FABP4-mediated lipid accumulation and lipolysis in tumor associated macrophages promote breast cancer metastasis.

A high density of tumor-associated macrophages (TAMs) is associated with poorer prognosis and survival in breast cancer patients. Recent studies have shown that lipid accumulation in TAMs can promote tumor growth and metastasis in various models. However, the specific molecular mechanisms that drive lipid accumulation and tumor progression in TAMs remain largely unknown. Herein, we demonstrated that unsaturated fatty acids (FAs), unlike saturated ones, are more likely to form lipid droplets in macrophages. Specifically, unsaturated FAs, including linoleic acids (LA), activate the FABP4/CEBPα pathway, leading to triglyceride synthesis and lipid droplet formation. Furthermore, FABP4 enhances lipolysis and FA utilization by breast cancer cells, which promotes cancer cell migration in vitro and metastasis in vivo . Notably, a deficiency of FABP4 in macrophages significantly reduces LA-induced lipid metabolism. Therefore, our findings suggest FABP4 as a crucial lipid messenger that facilitates unsaturated FA-mediated lipid accumulation and lipolysis in TAMs, thus contributing to the metastasis of breast cancer. Highlights: Unlike saturated fatty acids, unsaturated fatty acids preferentially promote lipid droplet formation in macrophages.Unsaturated fatty acids activate the FABP4/CEBPα axis for neutral lipid biosynthesis in macrophagesDeficiency of FABP4 compromised unsaturated fatty acid-mediated lipid accumulation and utilization in macrophagesFABP4-mediated lipid metabolism in macrophages contributes to breast cancer metastasis.

Development of a humanized anti-FABP4 monoclonal antibody for potential treatment of breast cancer.

BACKGROUND: Breast cancer is the most common cancer in women diagnosed in the U.S. and worldwide. Obesity increases breast cancer risk without clear underlying molecular mechanisms. Our studies demonstrate that circulating adipose fatty acid binding protein (A-FABP, or FABP4) links obesity-induced dysregulated lipid metabolism and breast cancer risk, thus potentially offering a new target for breast cancer treatment. METHODS: We immunized FABP4 knockout mice with recombinant human FABP4 and screened hybridoma clones with specific binding to FABP4. The potential effects of antibodies on breast cancer cells in vitro were evaluated using migration, invasion, and limiting dilution assays. Tumor progression in vivo was evaluated in various types of tumorigenesis models including C57BL/6 mice, Balb/c mice, and SCID mice. The phenotype and function of immune cells in tumor microenvironment were characterized with multi-color flow cytometry. Tumor stemness was detected by ALDH assays. To characterize antigen-antibody binding capacity, we determined the dissociation constant of selected anti-FABP4 antibodies via surface plasmon resonance. Further analyses in tumor tissue were performed using 10X Genomics Visium spatial single cell technology. RESULTS: Herein, we report the generation of humanized monoclonal antibodies blocking FABP4 activity for breast cancer treatment in mouse models. One clone, named 12G2, which significantly reduced circulating levels of FABP4 and inhibited mammary tumor growth, was selected for further characterization. After confirming the therapeutic efficacy of the chimeric 12G2 monoclonal antibody consisting of mouse variable regions and human IgG1 constant regions, 16 humanized 12G2 monoclonal antibody variants were generated by grafting its complementary determining regions to selected human germline sequences. Humanized V9 monoclonal antibody showed consistent results in inhibiting mammary tumor growth and metastasis by affecting tumor cell mitochondrial metabolism. CONCLUSIONS: Our current evidence suggests that targeting FABP4 with humanized monoclonal antibodies may represent a novel strategy for the treatment of breast cancer and possibly other obesity- associated diseases.

Age of Juice Introduction and Cardiometabolic Outcomes in Middle Childhood.

