Cardiac troponin I (cTnI) is widely recognized as a critical biomarker for the early diagnosis of acute myocardial infarction (AMI). Consequently, the precise and sensitive detection of cTnI during the initial phases of AMI is vital. In this study, we propose the development of an advanced bipolar electrochemiluminescence (ECL)-based miniaturized, cost-effective, and optimized biosensor incorporating novel nanostructures such as MXene (Ti_₃C_₂T_x-TiO₂) and Ce-MOF without using luminol's co-reactant (H₂O₂). The conjugation of Ce-MOF with MXene enhances ECL intensity due to increase in surface area and electron conductivity, respectively. Using a camera as the detection device, cTnI can be quantified within a wide range of 0.01 to 100 ng/mL. The proposed approach integrates principles of biotechnology and nanotechnology, enabling rapid and accurate quantification of this biomarker even at low concentrations and can be used for clinical diagnostics.

It is now apparent that cardiac form and function are governed at a system level by an integrated collective of heterogeneous single-cell programs that together regulate tissue homeostasis, drive disease emergence, and shape individualized responses to therapy. Current advances in single-cell proteomics and spatial multiomics by mass spectrometry imaging allow systematic dissection of clinically defined cardiovascular tissues with an unprecedented molecular resolving power, yet remain relatively underutilized in cardiovascular research. This compendium review works to stimulate new research into spatial regulation of the heart, emphasizing integration of single-cell proteomic regulation with comprehensive multiomic mass spectrometry imaging studies. In this context, we outline conceptual foundations, technological innovations, and biological insights that have resulted in the current success of single-cell proteomic and spatial multiomic analyses in cardiovascular disease. We provide an experimental design knowledge base of critical components in single-cell proteomics and spatial workflows by mass spectrometry imaging, essential for generating robust and reproducible data sets that are interpretable by advanced computational methods. Key cardiovascular discoveries by single-cell proteomics and multiomic mass spectrometry imaging are reviewed, highlighting how these approaches have provided new molecular insights into cardiac cell programming.

Cardiovascular function is tightly linked to tissue architectures, where the spatial organization of cells, extracellular matrix (ECM), vascular networks, and remodeling processes governs physiological performance and disease progression. Spatial proteomics has, therefore, emerged as a powerful framework for understanding cardiovascular biology and cardiovascular disease mechanisms by revealing spatially organized protein regulation across various physiological and pathological states. In this review, we focus on spatial proteomics strategies most relevant to cardiovascular research and discuss their applications through representative examples. These approaches can be broadly categorized into region-of-interest-based methods, which enable precise characterization of localized cellular heterogeneity, and tissue mapping strategies, which capture spatial organization and biologically relevant region-to-region variability across larger tissue domains. In addition, spatial proteomics platforms differ in their capacity for targeted or untargeted protein analysis, influencing both proteome coverage and their suitability for hypothesis-driven versus discovery-based studies. We evaluate the strengths and limitations of state-of-the-art technologies across 3 key parameters, molecular depth, spatial coverage, and spatial resolution, and discuss how these parameters shape study design and biological understanding. Building on these considerations, we argue that a comprehensive understanding of cardiovascular tissue biology requires spatial proteomics strategies that capture both localized molecular details and spatial organization across large tissue areas, as neither alone is sufficient to explain complex tissue behavior. We propose an integrated workflow in which untargeted, whole-tissue mapping of thousands of proteins is first used to unbiasedly discover spatial patterns and generate hypotheses by identifying candidate regions and proteins of interest, followed by hypothesis testing and validation using high-precision region-of-interest-based proteomics and targeted protein imaging. This sequential framework leverages the complementary strengths of tissue-wide mapping and region-of-interest-based approaches to provide multiscale, mechanistic insights into spatially organized disease processes. Finally, we discuss emerging directions that are poised to expand the scope of spatial proteomics in cardiovascular research.

To evaluate perspectives of counseling and decision making among birthing parents who chose termination or hospice birth due to a fetal congenital heart defect (CHD).

Qualitative analysis of semi-structured interviews with birthing parents who chose either termination or hospice birth due to severe fetal CHD. Participants were recruited from a purposive sample of those who received multidisciplinary counseling at a tertiary congenital heart surgical center between 2019-2023. Thematic analysis was conducted in five stages, using an integrated deductive-inductive approach.

In total, 20 individuals were eligible; 10 completed interviews. Identified themes were categorized in two domains: Experiences During Counseling and Individual Factors Affecting Decision Making. Themes in the first domain included: areas for improvement during counseling, perceived strengths of counseling, patient attributes affecting counseling, and views on provider recommendations. Themes in the second domain included: emotions affecting decision making, value for reproductive autonomy, family factors, internal factors, outside input, and desire for resources.

