A new prism next to motherhood's light: uncovering changes in neural function following childbirth.

Childbirth has far-reaching consequences for the mother's neural structure and function. In new research, Lotter and colleagues perform a comprehensive evaluation of neural function, hormone levels, and mood within a longitudinal design of post-partum women. The authors implicate new candidate neural processes following childbirth, which may have implications for resilience from and susceptibility to psychiatric disorders during this time.

Behavior Change Techniques Within Digital Interventions for the Treatment of Eating Disorders: Systematic Review and Meta-Analysis.

BACKGROUND: Previous systematic reviews of digital eating disorder interventions have demonstrated effectiveness at improving symptoms of eating disorders; however, our understanding of how these interventions work and what contributes to their effectiveness is limited. Understanding the behavior change techniques (BCTs) that are most commonly included within effective interventions may provide valuable information for researchers and developers. Establishing whether these techniques have been informed by theory will identify whether they target those mechanisms of action that have been identified as core to changing eating disorder behaviors. It will also evaluate the importance of a theoretical approach to digital intervention design. OBJECTIVE: This study aims to define the BCTs within digital self-management interventions or minimally guided self-help interventions for adults with eating disorders that have been evaluated within randomized controlled trials. It also assessed which of the digital interventions were grounded in theory and the range of modes of delivery included. METHODS: A literature search identified randomized controlled trials of digital intervention for the treatment of adults with eating disorders with minimal therapist support. Each digital intervention was coded for BCTs using the established BCT Taxonomy v1; for the application of theory using an adapted version of the theory coding scheme (TCS); and for modes of delivery using the Mode of Delivery Ontology. A meta-analysis evaluated the evidence that any individual BCT moderated effect size or that other potential factors such as the application of theory or number of modes of delivery had an effect on eating disorder outcomes. RESULTS: Digital interventions included an average of 14 (SD 2.6; range 9-18) BCTs. Self-monitoring of behavior was included in all effective interventions, with Problem-solving, Information about antecedents, Feedback on behavior, Self-monitoring of outcomes of behavior, and Action planning identified in >75% (13/17) of effective interventions. Social support and Information about health consequences were more evident in effective interventions at follow-up compared with postintervention measurement. The mean number of modes of delivery was 4 (SD 1.6; range 2-7) out of 12 possible modes, with most interventions (15/17, 88%) being web based. Digital interventions that had a higher score on the TCS had a greater effect size than those with a lower TCS score (subgroup differences: χ21=9.7; P=.002; I²=89.7%) within the meta-analysis. No other subgroup analyses had statistically significant results. CONCLUSIONS: There was a high level of consistency in terms of the most common BCTs within effective interventions; however, there was no evidence that any specific BCT contributed to intervention efficacy. The interventions that were more strongly informed by theory demonstrated greater improvements in eating disorder outcomes compared to waitlist or treatment-as-usual controls. These results can be used to inform the development of future digital eating disorder interventions. TRIAL REGISTRATION: PROSPERO CRD42023410060; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=410060.

Exploring the Impact of a Sleep App on Sleep Quality in a General Population Sample: Pilot Randomized Controlled Trial.