BACKGROUND: The American Academy of Pediatrics recommends juice introduction after 12 months of age. Juice consumption has been linked to childhood obesity and cardiometabolic risk. OBJECTIVES: To examine the prospective relationship between the age of juice introduction and primary and secondary cardiometabolic outcomes in middle childhood. METHODS: Parents reported the age of juice introduction on Upstate KIDS questionnaires completed between 4 and 18 months. The quantity and type of juice introduced were not measured. Anthropometry, blood pressure (BP), and arterial stiffness by pulse wave velocity (PWV) were measured for 524 children (age, 8-10 y) at study visits (2017-2019). Age- and gender-adjusted z-scores were calculated using the Centers for Disease Control and Prevention reference for anthropometrics. Plasma lipids, hemoglobin A1c (HbA1c), and C-reactive protein (CRP) in a subset of children were also measured (n = 248). Associations between age at juice introduction (categorized as <6, 6 to <12, ≥12 months), and outcomes were estimated using mean differences and odds ratios, applying generalized estimating equations to account for correlations between twins. RESULTS: Approximately 18% of children were introduced to juice at <6 months, 52% between 6 and <12 months, and 30% ≥ 12 months of age. Children who were introduced to juice before 6 months had higher systolic BP (3.13 mmHg; 95% confidence interval [CI]: 0.52, 5.74), heart rate (4.46 bpm; 95% CI: 1.05, 7.87), and mean arterial pressure (2.08 mmHg; 95% CI: 0.15, 4.00) compared with those introduced ≥12 months after covariate adjustment including sociodemographic factors and maternal prepregnancy body mass index. No adjusted differences in anthropometry, lipids, HbA1c, and CRP levels were found. CONCLUSIONS: Early juice introduction during infancy was associated with higher systolic BP, heart rate, and mean arterial pressure in middle childhood. This trial was registered at clinicaltrials.gov as NCT03106493 (https://clinicaltrials.gov/study/NCT03106493?term=upstate%20KIDS&rank=1).

Schools' readiness for child sexual abuse prevention education: Preliminary scale development using a Delphi method.

BACKGROUND: This study employed a Delphi method with a panel of experts to collaboratively design a new instrument to assess schools' readiness for school-based child sexual abuse prevention education. METHODS: An initial item pool was generated based on a review of existing empirical research and theoretical models. We invited researchers and stakeholders in the field of child sexual abuse prevention as experts to participate in a two-round online Delphi study in which they rated item importance and clarity, contributed their views on superfluous and/or missing items, gave rephrasing suggestions, and re-appraised revised items. Following the Delphi study, the instrument was pilot tested with a convenience sample of school staff. RESULTS: The initial item pool comprised 81 items in five construct sub-scales congruent with Wiener's Organizational Readiness for Change theory: contextual factors, informational assessment, change valence, change commitment, and change efficacy. In the Delphi study, 24 experts participated in round 1, and 13 participated in round 2. Based on Delphi study responses, the instrument was reduced to 56 items in the five construct subscales: contextual factors (28 items), informational assessment (13 items), change valence (6 items), change commitment (3 items), and change efficacy (6 items). The Schools' Readiness for Child Sexual Abuse Prevention Education (SR-CSAPE) was successfully pilot tested with school staff (n = 19) and minor changes to demographic items were incorporated. CONCLUSIONS: Informed by experts, the Schools' Readiness for Child Sexual Abuse Prevention Education (SR-CSAPE) is a newly-developed 56-item scale that identifies key organizational dimensions to schools' preparedness for CSA prevention education. Psychometric properties of the scale must be determined in future research.

Consensus definition and diagnostic criteria for neonatal encephalopathy-study protocol for a real-time modified delphi study.

BACKGROUND: 'Neonatal encephalopathy' (NE) describes a group of conditions in term infants presenting in the earliest days after birth with disturbed neurological function of cerebral origin. NE is aetiologically heterogenous; one cause is peripartum hypoxic ischaemia. Lack of uniformity in the terminology used to describe NE and its diagnostic criteria creates difficulty in the design and interpretation of research and complicates communication with families. The DEFINE study aims to use a modified Delphi approach to form a consensus definition for NE, and diagnostic criteria. METHODS: Directed by an international steering group, we will conduct a systematic review of the literature to assess the terminology used in trials of NE, and with their guidance perform an online Real-time Delphi survey to develop a consensus diagnosis and criteria for NE. A consensus meeting will be held to agree on the final terminology and criteria, and the outcome disseminated widely. DISCUSSION: A clear and consistent consensus-based definition of NE and criteria for its diagnosis, achieved by use of a modified Delphi technique, will enable more comparability of research results and improved communication among professionals and with families. IMPACT: The terms Neonatal Encephalopathy and Hypoxic Ischaemic Encephalopathy tend to be used interchangeably in the literature to describe a term newborn with signs of encephalopathy at birth. This creates difficulty in communication with families and carers, and between medical professionals and researchers, as well as creating difficulty with performance of research. The DEFINE project will use a Real-time Delphi approach to create a consensus definition for the term 'Neonatal Encephalopathy'. A definition formed by this consensus approach will be accepted and utilised by the neonatal community to improve research, outcomes, and parental experience.