In this study, birthing parents who chose termination or hospice for fetal CHD appreciated information extending beyond clinical outcomes to include family and financial impacts. Their value for reproductive autonomy reflects the need for clinicians to gain skills in empathetic and neutral counseling of all management options.

This study performs untargeted metabolomics on mouse serum and quantitative proteomics on xenograft tumors to explore the potential anti-tumor mechanisms of Inonotus obliquus polysaccharides (IOPs) against non-small cell lung cancer (NSCLC), revealing candidate pathways that warrant further experimental validation. Building on our prior discovery of IOP-induced apoptosis, we combined functional assays with multi-omics analyses using a well-characterized IOPs preparation (average molecular weight: 4.5 × 10⁴ Da; polysaccharide content: 70.3%; primarily composed of glucose). IOPs potently inhibited proliferation (MTT/colony formation) in LLC and H520 cells and suppressed tumor growth in an allograft model. Untargeted metabolomics of mouse serum revealed IOP-driven downregulation of lipid metabolism. Quantitative proteomics of tumors showed that IOPs regulate nuclear processes (transcription, DNA repair) and modulate the tumor immune microenvironment, as evidenced by enriched pathways of neutrophil extracellular trap (NET) formation, cell adhesion molecules, and Th1/Th2 cell differentiation. Collectively, these findings propose a potential working model in which IOPs may exert anti-tumor effects through coordinated nuclear regulation, metabolic reprogramming, and immune modulation. Our results provide preliminary evidence that IOPs may act beyond direct cytotoxicity, potentially involving systemic regulatory pathways. Further studies are needed to validate these findings and to assess its therapeutic potential in NSCLC.

The renin-angiotensin system (RAS) is a pivotal system for regulating blood volume, electrolyte balance, and systemic vascular resistance. The system exerts its functions through various central targets, particularly those located in the brain. Among these, the subfornical organ (SFO) plays a unique and integrative role. High permeability and the lack of a functional blood-brain barrier (BBB) enable the organ to monitor changes in body fluid composition and transduce these signals into autonomic and behavioral outputs. Its extensive neural projections facilitate the monitoring of circulating factors. The interaction between the RAS and the SFO has gained great attention regarding the activation of different receptors, including angiotensin AT1 and AT2 receptors, and molecular pathways such as protein kinase C, mitogen-activated protein kinase, and growth factor receptor pathways. These interactions are involved in disorders including hypertension and chronic kidney disease. This review summarizes current evidence on RAS-SFO interactions and their pathological significance.

Drugs that inhibit phosphodiesterase 10A (PDE10A) activity have shown efficacy in animal models. However, clinical trials of PDE10A inhibitors in patients with schizophrenia have failed to provide clinically significant results up to this point. Our study investigated whether alofropodect (previously referred to as CPL'36 or CPL500036), a PDE10A inhibitor with an improved pharmacological profile compared with other PDE10A inhibitors, including a fast dissociation rate and high activity, could improve symptoms of acute schizophrenia.

In this phase 2, randomised, double-blind, placebo-controlled, parallel-group trial (11 centres, three countries), investigators randomly assigned hospitalised patients with acute schizophrenia to treatment or placebo groups. The main inclusion criteria were age 18-65 years, a documented diagnosis of schizophrenia for at least 2 years before screening and a positive and negative syndrome scale (PANSS) total score ≥ 80. Participants were randomly assigned (1:1:1) to receive oral alofropodect (20 mg or 40 mg) or placebo administered once daily in the morning for 4 weeks. The primary endpoint of the study was an improvement in the PANSS positive subscale at week 4. The secondary endpoints included improvements in PANSS total and negative subscale scores, along with other efficacy and safety assessments. Clinical responders were defined as those with a ≥ 30% reduction in PANSS total score from baseline at week 4.

Between 24 May 2021 and 8 May 2024, investigators randomised 189 patients into three groups: 58 into the alofropodect 20 mg group, 66 into the alofropodect 40 mg group and 65 into the placebo group. The mean age was 41.7 years (standard deviation (SD) 10.1), and 119 (63%) participants were men, 70 (37%) were women. All participants were White. We measured the difference in PANSS positive subscale before and after treatment, and the change met the primary endpoints at week 4 with the group where alofropodect 20 mg was compared with placebo (- 3.70 [90% CI - 5.51 to - 1.89]; p < 0.001) and alofropodect 40 mg versus placebo (- 6.35 [90% CI - 8.12 to - 4.57]; p = 0.001). Both the 20-mg and 40-mg doses of alofropodect were effective in improving the total PANSS score compared with placebo and met most secondary efficacy endpoints. A clinical response was observed in 2 of 53 patients (3.8%) in the placebo group, 8 of 52 patients (15.4%) in the 20 mg group and 22 of 52 patients (42.3%) in the 40 mg group at week 4. The compound was well tolerated, with only a few serious adverse events. The discontinuation rates were similar in the placebo and treatment arms. Extrapyramidal symptoms (EPS) occurred only in the active treatment groups, but rates were low overall. Somnolence was also reported only in alofropodect groups. Vital signs and biochemical parameters remained unaffected by either dose at any time point. Specifically, blood glucose, total cholesterol and triglycerides did not increase at any dose compared with placebo within our study window.