BACKGROUND: A third of adults in Western countries have impaired sleep quality. A possible solution involves distributing sleep aids through smartphone apps, but most empirical studies are limited to small pilot trials in distinct populations (eg, soldiers) or individuals with clinical sleep disorders; therefore, general population data are required. Furthermore, recent research shows that sleep app users desire a personalized approach, offering an individually tailored choice of techniques. One such aid is Peak Sleep, a smartphone app based on scientifically validated principles for improving sleep quality, such as mindfulness meditation and cognitive behavioral therapy. OBJECTIVE: We aimed to test the impact of the smartphone app Peak Sleep on sleep quality and collect user experience data to allow for future app development. METHODS: This was a 2-arm pilot randomized controlled trial. Participants were general population adults in the United Kingdom (aged ≥18 years) who were interested in improving their sleep quality and were not undergoing clinical treatment for sleep disorder or using sleep medication ≥1 per week. Participants were individually randomized to receive the intervention (3 months of app use) versus a no-treatment control. The intervention involved free access to Peak Sleep, an app that offered a choice of behavioral techniques to support better sleep (mindfulness, cognitive behavioral therapy, and acceptance commitment therapy). The primary outcome was sleep quality assessed using the Insomnia Severity Index at baseline and 1-, 2-, and 3-month follow-ups. Assessments were remote using web-based questionnaires. Objective sleep data collection using the Oura Ring (Oura Health Oy) was planned; however, because the COVID-19 pandemic lockdowns began just after recruitment started, this plan could not be realized. Participant engagement with the app was assessed using the Digital Behavior Change Intervention Engagement Scale and qualitative telephone interviews with a subsample. RESULTS: A total of 101 participants were enrolled in the trial, and 21 (21%) were qualitatively interviewed. Sleep quality improved in both groups over time, with Insomnia Severity Index scores of the intervention group improving by a mean of 2.5 and the control group by a mean of 1.6 (between-group mean difference 0.9, 95% CI -2.0 to 3.8), with was no significant effect of group (P=.91). App users' engagement was mixed, with qualitative interviews supporting the view of a polarized sample who either strongly liked or disliked the app. CONCLUSIONS: In this trial, self-reported sleep improved over time in both intervention and control arms, with no impact by group, suggesting no effect of the sleep app. Qualitative data suggested polarized views on liking or not liking the app, features that people engaged with, and areas for improvement. Future work could involve developing the app features and then testing the app using objective measures of sleep in a larger sample. TRIAL REGISTRATION: ClinicalTrials.gov NCT04487483; https://www.clinicaltrials.gov/study/NCT04487483.

Rates of, and factors associated with, common mental disorders in homeworking UK Government response employees' during COVID-19: a cross-sectional survey and secondary data analysis.

INTRODUCTION: Working on the frontline during the COVID-19 pandemic has been associated with increased risk to mental health and wellbeing in multiple occupations and contexts. The current study aimed to provide an insight into the rate of probable mental health problems amongst United Kingdom (UK) Government employees who contributed to the COVID-19 response whilst working from home, and to ascertain what factors and constructs, if any, influence mental health and wellbeing in the sample population. METHOD: This paper reports on the findings from two studies completed by UK Government employees. Study 1: A cross-sectional online survey, containing standardised and validated measures of common mental health disorders of staff who actively contributed to the COVID-19 response from their own homes. Binary logistic regression was used to assess factors associated with mental health outcomes. Study 2: A secondary data analysis of cross-sectional survey data collected across three timepoints (May, June, and August) in 2020 focusing on the wellbeing of employees who worked from home during the COVID-19 pandemic. RESULTS: Study 1: 17.9% of participants met the threshold criteria for a probable moderate anxiety disorder, moderate depression, or post-traumatic stress disorder. Younger, less resilient, less productive individuals, with lower personal wellbeing and less enjoyment of working from home, were more likely to present with poorer mental health. Study 2: Found lower wellbeing was consistently associated with having less opportunities to look after one's physical and mental health, and having unsupportive line managers and colleagues. CONCLUSION: It is important to ensure UK Government employees' psychological needs are met whilst working from home and responding to enhanced incidents. It is recommended that workplaces should be seeking to continually build and improve employee resilience (e.g., through opportunities to increase social ties and support networks), essentially ensuring employees have necessary resources and skills to support themselves and others.

Stented endoscopic third ventriculostomy: technique, safety, and indications-a multicenter multinational study.

