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Dielectric metasurfaces have emerged as an unprecedented platform for precise wavefront manipulation at subwavelength scales with nearly zero loss. When aiming at dynamic applications such as AR/VR and LiDAR, high-quality factor (high-Q) phase gradient metasurfaces have emerged as a way to boost weak light-material interactions in flat-optical components. However, resonant features are naturally tied to polarization, limiting devices to operating on a single polarization state, which reduces the efficiency and adaptability of wave-shaping. Here, we propose polarization-independent high-Q phase gradient metasurfaces, where two cross-polarized dipolar guided mode resonances (DGMRs) with similar Q around 300 are spectrally aligned while being spatially tuned. Our simulations demonstrate that, by adding less than 5% geometric perturbation, the metasurface can steer arbitrarily polarized beams to 31° with diffraction efficiency >70%. These devices show potential for advancing programmable polarization-independent wavefront shaping and unlocking ways to efficiently sculpt nonlinear frequency generation and mixing processes.

Background: The understanding of the neural correlates of borderline personality disorder (BPD) is limited, but suggests alterations in limbic structures play a role in adult BPD. The developmental course of structural neural differences in BPD is unknown. Whether there is specificity for structural alterations in BPD compared with other psychiatric presentations, such as major depressive disorder (MDD), remains unexplored. The current study examined childhood trajectories of two limbic regions implicated in BPD, hippocampal and amygdala volume, as they relate to adolescent BPD symptoms as compared with MDD symptoms., Methods: Participants (N =175; 85 [48.6%] female) were from a 17-year longitudinal study of preschool depression. Participants completed up to 5 MRI scans from late childhood through adolescence. General linear models assessed the relationship between gray matter volume intercepts/slopes and BPD symptoms to understand the influence of the developmental trajectory of brain regions on BPD. Separate models assessed the relationship between MDD symptoms and volume intercepts to assess diagnostic specificity., Results: Lower childhood amygdala volume (intercept; age 13 centered) across scans was associated with higher adolescent BPD symptoms (β=-0.25, adj. p=.015). There was no relationship between the slope of amygdala volume and BPD symptoms. There was no relationship between hippocampal volume and BPD, nor any relationship between amygdala or hippocampal volume and MDD symptoms in adolescence., Conclusions: Our findings add evidence for the role of alterations in amygdala structure in BPD development. Decreased amygdala volume as early as age 13 may be an early indicator for the development of BPD in adolescence., (Copyright © 2025. Published by Elsevier Inc.)

Background: Intimate partner violence (IPV) poses a significant threat to the well-being of women and girls and is a highly prevalent form of gender-based violence. Evidence regarding the nutritional implications of IPV has focused primarily on intergenerational relationships with child nutrition and growth. There remains a knowledge gap regarding the association with women's own dietary intake., Objective: We investigated relationships between past year IPV (physical, emotional, sexual) and women's dietary habits, using the minimal dietary diversity tool (MDD-W)., Methods: The data sources analyzed were the cross-sectional Demographic and Health Surveys conducted in Cambodia (2021, N=5,618), Nepal (2022, N=4,155), Sierra Leone (2019, N=3,808), Nigeria (2018, N=8,313), Tajikistan (2017, N=4,792), Cote D'Ivoire (2022, N=3,654), Kenya (2022, N=10,717), and the Philippines (2022, N=12,240). Utilizing multivariable generalized linear models, we assessed the overall relationship between women's exposure to IPV and (i) the number of food groups consumed and (ii) minimum dietary diversity., Results: Our results reveal heterogeneous relationship patterns between IPV and women's diet. Although none of the pooled estimates were significant and there were large number of non-significant associations, IPV was associated with consuming a lower number of total food groups and reduced consumption of a diverse diet in Nigeria and the Philippines. There is evidence that in Tajikistan, physical violence relates to an increased number of food groups consumed., Conclusions: IPV is associated with altered dietary intake patterns within certain LMICs. The directionality of associations may depend on local food environments and food access. Further research is needed to clarify the pathways underlying these findings. These pathways may involve impacts of IPV that influence diet and food access, for example, mental health symptoms and disorders and related coping mechanisms., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2025. Published by Elsevier Inc.)

Autosomal dominant Alzheimer's disease (ADAD) is driven by rare variants in APP, PSEN1, and PSEN2. Although more than 200 pathogenic variants in these genes are known to cause ADAD, other variants are benign, may act as risk factors, or may even reduce Alzheimer's disease risk (e.g. protective). Classifying novel variants in APP, PSEN1, or PSEN2 as pathogenic, risk, benign, or protective is a critical step in evaluating disease risk profiles which further impacts eligibility for clinical trials focused on the ADAD population. Here, we classify 53 novel variants in APP, PSEN1, and PSEN2 based on bioinformatic data and cell-based assays. We identified 6 benign variants, 2 risk variants, and 32 likely pathogenic variants. Thirteen variants were associated with reduced Aβ levels in cell-based assays, consistent with a potential protective effect. Together, this study highlights the complexities associated with classification of rare variants in ADAD genes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

Colombia currently hosts nearly three million Venezuelan refugees and migrants and is home to seven million internally displaced Colombians. For forcibly displaced populations in Colombia, and especially for women, gender-based violence (GBV) poses a threat during transit and in their new homes where xenophobia, lack of accessible and adequate services, limited safe economic opportunities, and lack of information on access to services, further increase risk. The dearth of livelihood opportunities also affects forcibly displaced populations, especially women. This study will conduct a randomized-controlled trial (RCT) of HIAS' Entrepreneurship School with Gender Lens (ESGL), a program that targets forcibly displaced GBV survivors and women at-risk to help them develop business ideas, access needed support for the prevention of and response to GBV, and improve overall self-reliance. The RCT will be conducted within three cities in Colombia; approximately 80 eligible participants will be enrolled in each city and randomized to a treatment or control arm. Survey questionnaires will be administered to participants at baseline, eight months following baseline (endline), and 3-4 months after endline. Outcomes of interest include household self-reliance, mental health, resilience, empowerment, utilization of GBV services, and social support., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Stark et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Despite previous histopathologic evidence for its presence, the role of myocardial inflammation in the development and progression of cardiac transthyretin amyloidosis (ATTR-CA) remains insufficiently understood. Thus, this study sought to characterize the prevalence and potential prognostic implications of myocardial inflammation in ATTR-CA., Methods: A retrospective observational study including patients with ATTR-CA diagnosed by endomyocardial biopsy was conducted. Myocardial inflammation was diagnosed through a review of routine endomyocardial biopsy reports. Baseline characteristics were compared using the Mann-Whitney U test and the Pearson χ 2 test. Clinical outcomes were monitored via follow-up visits or telephone calls. Primary outcomes were all-cause death and a composite end point of all-cause death or heart failure hospitalization. Kaplan-Meier analyses, as well as univariable and age- and sex-adjusted multivariable Cox regression analyses, were used to assess differences in overall and composite end point-free survival between patients with ATTR-CA with and without myocardial inflammation., Results: A total of 103 patients with ATTR-CA (100 wild type; 3 variant) were enrolled. Median follow-up was 18.2 (8.0-31.1) months. Myocardial inflammation was prevalent in 32% (n=33/103) of patients with ATTR-CA. Among evaluable patients with myocardial inflammation, 96% (n=26/27) and 31% (n=9/29) had elevated CD68 (clusters of differentiation 68)-positive macrophage and CD3 (clusters of differentiation 3)-positive T-cell counts, respectively. Overall survival ( P =0.017) and composite end point-free survival ( P =0.014) were significantly impaired in patients with ATTR-CA with myocardial inflammation (n=33) compared with those without (n=70). Statistical significance for both associations was sustained after adjustment for age and sex, yielding adjusted hazard ratios of 4.72 (95% CI, 1.33-16.71; P =0.016) and 2.30 (95% CI, 1.04-5.11; P =0.041) for all-cause death and the composite end point, respectively., Conclusions: Our findings affirm previous evidence that myocardial inflammation is present in approximately one-third of all patients with ATTR-CA. Moreover, we provide first data indicating that myocardial inflammation may be associated with a higher risk of death and heart failure hospitalizations in ATTR-CA.

