticles on external and internal surfaces of asymmetric alumina hollow fibers for enhanced chromium (VI) photoreductions.

Heterogenous photocatalysis is a suitable alternative for wastewater treatment. The supporting of the solid catalyst in a porous material is suggested to facilitate catalyst recovery and reuse. Here we propose for the first time the evaluation of supporting silver (Ag)-decorated titanium dioxide (TiO2) catalysts on internal and external surfaces of alumina hollow fibers with asymmetric pore size distribution. The produced catalysts were considered for Cr(VI) photoreductions. The ultrasound-assisted process potentialized the distribution of Ag nanoparticles on the TiO2 surface. The loading of Ag nanoparticles at concentrations greater than 5 wt% was necessary to improve the TiO2 activity for Cr(VI) photoreduction. The loading of Ag nanoparticles at 30 wt% improved the Cr(VI) photoreduction of the single TiO2 catalyst from 40.49 ± 0.98 to 55.00 ± 0.83% after 180 min of reaction. Suspended and supported Ag-decorated TiO2 catalysts achieved total Cr(VI) photoreduction after 21 h of reaction. The adjusted reaction rate constant with the externally supported Ag-TiO2 catalyst was 3.57 × 10-3 ± 0.18 × 10-3 min-1. Similar reaction rate constants were achieved with suspended and internally supported catalysts (approximately 2.70 × 10-3 min-1). After 10 sequential reuses, all catalysts presented similar Cr(VI) photoreductions of approximately 66%. Nevertheless, the use of the externally supported catalyst is suggested for Cr(VI) photoreductions due to its superior catalyst activity at least in the first reuse cycles.

Senataxin and RNase H2 act redundantly to suppress genome instability during class switch recombination.

Class switch recombination generates distinct antibody isotypes critical to a robust adaptive immune system, and defects are associated with autoimmune disorders and lymphomagenesis. Transcription is required during class switch recombination to recruit the cytidine deaminase AID-an essential step for the formation of DNA double-strand breaks-and strongly induces the formation of R loops within the immunoglobulin heavy-chain locus. However, the impact of R loops on double-strand break formation and repair during class switch recombination remains unclear. Here, we report that cells lacking two enzymes involved in R loop removal-senataxin and RNase H2-exhibit increased R loop formation and genome instability at the immunoglobulin heavy-chain locus without impacting its transcriptional activity, AID recruitment, or class switch recombination efficiency. Senataxin and RNase H2-deficient cells also exhibit increased insertion mutations at switch junctions, a hallmark of alternative end joining. Importantly, these phenotypes were not observed in cells lacking senataxin or RNase H2B alone. We propose that senataxin acts redundantly with RNase H2 to mediate timely R loop removal, promoting efficient repair while suppressing AID-dependent genome instability and insertional mutagenesis.

The immune system is a complex network of cells and molecules, which helps to protect the body from invaders. The adaptive immune system can recognise millions of assailants, kill them, and 'learn' from this experience to mount an even quicker defence the next time the body is infected. To achieve this level of protection, specific immune cells, called B cells, divide when they come into contact with a molecule from a foreign particle, the antigen. The cloned B cells then produce millions of protective proteins, the antibodies, which patrol the blood stream and tag harmful particles for destruction. An antibody resembles a Y-shaped structure that contains a 'variable' region, which gives it the specificity to interact with an antigen, and a 'constant' region, which interacts with components of the immune system and determines the mechanisms used to destroy a pathogen. Based on the constant region, antibodies can be divided into five main classes. B cells are able to switch their production from one antibody class to another in an event known as class switch recombination, by making changes to the constant region. They do this by cutting out a portion of the genes for the constant region from their DNA and fusing the remaining DNA. The resulting antibodies still recognise the same target, but interact with different components of the immune system, ensuring that all the body's forces are mobilised. R-loops are temporary structures that form when a cell 'reads' the instructions in its DNA to make proteins. R-loops provide physical support by anchoring the transcription template to the DNA. They help control the activity of genes, but if they stay on the DNA for too long they could interfere with any form of. DNA repair ­ including the cutting and fusing mechanisms during class switch recombination. To find out more about this process, Zhao et al. used B-cells from mice lacking two specific proteins that usually help to remove R-loops. Without these proteins, the B cells generated more R-loops than normal. Nevertheless, the B-cells were able to undergo class switch recombination, even though their chromosomes showed large areas of DNA damage, and DNA sections that had been repaired contained several mistakes. Errors that occur during class switch recombination have been linked to immune disorders and B cell cancers. The study of Zhao et al. shows that even if R-loops do not affect some processes in B cells, they could still impact the overall health of their DNA. A next step would be to test if an inability to remove R-loops could indeed play a role in immune disorders and B-cell cancers.

