SEARCH · Search PubMed

Results for “Lead reconfiguration”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

222 recordsLinked to original sources

PubMed2026

Physical reconfiguration of limb electrodes for Precordial Bipolar Lead acquisition: Morphological validation against digital subtraction.

BACKGROUND: The V2 - V1 Precordial Bipolar Lead (PBL) selectively evaluates the right-to-left retrosternal axis and has shown diagnostic value beyond the standard 12‑lead electrocardiogram. However, its use has been limited by the need for raw electrocardiographic data and post-processing software. This study evaluated whether a simple physical reconfiguration of limb electrodes could reproduce the digitally derived V2 - V1 morphology with sufficient accuracy for clinical application. METHODS: Thirty-seven subjects underwent two sequential 10-s 12‑lead recordings using a Cardiovit FT-1 electrocardiograph sampled at 1000 Hz. In the standard recording, the digital PBL was calculated as V2 - V1. In the second recording, the right-arm and left-arm electrodes were repositioned to the V1 and V2 sites so that Lead I directly recorded the retrosternal dipole. Signals were filtered, synchronized, and analyzed using median beats. Morphological agreement was assessed with Pearson correlation on Z-normalized signals, while absolute agreement was evaluated using Lin's concordance correlation coefficient (CCC), intraclass correlation coefficient (ICC (Lewis, 1931; Nehb, 1938 [1,2])), root mean square error (RMSE), and Bland-Altman analysis. RESULTS: Mean Pearson correlation between digital and physical PBL was 0.955 (SD 0.043), with segment-specific correlations of 0.953 (SD 0.054) for QRS and 0.967 (SD 0.052) for ST-T. Lin's CCC and ICC(2,1) were both 0.871 (SD 0.110), and RMSE was 0.091 (SD 0.049) mV. Bland-Altman analysis showed minimal bias (-0.008 mV). CONCLUSIONS: Physical acquisition of the V2 - V1 PBL achieved high agreement with the digitally derived signal, supporting a simplified analog method for broader clinical implementation.

Humans↗

PubMed2026

Temporal redistribution of control reveals age-related differences in task switching at the level of preparation.

Task-switching studies often report minimal age-related differences in switch costs, leading to the conclusion that switching-related control processes are relatively preserved in aging. However, this conclusion is based on paradigms that confound preparatory and execution processes. This study examined whether age-related differences in semantic task-set reconfiguration may be underestimated due to this confound. In Experiment 1 (36 young and 30 older adults), participants performed an externally paced task-switching paradigm without control over preparation. In Experiment 2 (28 young and 28 older adults), a self-paced paradigm allowed participants to initiate stimulus onset, enabling measurement of preparation time. Across both experiments, reaction time (RT) and error rate (ER) showed reliable age effects but no interactions between age and condition, whereas switching-related condition effects varied across measures and experiments. The expression of switching-related costs differed across measures and task structures. Local switch costs were expressed in ER in Experiment 1 but in RT in Experiment 2. Global switch costs (all-switch vs. all-repeat) were observed in execution measures only in Experiment 1. In Experiment 2, preparation time showed reliable mixing, local, and global switching effects, with age-related amplification emerging specifically for global switching. These findings indicate that switching-related costs are redistributed across processing stages and behavioral measures. The results suggest that age-related modulation of semantic task-set reconfiguration may emerge more clearly during preparation than task execution, particularly under continuous switching demands. Preparation time is interpreted cautiously as reflecting participant-regulated preparatory processes rather than a pure measure of preparation efficiency.

Humans↗

PubMed2026

Dual-tasking reveals severity-dependent reorganization of cortical beta energy landscapes in Parkinson's disease.