Background: Air pollution is a major public health threat globally. Health studies, regulatory actions, and policy evaluations typically rely on air pollutant concentrations from single exposure models, assuming accurate estimations and ignoring related uncertainty. We developed a modeling framework, bneR, to apply the Bayesian Nonparametric Ensemble (BNE) prediction model that combines existing exposure models as inputs to provide air pollution estimates and their spatio-temporal uncertainty., Methods: The bneR modeling framework (1) harmonizes air pollutant datasets to use standardized inputs for the BNE algorithm; (2) applies the BNE algorithm to obtain the posterior predictive distribution of pollutant concentrations; and (3) generates visualizations. We applied bneR to estimate NO 2 concentrations and characterize uncertainty levels at high spatio-temporal resolution (daily, 1 km 2 ) over New York State (NYS) for 2015. We met with stakeholders and modelers to discuss bneR user-friendliness and interpretation of its estimates., Results: Using bneR, we harmonized the spatial scale of four input NO 2 models (using the finer resolution, 1 km 2 for BNE estimations), applied BNE to obtain the NO 2 daily posterior predictive distribution, and visualized the results. Over NYS, the daily average NO 2 concentration was 6.0 (interquartile range, IQR: 4.6-6.8) pbb with daily average uncertainty (as SD) of 1.2 (IQR: 1.0-1.3) ppb. BNE performed well with cross-validated RMSE=2.84 ppb and R 2 =0.80., Conclusion: Meeting stakeholders and modelers allowed us to understand that efficient communication on how uncertainty is estimated and interpreted is a key feature for these communities to engage in using bneR and its data products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Objectives: The detection of renal cell carcinoma (RCC) tumors in the earlier stages is of great importance for more effective treatment. Encouraged by the key role of imaging in the management of RCC, we conducted a systematic review and meta-analysis of the studies that made use of artificial intelligence (AI) for the detection of RCC to quantitatively determine the performance of AI for distinguishing related renal lesions., Materials and Methods: PubMed, Scopus, CENTRAL, and Embase electronic databases were systematically searched in November 2024 to identify studies that applied AI for the detection or classification of RCC. We conducted a meta-analysis to evaluate the diagnostic performance of utilized algorithms. Moreover, meta-regression was conducted over suspected covariates to evaluate potential sources of inter-study heterogeneity. Publication bias and quality assessment were also done for the included studies., Results: Sixty-four studies were included in this systematic review, of which 31 studies were selected for meta-analysis. The studies assessing algorithms' performance on internal validation showed pooled sensitivity and specificity of 85% (95% confidence interval [CI], 82 to 87) and 76% (95% CI, 70 to 80), respectively. Moreover, externally validated Al algorithms had a pooled sensitivity and specificity of 80% (95% CI, 73 to 84) and 90% (95% CI, 84 to 93), respectively. Studies that performed internal validation for clinician performance had a pooled sensitivity of 79% (95% CI, 72 to 85) and specificity of 60% (95% CI, 49 to 70)., Conclusion: The findings of the present study validate the acceptable performance of AI algorithms when contrasted with medical professionals in the identification and categorization of RCC. Nevertheless, the presence of heterogeneity between studies and the absence of coherence in the results underscore the necessity for the cautious interpretation of these results and additional prospective studies., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The somato-cognitive action network (SCAN) consists of three nodes interspersed within Penfield's motor effector regions. The configuration of the somato-cognitive action network nodes resembles the one of the 'plis de passage' of the central sulcus: small gyri bridging the precentral and postcentral gyri. Thus, we hypothesize that these may provide a structural substrate of the somato-cognitive action network. Here, using microdissections of sixteen human hemispheres, we consistently identified a chain of three distinct plis de passage with increased underlying white matter, in locations analogous to the somato-cognitive action network nodes. We mapped localizations of plis de passage into standard stereotactic space to seed fMRI connectivity across 9,000 resting-state fMRI scans, which demonstrated the connectivity of these sites with the somato-cognitive action network. Intraoperative recordings during direct electrical central sulcus stimulation further identified inter-effector regions corresponding to plis de passage locations. This work provides a critical step towards improved understanding of the somato-cognitive action network in both structural and functional terms. Further, our work has the potential to guide the development of refined motor cortex stimulation techniques for treating brain disorders, and operative resective techniques for complex surgery of the motor cortex., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Introduction: Aging adults with Down syndrome (DS) accumulate Alzheimer's disease (AD) neuropathology, including amyloid beta plaques and neurofibrillary tangles, by age 40., Methods: We present findings from an individual with DS who remained cognitively stable despite AD neuropathology. Clinical assessments, fluid biomarkers, neuroimaging, and neuropathological examinations were conducted to characterize her condition., Results: Her apolipoprotein E was ε2/ε3 and genome-wide association study data indicated mosaicism. Neuroimaging revealed stable yet elevated amyloid and moderately elevated tau levels, while neuropathology indicated intermediate AD neuropathologic change with Lewy body and cerebrovascular pathologies. The participant demonstrated stable cognitive functioning in her 60s, potentially attributed to genetic variations, cognitive resilience, and environmental enrichment., Discussion: These findings emphasize the complexity of AD progression in DS. Further investigation into factors influencing cognitive resilience in individuals with DS is warranted. Understanding the mechanisms underlying cognitive stability in DS could offer insights into resilience to AD neuropathology in people with DS and inform future interventions., Highlights: Findings from clinical assessments, fluid biomarkers, genotyping, neuroimaging, and neuropathological examinations of an individual with Down syndrome (DS) who remained cognitively stable despite Alzheimer's disease (AD) neuropathology are presented. Neuroimaging revealed stable yet elevated amyloid profiles and moderately elevated tau levels, while neuropathology indicated intermediate AD neuropathologic change with Lewy body and cerebrovascular pathologies. Despite the presence of AD pathology, the participant demonstrated intact cognitive functioning, potentially attributed to genetic variations, cognitive resilience, and environmental enrichment, emphasizing the complexity of AD progression in DS., (© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objective: Surgical treatments for degenerative lumbar spinal disorders involve decompression of neural structures and arthrodesis to address pain from unstable intervertebral segments. Lumbar instrumented facet fusion (IFF), a less invasive technique, has shown positive short-term outcomes, but reports on its long-term outcomes are scarce. This study aims to report its long-term biomechanical stability and clinical outcomes., Methods: This single-center retrospective observational case-series included patients who underwent single or two-level IFF for degenerative lumbar spinal disorders from January 1996 to January 2021. Patient demographics, Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) scores, and radiographic fusion were assessed using flexion-extension radiographs and CT scans. Instrument failures and fusion segment angles were measured., Results: A total of 494 patients underwent instrumented facet fusion during the studied period. Of those, 208 were followed up for more than 24 months (mean follow-up of 89.96 +/- 55.59 months). The overall fusion rate was 92.05%. Revision surgery due to adjacent segmental disease was done in 11.06% of patients. Screw loosening was observed in 6 patients, of whom 2 underwent revision surgery. Significant improvements in ODI and VAS were observed., Conclusion: Instrumented facet fusion is a safe and less invasive alternative method of lumbar spinal arthrodesis with comparable fusion rate and clinical outcome. This method show relatively low revision rate., (Copyright © 2025. Published by Elsevier Inc.)

Introduction: Recent guidance from the National Alzheimer's Coordinating Center (NACC) recommends remuneration for all Alzheimer's disease (AD) research participants. Given AD research recruitment challenges, we assessed the remuneration practices at Alzheimer's Disease Research Centers (ADRCs)., Methods: We surveyed 37 ADRCs about remuneration for longitudinal research participants. This included type of remuneration (i.e., compensation, reimbursement) and which study procedures are remunerated. We had a 100% response rate., Results: Most ADRCs (32/37) provide some remuneration but amounts and types varied. Most ADRCs reimburse for travel or food (n = 29), compensate for some study procedures (n = 32), but most do not remunerate study partners (n = 12) or offer financial incentives (n = 8). Few (n = 6) ADRCs pay for all procedures., Discussion: Two areas for potential change are compensating for annual clinical and cognitive assessments that are compulsory, and for study partners. Evaluation of the impact of remuneration on recruitment and retention is needed, including for underrepresented groups., Highlights: Recent guidance recommends remuneration for Alzheimer's disease research participants. We surveyed all Alzheimer's Disease Research Centers about their remuneration practices. Most centers provide some form of remuneration to participants but this is variable. Potential areas for change are remuneration for study partners and annual study visits. Evaluating the impact of remuneration on recruitment and retention is needed., (© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Pathogenic variants in TGFB3 may lead to a syndromic genetic aortopathy. Heritable thoracic aortic disease (HTAD) and arterial events may occur in TGFB3 -related disease but there are limited outcomes data on vascular events in this condition., Methods: Clinical data, phenotypical features and aortic outcomes in individuals with pathogenic/likely pathogenic (P/LP) TGFB3 variants enrolled in the Montalcino Aortic Consortium registry were reviewed., Results: 34 individuals (56% male, median age 42 years, IQR 17-49, range 3-74 years) with P/LP TGFB3 variants were studied. Craniofacial, cutaneous and musculoskeletal features seen in Loeys-Dietz syndrome were variably present. Extra-aortic cardiovascular features included arterial tortuosity (25%), extra-aortic arterial aneurysms (6%) and mitral valve prolapse (21%).Aortic dilation (Z-Score>2) was present in 10 individuals (29%) and aortic dissection occurred in 2 (6%). Type A aortic dissection occurred in two patients (aged between 55 years and 60 years), and one of these patients experienced a type B aortic dissection 6 years later. Seven adults (median age 62 years, range 32-69 years) with aortic root dilation (41-49 mm) are being followed. No patients have undergone prophylactic aortic surgery. Twenty-five per cent of children have aortic dilation. Sixty-eight per cent of the entire cohort remains free of aortic disease. No deaths have occurred., Conclusions: TGFB3 -related HTAD is characterised by late-onset and less penetrant thoracic aortic and arterial disease compared with other transforming growth factor β HTAD. Based on our data, a larger aortic size threshold for prophylactic aortic surgery is appropriate in patients with TGFB3 -related HTAD compared with HTAD due to TGFBR1 or TGFBR2 variants., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Preschool-onset major depressive disorder (PO-MDD) is an impairing pediatric mental health disorder that impacts children as young as three years old. There is limited work dedicated to uncovering neural measures of this early childhood disorder which could be leveraged to further understand both treatment responsiveness and future depression risk. Event-related potentials (ERPs) such as the P300 have been employed extensively in adult populations to examine depression-related deficits in cognitive and motivational systems. Few studies examine the prospective relationships between depression and P300, especially in young children. Moreover, limited research examines the relationship between P300 with psychotherapy treatment responsiveness in youths. The current study sought to examine the prospective relationships between pre-intervention P300 (i.e., choice-locked) elicited from the doors task in depressed preschool children (i.e., PO-MDD; ages 3-to-6) with reductions in depressive symptoms after completing an 18-week long dyadic psychotherapy intervention (n = 59). We also explored relations to risk for depression assessed at a follow-up visit during preadolescence (ages 8-to-12; n = 82). Those with PO-MDD exhibiting reduced choice (doors)-locked P300 demonstrated worse treatment response to psychotherapy and were more likely to meet criteria for depression during preadolescence. Moreover, the relationship between pre-intervention P300 and later preadolescence depression was significantly mediated by response to treatment. These findings suggest that deficits in brain systems linked to the choice-locked P300 component (i.e., cognitive and motivational) might be indicative of non-responsiveness to early dyadic psychotherapeutic intervention efforts for depression which impacts risk for recurrent patterns of depression in youths., Competing Interests: Compliance with Ethical Standards. Funding: National Institute of Mental Health Grants K23MH118426 (DJW); R01MH090786 (DJW & KEG); K01MH127412 (LH), and R01MH117436 (JLL & DMB). Conflict of Interest: The authors have no conflicts of interest to declare that are relevant to the content of this article. Ethical Approval: The study was approved by the Institutional Review Board at Washington University School of Medicine. Informed Consent: Informed written consent was provided to families and obtained before participation in the current project., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Functional magnetic resonance imaging (fMRI) has dramatically advanced non-invasive human brain mapping and decoding. Functional near-infrared spectroscopy (fNIRS) and high-density diffuse optical tomography (HD-DOT) non-invasively measure blood oxygen fluctuations related to brain activity, like fMRI, at the brain surface, using more-lightweight equipment that circumvents ergonomic and logistical limitations of fMRI. HD-DOT grids have smaller inter-optode spacing (~ 13 mm) than sparse fNIRS (~ 30 mm) and therefore provide higher image quality, with spatial resolution ~ 1/2 that of fMRI, when using the several source-detector distances (13-40 mm) afforded by the HD-DOT grid. Herein, simulations indicated reducing inter-optode spacing to 6.5 mm, creating a higher-density grid with more source-detector distances, would further improve image quality and noise-resolution tradeoff, with diminishing returns below 6.5 mm. We then constructed an ultra-high-density DOT system (6.5-mm spacing) with 140 dB dynamic range that imaged stimulus-evoked activations with 30-50% higher spatial resolution and repeatable multi-focal activity with excellent agreement with participant-matched fMRI. Further, this system decoded visual stimulus position with 19-35% lower error than previous HD-DOT, throughout occipital cortex., Competing Interests: Declarations. Competing interests: Drs. Culver and Trobaugh have financial ownership interests in EsperImage LLC and may financially benefit from products related to this research. The authors declare no other competing interests., (© 2025. The Author(s).)