PURPOSE: Endoscopic third ventriculostomy (ETV) is an effective treatment for obstructive hydrocephalus. Secondary stoma closure may be life threatening and is the most common reason for late ETV failure, mostly secondary to local scarring. Local stents intended to maintain patency are rarely used. In this study, we summarize our experience using stented ETV (sETV), efficacy, and safety. MATERIAL AND METHODS: Data was retrospectively collected from all consecutive patients who underwent ETV with stenting at four centers. Collected data included indications for using sETV, hydrocephalic history, surgical technique, outcomes, and complications. RESULTS: Sixty-seven cases were included. Forty had a primary sETV, and 27 had a secondary sETV (following a prior shunt, ETV, or both). The average age during surgery was 22 years. Main indications for sETV included an adjacent tumor (n = 15), thick or redundant tuber cinereum (n = 24), and prior ETV failure (n = 16). Fifty-nine patients (88%) had a successful sETV. Eight patients failed 11 ± 8 months following surgery. Reasons for failure included obstruction of the stent, reabsorption insufficiency, and CSF leak (n = 2 each), and massive hygroma and tumor spread (n = 1 each). Complications included subdural hygroma (n = 4), CSF leak (n = 2), and stent malposition (n = 1). There were no complications associated with two stent removals. CONCLUSION: Stented ETV appears to be feasible and safe. It may be indicated in selected cases such as patients with prior ETV failure, or as a primary treatment in cases with anatomical alterations caused by tumors or thickened tuber cinereum. Future investigations are needed to further elucidate its role in non-communicating hydrocephalus.

Medicaid Expansion and Restriction Policies for Hepatitis C Treatment.

Importance: Hepatitis C can be cured with direct-acting antivirals (DAAs), but Medicaid programs have implemented fibrosis, sobriety, and prescriber restrictions to control costs. Although restrictions are easing, understanding their association with hepatitis C treatment rates is crucial to inform policies that increase access to lifesaving treatment. Objective: To estimate the association of jurisdictional (50 states and Washington, DC) DAA restrictions and Medicaid expansion with the number of Medicaid recipients with filled prescriptions for DAAs. Design, Setting, and Participants: This cross-sectional study used publicly available Medicaid documents and claims data from January 1, 2014, to December 31, 2021, to compare the number of unique Medicaid recipients treated with DAAs in each jurisdiction year with Medicaid expansion status and categories of fibrosis, sobriety, and prescriber restrictions. Medicaid recipients from all 50 states and Washington, DC, during the study period were included. Multilevel Poisson regression was used to estimate the association between Medicaid expansion and DAA restrictive policies on jurisdictional Medicaid DAA prescription fills. Data were analyzed initially from August 15 to November 15, 2023, and subsequently from April 15 to May 9, 2024. Exposures: Jurisdictional Medicaid expansion status and fibrosis, sobriety, and prescriber DAA restrictions. Main Outcomes and Measures: Number of people treated with DAAs per 100 000 Medicaid recipients per year. Results: A total of 381 373 Medicaid recipients filled DAA prescriptions during the study period (57.3% aged 45-64 years; 58.7% men; 15.2% non-Hispanic Black and 52.2% non-Hispanic White). Medicaid nonexpansion jurisdictions had fewer filled DAA prescriptions per 100 000 Medicaid recipients per year than expansion jurisdictions (38.6 vs 86.6; adjusted relative risk [ARR], 0.56 [95% CI, 0.52-0.61]). Jurisdictions with F3 to F4 (34.0 per 100 000 Medicaid recipients per year; ARR, 0.39 [95% CI, 0.37-0.66]) or F1 to F2 fibrosis restrictions (61.9 per 100 000 Medicaid recipients per year; ARR, 0.62 [95% CI, 0.59-0.66]) had lower treatment rates than jurisdictions without fibrosis restrictions (94.8 per 100 000 Medicaid recipients per year). Compared with no sobriety restrictions (113.5 per 100 000 Medicaid recipients per year), 6 to 12 months of sobriety (38.3 per 100 000 Medicaid recipients per year; ARR, 0.65 [95% CI, 0.61-0.71]) and screening and counseling requirements (84.7 per 100 000 Medicaid recipients per year; ARR, 0.87 [95% CI, 0.83-0.92]) were associated with reduced treatment rates, while 1 to 5 months of sobriety was not statistically significantly different. Compared with no prescriber restrictions (97.8 per 100 000 Medicaid recipients per year), specialist consult restrictions was associated with increased treatment (66.2 per 100 000 Medicaid recipients per year; ARR, 1.05 [95% CI, 1.00-1.10]), while specialist required restrictions were not statistically significant. Conclusions and Relevance: In this cross-sectional study, Medicaid nonexpansion status, fibrosis, and sobriety restrictions were associated with a reduction in the number of people with Medicaid who were treated for hepatitis C. Removing DAA restrictions might facilitate treatment of more people diagnosed with hepatitis C.