Dual-task impairment is a hallmark of Parkinson's disease (PD), yet the large-scale neural mechanisms underlying postural-motor interference remain poorly understood. In particular, it is unclear how cortical network dynamics reorganize across disease severity when postural control competes with concurrent task demands. This study investigated EEG-derived beta-band cortical energy landscapes in healthy older adults, early-stage PD, and mid-stage PD during single- and dual-task conditions. Dual-task behavioral cost increased with disease severity for concurrent manual performance (p < 0.001), whereas a quadratic pattern was observed for postural performance. Energy landscape analysis revealed severity-dependent reconfiguration of cortical beta dynamics. Dual-task-related landscape changes in effective network flexibility (ΔNeff), landscape geometry (ΔEvar and ΔGmag), and dominant low-energy attractor organization (ΔLow mass and ΔLow area) showed significant monotonic trends (p < 0.05), reflecting progressive constrained cortical network dynamics with advancing PD severity. In addition, dual-task-related landscape alterations were associated with clinical severity, as indexed by Hoehn and Yahr stage (|r| = 0.353-0.423, p = 0.016-0.048), and showed associations with motor impairment, as measured by MDS-UPDRS part III scores (|r| = 0.333-0.455, p = 0.009-0.063). These findings demonstrate that dual-task demands induce severity-dependent reconfiguration of cortical beta energy landscapes in PD. Energy landscape geometry may capture systems-level neural constraints associated with dual-task susceptibility in PD, providing a physiologically grounded framework to characterize disease-related functional vulnerability.

Humans↗

PubMed2026

Transcription regulation of cell fate plasticity - from embryonic development to tissue regeneration.

Cell fate plasticity refers to the capacity of cells sharing the same genome to alter, reverse, or reconfigure their identity under physiological, pathological, or experimental conditions. This property underlies embryonic development, cellular reprogramming, and tissue regeneration, but becomes progressively restricted as lineage identity is stabilized. Embryonic development represents an intrinsic process of fate transitions, whereas reprogramming and regeneration reveal how differentiated cells can dedifferentiate or transdifferentiate under specific conditions. Across these contexts, plasticity is governed by multilayered regulatory networks involving transcription factors, epigenetic regulators, cofactors, and the core transcription machinery. Robust regulatory programs stabilize cell identity, whereas stochastic fluctuations in gene expression and chromatin state can prime cells for fate transitions, adding a tunable dimension to plasticity control. In this review, we synthesize recent advances in the regulation of cell fate plasticity across development, reprogramming, and regeneration, highlighting how transcription factors, epigenetic modifications, transcriptional cofactors, and core transcription machinery cooperate to control cell fate decisions and plasticity.

Animals↗

PubMed2026

Angiotensin II regulates anxiety and social-affective top-down and bottom-up attention control in a sex-dependent manner.

BACKGROUND: The renin-angiotensin system (RAS) has been increasingly recognized as potent modulator of cognitive and affective functions, with angiotensin II type 1 receptor (AT1R) antagonists emerging as repurposing candidate for anxiety and stress-related disorders. However, it remains unclear whether transient AT1R blockade modulates emotional attentional control and whether these effects are sex-dependent. METHODS: We conducted a preregistered, randomized, double-blind, placebo-controlled pharmacological eye-tracking study in 79 healthy adults (males and females) and determined effects of transient AT1R blockade via losartan (50 mg) on emotional attention control using a validated anti-saccade paradigm with social (emotional faces) and non-social stimuli. Treatment effects on state anxiety and oculomotor responses were characterized using traditional metrics and a novel trial-history informed dynamic control framework. RESULTS: Losartan reduced state anxiety irrespective of sex but induced sexually dimorphic effects on attentional control. In females, losartan enhanced performance by reducing endpoint error without altering latency. Conversely, in males, losartan increased endpoint error and prolonged latency of the first correct saccade. Trial-history analyses revealed losartan reduced error probabilities following errors and repeat trials in both sexes. Yet, following correct trials, females receiving losartan maintained lower error probabilities, while males exhibited higher errors, potentially reflecting failure to disengage from effortful control. CONCLUSIONS: The RAS modulates anxiety and attentional control, the latter sex-dependently. AT1R blockade reconfigures attentional processing and adaptive control, suggesting sex-specific therapeutic potential in disorders characterized by excessive anxiety and attentional dysregulation. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov; https://clinicaltrials.gov/;NCT06329050.

Humans↗

PubMed2026

Comparison between measured and synthesized posterior lead electrocardiograms during percutaneous coronary intervention-induced myocardial ischemia.