Background: Cerebral edema (CED) is associated with poorer outcome in patients with acute ischemic stroke (AIS). The aim of the study was to investigate the factors contributing to greater early CED formation in patients with AIS who underwent endovascular therapy (EVT) and its association with functional outcome., Methods: We conducted a multicenter cohort study of patients with an anterior circulation AIS undergoing EVT. The volume of cerebrospinal fluid (CSF) was extracted from baseline and 24-hour follow-up CT using an automated algorithm. The severity of CED was quantified by the percentage reduction in CSF volume between CT scans (∆CSF). The primary endpoint was a shift towards an unfavorable outcome, assessed by modified Rankin Scale (mRS) score at 3 months. Multivariable ordinal logistic regression analyses were performed. The ∆CSF threshold that predicted unfavorable outcome was selected using receiver operating characteristic curve analysis., Results: We analyzed 201 patients (mean age 72.7 years, 47.8% women) in whom CED was assessable for 85.6%. Higher systolic blood pressure during EVT and failure to achieve modified Thrombolysis In Cerebral Infarction (mTICI) 3 were found to be independent predictors of greater CED. ∆CSF was independently associated with the probability of a one-point worsening in the mRS score (common odds ratio (cOR) 1.05, 95% CI 1.03 to 1.08) after adjusting for age, baseline mRS, National Institutes of Health Stroke Scale (NIHSS), and number of passes. Displacement of more than 25% of CSF was associated with an unfavorable outcome (OR 6.09, 95% CI 3.01 to 12.33) and mortality (OR 6.72, 95% CI 2.94 to 15.32)., Conclusions: Early CED formation in patients undergoing EVT was affected by higher blood pressure and incomplete reperfusion. The extent of early CED, measured by automated ∆CSF, was associated with worse outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Inflammation contributes to morbidity following subarachnoid hemorrhage (SAH). The authors of this study evaluate how applying noninvasive transauricular vagus nerve stimulation (taVNS) can target this deleterious inflammatory response following SAH and reduce the rate of radiographic vasospasm., Methods: In this prospective, triple-blinded, randomized controlled trial, 27 patients were randomized to taVNS or sham stimulation. Serial blood and CSF samples were collected every 3 days to quantify inflammatory markers. Radiographic cerebral vasospasm severity and functional outcomes (modified Rankin Scale scores) were analyzed., Results: No adverse events occurred. Radiographic vasospasm was significantly reduced (p = 0.018), with serial vessel caliber measurements demonstrating a more rapid return to normal than in the sham-treated group (p < 0.001). In the taVNS group, tumor necrosis factor-α was significantly reduced in both plasma (days 7 and 10) and CSF (day 13); interleukin-6 was also significantly reduced in plasma (day 4) and CSF (day 13) (p < 0.05). Patients receiving taVNS had higher rates of favorable outcomes at discharge (38.4% vs 21.4%) and first follow-up (76.9% vs 57.1%). Patients treated with taVNS had significant improvement in modified Rankin Scale scores from admission to first follow-up (p = 0.014), unlike patients in the sham-treated group (p = 0.18). The taVNS group had a significantly lower rate of discharge to a skilled nursing facility or hospice (p = 0.04)., Conclusions: taVNS is a noninvasive method of neuro- and systemic immunomodulation. This trial supports the finding that taVNS following SAH can mitigate the inflammatory response, reduce radiographic vasospasm, and potentially improve functional and neurological outcomes.

Objective: To determine whether chronodisruption is associated with achieving pregnancy., Design: Pilot prospective cohort study., Subjects: One hundred eighty-three women desiring pregnancy were recruited from the local community of an academic medical center located in the Midwest and provided sleep information between February 1, 2015, and November 30, 2017., Exposure: Sleep and activity data were obtained via actigraphy watches worn continuously for two weeks to assess measures of chronodisruption, including sleep period onset, offset, mid-time, and duration; as well as variability in each of these measures., Main Outcome Measures: Time to becoming pregnant over one-year of follow-up., Results: Of the 183 eligible women, 82 became pregnant over a median of 2.8 months of follow-up. Greater inter-daily variability in time of sleep onset and variability in sleep duration were associated with a longer time to achieving pregnancy after adjusting for age, body mass index, race, education, income, and smoking status (adjusted hazard ratio [aHR] 0.60, 95% CI 0.36 - 0.999 comparing participants with a standard deviation of >1.8 hours to <1.8 hours in daily time of sleep onset; and aHR 0.58, 95% CI 0.36-0.98 comparing participants with a standard deviation of > 2.3 hours to <2.3 hours in daily sleep duration). In adjusted analyses, no statistically significant associations were observed for average time of sleep onset and offset, mid-sleep time, and sleep duration; or for variability in time of sleep offset and mid-time., Conclusion: Higher day-to-day variability in time of sleep onset and sleep duration - two measures of chronodisruption - were associated with a longer time to achieving pregnancy over one year of follow-up in women desiring pregnancy. If replicated in additional studies, these findings could point to lifestyle interventions to help women achieve a desired pregnancy., (Copyright © 2025. Published by Elsevier Inc.)

The Jezero crater floor features a suite of related, iron-rich lavas that were examined and sampled by the Mars 2020 rover Perseverance, and whose textures, minerals, and compositions were characterized by the Planetary Instrument for X-ray Lithochemistry (PIXL). This suite, known as the Máaz formation (fm), includes dark-toned basaltic/trachy-basaltic rocks with intergrown pyroxene, plagioclase feldspar, and altered olivine and overlying trachy-andesitic lava with reversely zoned plagioclase phenocrysts in a K-rich groundmass. Feldspar thermal disequilibrium textures indicate that they were carried from their crustal staging area. Bulk and mafic minerals have very high FeO and low MgO to FeO total ratios, which are partially reproduced by thermodynamic models involving high-degree fractional crystallization of a gabbroic assemblage and possibly also assimilation of iron-rich basement. Together, these in situ constraints on petrogenesis provide a uniquely detailed record of intracrustal processes beneath Jezero crater during a time period not represented by Mars samples to date.

Tumors are complex ecosystems of interacting cell types. The concept of cancer hallmarks distills this complexity into underlying principles that govern tumor growth. Here, we explore the spatial distribution of cancer hallmarks across 63 primary untreated tumors from 10 cancer types using spatial transcriptomics. We show that hallmark activity is spatially organized, with the cancer compartment contributing to the activity of seven out of 13 hallmarks, while the tumor microenvironment (TME) contributes to the activity of the rest. Additionally, we discover that genomic distance between tumor subclones correlates with differences in hallmark activity, even leading to clone-hallmark specialization. Finally, we demonstrate interdependent relationships between hallmarks at the junctions of TME and cancer compartments and how they relate to sensitivity to different neoadjuvant treatments in 33 bladder cancer patients from the DUTRENEO trial. In conclusion, our findings may improve our understanding of tumor ecology and help identify new drug biomarkers., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

While media reports of educator sexual misconduct (ESM) often note educators' use of electronic communication, few have systematically explored electronic communication use in ESM. This study describes educators who use electronic communication when committing sexual misconduct and the nature of this communication. The author inductively and deductively coded Kentucky Education Professional Standards Board disciplinary action records ( N  = 74) to descriptively and statistically analyze electronic communication use by educator characteristics. In this sample, most educators used electronic communication and committed misconduct both in-person and through electronic means. Educators who were male, taught middle school, or held a Rank III certification more often committed misconduct solely through electronic communication. Future research recommendations and ESM prevention, such as proactive policies and trainings targeting electronic communication, are discussed.