Neighborhood Characteristics Associated with Running in Metro Vancouver: A Preliminary Analysis.

Running can improve physical health and psychological wellbeing. However, the characteristics of conducive running environments are relatively unknown. This study determines neighborhood factors that attract running and explores how age and gender mediate built environment preferences. Spatial patterns of runners in Metro Vancouver were identified using crowdsourced fitness data from Strava, a popular application for tracking physical activities. The influence of socio-economic status (SES), green and/or blue space, and urbanicity on route popularity was assessed using a Generalized Linear Model (GLM). The influence of these neighborhood variables was also calculated for runners by age and gender. The results show high neighborhood SES, the presence of green and/or blue space, and high population density are associated with increased running activities in all age and gender groups. This study contributes a novel approach to understanding conducive running environments by demonstrating the utility of crowdsourced data in combination with data about urban environments. The patterns of this large group of runners can be used to inform planning for cities that promote running, as well as seek to encourage equal participation among different ages and genders.

Visual disorders and mal de debarquement syndrome: a potential comorbidity questionnaire-based study.

Aim: Mal de debarquement syndrome (MdDS) is a neurological condition characterized by a constant sensation of self-motion; onset may be motion-triggered (MT) or non-motion-triggered/spontaneous (NMT/SO). People with MdDS experience similar symptoms to those with vertical heterophoria, a subset of binocular visual dysfunction. Hence, we aimed to explore potential visual symptom overlaps. Methods: MdDS patients (n = 196) and controls (n = 197) completed a visual health questionnaire. Results: Compared with controls, the MdDS group demonstrated higher visual disorder scores and visual complaints. NMT/SO participants reported unique visual symptoms and a higher prevalence of mild traumatic brain injury. Conclusion: Our findings suggest visual disorders may coexist with MdDS, particularly the NMT/SO subtype. The difference in visual dysfunction frequency and medical histories between subtypes, warrants further investigation into differing pathophysiological mechanisms.

Light Emitting Diode Photobiomodulation Enhances Oxidative Redox Capacity in Murine Macrophages Stimulated with Bothrops jararacussu Venom and Isolated PLA2s.

Photobiomodulation therapy associated with conventional antivenom treatment has been shown to be effective in reducing the local effects caused by bothropic venoms in preclinical studies. In this study, we analyzed the influence of photobiomodulation using light emitting diode (LED) on the oxidative stress produced by murine macrophages stimulated with Bothrops jararacussu venom and it isolated toxins BthTX-I and BthTX-II. Under LED treatment, we evaluated the activity of the antioxidant enzymes catalase, superoxide dismutase, and peroxidase as well as the release of hydrogen peroxide and the enzyme lactate dehydrogenase. To investigate whether NADPH oxidase complex activation and mitochondrial pathways could contribute to hydrogen peroxide production by macrophages, we tested the effect of two selective inhibitors, apocynin and CCCP3, respectively. Our results showed that LED therapy was able to decrease the production of hydrogen peroxide and the liberation of lactate dehydrogenase, indicating less cell damage. In addition, the antioxidant enzymes catalase, superoxide dismutase, and peroxidase increased in response to LED treatment. The effect of LED treatment on macrophages was inhibited by CCCP3, but not by apocynin. These findings show that LED photobiomodulation treatment protects macrophages, at least in part, by reducing oxidative stress caused B. jararacussu venom and toxins.