BACKGROUND: Posterior/inferolateral myocardial ischemia is frequently underrecognized on standard 12‑lead electrocardiography (ECG). Synthesized posterior leads derived from the standard 12‑lead ECG have been proposed as an alternative to directly measured posterior leads; however, their accuracy under controlled ischemic conditions has not been fully validated. METHODS: We prospectively enrolled 26 consecutive patients undergoing percutaneous coronary intervention (PCI) in whom simultaneously recorded measured and synthesized posterior lead ECGs (V7-V9) were obtained during balloon-induced myocardial ischemia. ST-segment deviation was measured at the ST junction (STJ), 40 ms (ST1), and 80 ms (ST2) thereafter. Agreement between measured and synthesized posterior leads was assessed using Pearson correlation and Bland-Altman analyses. As an exploratory patient-level analysis, diagnostic performance was compared with reciprocal anterior ST-segment depression (V1-V4). RESULTS: Strong correlations were observed between measured and synthesized posterior lead ST-segment deviations (V7: r = 0.89; V8: r = 0.86; V9: r = 0.83; all P < 0.001). Bland-Altman analysis demonstrated minimal systematic bias (within ±0.004 mV) and narrow limits of agreement. Synthesized posterior leads showed higher diagnostic performance than reciprocal anterior ST-segment depression (AUC 0.917 vs. 0.708), although the difference was not statistically significant (DeLong test, P = 0.197). Using a 0.05 mV threshold, synthesized posterior leads demonstrated 83.3% sensitivity, 100% specificity, and 96.2% overall accuracy. CONCLUSIONS: Synthesized posterior leads closely reproduced measured posterior lead ST-segment deviations during percutaneous coronary intervention (PCI)-induced myocardial ischemia, supporting the technical validity of posterior lead reconstruction. Larger prospective studies are warranted to determine whether synthesized posterior leads provide incremental diagnostic value beyond careful interpretation of the standard 12‑lead ECG.

Humans↗

PubMed2026

Systematic multi-domain screening of lead-specific electrocardiographic features associated with sudden cardiac death.

UNLABELLED: Electrocardiogram (ECG) provides four-dimensional view to the electrical properties of the heart. We performed a comprehensive multi-domain screening to find the most significant lead-specific ECG features associated with sudden cardiac death (SCD). METHODS: We analyzed retrospective data from 21,176 consecutive patients undergoing coronary angiography in Tampere University Hospital between 2007 and 2018. 937 ECG variables provided by the 12SL algorithm were used for the analysis. From those, the significant lead-specific ECG variables were categorized into three subgroups: P-wave, QRS complex, and ST-segment/T-wave. The most significant (i.e., lowest P-value) independent lead-specific ECG variables were tested in multivariate analysis after filtering correlating variables with weaker associations with SCD. RESULTS: Among ventricular depolarization (QRS complex) variables, the strongest associations with SCD were observed for QRS intrinsicoid deflection (lead I) (p = 4.6 × 10-8), QRS peak-to-peak amplitude (lead aVR) (p = 1.9 × 10-5), and Q-wave amplitude (lead V1) (p = 7.6 × 10-6). Among repolarization (ST-segment and T-wave) variables, the strongest predictors of SCD were T-wave amplitude (lead aVR) (p = 3.5 × 10-7) and ST-segment end amplitude (lead aVL) (p = 8.1 × 10-5). The strongest associations with SCD among atrial depolarization (P-wave) variables were P-wave onset amplitude (lead V6) (p = 3.1 × 10-6), P'-wave amplitude (lead V2) (p = 2.1 × 10-5), and P-wave duration (lead V2) (p = 2.4 × 10-3). These variables remained significant in multivariate analysis alongside global ECG variables (e.g., heart rate, QRS duration, and LVH). CONCLUSION: Systematic screening and utilizing the full prognostic potential of the 12‑lead ECG reveal several key elements of the electrical properties of the heart that associate with SCD.

Humans↗

PubMed2026

Non-destructive prediction of lead content in oilseed rape leaves by fluorescence hyperspectral technology based on neural network.

