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Background Childhood trauma is highly prevalent among individuals with cocaine use disorder (iCUD), and both entail social cognition deficits, including impaired mentalizing (social inference) capacity. Here we sought to examine the neuro-circuits underlying these associations using task-based neuroimaging. We hypothesized that childhood trauma and CUD would show altered brain activation of the mentalizing network, related to deficits in real-world social capacities. Methods Participants (45 iCUD and 34 healthy controls (HC), with high/low trauma) performed the validated Why/How fMRI task, probing Why versus How photographed naturalistic behaviors are performed. Whole-brain analyses used a Why > How contrast at the first level, followed by group comparisons at the second level, with cluster-level family-wise error correction (p _FWE < .05). Social functioning and clinical measures were obtained using validated self-report instruments. Results Mentalizing task behavior outcomes were worse in iCUD than HC (F _(1,75)  = 4.45, p < .05), with no effect of trauma severity on accuracy. A significant interaction was observed in the precuneus, with greater BOLD responses in iCUD-low than HC-low, and lower responses in iCUD-high than HC-high. High-trauma individuals showed increased frontal pole activation, correlating positively with mentalizing accuracy (r ₍₃₉₎  > = .24, p < .05) and social anxiety (r ₍₇₉₎  = .29, p = .01), and negatively with resilience (r ₍₃₉₎ <= - .37, p < .001). Conclusion Greater frontal activation in high-trauma individuals may support task accuracy but is linked to poorer real-world social functioning. Additionally, the link between CUD diagnosis and precuneus activity depends on trauma severity, offering neural insights into how trauma history may influence CUD and social function.

Understanding how immune cells respond to early oncogenic events is essential for designing immune-based strategies to intercept breast cancer. Mouse models that induce mammary tumorigenesis through Cre-mediated genetic manipulations can be used to study these early events. However, the immune effects of different induction methods remain unclear. Here, we compare adenovirus-delivered Cre with tamoxifen-inducible CreER systems in models targeting luminal mammary epithelial cells for p53-loss. We find that transient intraductal adenoviral infection produces not only an acute immune response but also long-lasting reshaping of the mammary gland immune microenvironment. Adenovirus exposure induces robust and persistent CD8 ⁺ T-cell infiltration dominated by CD103 ⁺ tissue-resident T cells displaying heightened activation. This sustained antiviral T-cell signature obscures the p53-loss-driven CD8 ⁺ T-cell activation detectable in the CreER/tamoxifen model. Adenoviral infection also transiently skews CD4 ⁺ T cells toward IFN-γ-producing antiviral states and compresses the myeloid compartment, whereas tamoxifen-induced p53-loss increases macrophage abundance and activates CD8 ⁺ T-cells during premalignancy. Despite similar tumor latencies across induction strategies, our findings demonstrate that adenoviral infection exerts long-term immunological effects that can confound interpretation of immune dynamics during early mammary tumorigenesis. These results emphasize the importance of induction-method selection when using genetically engineered mouse models to study cancer-immune interactions.

Introduction: The COVID-19 pandemic and subsequent influenza outbreaks highlighted disparities in timely access to tests and treatments. To address this gap, a nationwide Home Test to Treat (HTTT) program was launched to provide home test kits, telehealth consultations, and medication delivery for COVID-19 and influenza. This study explored participant experiences, factors influencing satisfaction levels, and recommendations for future programs. Methods In-depth interviews were conducted with 48 participants enrolled in the HTTT program. Purposive sampling was used to obtain experiences from diverse backgrounds. Content analysis was used to extract the final coding scheme. Results Interviewees reported a range of experiences, from positive to negative. Many of them were satisfied with efficient communication with telehealth providers, timely and convenient access to resources, and a seamless transition from enrollment to prescription. However, some interviewees noted limited interactions with telehealth providers, delayed access to treatment and cost challenges, and navigation and coordination challenges. For a future home-based Teat to Treat program, interviewees recommended improving inclusivity, offering more comprehensive consultation, enhancing user-friendliness, and increasing awareness through diverse platforms Discussion This study highlights a home-based Test to Treat program as a feasible way to improve access to COVID-19 and influenza care. Enhancing interactions with providers, comprehensive care, and support for marginalized populations may further expand the program and reduce disparities in access to tests and treatments.