Quality-controlled R-loop meta-analysis reveals the characteristics of R-loop consensus regions.

R-loops are three-stranded nucleic acid structures formed from the hybridization of RNA and DNA. While the pathological consequences of R-loops have been well-studied to date, the locations, classes, and dynamics of physiological R-loops remain poorly understood. R-loop mapping studies provide insight into R-loop dynamics, but their findings are challenging to generalize. This is due to the narrow biological scope of individual studies, the limitations of each mapping modality, and, in some cases, poor data quality. In this study, we reprocessed 810 R-loop mapping datasets from a wide array of biological conditions and mapping modalities. From this data resource, we developed an accurate R-loop data quality control method, and we reveal the extent of poor-quality data within previously published studies. We then identified a set of high-confidence R-loop mapping samples and used them to define consensus R-loop sites called 'R-loop regions' (RL regions). In the process, we identified a stark divergence between RL regions detected by S9.6 and dRNH-based mapping methods, particularly with respect to R-loop size, location, and colocalization with RNA binding factors. Taken together, this work provides a much-needed method to assess R-loop data quality and offers novel context regarding the differences between dRNH- and S9.6-based R-loop mapping approaches.

The IMPACT Act of 2014: Standardizing patient assessment data to support care coordination, quality outcomes, and interoperability.

The Improving Medicare Post-Acute Care Transformation Act of 2014 (IMPACT Act) addressed the need for uniform, clinical, and demographic data in post-acute care (PAC) settings. Structured, uniform data enables potential interoperable data exchange, quality comparisons across PAC provider types, and the capacity to explore a Medicare unified PAC payment system. Standardized patient assessment data elements were developed for clinical domains such as cognitive function and mental status, special services, treatments, and interventions, and medical conditions and comorbidities to create a common language that can be used to bolster a patient's needs and goals to improve clinical outcomes. Clinical care, decision making, and care planning were at the center of all decisions made to standardize specific data elements. In addition, all standardized data were mapped to nationally accepted vocabulary standards to support electronic health information exchange. The standardized patient assessment data elements present the foundation for uniform language across the PAC continuum to promote a greater quality of care for every patient.

An Exploratory Spatiotemporal Analysis of Socio-Environmental Patterns in Severe Maternal Morbidity.

OBJECTIVES: Severe Maternal Morbidity (SMM) is a group of pregnancy complications in which a woman nearly dies. Despite its increasing prevalence, little research has evaluated geographic patterns of SMM and the underlying social determinants that influence excess risk. This study examined the spatial clustering of SMM across South Carolina, US, and its associations with place-based social and environmental factors. METHODS: Hospitalized deliveries from 2012 to 2017 were analyzed using Kulldorff's spatial scan statistic to locate areas with abnormally high rates of SMM. SMM patients inside and outside risk clusters were compared using Generalized Estimating Equations (GEE) to determine underlying individual and community-level risk factors. RESULTS: GEE models revealed that the odds of living in a high-risk SMM21 (SMM including blood transfusions) cluster was 2.49 times higher among Black patients (p < .001) compared to those outside of a high-risk cluster. Women residing in a high-risk SMM20 (SMM excluding blood transfusions) cluster were 1.38 times more likely to experience the most number of extremely hot days and 1.70 times more likely to present with obesity than women in a low-risk SMM cluster (p < .001). CONCLUSIONS: This study is the first to characterize the geographic clustering of SMM risk in the US. Our geospatial approach contributes a novel understanding to factors which influence SMM beyond patient-level characteristics and identifies the impact of hot ambient temperature on maternal morbidity. Findings address an important literature gap surrounding place-based risk factors by explaining the contextual social and built environmental factors that drive SMM risk.