Single-year change in views of democracy and society and support for political violence in the USA: findings from a 2023 nationally representative survey.

BACKGROUND: A 2022 survey in the USA found concerningly high prevalences of support for and personal willingness to engage in political violence, of beliefs associated with such violence, and of belief that civil war was likely in the near future. It is important to determine the durability of those findings. METHODS: Wave 2 of a nationally representative cohort survey was conducted May 18-June 8, 2023; the sample comprised all respondents to 2022's Wave 1. Outcomes are expressed as weighted proportions; changes from 2022 to 2023 are for respondents who participated in both surveys, based on aggregated individual change scores. RESULTS: The completion rate was 84.2%; there were 9385 respondents. After weighting, 50.7% (95% confidence interval (CI) 49.4%, 52.1%) were female; weighted mean (SD) age was 48.5 (25.9) years. About 1 in 20 respondents (5.7%, 95% CI 5.1%, 6.4%) agreed strongly/very strongly that "in the next few years, there will be civil war in the United States," a 7.7% decrease. In 2023, fewer respondents considered violence to be usually/always justified to advance at least 1 of 17 specific political objectives [25.3% (95% CI 24.7%, 26.5%), a 6.8% decrease]. However, more respondents thought it very/extremely likely that within the next few years, in a situation where they consider political violence justified, "I will be armed with a gun" [9.0% (95% CI 8.3%, 9.8%), a 2.2% increase] and "I will shoot someone with a gun" [1.8% (95% CI 1.4%, 2.2%), a 0.6% increase]. Among respondents who considered violence usually/always justified to advance at least 1 political objective, about 1 in 20 also thought it very/extremely likely that they would threaten someone with a gun (5.4%, 95% CI 4.0%, 7.0%) or shoot someone (5.7%, 95% CI 4.3%, 7.1%) to advance such an objective. CONCLUSIONS: In this cohort, support for political violence declined from 2022 to 2023, but predictions of firearm use in political violence increased. These findings can help guide prevention efforts, which are urgently needed.

Contribution of Ultra-Processed Foods to Weight Gain Recurrence 5 Years After Metabolic and Bariatric Surgery.

BACKGROUND: The aim of this study was to evaluate evolution of ultra-processed food intake and recurrent weight gain in patients who underwent Roux-en-Y gastric bypass. MATERIALS AND METHODS: This study is an observational longitudinal study that evaluated patients who underwent metabolic and bariatric surgery at four time points: before surgery and at 3, 12, and 60 months after surgery. Anthropometric and dietary intake data were collected through two 24-h dietary recalls. All foods consumed were classified according to degree of processing. Recurrent weight gain was considered the difference between current weight and nadir weight. RESULTS: The sample consisted of 58 patients with a mean age of 38.7 ± 8.9 years and 68% female. After 60 months, mean excess weight loss and recurrent weight gain were 73.6 ± 27.2% and 22.5 ± 17.4%. Calorie and macronutrient intake decreased significantly between the pre-surgery period, and 3 and 12 months post-surgery; however, there was no significant difference after 60 months. In relation to food groups or macronutrients, no difference was observed between the pre-surgery period and 60 months post-surgery. The contribution of unprocessed or minimally processed foods to calorie intake gradually decreased after 3 months post-surgery. CONCLUSION: The profile of dietary intake after 60 months of metabolic and bariatric surgery tends to approach that of the pre-surgery period. The contribution of unprocessed and minimally processed foods to calorie intake decreased after 60 months, while ultra-processed food contribution increased.

Effectiveness of a two-component nutritional strategy for blood pressure control in individuals with hypertension users of a public health system: a randomized controlled clinical trial.