Advances in Clinical Imaging of Vascular Inflammation: A State-of-the-Art Review.

Vascular inflammation is a major contributor to cardiovascular disease, particularly atherosclerotic disease, and early detection of vascular inflammation may be key to the ultimate reduction of residual cardiovascular morbidity and mortality. This review paper discusses the progress toward the clinical utility of noninvasive imaging techniques for assessing vascular inflammation, with a focus on coronary atherosclerosis. A discussion of multiple modalities is included: computed tomography (CT) imaging (the major focus of the review), cardiac magnetic resonance, ultrasound, and positron emission tomography imaging. The review covers recent progress in new technologies such as the novel CT biomarkers of coronary inflammation (eg, the perivascular fat attenuation index), new inflammation-specific tracers for positron emission tomography-CT imaging, and others. The strengths and limitations of each modality are explored, highlighting the potential for multi-modality imaging and the use of artificial intelligence image interpretation to improve both diagnostic and prognostic potential for common conditions such as coronary artery disease.

Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer.

Small cell lung cancers (SCLCs) are composed of heterogeneous subtypes marked by lineage-specific transcription factors, including ASCL1, NEUROD1, and POU2F3. POU2F3-positive SCLCs, ∼12% of all cases, are uniquely dependent on POU2F3 itself; as such, approaches to attenuate POU2F3 expression may represent new therapeutic opportunities. Here using genome-scale screens for regulators of POU2F3 expression and SCLC proliferation, we define mSWI/SNF complexes as top dependencies specific to POU2F3-positive SCLC. Notably, chemical disruption of mSWI/SNF ATPase activity attenuates proliferation of all POU2F3-positive SCLCs, while disruption of non-canonical BAF (ncBAF) via BRD9 degradation is effective in pure non-neuroendocrine POU2F3-SCLCs. mSWI/SNF targets to and maintains accessibility over gene loci central to POU2F3-mediated gene regulatory networks. Finally, clinical-grade pharmacologic disruption of SMARCA4/2 ATPases and BRD9 decreases POU2F3-SCLC tumor growth and increases survival in vivo. These results demonstrate mSWI/SNF-mediated governance of the POU2F3 oncogenic program and suggest mSWI/SNF inhibition as a therapeutic strategy for POU2F3-positive SCLCs.

Subjective and objective assessment of color match of universal tinted sunscreens in Fitzpatrick skin phototypes I-VI.

BACKGROUND: Tinted sunscreens not only shield against UV rays but also provide protection against visible light, as opposed to traditional sunscreens. Universal tinted sunscreens are marketed to complement all skin tones. OBJECTIVE: To assess color match and subject satisfaction for 7 universal tinted sunscreens across various price ranges in all Fitzpatrick skin phototypes (SPT). METHODS: Products A-G were applied at concentrations of 1 and 2 mg/cm2 on the dorsal arms of 30 subjects spanning SPT I-VI. Photography, colorimetry, and subject and investigator surveys were utilized to determine color match. RESULTS: Using colorimetry analysis at the recommended 2 mg/cm2 concentration, two of seven products were identified as suitable matches for SPT I-II, while six out of seven were determined to be a good match for SPT III-IV. However, only one product was found to be a good match for SPT V-VI at the recommended concentration according to colorimetry results. CONCLUSION: Universal tinted sunscreens do not provide an adequate color match for all skin phototypes, especially for individuals with very fair or very dark skin tones.