Perceived Experiences of Community Violence Among Adolescents: A School Survey From Rio de Janeiro, Brazil.

Community violence (CV) is a global public health problem due to its high frequency and severe consequences. Although CV is one of the leading causes of death among adolescents, little is known about the everyday CV situations that do not lead to death. This study aimed to estimate the frequency of exposure to and involvement in CV situations among adolescent students from public and private schools in the city of Rio de Janeiro, Brazil. This was a cross-sectional study of 693 individuals in their second year of high school selected through stratified multistage random sampling. Information about their exposure to and involvement in CV was collected through a self-completed multidimensional questionnaire in the classrooms. For approximately 30% of the adolescents, someone close to them had been murdered, and 40% had already seen the corpse of a victim of homicide. Seventeen percent reported having been directly involved in CV situations. Approximately 38%, 13%, and 25% had been victims of robberies, interpersonal aggression, and death threats to either themselves or their relatives, respectively. Many of these situations occurred more than once. In general, CV was more frequently reported by boys and by those who did not live with both parents. Adolescents from higher economic classes experienced more interpersonal aggression and felt a greater need to carry a gun. Those who belonged to the lower economic classes and studied in public schools were more exposed to lethal violence than other students. The results call attention to the very high percentage of adolescent students that are involved in CV situations as well as to the differences in violence rates among population subgroups. Such findings should be considered when planning CV prevention and management actions in schools and other socialization spaces for adolescents.

PRMT1-dependent regulation of RNA metabolism and DNA damage response sustains pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that has remained clinically challenging to manage. Here we employ an RNAi-based in vivo functional genomics platform to determine epigenetic vulnerabilities across a panel of patient-derived PDAC models. Through this, we identify protein arginine methyltransferase 1 (PRMT1) as a critical dependency required for PDAC maintenance. Genetic and pharmacological studies validate the role of PRMT1 in maintaining PDAC growth. Mechanistically, using proteomic and transcriptomic analyses, we demonstrate that global inhibition of asymmetric arginine methylation impairs RNA metabolism, which includes RNA splicing, alternative polyadenylation, and transcription termination. This triggers a robust downregulation of multiple pathways involved in the DNA damage response, thereby promoting genomic instability and inhibiting tumor growth. Taken together, our data support PRMT1 as a compelling target in PDAC and informs a mechanism-based translational strategy for future therapeutic development.Statement of significancePDAC is a highly lethal cancer with limited therapeutic options. This study identified and characterized PRMT1-dependent regulation of RNA metabolism and coordination of key cellular processes required for PDAC tumor growth, defining a mechanism-based translational hypothesis for PRMT1 inhibitors.

Spatial Clustering of Adolescent Bereavement in the United States During the COVID-19 Pandemic.

PURPOSE: Few studies have examined grief and bereavement in the context of a pandemic, particularly among young people during the ongoing COVID-19 pandemic. METHODS: The objective of this study is to examine spatiotemporal clustering of bereavement using data from Crisis Text Line, an SMS-based intervention with widespread usage among youth and adolescents in the United States from January 2017 to September 2020. RESULTS: Results found significant spatial clustering of bereavement during the pandemic period in the late summer months compared with the onset of the pandemic. CONCLUSION: Our study provides the first evidence of elevated bereavement in adolescents using a technique for rapidly identifying clusters of bereavement risk among this vulnerable subgroup. Findings can be leveraged for targeted interventions and supportive counseling in geographic hotspots.

Photobiomodulation induces murine macrophages polarization toward M2 phenotype.