Based on fluorescence hyperspectral imaging (FHSI), this study targeted rapid, non-destructive quantification of lead (Pb) content in oilseed rape leaves treated with varying silicon (Si) concentrations, acquiring fluorescence spectra over the 484.43-1001.61 nm wavelength range. To optimize spectral data quality, preprocessing methods (Savitzky-Golay smoothing, first derivative, detrending) were comprehensively compared. Characteristic wavelengths were then selected via interval variable iterative shrinkage, which effectively compressed data dimensionality and reduced computational load. A hybrid SE-CL1DA model, fusing a 1D convolutional neural network, a long short-term memory network and SE attention mechanism was constructed, with Bayesian optimization tuning hyperparameters to boost stability. The BO-SE-CL1DA outperformed both traditional machine learning and insufficiently optimized deep learning model (Rp2=0.9609, RMSE = 0.0377 mg/kg, RPD = 5.1736), thus enabling accurate Pb estimation, supporting Si-regulated heavy metal stress management and facilitating agricultural contamination monitoring.

Plant Leaves↗

PubMed2026

Feasibility and efficacy of left bundle branch area pacing guided by modified chest lead 1.

BACKGROUND: Left bundle branch area pacing (LBBAP) typically requires 12‑lead electrocardiogram (ECG) measurements using an electrophysiology (EP) recording system. However, a simplified approach using modified chest lead 1 (MCL1) is potentially feasible. This study aimed to compare the success rate and pacing outcomes of LBBAP guided by MCL1 with those guided by the 12‑lead ECG using an EP recording system. METHODS: This retrospective, single-center study included patients with preserved left ventricular ejection fraction who underwent LBBAP for bradyarrhythmia. LBBAP was either guided by 12‑lead ECG using an EP recording system or by MCL1. In the MCL1 group, a follow-up examination with a 12‑lead ECG using an EP recording system was conducted within one week postoperatively. RESULTS: A total of 65 patients underwent LBBAP (EP recording system group: n = 35; MCL1 group: n = 30). The overall success rate of LBBAP was 84.6%, with no significant difference between groups (88.5% vs. 80.0%, p = 0.49). No significant differences were observed in the paced QRS duration (140.4 ± 8.0 vs. 141.9 ± 13.1 ms, p = 0.54), V6-V1 interpeak interval (39.7 ± 16.5 vs. 38.3 ± 15.6 ms, p = 0.79), or V6 R-wave peak time (69.8 ± 12.3 vs. 71.5 ± 12.1 ms, p = 0.68). CONCLUSIONS: MCL1-guided LBBAP was feasible and achieved a high success rate, with outcomes comparable to those of conventional EP recording system-guided implantation. This simplified approach may reduce procedural complexity and may allow LBBAP implantation without the routine use of an EP recording system.

Humans↗

PubMed2026

Human endogenous retroviruses leading to autoimmune diseases.

Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and were long regarded as inert remnants of ancestral retroviral infections. Increasing evidence indicates that HERVs are active genomic elements capable of influencing transcriptional programs, modulating immune responses, and contributing to disease pathogenesis. Under physiological conditions, HERV expression is tightly controlled by epigenetic mechanisms; however, infections, chronic inflammation, aging, and diverse environmental stimuli can promote HERV reactivation. HERV-derived RNAs and proteins engage innate immune sensors and trigger antiviral-like responses through mechanisms of viral mimicry, leading to activation of type I interferon and other inflammatory pathways. HERV dysregulation has been associated with disease-relevant immune pathways. This review summarizes recent advances linking HERVs to autoimmune disease pathogenesis and discusses their potential translational relevance as biomarkers and therapeutic targets.

Humans↗

PubMed2026

Shielding performance and clinical applicability of lead-free materials in computed tomography.

Owing to the high radiation exposure associated with computed tomography (CT) examinations and the image quality degradation caused by conventional radiation shielding materials, this study evaluated the dose reduction performance and image quality maintenance potential of a newly developed lead-free composite shielding material. This material was composed of bismuth, tungsten, tungsten carbide, aluminium, and polyurethane. Phantom-based dose measurements demonstrated that the shielding material achieved dose reduction rates ranging from 17.6% to 37.6%, depending on tube voltage. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and changes in tube current-time product (mAs) under a scout-based automatic exposure control (AEC) protocol were analysed according to the presence or absence of the shielding material across regions. For the clinical evaluation, CT scans were performed on four patients. Furthermore, the images were reviewed to evaluate whether this material affected image quality. The shielding material exhibited radiation reduction levels comparable to those reported in previous studies. SNR and CNR analyses showed minor statistical variations in certain regions; however, most differences were not statistically significant, and even significant differences remained within a range that did not compromise diagnostic image quality. Under the scout-based AEC protocol, the use of the shielding material resulted in less than 1% variation in mAs values. No visually perceptible artefacts or clinically significant image quality degradation were observed. The proposed composite shielding material demonstrated the potential to mitigate some limitations of conventional shielding materials and showed preliminary clinical feasibility as an adjunctive strategy for radiation dose reduction in CT examinations.