Purpose: Innate immune cell-based therapies have shown promising antitumor activity against solid and hematologic malignancies. AFM24, a bispecific innate cell engager, binds CD16A on natural killer (NK) cells/macrophages and EGFR on tumor cells, redirecting antitumor activity towards tumors. The safety and tolerability of AFM24 was evaluated in this Phase 1/2a dose escalation/dose expansion study in patients with recurrent or persistent, advanced solid tumors known to express EGFR., Methods: The main objective in Phase 1 was to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). The primary endpoint was the incidence of dose-limiting toxicities (DLTs) during the observation period. Secondary endpoints included the incidence of treatment emergent adverse events and pharmacokinetics., Results: In the dose escalation phase, 35 patients received AFM24 weekly across seven dose cohorts (14-720 mg). One patient experienced a DLT of Grade 3 infusion-related reaction (IRR). IRRs were mainly reported after the first infusion; these were manageable with premedication and a gradual increase in infusion rate. Pharmacokinetics were dose-proportional and CD16A receptor occupancy on NK cells approached saturation between 320-480 mg. Paired tumor biopsies demonstrated activation of innate and adaptive immune responses within the tumor. Best objective response was stable disease in 10/35 patients; four had stable disease for 4.3-7.1 months., Conclusions: AFM24 was well tolerated with 480 mg established as the RP2D. AFM24 could be a novel therapy for patients with EGFR-expressing solid tumors with suitable tolerability and appropriate pharmacokinetic properties for further development in combination with other immuno-oncology therapeutics.

Competing Interests: Competing interests: The authors declare no competing interests.

Branch-point syntheses in nonribosomal peptide assembly are rare but useful strategies to generate tripodal peptides with advantageous hexadentate iron-chelating capabilities, as seen in siderophores. However, the chemical logic underlying the peptide branching by nonribosomal peptide synthetase (NRPS) often remains complex and elusive. Here, we review the common strategies for the biosynthesis of branched nonribosomal peptides (NRPs) and present our biochemical investigation on the NRPS-catalyzed assembly of fimsbactin A, a branched mixed-ligand siderophore produced by the human pathogenic strain Acinetobacter baumannii . We untangled the unusual branching mechanism of fimsbactin A biosynthesis through a combination of bioinformatics, site-directed mutagenesis, in vitro reconstitution, molecular modeling, and molecular dynamics simulation. Our findings clarify the roles of the fimsbactin NRPS enzymes, uncovering catalytically redundant domains and identifying the multifunctional nature of the FbsF cyclization (Cy) domain. We demonstrate the dynamic interplay between l-serine and 2,3-dihydroxybenzoic acid derived dipeptides, partitioning between amide and ester forms via a 1,2- N -to- O -acyl shift orchestrated by the noncanonical, multichannel FbsF Cy domain. The branching event occurs in a secondary condensation event facilitated by this Cy domain with two dipeptidyl intermediates, which generates a branched tetrapeptide thioester. Finally, the terminal condensation domain of FbsG recruits a soluble nucleophile to release the final product. This study advances our understanding of the intricate biosynthetic pathways and chemical logic employed by NRPSs, shedding light on the mechanisms underlying the synthesis of complex branched peptides.

Dysregulation of genes encoding the homologous to E6AP C-terminus (HECT) E3 ubiquitin ligases has been linked to cancer and structural birth defects. One member of this family, the HECT-domain-containing protein 1 (HECTD1), mediates developmental pathways, including cell signaling, gene expression, and embryogenesis. Through GeneMatcher, we identified 14 unrelated individuals with 15 different variants in HECTD1 (10 missense, 3 frameshift, 1 nonsense, and 1 splicing variant) with neurodevelopmental disorders (NDDs), including autism, attention-deficit/hyperactivity disorder, and epilepsy. Of these 15 HECTD1 variants, 10 occurred de novo, 3 had unknown inheritance, and 2 were compound heterozygous. While all individuals in this cohort displayed NDDs, no genotype-phenotype correlation was apparent. Conditional knockout of Hectd1 in the neural lineage in mice resulted in microcephaly, severe hippocampal malformations, and complete agenesis of the corpus callosum, supporting a role for Hectd1 in embryonic brain development. Functional studies of select variants in C. elegans revealed dominant effects, including either change-of-function or loss-of-function/haploinsufficient mechanisms, which may explain phenotypic heterogeneity. Significant enrichment of de novo variants in HECTD1 was also shown in an independent cohort of 53,305 published trios with NDDs or congenital heart disease. Thus, our clinical and functional data support a critical requirement of HECTD1 for human brain development., Competing Interests: Declaration of interests K.G.M. and M.J.G.S. are employees of GeneDx, LLC., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Determine if molecular classification using mismatch repair (MMR) and p53 protein expression predicts recurrence-free survival (RFS) and overall survival (OS) in endometrial cancer (EC) patients treated with chemotherapy and radiation (CRT) versus chemotherapy (CT)., Methods: GOG-0258, a phase III randomized trial (NCT00942357), compared CRT to CT. Immunohistochemistry assessed MMR and p53 status. Kaplan-Meier curves and adjusted Cox models analyzed survival outcomes by molecular subtype., Results: ECs classified as deficient MMR (dMMR) (27 %), p53 abnormal (p53abn) (24 %), and p53 wild type (p53wt) (49 %). p53abn were more frequent in patients that were older, Black, and had serous histology (p < 0.001). Median follow up was 113 months. Five-year RFS and OS were worse with p53abn (29 % [Hazard Ratio (HR) = 3.39 (95 % Confidence Interval (CI): 2.34-4.91)] and 39 % [HR = 4.64 (95 % CI: 3.16-6.79)] compared to those with p53wt (referent) (p < 0.001). The five-year RFS and OS for dMMR cancers were (58 % [HR = 1.30 (95 % CI: 0.85-1.97)] and 77 % [HR = 1.53 (95 % CI: 0.99-2.36)] compared to those with p53wt (69 % and 85 %). After adjusting for age, gross residual disease, and treatment, p53wt improved RFS with CRT compared to CT in an exploratory analysis (77 % vs 60 %; HR = 0.54 (95 % CI: 0.32-0.94). The 5-year and 10-year OS rates were similar in CRT compared to CT in all subgroups., Conclusion: Molecular classification appears to be predictive and prognostic, with worse survival in those with p53abn tumors. In an exploratory analysis, p53wt appears to predict improved RFS, favoring CRT over CT. There was no difference in treatment efficacy based on molecular subtype for OS., Competing Interests: Declaration of competing interest Dr. Aine Clements received payment to Duke for tumor testing for research project from American Association of OB/Gyn Foundation Bridge Award, Ohio Health Research Institute Agreement, and Kay Yow Cancer Fund/The V Foundation for Cancer Research. Dr. Danielle Enserro received Cooperative group/NCTN Grant Funding for all aspects of this trial, including travel to Group meetings, study monitoring, statistical analysis, manuscript writing, etc. Dr. Kyle C. Strickland received support to attend meetings from Labcorp. He also owns Labcorp stock and is employed by Labcorp. Dr. Rebecca A. Previs received support to attend meetings from Labcorp. She also owns Labcorp stock and is employed by Labcorp. Dr. David Mutch received an NIH p50 Route 66 Endometrial SPORE P50CA265793 grant/contract. Dr. Matthew Powell received consulting fees from GSK, Merck, AstraZeneca, Aadi Bioscience, Genmab, Seagen and Eisai. Dr. David S. Miller's institution received grants/contracts from Advenchen, Forty Seen, Merck, Syros, US BIOTEST, Regeneron and Karyopharm. He also received consulting fees from Karyopharm, Incyte, Eisai, Merck, GlaxoSmithKline and Immunogen. Dr. Casey Cosgrove's institution received research support from GSK. She received payment for authorship from UpToDate. She received personal consulting fees from GSK, Intuitive and Merck. She received support for attending meetings and/or travel from the GOG. She also participated on an Advisory Board from GSK. Dr. Mark S. Shahin received consulting fees from GSK, AZ, Eisai, Abbvie/Immunogen, Pizer/Genmab. He also has a leadership or fiduciary role in Unite For Her. Dr. Bradley Corr participated on Advisory Boards for GSK, Immunogen, AstraZeneca, Eisai, Gilead, Zentalis, Merck and Corecept. Dr. Angeles Alvarez Secord's institution received clinical trial grants from Abbvid, Aravive, AstraZeneca, Clovis, Eisai, Ellipses GSK, I-MAB Biopharma, Merck, Oncoquest/Canaria Bio, Roche, Genentech, Seagen Inc., VBL Therapeutics and Zentalis. Her institution received grants from Mersana and Myriad for translational research, as well as clinical trial grants and grant for translational research from Immunogen. She received payment to herself for Educational Program events including Curio Science, @Point of Care, Clinical Care Options, ASCO, Peerview, Research to Practice, Bio ASCEND, GOG Foundation, and Clinical HMP Global Great Debates. She personally received support for attending meetings and/or travel to from GOG Foundation, NRG Oncology, Society of Gynecologic Oncology. She has also participated (uncompensated) on Data Safety Monitoring Board or Advisory Board for AstraZeneca, Clovis, Gilead, GSK, Immunogen, Imvax, Merck, Mersana, Natera, Oncoquest/CanariaBio, and Onconova and (compensated) an Advisory Board for AbbVie. She received stock options from Amgen ($570.20) and Johnson & Johnson ($178.96) and royalities from UpToDate. She received payment to herself from GOG Foundation. She received payment from the GOG Foundation Board of Directors; to her institution for serving as NRG Committee Vice Chair; and uncompensated for SGO Board of Directors; FWC Board of Director; AAOGF Board of Trustees and AGOS Council. All other co-authors have no Conflicts of Interest to disclose., (Copyright © 2025. Published by Elsevier Inc.)