Reliability of the Vitiligo Area Scoring Index measurement tool for vitiligo.

Background: A reliable instrument is needed to assess vitiligo severity and treatment response. Objective: To assess inter- and intrarater variability and accuracy of the Vitiligo Area Scoring Index among trained raters and to evaluate a proposed Vitiligo Area Scoring Index using equidistant 10% depigmentation increments (VASI 10%). Methods: In this prospective study, 12 raters evaluated images of 10 participants with vitiligo on 2 occasions using total body Vitiligo Area Scoring Index (T-VASI) and facial Vitiligo Area Scoring Index (F-VASI) scores after training. Inter- and intrarater reliabilities and accuracy vs digital scores were determined using intraclass correlation coefficients. VASI 10% scores were evaluated separately for interrater reliability and accuracy. Results: F-VASI interrater reliability improved from "moderate" to "good" between time points, while T-VASI was "good" at both time points. Intrarater reliability ranged from "good" to "excellent" for T-VASI and "poor" to "excellent" for F-VASI. Accuracy intraclass correlation coefficient was "good" to "excellent" for most raters. Interrater reliability using VASI 10% was "moderate" for both T-VASI and F-VASI. Limitations: Small participant population and number of raters; participants were not assessed in person; no repeated VASI 10% measures. Conclusion: Vitiligo Area Scoring Index generally provides good to excellent reliability for assessment of vitiligo by raters who receive standardized training.

Transsphenoidal retrieval of a needlefish beak remnants from the optic canal.

KEY POINTS: Penetrating orbital trauma from marine creatures, especially needlefish, should be considered after injuries sustained in open water. Advances in endoscopic sinus surgery have enabled surgeons to remove certain orbital foreign bodies through endoscopic endonasal approaches. 3D segmentation is a valuable pre-operative tool in complex endoscopic orbital cases.

Development of a Consolidated Health Facility Masterlist Using Data From Polio Electronic Surveillance in the World Health Organization African Region.

Geospatial data reporting from surveillance and immunization efforts is a key aspect of the World Health Organization (WHO) Global Polio Eradication Initiative in Africa. These activities are coordinated through the WHO Regional Office for Africa Geographic Information Systems Centre. To ensure the accuracy of field-collected data, the WHO Regional Office for Africa Geographic Information Systems Centre has developed mobile phone apps such as electronic surveillance (eSURV) and integrated supportive supervision (ISS) geospatial data collection programs. While eSURV and ISS have played a vital role in efforts to eradicate polio and control other communicable diseases in Africa, disease surveillance efforts have been hampered by incomplete and inaccurate listings of health care sites throughout the continent. To address this shortcoming, data compiled from eSURV and ISS are being used to develop, update, and validate a Health Facility master list for the WHO African region that contains comprehensive listings of the names, locations, and types of health facilities in each member state. The WHO and Ministry of Health field officers are responsible for documenting and transmitting the relevant geospatial location information regarding health facilities and traditional medicine sites using the eSURV and ISS form; this information is then used to update the Health Facility master list and is also made available to national ministries of health to update their respective health facility lists. This consolidation of health facility information into a single registry is expected to improve disease surveillance and facilitate epidemiologic research for the Global Polio Eradication Initiative, as well as aid public health efforts directed at other diseases across the African continent. This review examines active surveillance using eSURV at the district, country, and regional levels, highlighting its role in supporting polio surveillance and immunization efforts, as well as its potential to serve as a fundamental basis for broader public health initiatives and research throughout Africa.

Photoprotection: Current developments and controversies.