Radiation Protection↗

PubMed2026

DNM1L depletion leads to accelerated heteroplasmy shifting of m.10191C allele through ATG7-dependent pathways.

Nucleotide composition bias in mitochondrial DNA (mtDNA) makes the heavy strand prone to form a DNA secondary structure called a guanine quadruplex (G4). This secondary structure has been shown to inhibit polymerase processivity in vitro. We previously identified pathogenic mtDNA variants that lead to increased G4-forming propensity, including a T to C mutation at m.10191 (m.10191 T > C) that causes Leigh syndrome. Cells treated with G4 binding agent (G4BA) berberine show a reduction in m.10191C pathogenic heteroplasmy levels. To help better understand the underlying mechanism behind berberine-induced heteroplasmy shift, we examined the relationship between mitochondrial fission and berberine-mediated shift. Here we show that knockdown of the fission factor DNM1L leads to an accelerated heteroplasmy shift towards the healthy mtDNA allele, lowering m.10191C by 10% in 3 weeks, compared to the 5 weeks required for berberine alone. The specific mechanism involves ATG7, as knockdown of ATG7 is able to partially delay this accelerated heteroplasmy shift. Taken together, we show that DNM1L knockdown is able to accelerate berberine-induced m.10191C heteroplasmy shifting through an autophagy-related mechanism.

Humans↗

PubMed2026

Leading with Innovation: Maternal Health Transformation in New York City Health + Hospitals.

New York City's (NYC) maternal health crisis drew close attention in the late 2010s, driven by alarming data: Approximately 30 women died annually during childbirth in NYC, Black non-Hispanic women were 12 times more likely to die than white women, and more than 3,000 women experienced life-threatening birth complications each year. In response, NYC committed $12.8 million in July 2018 to reduce maternal mortality and eliminate racial disparities.NYC Health + Hospitals (H+H)-the nation's largest public health system, serving 1.1 million patients annually with roughly 15,000 births per year-became the primary vehicle for this initiative. With 80 percent of the system's deliveries covered by Medicaid and a patient population that is 51.2 percent Hispanic and 27.1 percent Black, H+H is uniquely positioned to lead the fight against maternal health inequity.Three flagship programs anchor H+H's response to the city's maternal mortality rate. The OB Simulation Program, launched in 2012 and expanded in 2018, was the first in the nation to use mannequins of color to train thousands of providers in obstetric emergencies. The Maternal Home Program, piloted at H+H's Kings County Hospital in 2019 and scaled system-wide by 2021, has served more than 10,341 patients, generating more than 33,000 referrals for social, behavioral health, and community resources. The Cardio-Obstetrics Program located at Kings County Hospital targets cardiovascular disease-the leading cause of maternal death among Black women-through screening, education, and community outreach. These programs are a health equity imperative, made more urgent by impending federal Medicaid cuts resulting from the H.R.1 One Big Beautiful Bill Act (passed on July 4, 2025).

Humans↗

PubMed2026

Reliability-aware hierarchical learning for Chagas disease screening from 12-lead ECGs: tackling label uncertainty and class imbalance.

Objective.Chagas disease, a neglected tropical disease (NTD) with significant cardiovascular impact, remains underdiagnosed in resource-limited regions. Electrocardiogram (ECG) screening offers a low-cost tool for detecting cardiac involvement, yet algorithm development is challenged by label noise, data scarcity, and the latent nature of infection. This study proposes a robust ECG-based screening framework that explicitly addresses these constraints.Approach.We introduce aReliability-Aware Hierarchical Learningstrategy that calibrates supervision according to data provenance, prioritizing serology-confirmed labels over noisy self-reports. To mitigate data scarcity, we compare a specialized convolutional neural network (CNN) trained from scratch with a transfer learning approach based on a Spatio-Temporal ECG foundation Model (FM). Performance is evaluated across varying data scales, and the representation structure is analyzed to interpret model behavior.Main results.On the official hidden test set of the George B. Moody PhysioNet/Computing in Cardiology Challenge 2025, our approach achieved a Challenge Score of 0.163. We observe that while the specialized CNN performs competitively in data-rich regimes, the FM exhibits superior robustness in extreme low-resource settings. Furthermore, performance reaches a plateau imposed by underlying disease physiology. Bimodal score distributions suggest that models distinguish established cardiomyopathy from indeterminate infection, which remains electrophysiologically indistinguishable from healthy controls.Significance.These findings clarify both the potential and intrinsic limits of ECG-based AI screening for NTD-associated cardiac involvement. Reliability-aware supervision and data-efficient transfer learning provide a practical framework toward scalable and clinically meaningful ECG screening systems in resource-constrained environments.