Importance: Given the favorable overall prognosis of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) and the morbidity of increased adjuvant therapy associated with positive surgical margins, large-scale studies on the accuracy of frozen sections in predicting final surgical margin status in HPV-related OPSCC are imperative. Final surgical margin status is the definitive assessment of tumor clearance as determined through surgeon-pathologist collaboration based on permanent analysis of frozen section margins, main specimens, and supplemental resections., Objectives: To assess the accuracy and testing properties of intraoperative frozen section histology (IFSH) in assessing final surgical margin status in patients undergoing transoral surgery for HPV-related OPSCC., Design, Setting, and Participants: This retrospective, single-institution cohort study was conducted at the Washington University in Saint Louis School of Medicine and included 299 patients who underwent transoral surgery for HPV-related OPSCC between January 2015 and December 2021 who were identified using an institutional cancer registry. Forty-five patients were excluded due to piecemeal resections, no frozen sections sent during surgery, unknown primaries, or no residual tumor identified during surgery after a diagnostic biopsy. Pathology reports of patients with at least 1 margin assessed by IFSH were reviewed. The data were analyzed between January and February 2024., Main Outcomes and Measures: The accuracy of IFSH for individual margins and overall final surgical margin status was evaluated through calculating sensitivity, specificity, positive predictive values, and negative predictive values from 1482 margins from 254 patients., Results: Of 254 participants, 29 (11.4%) were female, and the mean (SD) age was 60.7 (9.4) years. IFSH demonstrated an accuracy of 97.1%, sensitivity of 72.2%, and specificity of 99.1% for individual margins compared with final pathology results of the same tissue. However, IFSH had a sensitivity of only 21.7% in determining the overall final surgical margin status, with 18 patients (7.1%) having at least 1 positive margin undetected intraoperatively. Positive final surgical margin status was associated with worse disease-specific survival (hazard ratio, 3.26; 95% CI, 1.05-10.13) and higher rates of locoregional recurrence (hazard ratio, 5.02; 95% CI, 1.25-20.19), while no definitive conclusion can be made about the prognostic effect of final tumor specimen histopathology status due to imprecision in the effect size estimates., Conclusion: The study results suggest that despite high accuracy for individual margins, IFSH has limitations in predicting final surgical margin status in HPV-related OPSCC, particularly for base of tongue primaries and deep margins. However, IFSH remains important for guiding intraoperative reresection and is associated with improved oncologic outcomes.

Importance: Fracture-related infection (FRI) is a serious complication following fracture fixation surgery. Current treatment of FRIs entails debridement and 6 weeks of intravenous (IV) antibiotics. Lab data and retrospective clinical studies support use of oral antibiotics, which are less expensive and may have fewer complications than IV antibiotics., Objective: To evaluate the effectiveness of treatment of FRI with oral vs IV antibiotics., Design, Setting, and Participants: The POvIV multicenter, prospective randomized clinical trial was conducted across 24 trauma centers in the US among patients aged 18 to 84 years who had fracture repair or arthrodesis with fixation with implants and developed an FRI without radiographic evidence of osteomyelitis. Patients were enrolled between March 2013 and September 2018 and followed up for 12 months after hospitalization for treatment of their FRI., Intervention: Oral vs IV antibiotics following FRI., Main Outcomes and Measures: The primary outcome was number of surgical interventions, and the primary hypothesis was noninferiority of oral vs IV antibiotics with respect to the number of study injury-related surgical interventions by 1 year. Unadjusted modified intent-to-treat (mITT) and adjusted per-protocol (PP) analyses were prespecified. A post hoc adjusted mITT analysis was conducted to resolve discrepancies between the results of the prespecified mITT and PP analyses. Recurrence of a deep surgical site infection was a key secondary outcome., Results: Among 233 total patients, mean (SD) age was 46.0 (13.9) years, and 53 patients were female (22.7%). The mean number of surgical interventions within 1 year was 1.3 and 1.1 for the oral and IV groups, respectively. The upper bound of the 95% confidence interval of the mean difference with unadjusted mITT analysis was 0.59, which was lower than the prespecified noninferiority margin of 0.67, indicating noninferiority of oral to IV antibiotics. Adjusted PP analysis did not support noninferiority of the number of reoperations. A post hoc adjusted mITT analysis also showed noninferiority. The treatment effects estimates for the key secondary outcome of reinfection showed a similar pattern as those for the primary outcome., Conclusions and Relevance: In this prospective randomized clinical trial, oral antibiotic treatment was noninferior to IV treatment with respect to the primary outcome of number of surgical interventions based on mITT analysis. However, there is some uncertainty in these findings based on preplanned and post hoc secondary analyses. A similar pattern of treatment effect estimates was observed for the secondary outcome of recurrence of infection., Trial Registration: ClinicalTrials.gov Identifier: NCT01714596.

Microorganisms adapted to high hydrostatic pressures at depth in the oceans and within the subsurface of Earth's crust represent a phylogenetically diverse community thriving under extreme pressure, temperature, and nutrient availability conditions. To better understand the microbial function, physiological responses, and metabolic strategies at in-situ conditions requires high-pressure (HP) continuous culturing techniques that, although commonly used in bioengineering and biotechnology applications, remain relatively rare in the study of the Earth's microbiomes. Here, we focus on recent developments in the design of HP chemostats, with particular emphasis on adaptations for delivery and sampling of dissolved gases. We present protocols for sterilization, inoculation, agitation, and sampling strategies that minimize cell lysis, applicable to a wide range of chemostat designs.

The hydrolysis rates of many organic chemicals are accelerated under alkaline conditions by the presence of hydroxide (HO - ), which is typically assumed to be the predominant species contributing to base-catalyzed hydrolysis in both natural waters and laboratory buffers used in standard protocols. In this study, we demonstrated that weak bases (e.g., carbonates and phosphates) are able to catalyze the hydrolysis of the proherbicide isoxaflutole, an emerging contaminant of concern in water resources, under conditions relevant to both natural waters and laboratory protocols. Second-order rate constants for isoxaflutole hydrolysis catalyzed by individual bases were correlated with the p K a , resulting in hydrolysis rates predicted in natural waters overestimated by 5- to 30-fold from pH 7.0 to 8.5. In comparison, our corrected rate constants accurately predicted isoxaflutole hydrolysis measured in natural waters within a factor of 5. While isoxaflutole hydrolysis in surface water remains predominantly catalyzed by HO - following standard assumptions, carbonate species (particularly bicarbonate) are predicted to drive the reaction in as many as 83% of groundwater systems.- following standard assumptions, carbonate species (particularly bicarbonate) are predicted to drive the reaction in as many as 83% of groundwater systems.

Recent studies have demonstrated the ability to switch weakly coupled interlayer magnetic orders by using electric polarization in insulating van der Waals heterostructures. However, controlling strongly coupled intralayer magnetic orders remains a significant challenge. In this work, we propose that frustrated multiferroic heterostructures can exhibit enhanced intralayer magnetoelectric coupling. Through first-principles calculations, we have investigated a heterostructure composed of MnBr 2 and Nb 3 I 8 , wherein there is a competition between frustrated intralayer magnetic orders within the MnBr 2 and interlayer magnetic coupling via a unique spin-local field effect. As a result, manipulating the vertical electric polarization of the Nb 3 I 8 layer successfully controls the ground-state intralayer magnetic order in the frustrated MnBr 2 layer, inducing transitions between zigzag antiferromagnetic and ferromagnetic orders. Our findings offer a novel approach to controlling intralayer spin structures, paving the way for advancements in spintronic applications in a single atomic layer, which cannot be achieved by interlayer magnetoelectric coupling.

The field of artificial intelligence (AI) has entered a new cycle of intense opportunity, fueled by advances in deep learning, including generative AI. Applications of recent advances affect many aspects of everyday life, yet nowhere is it more important to use this technology safely, effectively, and equitably than in health and health care. Here, as part of the National Academy of Medicine's Vital Directions for Health and Health Care: Priorities for 2025 initiative, which is designed to provide guidance on pressing health care issues for the incoming presidential administration, we describe the steps needed to achieve these goals. We focus on four strategic areas: ensuring safe, effective, and trustworthy use of AI; promotion and development of an AI-competent health care workforce; investing in AI research to support the science, practice, and delivery of health and health care; and promotion of policies and procedures to clarify AI liability and responsibilities.