Activation of glucagon-like peptide-1 receptor (GLP-1R) could affect cancer treatment responses through direct action in tumor or immune cells. However, the field lacks a comprehensive assessment of GLP-1R expression and activity across human tumors. Herein, we report detection GLP-1R across multiple human tumor types and focus on triple-negative breast cancer (TNBC) for deeper analysis. In TNBC, GLP-1R is present in immune and tumor cell compartments. GLP-1 treatment of cancer cells activated survival pathways, drove proliferation, induced paclitaxel resistance and dampened cytokine secretion, effects that required expression of GLP-1R. Spatial transcriptomics of human tumors revealed that GLP-1 exposure remodeled the tumor microenvironment, promoted a mesenchymal transition in malignant cells and disrupted productive macrophage inflammation in tumor-proximate niches. Patients taking GLP-1 drugs during neoadjuvant chemotherapy experienced reduced pathological complete response rates (pCR: 30.8%) compared to controls (65%, p<0.001). Thus, GLP-1-exposure acts on tumor and immune cells to impair chemoimmunotherapy efficacy in TNBC.

Background Cervical cancer remains a preventable malignancy with high morbidity and mortality in low- and middle-income countries (LMICs). Screening uptake is suboptimal in sub-Saharan Africa, and the influence of socioeconomic status (SES) on screening behaviour among women remains insufficiently explored. Aim To determine the effect of SES on cervical cancer screening uptake among mothers of vaccine-eligible adolescent girls in Lagos, Nigeria. Methods This secondary analysis used baseline data from the mHealth-HPVac trial, including 180 sexually active mothers of unvaccinated girls aged 9-14 years. The primary outcome was self-reported cervical cancer screening within the previous 10 years. A multivariable logistic regression model was used to examine the association between SES and screening uptake, adjusting for age and tribe. Education and income were tested as an interaction term but excluded due to model instability. Results Overall, 51.7% of participants reported prior cervical screening. Women who had been screened were significantly older than unscreened women (45.4 ± 6.7 vs 41.7 ± 7.2 years; p < 0.001). Screening uptake did not differ significantly by marital status, education, employment, income class, tribe, or residential distance to screening facilities. In adjusted models, neither middle-income (adjusted odds ratio = 1.72, 95% CI: 0.75-3.98) nor high-income status (adjusted odds ratio = 1.22, 95% CI: 0.45-3.30) was associated with screening. Conclusion Cervical cancer screening uptake among mothers in Lagos is moderate, and SES was not independently associated with screening. Interventions should target structural or behavioural factors rather than focusing solely on economic disparities. Larger, adequately powered population-based studies are therefore needed to validate these findings and better delineate the socioeconomic gradients in screening behaviour among Nigerian women.

Magnetically actuated microrobots offer transformative potential for biomedical applications such as targeted drug delivery and minimally invasive diagnostics. However, existing fabrication methods are constrained by challenges in magnetic material integration, structural robustness, and reproducibility. In this work, we present an improved direct-printing strategy that integrates permanent micro-magnets into microrobots during the two-photon polymerization (TPP) process, thereby eliminating the need for post-assembly alignment or insertion. To enhance magnetic-material compatibility and interfacial reliability, a sputtering-based surface modification technique is introduced, enabling robust integration of both pre-coated and surface-treated magnets. Using this approach, four functional microrobotic platforms are demonstrated: (1) a helical microswimmer for efficient propulsion, (2) a micro-scale tumbling microrobot for terrain locomotion, (3) a compliant micro-gripper for precise grasping and manipulation, and (4) a mini-MicroTumbler (MMT) incorporating a sputter-modified magnet for stable microscale actuation. Performance characterization was conducted under varying actuation frequencies and environments. The microswimmer exhibited frequency-dependent propulsion consistent with magnetic step-out behavior, the MicroTumbler achieved stable locomotion across inclined surfaces, the micro-gripper demonstrated controllable deformation and object manipulation, and the MMT showed reliable frequency-dependent motion.This study establishes a scalable, material-flexible, and high-fidelity fabrication method for embedded-magnet microrobots, broadening the design space and enabling the next generation of multifunctional, magnetically actuated microsystems.

We previously showed that rats with a protein-coding mutation in Adenylate cyclase 3 (Adcy3) (Adcy3 ^mut/mut ) have increased adiposity. ADCY3 catalyzes the production of cyclic AMP (cAMP), a key secondary messenger that regulates lipolysis and thermogenesis. Here, we assessed how Adcy3 ^mut/mut affects lipolysis, thermogenesis, and cAMP signaling. Adcy3 ^mut/mut and wild-type (WT) males and female rats were fed a high-fat diet for 12 weeks. We measured body weight, fat mass, serum free fatty acids (FFA) during a 48-hour fast, body temperature during acute cold exposure, and triglyceride lipase gene expression after a 48-hour fast and after prolonged cold exposure. We also measured cAMP production in response to a β-3 adrenergic receptor agonist (CL 316,243) in adipose tissue ex vivo . Adcy3 ^mut/mut rats displayed increased adiposity, decreased serum FFA, and downregulated adipose triglyceride lipase gene expression. Additionally, cAMP production was decreased in Adcy3 ^mut/mut adipose tissue compared with WT adipose tissue in response to ex vivo stimulation with CL 316,243. Adcy3 ^mut/mut females, but not males, showed a trend toward decreased body temperature during acute cold exposure. These findings demonstrate that a mutation in the transmembrane domain of ADCY3 results in partial loss of enzymatic function, decreasing lipolytic responsiveness and contributing to increased adiposity.