Alofropodect was effective in the treatment of acute schizophrenia symptoms and was well-tolerated, warranting further investigation in larger clinical studies.

Clinicaltrials.gov identifier: NCT05278156; registration date: 2022-02-09.

Bulimia nervosa (BN) is common and has a global presence and burden. BN shares features with anorexia nervosa and binge eating disorder, but its cardinal feature is recurrent binge eating followed by extreme weight control or compensatory behaviours in association with high levels of weight and shape, and other body image and eating, preoccupations. The last three decades have seen advances in understanding the risk factors and psychobehavioural mechanisms of BN. These advances have informed primary prevention programmes that are effective in preventing the onset of risk factors and, in one selective programme, the onset of BN itself. First-line treatment for BN is psychological therapy, namely cognitive behaviour therapy for eating disorders. However, the challenge of a large treatment gap and the need to improve prevention and early detection of BN remains. Adaptations of treatments to increase their accessibility and reduce cost, alongside the growth of co-design and incorporation of lived experience expertise in research, are assisting in developing programmes that may effectively close this treatment gap. An increasingly sophisticated approach to understanding the neuroscience of BN has the potential to inform novel treatments in both psychological and biological spheres.

Trajectories of age-related neurocognitive decline are nonuniform, and are impacted by numerous environmental and physiological factors. Earlier life phases set the stage for later life neurocognitive function, with midlife marking a critical transition characterized by increasing variability in cognitive, affective, and physiological functioning. Despite its importance, this turbulent period remains underrepresented in open neuroimaging data resources. To address this gap, the Nathan Kline Institute - Rockland Sample (NKI-RS) created 'Mapping Interindividual Variation in the Aging Connectome' (MIVAC), an openly shared, multimodal dataset designed to map brain aging trajectories beginning in midlife and assess the influence of key modifiable factors linked to dementia prevention such as cardiorespiratory fitness, sleep, and mood. This longitudinal investigation includes 348 community-ascertained participants aged 38 to 71 years at baseline, with 219 participants completing 3 annual timepoints. Data collection incorporated deep phenotyping, including detailed assessment of cognitive, behavioral, medical, and cardiorespiratory fitness domains, to compliment multimodal neuroimaging (resting-state fMRI, diffusion MRI, morphometric MRI, and arterial spin labeling) and biospecimen collection. The protocol harmonizes with prior NKI-RS sub studies, enabling lifespan cross-sectional or longitudinal questions, while incorporating age-specific considerations for cognitive and neural aging. The full dataset is openly available.

People with disabilities, including Deaf and hard-of-hearing (DHH) individuals, face disproportionate disaster risks due to communication barriers. Emergency alert systems are predominantly auditory-based, limiting their effectiveness for DHH populations. This gap is especially critical during armed conflict, where timely alerts can be life-saving.

This study examined emergency alert system accessibility and associated psychological distress among DHH adults during active armed conflict.

A cross-sectional online survey was conducted in Israel (October-November 2023) during the early phase of the Israel-Hamas War among DHH adults (N = 167), assessing daytime and nighttime alert accessibility and psychological distress. Analyses included McNemar's test, repeated-measures ANOVA with Bonferroni correction, independent-samples t-tests, and one- and two-way ANOVA. Effect sizes were reported throughout.

Participants included 87 Deaf (52.1%), 73 hard-of-hearing (43.7%), and 7 (4.2%) identifying as "other," with a mean age of 55.3 years (SD = 16.4). While 69.5% received alerts via the national application during daytime, only 32.3% did so at night, indicating a substantial nighttime accessibility gap. Alert accessibility was only partially associated with psychological distress. Women reported significantly higher distress than men (p < .019). No significant differences emerged between Deaf and hard-of-hearing participants in alert use or distress levels. Education level did not predict alert accessibility, suggesting structural rather than user-dependent barriers.

DHH individuals face systematic barriers to accessing emergency alerts, particularly at night. Equitable disaster preparedness requires multimodal systems incorporating visual, vibration, and text-based channels. Culturally accessible mental health support should be integrated into emergency response protocols.