Introduction: Prostate cancer (PCa) is the most commonly diagnosed cancer in men in the United States, following skin cancer, with an incidence rate of 112.7 per 100,000 men per year. The need for a reliable, non-invasive diagnostic tool for early PCa detection (screening, biochemical residual disease) remains unmet due to the limitations of PSA testing, which often leads to overdiagnosis and overtreatment. The PROSTest is a novel, blood-based qPCR assay that assesses gene expression to diagnose PCa and predict patient outcomes to different treatments. This study aimed to validate the sensitivity and specificity of the PROSTest in a diverse cohort of US-based PCa patients compared to healthy controls., Materials and Methods: This prospective study included 143 PCa patients and 92 healthy controls. Blood samples were collected, and the PROSTest was conducted following RNA isolation and cDNA production, using a predefined 27-gene algorithm to provide a binary output. The assay's sensitivity and specificity were evaluated using receiver operating characteristic (ROC) analysis, with a 50% score cut-off distinguishing PCa from non-PCa patients. Analytical reproducibility was assessed with intra- and inter-assay comparisons of Ct values and PROSTest scores., Results: The PROSTest demonstrated a sensitivity of 94% (95% CI 89-98%) and a specificity of 88% (95% CI 80-94%) in distinguishing PCa patients from controls, with an area under the ROC curve (AUROC) of 0.97. The false positive rate among controls was 12%. Intra- and inter-assay reproducibility was confirmed with no significant differences in Ct values or PROSTest scores between operators or assays. PROSTest scores were significantly higher in PCa patients compared to controls and in those undergoing treatment versus untreated patients., Conclusion: This validation study confirms the high sensitivity and specificity of the PROSTest in detecting PCa in a diverse USA cohort. The assay's robustness and reproducibility support its potential as a reliable diagnostic tool for PCa detection and monitoring. Further studies are warranted to evaluate its utility across broader populations and treatment settings., (© 2025 The Author(s). The Prostate published by Wiley Periodicals LLC.)

Purpose: The cancer/testis antigen New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a promising target in myxoid/round cell liposarcoma (MRCLS)., Methods: In this pilot study, we assessed the adoptive T-cell therapy NY-ESO-1c 259 T letetresgene autoleucel (lete-cel) in patients with human leukocyte antigen (HLA)-A*02:01-, HLA-A*02:05-, and/or HLA-A*02:06-positive advanced/metastatic NY-ESO-1-expressing MRCLS. Patients underwent a reduced-dose (cohort 1) or standard-dose (cohort 2) lymphodepletion regimen (LDR). The primary end point was investigator-assessed overall response rate (ORR). Safety was assessed through adverse event (AE) reports. Correlative biomarker analyses were performed post hoc. The trial is registered at ClinicalTrials.gov (identifier: NCT02992743)., Results: Of 23 enrolled patients, 10 in cohort 1 and 10 in cohort 2 received lete-cel. Investigator-assessed ORR was 20% (95% CI, 2.5 to 55.6) and 40% (95% CI, 12.2 to 73.8), median duration of response was 5.3 months (95% CI, 1.9 to 8.7) and 7.5 months (95% CI, 6.0 to not estimable [NE]), and median progression-free survival was 5.4 months (95% CI, 2.0 to 11.5) and 8.7 months (95% CI, 0.9 to NE) in cohorts 1 and 2, respectively. AEs included cytokine release syndrome and cytopenias, consistent with T-cell therapy/LDR. Post hoc correlative biomarkers showed T-cell expansion and persistence in both cohorts., Conclusion: To our knowledge, this study is the first demonstrating the clinical promise of lete-cel in HLA-/NY-ESO-1-positive patients with advanced MRCLS.

Supercritical (sc) CO 2 in geologic carbon sequestration (GCS) can chemically and mechanically deteriorate wellbore cement, raising concerns for long-term operations. In contrast to the conventional view of "sulfate attack" on cement, we found that adding 0.15 M sulfate to the acidic brine can significantly reduce the impact of scCO 2 attack on Portland cement, resulting in stronger cement than that found in a sulfate-free system. Scanning electron microscopy revealed a decreased total attack depth in reacted cement in the presence of sulfate. With a newly defined minimum porosity term in reactive transport modeling, our model suggests that sulfate caused CaCO 3 to fill more nanopore spaces in the cement. Small angle X-ray scattering experiments also showed that sulfate can decrease the pore sizes of the carbonate layer. The results suggest that the interactions between sulfate and cement can generate a less porous CaCO 3 layer, which better resists acidic brine. Using this mechanism as a proof-of-concept, we tested the incorporation of sodium sulfate into Portland cement and synthesized new cement composites that show stronger resistance against scCO 2 attacks. These newly discovered interfacial interactions between CaCO 3 and sulfate provide new insights into engineering mechanically strong and green materials for safer GCS.

Introduction: Recurrent portal hypertension (PH) after liver transplant (LT) and its management are not well-studied. This study aims to evaluate the impact of transjugular intrahepatic portosystemic shunt (TIPS) on outcomes of recurrent PH., Methods: From a cohort of 1846 LT recipients, 36 patients who underwent TIPS creation after LT were identified and considered as cases. To streamline comparison with the remaining LT patients without TIPS, a representative subset comprising more than 20% of the entire population (381/1810) was randomly selected. Diuretic refractory ascites, and endoscopic findings were reviewed to detect recurrent PH in patients without TIPS. Repeat transplantation, and graft and overall survival were compared between recurrent PH patients with and without TIPS. Survival analysis with multivariable Cox regression analysis was used for risk factors of survival., Results: Out of 1846 patients, 36 (2%) underwent TIPS after LT. Among the control group, 24 (of 381, 6.3%) patients had recurrent PH. TIPS resulted in ascites resolution in 25 (of 36, 74%). Repeat transplant was more frequent in recurrent PH without TIPS, than recurrent PH with TIPS (33% vs. 11%, p=0.035). Median overall survival after TIPS was 2.4 years (95% CI: 0.6-3.2). Transplant-free survival after initial LT was not different between patients with or without TIPS (8.6 years vs. 7.6 years, p=0.360). Multivariable Cox regression showed that repeat transplant was associated with reduced mortality in recurrent PH (HR=0.15, p=0.016)., Conclusion: Recurrent PH after LT is rare, but adversely impacts patient outcomes. However, TIPS in recurrent PH improves ascites without worsening survival., (Copyright © 2025. Published by Elsevier Inc.)

Objectives: Caregivers of those with neurodegenerative disease (ND) manage complex symptoms which impact their wellbeing. Self-compassion can promote maintenance of wellbeing during challenging experiences, including caregiving. Little guidance exists for observationally studying self-compassion or targeted interventions for this population. Our objective was to complete a scoping review of research describing self-compassion in the context of caregiver wellbeing of caregivers of those living with ND., Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for Scoping Reviews (PRISMA-ScR) guidelines, 3 online databases identified 350 peer-reviewed articles, 18 of which were included in this study. Eligibility included being written in English, targeting caregivers of those living with ND, and examination of self-compassion. Articles were organized by the incorporation or characterization of self-compassion in the study design., Results: Alzheimer's disease predominated study samples of care recipients. Across study types self-compassion appeared as a theoretical concept, emerging theme, variable associated with other outcomes, and main outcome variable. Self-compassion is frequently measured using the Self-Compassion Scale, full or short form ., Significance of Results: The study of self-compassion with caregivers of individuals living with ND is growing. Current literature is somewhat unfocussed, leading to gaps in understanding conceptualization to achieve maximum intervention benefits. Clarifying the role of self-compassion in caregiver wellbeing will provide a lens through which non-pharmacologic, psychotherapeutic, and behavioral intervention development may be framed to reduce negative psychological outcomes. The most frequently represented ND is Alzheimer's disease or other dementia, obscuring other NDs like amyotrophic lateral sclerosis, Parkinson's disease, and others.

Task-free brain activity affords unique insight into the functional structure of brain network dynamics and has been used to identify neural markers of individual differences. In this work, we present an algorithmic optimization framework that directly inverts and parameterizes brain-wide dynamical-systems models involving hundreds of interacting neural populations, from single-subject M/EEG time-series recordings. This technique provides a powerful neurocomputational tool for interrogating mechanisms underlying individual brain dynamics ("precision brain models") and making quantitative predictions. We extensively validate the models' performance in forecasting future brain activity and predicting individual variability in key M/EEG metrics. Last, we demonstrate the power of our technique in resolving individual differences in the generation of alpha and beta-frequency oscillations. We characterize subjects based upon model attractor topology and a dynamical-systems mechanism by which these topologies generate individual variation in the expression of alpha vs. beta rhythms. We trace these phenomena back to global variation in excitatory-inhibitory balance, highlighting the explanatory power of our framework to generate mechanistic insights., Competing Interests: Competing interests statement:The authors declare no competing interest.