OBJECTIVE: To evaluate the effectiveness of a nutritional strategy based on two components and adapted for the public health system on blood pressure, cardiometabolic features, self-care, qualify of life and diet quality in individuals with hypertension. METHODS: NUPRESS was an open-label, parallel-group, superiority randomized controlled clinical trial in which participants at least 21 years with hypertension and poorly controlled blood pressure were randomly assigned (1 : 1 allocation ratio) to either an individualized dietary prescription according to nutritional guidelines (control group, n  = 205); or a two-component nutrition strategy, including a goal-directed nutritional counseling and mindfulness techniques (NUPRESS [intervention] group, n  = 205). Primary outcomes were SBP (mmHg) after 24 weeks of follow up and blood pressure control, defined as either having SBP more than 140 mmHg at baseline and achieving 140 mmHg or less after follow-up or having SBP 140 mmHg or less at baseline and reducing the frequency of antihypertensive drugs in use after follow-up. RESULTS: In total, 410 participants were randomized and submitted to an intention-to-treat analysis regarding primary outcomes. Both groups decreased blood pressure, but after adjusting for baseline values, there was no significant difference between them on SBP [intervention-control difference: -0.03 (-3.01; 2.94); P  = 0.98] nor blood pressure control [odds ratio 1.27 (0.82; 1.97); P  = 0.28]. No differences between groups were also detected regarding secondary and tertiary outcomes. CONCLUSION: There was no difference between a two-component nutritional strategy and an established dietary intervention on blood pressure in participants with hypertension.

Firearm Ownership and Support for Political Violence in the United States.

Importance: Little is known about support for and willingness to engage in political violence in the United States. Such violence would likely involve firearms. Objective: To evaluate whether firearm owners' and nonowners' support for political violence differs and whether support among owners varies by type of firearms owned, recency of purchase, and frequency of carrying a loaded firearm in public. Design, Setting, and Participants: This cross-sectional nationally representative survey study was conducted from May 13 to June 2, 2022, among US adult members of the Ipsos KnowledgePanel, including an oversample of firearm owners. Exposure: Firearm ownership vs nonownership. Main Outcomes and Measures: Main outcomes concern (1) support for political violence, in general and to advance specific political objectives; (2) personal willingness to engage in political violence, by severity of violence and target population; and (3) perceived likelihood of firearm use in political violence. Outcomes are expressed as weighted proportions and adjusted prevalence differences, with P values adjusted for the false-discovery rate and reported as q values. Results: The analytic sample comprised 12 851 respondents: 5820 (45.3%) firearm owners, 6132 (47.7%) nonowners without firearms at home, and 899 (7.0%) nonowners with firearms at home. After weighting, 51.0% (95% CI, 49.9%-52.1%) were female, 8.5% (95% CI, 7.5%-9.5%) Hispanic, 9.1% (95% CI, 8.1%-10.2%) non-Hispanic Black, and 62.6% (95% CI, 61.5%-63.8%) non-Hispanic White; the mean (SD) age was 48.5 (18.0) years. Owners were more likely than nonowners without firearms at home to consider violence usually or always justified to advance at least 1 of 17 specific political objectives (owners: 38.8%; 95% CI, 37.3%-40.4%; nonowners: 29.8%; 95% CI, 28.5%-31.2%; adjusted difference, 6.5 percentage points; 95% CI, 4.5-9.3 percentage points; q < .001) but were not more willing to engage in political violence. Recent purchasers, owners who always or nearly always carry loaded firearms in public, and to a lesser extent, owners of assault-type rifles were more supportive of and willing to engage in political violence than other subgroups of firearm owners. Conclusions and Relevance: In this study of support for political violence in the United States, differences between firearm owners and nonowners without firearms at home were small to moderate when present. Differences were greater among subsets of owners than between owners and nonowners. These findings can guide risk-based prevention efforts.

Magnesium sulfate and risk of hypoxic-ischemic encephalopathy in a high-risk cohort.