Photobiomodulation using light-emitting diode (LED) treatment has analgesic and anti-inflammatory effects which can be an effective therapeutic associated with serum therapy for local treatment of snakebites. Here we explored the effects of LED treatment on isolated macrophage under Bothrops jararacussu venom. Results showed that LED induced IL-6 and TNF-α genes down-regulation and, TGF and ARG1 genes up-regulation which indicates a polarization of macrophages to an M2 phenotype contributing to both tissue repair and resolution of inflammation.

Recognition of RNA by the S9.6 antibody creates pervasive artifacts when imaging RNA:DNA hybrids.

The S9.6 antibody is broadly used to detect RNA:DNA hybrids but has significant affinity for double-stranded RNA. The impact of this off-target RNA binding activity has not been thoroughly investigated, especially in the context of immunofluorescence microscopy. We report that S9.6 immunofluorescence signal observed in fixed human cells arises predominantly from ribosomal RNA, not RNA:DNA hybrids. S9.6 staining was unchanged by pretreatment with the RNA:DNA hybrid-specific nuclease RNase H1, despite verification in situ that S9.6 recognized RNA:DNA hybrids and that RNase H1 was active. S9.6 staining was, however, significantly sensitive to RNase T1, which specifically degrades RNA. Additional imaging and biochemical data indicate that the prominent cytoplasmic and nucleolar S9.6 signal primarily derives from ribosomal RNA. Importantly, genome-wide maps obtained by DNA sequencing after S9.6-mediated DNA:RNA immunoprecipitation (DRIP) are RNase H1 sensitive and RNase T1 insensitive. Altogether, these data demonstrate that imaging using S9.6 is subject to pervasive artifacts without pretreatments and controls that mitigate its promiscuous recognition of cellular RNAs.

CARM1 Inhibition Enables Immunotherapy of Resistant Tumors by Dual Action on Tumor Cells and T Cells.

A number of cancer drugs activate innate immune pathways in tumor cells but unfortunately also compromise antitumor immune function. We discovered that inhibition of CARM1, an epigenetic enzyme and cotranscriptional activator, elicited beneficial antitumor activity in both cytotoxic T cells and tumor cells. In T cells, Carm1 inactivation substantially enhanced their antitumor function and preserved memory-like populations required for sustained antitumor immunity. In tumor cells, Carm1 inactivation induced a potent type 1 interferon response that sensitized resistant tumors to cytotoxic T cells. Substantially increased numbers of dendritic cells, CD8 T cells, and natural killer cells were present in Carm1-deficient tumors, and infiltrating CD8 T cells expressed low levels of exhaustion markers. Targeting of CARM1 with a small molecule elicited potent antitumor immunity and sensitized resistant tumors to checkpoint blockade. Targeting of this cotranscriptional regulator thus offers an opportunity to enhance immune function while simultaneously sensitizing resistant tumor cells to immune attack. SIGNIFICANCE: Resistance to cancer immunotherapy remains a major challenge. Targeting of CARM1 enables immunotherapy of resistant tumors by enhancing T-cell functionality and preserving memory-like T-cell populations within tumors. CARM1 inhibition also sensitizes resistant tumor cells to immune attack by inducing a tumor cell-intrinsic type 1 interferon response.This article is highlighted in the In This Issue feature, p. 1861.

Best practices for the visualization, mapping, and manipulation of R-loops.

R-loops represent an abundant class of large non-B DNA structures in genomes. Even though they form transiently and at modest frequencies, interfering with R-loop formation or dissolution has significant impacts on genome stability. Addressing the mechanism(s) of R-loop-mediated genome destabilization requires a precise characterization of their distribution in genomes. A number of independent methods have been developed to visualize and map R-loops, but their results are at times discordant, leading to confusion. Here, we review the main existing methodologies for R-loop mapping and assess their limitations as well as the robustness of existing datasets. We offer a set of best practices to improve the reproducibility of maps, hoping that such guidelines could be useful for authors and referees alike. Finally, we propose a possible resolution for the apparent contradictions in R-loop mapping outcomes between antibody-based and RNase H1-based mapping approaches.