Multimodal digital health assessments overcome the limitations of patient-reported outcomes by allowing for continuous and passive monitoring but remain underutilized in older adult lifestyle interventions for brain health. Therefore, we aim to (1) report ecological momentary assessment (EMA) and ActiGraph adherence among older adults during a lifestyle intervention; and (2) use dynamic data collected via EMA and ActiGraph to examine person-specific patterns of mindfulness, steps, and sleep throughout the intervention. We analyzed EMA and ActiGraph data from a pilot study of the 8-week My Healthy Brain program (N = 10) lifestyle group for older adults (60+) with subjective cognitive decline. EMA adherence metrics included proportion of EMA completed and the proportion of days with at least 10 mindfulness minutes. ActiGraph GT9X adherence metrics included the number of valid wear days (≥ 7 h) and the number of days participants achieved their step goal. We used linear mixed-effects models to examine person-specific patterns of step count, sleep efficiency, and mindfulness practice. On average, participants completed 39 of the 49 possible EMAs (80%) during the program. ActiGraph adherence was slightly higher than EMA (M = 61.40 days, 87.71%). Participants achieved the daily mindfulness goal (10 min/day) and step goal on 46.32% and 55.10% of days, respectively. Dynamic data revealed that on average, participant step counts increased by approximately 16.5 steps per day (b = 16.495, p = 0.002). However, some participants exhibited no changes while improvements made by other participants returned to baseline levels of activity. There was substantial heterogeneity in trajectories of mindfulness practice and sleep efficiency. EMA and ActiGraph are feasible for older adults enrolled in dementia risk reduction lifestyle interventions. Future studies are needed to better understand how mechanisms of lifestyle behaviors captured by EMA and ActiGraph are related to cognitive outcomes in older adults., Competing Interests: Declarations. Conflict of interest: Matthew W. Schroeder, Madelyn R. Frumkin, Ryan A. Mace have no conflicts of interest to disclose. Ethical approval: The Mass General Brigham Institutional Research Board (IRB) approved all study procedures (IRB # 2020P004087). Consent to participate: All participants provided written informed consent to participate in this study. Human and animal rights and informed consent: All procedures followed were in accordance with ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The Report and Placement Integrated Data System (RAPIDS) integrates two U.S. national data systems-NCANDS' child maltreatment report (CMR) records and AFCARS' foster care (FC) records-into a single longitudinal dataset spanning 2006-2021. This integration enables comprehensive child maltreatment analysis by linking the annual files from these previously separate systems., Objective: To explore benefits of RAPIDS data in understanding CMR outcomes., Participants and Setting: Children aged 0-10 years with CMRs in 2018 (N = 2,371,119)., Methods: Using logistic regression, we modeled five outcomes: two current outcomes from 2018 index reports (substantiation and foster care entry) and three future outcomes within two years (re-report, substantiated re-report, and foster are entry). For each outcome, we compared models using only index report data without RAPIDS variables against models incorporating RAPIDS-enabled variables that capture longitudinal patterns across reports, placements, and siblings., Results: RAPIDS data improved model performance across all outcomes, with greater gains for future outcomes. Overall model fit (Tjur's R 2 ) increased for substantiation (11.75 % → 12.53 %), FC entry (4.17 % → 6.38 %), rereport (0.94 % → 4.99 %), substantiated rereport (1.04 % → 3.31 %), and future FC entry (0.85 % → 2.51 %). Predictive performance also improved: at 80 % sensitivity, specificity increased for substantiation (54 % → 56 %), FC entry (52 % → 58 %), rereport (27 % → 36 %), substantiated rereport (33 % → 42 %), and future FC entry (37 % → 49 %). Additionally, RAPIDS data enabled analysis of a wider array of predictors and their associations with outcomes, fully utilizing national longitudinal CMR and FC records., Conclusions: RAPIDS data enhance explanatory power and predictive accuracy, enabling nationwide, longitudinal analysis of CMR and FC records and offering valuable insights into risk and protective factors., Competing Interests: Declaration of competing interest None, (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Spatially resolved transcriptomics (SRT) measures mRNA transcripts at thousands of locations within a tissue slice, revealing spatial variations in gene expression and cell types. SRT has been applied to tissue slices from multiple time points during the development of an organism. We introduce developmental spatiotemporal optimal transport (DeST-OT), a method to align spatiotemporal transcriptomics data using optimal transport (OT). DeST-OT uses semi-relaxed OT to model cellular growth, death, and differentiation processes. We also derive a growth distortion metric and a migration metric to quantify the plausibility of spatiotemporal alignments. DeST-OT outperforms existing methods on the alignment of spatiotemporal transcriptomics data from developing mouse kidney and axolotl brain. DeST-OT estimated growth rates also provide insights into the gene expression programs governing the growth and differentiation of cells over space and time., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are increasingly being used to treat diabetes and obesity. However, their effectiveness and risks have not yet been systematically evaluated in a comprehensive set of possible health outcomes. Here, we used the US Department of Veterans Affairs databases to build a cohort of people with diabetes who initiated GLP-1RA (n = 215,970) and compared them to those who initiated sulfonylureas (n = 159,465), dipeptidyl peptidase 4 (DPP4) inhibitors (n = 117,989) or sodium-glucose cotransporter-2 (SGLT2) inhibitors (n = 258,614), a control group composed of an equal proportion of individuals initiating sulfonylureas, DPP4 inhibitors and SGLT2 inhibitors (n = 536,068), and a control group of 1,203,097 individuals who continued use of non-GLP-1RA antihyperglycemics (usual care). We used a discovery approach to systematically map an atlas of the associations of GLP-1RA use versus each comparator with 175 health outcomes. Compared to usual care, GLP-1RA use was associated with a reduced risk of substance use and psychotic disorders, seizures, neurocognitive disorders (including Alzheimer's disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions. There was an increased risk of gastrointestinal disorders, hypotension, syncope, arthritic disorders, nephrolithiasis, interstitial nephritis and drug-induced pancreatitis associated with GLP-1RA use compared to usual care. The results provide insights into the benefits and risks of GLP-1RAs and may be useful for informing clinical care and guiding research agendas., Competing Interests: Competing interests: Y.X. and Z.A.A. are uncompensated consultants for Pfizer. No other potential competing interests relevant to this article are reported., (© 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Across multiple procedural specialties, female trainees tend to perform fewer procedures and receive less autonomy than their male counterparts. However, there is currently no data on procedure contribution levels for radiology trainees., Objective: To evaluate whether there was a difference in the degree of reported participation in ultrasound-guided procedures between male and female trainees at our institution., Methods: This retrospective study assessed for differences in the reported level of participation between male and female trainees in ultrasound (US) guided paracentesis and thoracentesis. We performed a radiology information system (RIS) search of US guided procedures performed on adult patients from 7/1/2018 to 2/29/2024. Trainee participation levels in the procedures were determined per available reports and classified into independently performed, assisted, or observed. We evaluated the differential reporting of procedure contributions for male and female trainees based on observed vs. expected frequencies, as well as the effect of the trainees' and supervising physicians' gender and experience level on these contributions., Results: A total of 189 trainees (52 female, 137 male) and 58 supervising physicians (18 female and 40 male) were included. The study evaluated 4156 reports, which showed no difference in the percentage of independently completed procedures (females 80.9% vs. 81.9%, X 2 (1, N = 4156) = 0.494, p = 0.48) except when supervised by junior physicians less than 2 years out of training (females 81.0% vs. 86.5%, X 2 (1, N = 1908) = 8.19, p = 0.0042). However, female trainees were more likely than male trainees to report observing procedures (females 9.2% vs. 5.2%, X2 (1, N = 4156) = 21.1, p < 0.00001) rather than actively participating in procedures despite a similar training level; this difference was not observed when supervising physicians were females., Conclusion: Female radiology trainees report a similar percentage of independently performed procedures but a lower rate of active participation than male trainees., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Patients with obstructive sleep apnoea (OSA) are considered more sensitive to opioids and at increased risk of opioid-induced respiratory depression. Nonetheless, whether OSA treatment (continuous positive airway pressure, CPAP; or bilevel positive airway pressure, BIPAP) modifies this risk remains unknown. Greater opioid sensitivity can arise from altered pharmacokinetics or pharmacodynamics. This preplanned analysis of a previous cohort study of remifentanil clinical effects in OSA tested the null hypothesis that the pharmacokinetics, pharmacodynamics, or both of remifentanil, a representative μ-opioid agonist, are not altered in adults with treated or untreated OSA., Methods: A single-centre, prospective, open-label, cohort study administered a stepped-dose, target-controlled remifentanil infusion (target effect-site concentrations 0.5, 1, 2, 3, 4 ng ml -1 ) to awake adult volunteers (median age 52 yr, range 23-70) without OSA (n=20), with untreated OSA (n=33), or with treated OSA (n=21). Type III (in-home) polysomnography verified OSA. Remifentanil plasma concentrations, end-expired CO 2 , thermal heat tolerance, and pupil diameter (miosis) were assessed. Population pharmacokinetic (clearance, volume of distribution) and pharmacodynamic (miosis, thermal heat tolerance, end-expired CO 2 ) models were developed., Results: Remifentanil clearance (median) was 147, 143, and 155 L h -1 (P=0.472), and volume of distribution was 19.6, 15.5, and 17.7 L (P=0.473) for subjects without OSA, untreated OSA, or treated OSA, respectively. Total body weight was an influential covariate on both remifentanil clearance and central volume of distribution. There were no statistically or clinically significant differences between the three groups in miosis EC 50 or Emax, or the slopes of thermal heat tolerance or end-expired CO 2 vs remifentanil concentration. At a plasma remifentanil concentration of 4 ng ml -1 , in participants without OSA, with untreated OSA, or with treated OSA, respectively, model-estimated pupil area (12%, 13%, and 17% of baseline, P=0.086), thermal heat tolerance (50°C, 51°C, and 51°C, P=0.218), and end-expired CO 2 (6.3 kPa, 6.4 kPa, and 6.7 kPa, P=0.257) were not statistically different between groups., Conclusions: OSA (untreated or treated) did not influence remifentanil pharmacokinetics or pharmacodynamics (miosis, analgesia, respiratory depression). Results support the null hypothesis that neither pharmacokinetics nor pharmacodynamics of remifentanil, a representative μ-opioid, are altered in adults with treated or untreated OSA. These findings provide a mechanistic explanation for the lack of influence of OSA or OSA treatment on the clinical miotic, sedative, analgesic, or respiratory depressant response to remifentanil in awake adults. The conventional notion that OSA alters sensitivity to the effects of opioids in awake adults is not supported by our findings, such that opioid dosing might not need adjustment for pharmacokinetic or pharmacodynamic considerations., Clinical Trial Registration: ClinicalTrials.gov, NCT02898792, https://clinicaltrials.gov/ct2/show/NCT02898792. First Posted: September 13, 2016., Competing Interests: Declaration of interest The authors declare no competing interests., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Purpose: To assess the patient barriers to adherence with appointment follow-up in patients with ocular inflammatory disorders across the United States., Methods: This was a multicenter study of adult and pediatric patients at the Wilmer Eye Institute, University of Texas at Austin, University of Wisconsin-Madison, University of Minnesota, Minneapolis Veterans Administration Hospital, and Washington University of St. Louis. The primary outcome was self-reported adherence to follow-up visits. Secondary outcomes were the reasons for missing follow-up including sub analyses of patient demographics. Eligible patients completed a self-reporting survey to assess barriers to attending follow-up visits., Results: The survey was fully completed by 210 subjects and partially by 40 (250 in total), of whom were 67% white, 59% female, and 51% had a college or advanced degree. Most patients had bilateral (68%), anterior (51%) uveitis. Patients were treated with topical corticosteroids (33%), immunosuppressive agents (23%), or both (22%). Most patients (79%) did not miss or cancel appointments. Ninety-seven percent of patients had medical insurance and some paid (39%) more than 40 dollars for their copay. Copay costs limited the number of visits patients could attend in 7% of patients. Eight percent of patients missed appointments due to inability to take off time from work and 5% missed visits due to lack of transportation., Conclusion: Most patients with ocular inflammation reported good adherence to follow-up appointments. Insurance type, copay costs, transportation, patient scheduling, and patient understanding were all minimally reported to effect patient visit attendance.