BACKGROUND: Hypoxic-ischemic encephalopathy contributes to morbidity and mortality among neonates ≥36 weeks of gestation. Evidence of preventative antenatal treatment is limited. Magnesium sulfate has neuroprotective properties among preterm fetuses. Hypertensive disorders of pregnancy are a risk factor for hypoxic-ischemic encephalopathy, and magnesium sulfate is recommended for maternal seizure prophylaxis among patients with preeclampsia with severe features. OBJECTIVE: (1) Determine trends in the incidence of hypertensive disorders of pregnancy, antenatal magnesium sulfate, and hypoxic-ischemic encephalopathy; (2) evaluate the association between hypertensive disorders of pregnancy and hypoxic-ischemic encephalopathy; and (3) evaluate if, among patients with hypertensive disorders of pregnancy, the odds of hypoxic-ischemic encephalopathy is mitigated by receipt of antenatal magnesium sulfate. STUDY DESIGN: We analyzed a prospective cohort of live births ≥36 weeks of gestation between 2012 and 2018 within the California Perinatal Quality Care Collaborative registry, linked with the California Department of Health Care Access and Information files. We used Cochran-Armitage tests to assess trends in hypertensive disorders, encephalopathy diagnoses, and magnesium sulfate utilization and compared demographic factors between patients with or without hypertensive disorders of pregnancy or treatment with magnesium sulfate. Hierarchical logistic regression models were built to explore if hypertensive disorders of pregnancy were associated with any severity and moderate/severe hypoxic-ischemic encephalopathy. Separate hierarchical logistic regression models were built among those with hypertensive disorders of pregnancy to evaluate the association of magnesium sulfate with hypoxic-ischemic encephalopathy. RESULTS: Among 44,314 unique infants, the diagnosis of hypoxic-ischemic encephalopathy, maternal hypertensive disorders of pregnancy, and the use of magnesium sulfate increased over time. Compared with patients with hypertensive disorders of pregnancy alone, patients with hypertensive disorders treated with magnesium sulfate represented a high-risk population. They were more likely to be publicly insured, born between 36 and 38 weeks of gestation, be small for gestational age, have lower Apgar scores, require a higher level of resuscitation at delivery, have prolonged rupture of membranes, experience preterm labor and fetal distress, and undergo operative delivery (all P<.002). Hypertensive disorders of pregnancy were associated with hypoxic-ischemic encephalopathy (adjusted odds ratio, 1.26 [95% confidence interval, 1.13-1.40]; P<.001) and specifically moderate/severe hypoxic-ischemic encephalopathy (adjusted odds ratio, 1.26 [95% confidence interval, 1.11-1.42]; P<.001). Among patients with hypertensive disorders of pregnancy, treatment with magnesium sulfate was associated with 29% reduction in the odds of neonatal hypoxic-ischemic encephalopathy (adjusted odds ratio, 0.71 [95% confidence interval, 0.52-0.97]; P=.03) and a 37% reduction in the odds of moderate/severe neonatal hypoxic-ischemic encephalopathy (adjusted odds ratio, 0.63 [95% confidence interval, 0.42-0.94]; P=.03). CONCLUSION: Hypertensive disorders of pregnancy are associated with hypoxic-ischemic encephalopathy and, specifically, moderate/severe disease. Among people with hypertensive disorders, receipt of antenatal magnesium sulfate is associated with a significant reduction in the odds of hypoxic-ischemic encephalopathy and moderate/severe disease in a neonatal cohort admitted to neonatal intensive care unit at ≥36 weeks of gestation. The findings of this observational study cannot prove causality and are intended to generate hypotheses for future clinical trials on magnesium sulfate in term infants.

Structural brain networks correlating with poststroke cognition.

Cognitive deficits are a common and debilitating consequence of stroke, yet our understanding of the structural neurobiological biomarkers predicting recovery of cognition after stroke remains limited. In this longitudinal observational study, we set out to investigate the effect of both focal lesions and structural connectivity on poststroke cognition. Sixty-two patients with stroke underwent advanced brain imaging and cognitive assessment, utilizing the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE), at 3-month and 12-month poststroke. We first evaluated the relationship between lesions and cognition at 3 months using voxel-based lesion-symptom mapping. Next, a novel correlational tractography approach, using multi-shell diffusion-weighted magnetic resonance imaging (MRI) data collected at both time points, was used to evaluate the relationship between the white matter connectome and cognition cross-sectionally at 3 months, and longitudinally (12 minus 3 months). Lesion-symptom mapping did not yield significant findings. In turn, correlational tractography analyses revealed positive associations between both MoCA and MMSE scores and bilateral cingulum and the corpus callosum, both cross-sectionally at the 3-month stage, and longitudinally. These results demonstrate that rather than focal neural structures, a consistent structural connectome underpins the performance of two frequently used cognitive screening tools, the MoCA and the MMSE, in people after stroke. This finding should encourage clinicians and researchers to not only suspect cognitive decline when lesions affect these tracts, but also to refine their investigation of novel approaches to differentially diagnosing pathology associated with cognitive decline, regardless of the aetiology.

Perceiving and misperceiving speech: lexical and sublexical processing in the superior temporal lobes.