This review aimed at summarizing some of the key points that were discussed during the photoprotection session at the International Forum of Dermatology in 2022. This international conference was designed to address prominent topics of clinical dermatology in a holistic way, allowing to articulate multiple viewpoints. Therefore, this review does not claim to be exhaustive, but is instead intended to give an overview of recent developments and ongoing controversies in the field of photoprotection. Cumulative ultraviolet radiation (UVR) exposure is the major aetiological factor in the development of photoageing, photoimunosuppression and photocarcinogenesis. UVA (320-400 nm) penetrates into the dermis and damages DNA and other intracellular and acellular targets primarily by generating reactive oxygen species (ROS). It is the major contributor to photoageing, characterized by fine and coarse wrinkles, dyspigmentation and loss of elasticity. UVB (290-320 nm) is responsible for sunburns through direct damage to DNA by the formation of 6-4 cyclobutane pyrimidine dimers (CPDs) and pyrimidine 6-4 pyrimidone photoproducts. Both UVA and UVB exposure increase the risk of basal cell carcinoma, squamous cell carcinoma and melanoma. In recent years, visible light (VL; 400-700 nm) has also been implicated in the exacerbation of conditions aggravated by sun exposure such as hyperpigmentation and melasma. Photoprotection is a critical health strategy to reduce the deleterious effects of UVR and VL. Comprehensive photoprotection strategies include staying in the shade when outdoors, wearing photoprotective clothing including a wide-brimmed hat, and sunglasses, and the use of sunscreen. Due to the absorption of UV filters, the safety of sunscreens has been questioned. Newer sunscreens are becoming available with filters with absorption even beyond the UV spectrum, offering enhanced protection compared with older products. Prevention of photocarcinogenesis, sun-induced or sunlight-exacerbated hyperpigmentary conditions and drug-induced photosensitivity is an important reason for adopting comprehensive photoprotection strategies.

Protocol modifications reduce risk of delayed pericardial effusions after vein of Marshall ethanol infusion: follow-up from the Maine experience.

BACKGROUND: While ethanol infusion into the vein of Marshall (VOM) as an adjunct to atrial fibrillation ablation has shown promise, adoption has been limited by the technical expertise required, unclear antiarrhythmic mechanism, and complication risk. Delayed pericardial effusions have been associated with ethanol infusion into the VOM in prior studies. Very little is known about how the procedural approach itself can impact the risk of delayed effusions. We sought to understand the incidence and influence of procedural technique on complications including delayed pericardial effusions from VOM ethanol infusion at a large single medical center. METHODS: A total of 275 atrial ablation cases wherein VOM ethanol infusion was attempted were identified from the time of the program's inception in 2019 at Maine Medical Center (Portland, ME) until October of 2023. Cases were classified into phase I cases (early experience) and phase II cases (later experience) based upon temporal programmatic changes in the ethanol dose and infusion rate as well as the use of routine VOM venography. Procedural details and complications were adjudicated from the medical record. RESULTS: The overall VOM ethanol infusion success was 91.4%. Nine complications (3.3%) occurred in eight patients (2.9% of patients). These were more frequent in phase I (5.8%) compared to phase II (1.3%, p = 0.047). This difference was driven by a difference in delayed presentations of tamponade, which occurred in four patients in phase I (3.3%) and in no patients in phase II (0%, p = 0.037). Twelve-month estimated atrial arrhythmia freedom did not differ between groups (73.8% phase I vs 70.4% phase II, p = 0.24). CONCLUSION: In our single-center experience, adjustments to the procedural approach with lower ethanol infusion rate and dosage, combined with utilizing selective VOM venography, associated with a lowering of complication rates and in particular, delayed pericardial tamponade.

Ion Mobility-Mass Spectrometry and Collision-Induced Unfolding Rapidly Characterize the Structural Polydispersity and Stability of an Fc-Fusion Protein.