Magnetization switching by charge current without a magnetic field is essential for device applications and information technology. It generally requires a current-induced out-of-plane spin polarization beyond the capability of conventional ferromagnet/heavy-metal systems, where the current-induced spin polarization aligns in-plane orthogonal to the in-plane charge current and out-of-plane spin current. Here, a new approach is demonstrated for magnetic-field-free switching by fabricating a van-der-Waals magnet and oxide Fe 3 GeTe 2 /SrTiO 3 heterostructure. This new magnetic-field-free switching is possible because the current-driven accumulated spins at the Rashba interface precess around an emergent interface magnetism, eventually producing an ultimate out-of-plane spin polarization. This interpretation is further confirmed by the switching polarity change controlled by the in-plane initialization magnetic fields with clear hysteresis. Van-der-Waals magnet and oxide are successfully combined for the first time, especially taking advantage of spin-orbit torque on the SrTiO 3 oxide. This allows this study to establish a new way of magnetic field-free switching. This work demonstrates an unusual perpendicular switching application of large spin Hall angle materials and precession of accumulated spins, and in doing so, opens up a new field and opportunities for van-der-Waals magnets and oxide spintronics., (© 2025 Wiley‐VCH GmbH.)

Background: Takotsubo syndrome (TTS) primarily manifests as a cardiomyopathy induced by physical or emotional stress, remains a poorly understood condition with no established treatments. In this study, we investigated the potential of sacubitril/valsartan (sac/val) to increase the survival of TTS patients and reduce inflammation and myocardial fibrosis in experimental models., Aim: This study aimed to evaluate whether sac/val could improve survival rates in TTS patients, mitigate cardiac remodeling in vivo, and explore its anti-inflammatory and antifibrotic mechanisms in vitro., Methods: Clinical cases from the Chinese Takotsubo syndrome (ChiTTS) registry were analyzed to assess patient survival rates. In addition, we used isoprenaline (ISO)-induced TTS-like animal models, pre-treated with sac/val, to evaluate cardiac function and inflammatory response. Additionally, the effects of isoprenaline on cardiomyocytes and myocardial fibroblasts, as well as protection from rhBNP, were thoroughly studied., Results: In TTS patients with a left ventricular ejection fraction (LVEF) ≤ 0.45, hyperglycemia, emotional stress, and inflammation were identified as independent risk factors. Moreover, the baseline characteristics of the TTS patients, heart rate, emotional triggers, female sex (%), WBC count, IL-6 concentration, PCT, ALT, AST and TG were significantly associated with decreasing left ventricular ejection fraction. In TTS patients, sac/val reduced inflammation, evidenced by lower levels of white blood cells and interleukin 6, compared to patients who did not receive sac/val by day 30. In animal models, Sac/val improved cardiac dysfunction in ISO-induced TTS-like cardiomyopathy and decreased myocardial inflammatory responses (IL-18 and Mac-3) by inhibiting the TLR4/NF-κB pathway and fibrosis through the inhibition of the TGFβ 1 /Smad pathway., Conclusions: This study revealed that sac/val decreased inflammatory responses, myocardial edema, and fibrosis, resulting in an increased percentage of survivors in the TTS group. Similar to findings from in vivo and in vitro experiments, sac/val exerted cardioprotective effects by reducing the inflammatory response and reversing myocardial remodeling mediated by the TLR4/NF-κB and TGFβ 1 /Smad pathways. In conclusion, these findings highlight the anti-inflammatory and antifibrotic effects of sac/val in individuals with TTS., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest. The graphic abstract is created using Fig draw (www.figdraw.com)., (Copyright © 2024. Published by Elsevier Ltd.)

Pregnancy is a period of profound biological transformation. However, we know remarkably little about pregnancy-related brain changes. To address this gap, we chart longitudinal changes in brain structure during pregnancy and explore potential mechanisms driving these changes. Ten participants (Mean age = 28.97 years) are assessed 1-6 times (median = 3) during their pregnancy. Each visit includes anatomical and diffusion-weighted MRI, and assessments of waking salivary hormones, hair hormones, and inflammatory cytokines. Here we observe a reduction in gray matter volume and an increase in neurite density index (NDI), a proxy of axon density, in white matter tracts across pregnancy. Progesterone levels are associated with reductions in brain volumetric measurements, and both progesterone and estradiol levels are linked to increases in NDI in white matter tracts. This study highlights the profound neurobiological changes experienced by pregnant individuals and provides insights into neuroplasticity in adulthood., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Despite the widespread use of the Research Domain Criteria (RDoC) framework in psychiatry and neuroscience, recent studies suggest that the RDoC is insufficiently specific or excessively broad relative to the underlying brain circuitry it seeks to elucidate. To address these concerns, we employ a latent variable approach using bifactor analysis. We examine 84 whole-brain task-based fMRI (tfMRI) activation maps from 19 studies with 6192 participants. A curated subset of 37 maps with a balanced representation of RDoC domains constitute the training set, and the remaining held-out maps form the internal validation set. External validation is conducted using 36 peak coordinate activation maps from Neurosynth, using terms of RDoC constructs as seeds for topic meta-analysis. Here, we show that a bifactor model incorporating a task-general domain and splitting the cognitive systems domain better fits the examined corpus of tfMRI data than the current RDoC framework. We also identify the domain of arousal and regulatory systems as underrepresented. Our data-driven validation supports revising the RDoC framework to reflect underlying brain circuitry more accurately., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Most cancer survivors have multiple cardiovascular risk factors, increasing their risk of poor cardiovascular and cancer outcomes. The Automated Heart-Health Assessment (AH-HA) tool is a novel electronic health record clinical decision support tool based on the American Heart Association's Life's Simple 7 cardiovascular health (CVH) metrics to promote CVH assessment and discussion in outpatient oncology. Before proceeding to future implementation trials, it is critical to establish the acceptability of the tool among providers and survivors., Objective: We assessed provider and survivor acceptability of the AH-HA tool and provider training at practices randomized to the AH-HA tool arm within WF-1804CD., Methods: Providers (physicians, nurse practitioners, physician assistants) completed a survey to assess acceptability of the AH-HA training, immediately following training. Providers also completed surveys to assess AH-HA tool acceptability and potential sustainability. Tool acceptability was assessed after 30 patients were enrolled at the practice with both a survey developed for the study as well as with domains from the Unified Theory of Acceptance and Use of Technology (UTAUT) survey (Performance Expectancy, Effort Expectancy, Attitude Toward using Technology, and Facilitating Conditions). Semi-structured interviews at the end of the study captured additional provider perceptions of the AH-HA tool. Post-treatment survivors (breast, prostate, colorectal, endometrial, and lymphomas) completed a survey to assess acceptability of the AH-HA tool immediately after the designated study appointment., Results: Providers (n=15) reported high overall acceptability of the AH-HA training (mean=5.8, SD=1.0) and tool (mean=5.5, SD =1.4); provider acceptability was also supported by UTAUT scores (e.g., Effort Expectancy mean=5.6, SD=1.5). Qualitative data also supported provider acceptability of different aspects of the AH-HA tool (e.g., It helps focus the conversation and give the patient a visual of continuum of progress). Providers were more favorable about using the AH-HA tool for post-treatment survivorship care. Enrolled survivors (n=245) were an average of 4.4 years post-treatment (SD =3.7). Most survivors reported that they strongly agreed/agreed that they liked the AH-HA tool (94.3%, n=231). A larger proportion of survivors with high health literacy strongly agreed/agreed that it was helpful to see their heart health score (98.2%, n=161) compared to survivors with lower health literacy scores (89.5%, n=68; p=0.005)., Conclusions: Quantitative surveys and qualitative interview data both demonstrate high acceptability of the AH-HA tool among both providers and survivors. Although most survivors found it helpful to see their heart health score, there may be room for improving communication with survivors who have lower health literacy., Clinicaltrial: Trial Registration: NCT03935282., International Registered Report: RR2-https://doi-org.wake.idm.oclc.org/10.1016/j.conctc.2021.100808.