Listeners can use prior knowledge to predict the content of noisy speech signals, enhancing perception. However, this process can also elicit misperceptions. For the first time, we employed a prime-probe paradigm and transcranial magnetic stimulation to investigate causal roles for the left and right posterior superior temporal gyri (pSTG) in the perception and misperception of degraded speech. Listeners were presented with spectrotemporally degraded probe sentences preceded by a clear prime. To produce misperceptions, we created partially mismatched pseudo-sentence probes via homophonic nonword transformations (e.g. The little girl was excited to lose her first tooth-Tha fittle girmn wam expited du roos har derst cooth). Compared to a control site (vertex), inhibitory stimulation of the left pSTG selectively disrupted priming of real but not pseudo-sentences. Conversely, inhibitory stimulation of the right pSTG enhanced priming of misperceptions with pseudo-sentences, but did not influence perception of real sentences. These results indicate qualitatively different causal roles for the left and right pSTG in perceiving degraded speech, supporting bilateral models that propose engagement of the right pSTG in sublexical processing.

Cardiovascular Health Trajectories in Adolescence and Their Association With Sociodemographic and Cardiometabolic Outcomes in Spain.

PURPOSE: To determine cardiovascular health (CVH) trajectories and their association with sociodemographic and cardiometabolic outcomes in adolescence. METHODS: One thousand eighty adolescents attending 24 secondary schools enrolled in the SI! Program for Secondary Schools trial in Spain were assessed at approximately 12, 14, and 16 years of age. CVH was assessed according to American Heart Association criteria based on seven metrics (smoking status, body mass index, physical activity, diet, blood pressure, total cholesterol, and blood glucose), and CVH trajectories were identified by latent class trajectory modeling. Associations between CVH trajectories, sociodemographic characteristics, and cardiometabolic outcomes were analyzed using generalized linear and Poisson models. RESULTS: Five CVH trajectory groups were identified: poor-stable (27 adolescents [2.5%]), intermediate-substantial rise (79 [7.3%]), intermediate-substantial decline (63 [5.8%]), intermediate-mild decline (403 [37.3%]), and intermediate-mild rise (508 [47.1%]). Boys and adolescents from families with low-average income, low-intermediate educational attainment, and a migrant background more frequently belonged to groups with lower baseline CVH and poor or declining trajectories. The intermediate-substantial decline group had the highest prevalence ratio for overweight/obesity (3.84; 95% confidence interval: 2.86-5.16) and metabolic syndrome (4.93; 95% confidence interval: 1.21-20.04) at age 16, whereas prevalence was lowest in the intermediate-mild rise group. DISCUSSION: Adolescent CVH trajectories differ according to socioeconomic characteristics and are associated with cardiometabolic outcomes. Primordial prevention interventions should be implemented early in life, taking into account CVH trajectories and with a particular focus on vulnerable populations.

Purchaser, firearm, and retailer characteristics associated with crime gun recovery: a longitudinal analysis of firearms sold in California from 1996 to 2021.

BACKGROUND: Firearm violence is a major cause of death and injury in the United States. Tracking the movement of firearms from legal purchase to use in crimes can help inform prevention of firearm injuries and deaths. The last state-wide studies analyzing crime gun recoveries used data from over 20 years ago; thus, an update is needed. METHODS: We used data for 5,247,348 handgun and 2,868,713 long gun transactions and law enforcement recoveries from California crime gun recovery (2010-2021) and California's Dealer Records of Sales records. Covariates included characteristics of dealership sales, firearms and their transactions, and purchaser's demographic characteristics, purchasing history, criminal history (from firearm purchaser criminal history records), and neighborhood socioeconomic status. Analyses for handguns and long guns was conducted separately. In multivariable analysis, we included correlates into a Cox proportional hazard model accounting for left truncation and clustering between the same firearm, purchaser, dealerships, and geographic location. Covariates that remained significant (P < 0.05) were retained. For handguns, we evaluated associations of violent and weapons crimes separately. In supplementary analyses, we examined interactions by purchasers' race and ethnicity. RESULTS: In total, 38,441 handguns (0.80%) and 6,806 long guns (0.24%) were recovered in crimes. A firearm dealer's sales volume, percent of transactions that were denials, pawns, pawn redemptions, and firearms that became crime guns were each positively associated with firearm recovery in crime. Handguns that were inexpensive, larger caliber, and that had been reported lost or stolen were positively associated with recovery in crimes. Purchaser characteristics associated with crime gun recovery included: being younger, female, Black, Hispanic, Native American or Pacific Islander, or other race/ethnicity (vs white), having previous arrests, living in close proximity to the firearm dealership, and living in a more socially vulnerable census tract. Associations with race and ethnicity were modified by previous infraction-only arrests. CONCLUSIONS: This study confirms that many previously studied correlates of firearm recovery are still relevant today. We were able to expand on previous research by examining novel associations including purchasers' criminal history and previous firearm transaction history. These results provide evidence that can be used to disrupt firearm use in crimes.