Fc-fusion proteins are an emerging class of protein therapeutics that combine the properties of biological ligands with the unique properties of the fragment crystallizable (Fc) domain of an immunoglobulin G (IgG). Due to their diverse higher-order structures (HOSs), Fc-fusion proteins remain challenging characterization targets within biopharmaceutical pipelines. While high-resolution biophysical tools are available for HOS characterization, they frequently demand extended time frames and substantial quantities of purified samples, rendering them impractical for swiftly screening candidate molecules. Herein, we describe the development of ion mobility-mass spectrometry (IM-MS) and collision-induced unfolding (CIU) workflows that aim to fill this technology gap, where we focus on probing the HOS of a model Fc-Interleukin-10 (Fc-IL-10) fusion protein engineered using flexible glycine-serine linkers. We evaluate the ability of these techniques to probe the flexibility of Fc-IL-10 in the absence of bulk solvent relative to other proteins of similar size, as well as localize structural changes of low charge state Fc-IL-10 ions to specific Fc and IL-10 unfolding events during CIU. We subsequently apply these tools to probe the local effects of glycine-serine linkers on the HOS and stability of IL-10 homodimer, which is the biologically active form of IL-10. Our data reveals that Fc-IL-10 produces significantly more structural transitions during CIU and broader IM profiles when compared to a wide range of model proteins, indicative of its exceptional structural dynamism. Furthermore, we use a combination of enzymatic approaches to annotate these intricate CIU data and localize specific transitions to the unfolding of domains within Fc-IL-10. Finally, we detect a strong positive, quadratic relationship between average linker mass and fusion protein stability, suggesting a cooperative influence between glycine-serine linkers and overall fusion protein stability. This is the first reported study on the use of IM-MS and CIU to characterize HOS of Fc-fusion proteins, illustrating the practical applicability of this approach.

Loss of Kmt2c or Kmt2d drives brain metastasis via KDM6A-dependent upregulation of MMP3.

KMT2C and KMT2D, encoding histone H3 lysine 4 methyltransferases, are among the most commonly mutated genes in triple-negative breast cancer (TNBC). However, how these mutations may shape epigenomic and transcriptomic landscapes to promote tumorigenesis is largely unknown. Here we describe that deletion of Kmt2c or Kmt2d in non-metastatic murine models of TNBC drives metastasis, especially to the brain. Global chromatin profiling and chromatin immunoprecipitation followed by sequencing revealed altered H3K4me1, H3K27ac and H3K27me3 chromatin marks in knockout cells and demonstrated enhanced binding of the H3K27me3 lysine demethylase KDM6A, which significantly correlated with gene expression. We identified Mmp3 as being commonly upregulated via epigenetic mechanisms in both knockout models. Consistent with these findings, samples from patients with KMT2C-mutant TNBC have higher MMP3 levels. Downregulation or pharmacological inhibition of KDM6A diminished Mmp3 upregulation induced by the loss of histone-lysine N-methyltransferase 2 (KMT2) and prevented brain metastasis similar to direct downregulation of Mmp3. Taken together, we identified the KDM6A-matrix metalloproteinase 3 axis as a key mediator of KMT2C/D loss-driven metastasis in TNBC.

Novel Measurement of the Neutron Magnetic Form Factor from A=3 Mirror Nuclei.

The electromagnetic form factors of the proton and neutron encode information on the spatial structure of their charge and magnetization distributions. While measurements of the proton are relatively straightforward, the lack of a free neutron target makes measurements of the neutron's electromagnetic structure more challenging and more sensitive to experimental or model-dependent uncertainties. Various experiments have attempted to extract the neutron form factors from scattering from the neutron in deuterium, with different techniques providing different, and sometimes large, systematic uncertainties. We present results from a novel measurement of the neutron magnetic form factor using quasielastic scattering from the mirror nuclei ^{3}H and ^{3}He, where the nuclear effects are larger than for deuterium but expected to largely cancel in the cross-section ratios. We extracted values of the neutron magnetic form factor for low-to-modest momentum transfer, 0.6