The remaining unacceptably high mortality of influenza-induced acute respiratory distress syndrome underscores the urgent need to identify key cellular drivers of host responses. Endothelial cells (ECs) are increasingly recognized for their immunomodulatory roles, but whether they function as antigen-presenting cells (APCs) following respiratory viral infection remains unknown. Here, we show that influenza A virus H1N1 restrictively infects pulmonary microvascular ECs (PMVECs) during late-stage acute lung injury, triggering robust MHC class I (MHC-I) upregulation in vitro, in vivo, and in ex vivo human precision-cut lung slices. Infected PMVECs present H1N1 antigens via MHC-I and co-stimulatory CD40 to lung-resident CD8⁺ T cells, driving their proliferation and effector function (Granzyme B, IFNγ) to promote viral clearance and resolve inflammation. This process is IFNγ-dependent and STAT1-regulated, forming a positive feedback loop that enhances PMVEC antigen presentation and CD8⁺ T cells activation. By contrast, the emerging H5N1 (A/Texas/37/2024) infect pulmonary ECs earlier and more broadly but elicits weaker pulmonary EC-driven CD8 + T cell responses, potentially contributing to its higher pathogenicity. These findings reveal PMVECs as active APCs in antiviral defense and highlight new avenues for immunotherapeutic intervention.

Psychosocial stress is an established cardiovascular risk factor, yet its influence on chemotherapy-induced cardiotoxicity remains poorly understood. Doxorubicin (DOX), a widely used chemotherapeutic agent, is known to induce cardiotoxicity. However, whether concurrent psychosocial stress exacerbates this effect is unclear. This study aimed to determine the impact of chronic subordination stress (CSS) on DOX-induced cardiotoxicity using a clinically relevant 'two-hit' mouse model. Twelve-week-old male C57BL/6N mice were subjected to CSS for 26 days. DOX (8 mg/kg/week) or vehicle was administered during the final 3 weeks of CSS. Cardiac function was evaluated using echocardiography, while myocardial fibrosis was assessed histologically. Bulk RNA sequencing was conducted to identify differentially expressed genes (DEGs), with key genes validated by real-time PCR. Neither CSS nor DOX alone induced significant cardiac dysfunction. However, the combination of CSS and DOX led to both systolic and diastolic dysfunction, myocardial fibrosis, and increased mortality. Expression of cardiac stress markers Nppa and Nppb was significantly elevated by DOX, with CSS further amplifying Nppa expression. RNA sequencing revealed upregulation of pro-fibrotic genes ( Lgals3, Sprr1a ) and the pro-inflammatory cytokine Il6 under combined CSS and DOX exposure. Gene set enrichment analysis showed dysregulation in metabolic, inflammatory, and cell cycle-related pathways. Psychosocial stress significantly worsens DOX-induced cardiotoxicity by promoting cardiac dysfunction, fibrosis, and maladaptive gene expression. This study highlights psychosocial stress as a critical risk factor for adverse cardiovascular outcomes in cancer patients receiving potentially cardiotoxic chemotherapy.

Ferritin, consisting of ferritin heavy chain (FTH1) and light chain (FTL) subunits, is an essential intracellular iron storage protein fundamental for cellular function. However, the source and the biological role of extracellular ferritin (ex-ferritin) are less understood. Recent studies have linked elevated serum ex-ferritin with adverse outcomes in individuals with acute respiratory distress syndrome (ARDS). In this study, we demonstrate that both FTH1 and FTL are significantly enriched in the serum, blood monocytes, and alveolar macrophages (AMs) of individuals with ARDS, a phenomenon we successfully replicate in a murine hyperoxia-induced acute lung injury (HALI) model. We show that FTH1 is consistently upregulated in macrophages during lung injury development, and mice with a targeted deletion of FTH1 in myeloid (LysMcre) or resident lung macrophage (Cd11ccre) populations exhibit attenuated HALI. This reduced injury is linked to macrophage resistance to ferroptotic cell death, ferritinophagy, altered airway inflammatory responses, and lower lung extracellular iron and higher levels of FTL-ex-ferritin. Transplantation of FTL-ex-ferritin-enriched bronchoalveolar lavage fluid to wild-type mice protected against HALI. The ratio of FTL-ex-ferritin to FTH1 in the serum of individuals with ARDS who died was higher than that of those that survived, suggesting that the balance between FTH1 and FTL may play a role in injury modulation. Our findings highlight macrophage ferritin as a key regulator of macrophage survival and the response of the lung to injury, presenting a potentially targetable pathway for ARDS treatment.