Development of Convolutional Neural Network to Segment Ultrasound Images of Histotripsy Ablation.

OBJECTIVE: Histotripsy is a focused ultrasound therapy that ablates tissue via the action of bubble clouds. It is under investigation to treat a number of ailments, including renal tumors. Ultrasound imaging is used to monitor histotripsy, though there remains a lack of definitive imaging metrics to confirm successful treatment outcomes. In this study, a convolutional neural network (CNN) was developed to segment ablation on ultrasound images. METHODS: A transfer learning approach was used to replace classification layers of the residual network ResNet-18. Inputs to the classification layers were based on ultrasound images of ablated red blood cell phantoms. Digital photographs served as the ground truth. The efficacy of the CNN was compared to subtraction imaging, and manual segmentation of images by two board-certified radiologists. RESULTS: The CNN had a similar performance to manual segmentation, though was improved relative to segmentation with subtraction imaging. Predictions of the network improved over the course of treatment, with the Dice similarity coefficient less than 20% for fewer than 500 applied pulses, but 85% for more than 750 applied pulses. The network was also applied to ultrasound images of ex vivo kidney exposed to histotripsy, which indicated a morphological shift in the treatment profile relative to the phantoms. These findings were consistent with histology that confirmed ablation of the targeted tissue. CONCLUSION: Overall, the CNN showed promise as a rapid means to assess outcomes of histotripsy and automate treatment. SIGNIFICANCE: Data collected in this study indicate integration of CNN image segmentation to gauge outcomes for histotripsy ablation holds promise for automating treatment procedures.

Polygenic Variation Underlying Educational Attainment and Attention-Deficit/Hyperactivity Disorder Indexes Behavior Ratings of Executive Functions in Child Psychiatry Outpatients.

OBJECTIVE: We leveraged common genetic variation underlying ADHD, educational attainment (EA) and cognition (COG) to understand the nature of the Behavior Rating Inventory for Executive Functions (BRIEF) and its relationship to academic functioning. METHOD: Participants were 991 youth, ages 7 to 17, consecutively referred for neuropsychiatric evaluation. Polygenic scores (PGS) for ADHD, EA, and COG were related to the BRIEF using regression analyses. Structural equation models were used to examine the associations between the PGS, BRIEF and academic outcomes (math, reading, and special education services [EDPLAN]). RESULTS: After modeling the PGS together, only the EA and ADHD PGS significantly associated with the BRIEF. The BRIEF partially mediated the relationships between EA PGS with math and EDPLAN and fully mediated the relationship between ADHD PGS and EDPLAN. CONCLUSION: Genetic data extend evidence that the BRIEF measures a construct relevant to educational success that differs from what is indexed by cognitive testing.

MAGA Republicans' views of American democracy and society and support for political violence in the United States: Findings from a nationwide population-representative survey.

BACKGROUND: Identifying groups at increased risk for political violence can support prevention efforts. We determine whether "Make America Great Again" (MAGA) Republicans, as defined, are potentially such a group. METHODS: Nationwide survey conducted May 13-June 2, 2022 of adult members of the Ipsos KnowledgePanel. MAGA Republicans are defined as Republicans who voted for Donald Trump in the 2020 presidential election and deny the results of that election. Principal outcomes are weighted proportions of respondents who endorse political violence, are willing to engage in it, and consider it likely to occur. FINDINGS: The analytic sample (n = 7,255) included 1,128 (15.0%) MAGA Republicans, 640 (8.3%) strong Republicans, 1,571 (21.3%) other Republicans, and 3,916 (55.3%) non-Republicans. MAGA Republicans were substantially more likely than others to agree strongly/very strongly that "in the next few years, there will be civil war in the United States" (MAGA Republicans, 30.3%, 95% CI 27.2%, 33.4%; strong Republicans, 7.5%, 95% CI 5.1%, 9.9%; other Republicans, 10.8%, 95% CI 9.0%, 12.6%; non-Republicans, 11.2%, 95% CI 10.0%, 12.3%; p < 0.001) and to consider violence usually/always justified to advance at least 1 of 17 specific political objectives (MAGA Republicans, 58.2%, 95% CI 55.0%, 61.4%; strong Republicans, 38.3%, 95% CI 34.2%, 42.4%; other Republicans, 31.5%, 95% CI 28.9%, 34.0%; non-Republicans, 25.1%, 95% CI 23.6%, 26.7%; p < 0.001). They were not more willing to engage personally in political violence. INTERPRETATION: MAGA Republicans, as defined, are more likely than others to endorse political violence. They are not more willing to engage in such violence themselves; their endorsement may increase the risk that it will occur.

Ophthalmic acid is a glutathione regulating tripeptide.

Since its discovery in 1958 in the lens of cows, ophthalmic acid (OPH) has stood in the shadow of its anti-oxidant analog: glutathione (GSH). Lacking the thiol group that gives GSH many of its important properties, ophthalmic acid's function has remained elusive, and it has been widely presumed to be an accidental product of the same enzymes. In this review, we compile evidence demonstrating that OPH is a ubiquitous metabolite found in bacteria, plants, fungi, and animals, produced through several layers of metabolic regulation. We discuss the limitations of the oft-repeated suggestions that aberrations in OPH levels should solely indicate GSH deficiency or oxidative stress. Finally, we discuss the available literature and suggest OPH's role in metabolism as a GSH-regulating tripeptide; controlling both cellular and organelle influx and efflux of GSH, as well as modulating GSH-dependent reactions and signaling. Ultimately, we hope that this review reinvigorates and directs more research into this versatile metabolite.

Does the External Pericardial Lateral Tunnel Fontan Pathway Enlarge to Accommodate Somatic Growth? A Preliminary Analysis.

Objectives: An ideal Fontan pathway should be capable of adapting to changes in circulatory demands. The external pericardial lateral tunnel Fontan (EPLTF) is constructed of viable, autologous tissue and may be capable of changing in size. We investigated the ability of the EPLTF to enlarge with increasing physiologic demands of somatic growth. Methods: Retrospective review of echocardiographic images for patients with a minimum of five years follow-up after EPLTF. Serial echocardiographic measurements of the EPLTF pathway were obtained at three distinct locations: the inferior vena cava junction with the EPLTF, midsection of the EPLTF, and cross-sectional area of the EPLTF visualized in a four-chamber view. Body surface area (BSA) was calculated at the time of each echocardiographic measurement. Changes in echocardiographic measurements over time were analyzed and compared with changes in BSA. Results: A total of 332 echocardiographic studies from 38 patients were reviewed. Significant enlargement of the EPLTF pathway is observed at the inferior vena caval junction (P < .001), midsection (P < .01), and cross-sectional area (P < .001). Repeated measures correlation between pathway measurements and BSA is highly significant (P < .001). Conclusions: The EPLTF pathway enlarges over time in correlation with increasing BSA. Further research is needed to define ideal pathway size, differentiate normal physiologic growth from pathologic enlargement, and correlate changes with clinical outcomes.

Trauma exposure and associated sleep problems in Black adolescent and young adult students attending an alternative high school.

OBJECTIVE: Given the dearth of literature examining the link between trauma exposure and sleep among youth and young adults of color, the current study examined the association between individual types of trauma exposure, accumulation within subtypes of trauma exposure, and overall cumulative trauma exposure with sleep problems in a sample of Black students attending an alternative high school. METHOD: Participants were recruited from an alternative high school in a large, southeastern city in the United States, of which all students qualify for free/reduced lunch. The sample included 101 students (53% female) ages 16-24 (M = 17.86 years, SD = 1.36) who identified as Black. RESULTS: Participants reported a high rate of trauma exposure (M = 6.03 unique traumatic experiences, SD = 2.63). Linear regression models showed that exposure to more overall cumulative trauma and to interpersonal loss was significantly associated with higher levels of insomnia symptoms. Threats to health were significantly related to daytime sleepiness. Other threats to safety were associated with restless legs syndrome symptoms. CONCLUSIONS: Adolescence and young adulthood are a time of complex sleep-related issues. Black youth and young adults have elevated risk of trauma exposure and sleep problems; therefore, targeted assessment and intervention are warranted. Clinicians and researchers addressing sleep in youth and young adults, and those working within alternative school settings, should also consider a trauma-informed lens to optimize outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).