Humans↗

PubMed2026

Orchard netting impacts on biodiversity leading to cascading effects at the ecosystem level.

Agriculture must ensure food production without further compromising the ecosystem functions upon which it depends. Agricultural practices should therefore avoid harming farmland biodiversity, especially of taxa that supply the key ecosystem services (e.g. pollination, pest control and nutrient uptake) that ultimately support crop production. Orchards are among the largest permanent plantations worldwide and are increasingly characterised by the spread of plastic nets used to protect fruits/nuts from either abiotic (anti-hail, anti-rain, shade nets) or biotic (exclusion nets) hazards. Despite having received little attention to date, these nets may impact natural communities, acting both as physical barriers and as drivers of habitat changes to which biota must respond. Species-level responses to netting depend on the organism's ability to enter the netted environment and successfully exploit available resources. Net-mediated ecological filtering and plastic behavioural responses may alter species interactions, leading to cascading ecological impacts that may create species-poorer 'netted communities' with simplified ecological networks. Such changes may erode biological control potential, other ecosystem functions, and overall system stability. We conducted a systematic review on the effects of protection nets on biota, and reported novel empirical evidence on anti-hail nets' impacts on communities of orchard-dwelling birds, flower-visiting insects, and rodents. In total, we identified 48 studies from the literature, however this literature was strongly biased towards apple orchards, western countries, and pest taxa. Net deployment was highly effective in deterring target pest species, in some cases regardless of their original function, as even weather-protection nets limited pest populations. Side effects on non-target taxa were also often reported, such as decreases in pollinators and natural enemies, and/or increases in secondary pests or microbial diseases. However, most assessments largely disregarded non-pest taxa and the broader ecological consequences of netting. The few studies that addressed the effects of nets at the guild/community level, including our empirical study, confirmed that orchard netting resulted in species-poor assemblages, with possible ecosystem-level consequences. We propose that future assessments should pay more attention to the indirect effects of netting on non-target taxa, and on the supply of crop-supporting ecosystem services mediated by wild species occurring in agroecosystems. Due to the trade-offs between these services and net-mediated crop protection, integrated alternatives should be tested to improve the environmental sustainability of food production and biodiversity conservation in farmed landscapes.

Biodiversity↗

PubMed2026

In Vivo Genome Editing Approach to Disrupt Hydroxyacid Oxidase 1 for the Treatment of Primary Hyperoxaluria Type 1.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder that leads to kidney and liver failure. PH1 is caused by a mutation in the alanine glyoxylate aminotransferase (AGXT) gene, which encodes a key metabolic enzyme that converts glyoxylate to glycine in the liver. Inability to metabolize glyoxylate leads to oxalate overproduction, yielding insoluble calcium oxalate crystals; accumulation of these crystals leads to progressive organ failure. Here, we used a novel, minimally disruptive genome-editing approach to disrupt the mechanism of action of hydroxyacid oxidase 1 (HAO1), an upstream enzyme in the glyoxylate metabolic pathway. Successful gene editing and disruption of the HAO1 gene is expected to increase levels of glycolate, a harmless intermediate of the glycine metabolic pathway, thereby preventing the formation of calcium oxalate crystals. We intravenously administered an adeno-associated virus (AAV) vector expressing the M1HAO1 meganuclease to both wild-type and Agxt-/- mice, a mouse model of PH1. We observed >30% editing of HAO1 in Agxt-/- mice, correlating with a dose-dependent increase in serum glycolate levels. At the highest dose tested, urine glycolate levels increased by 79%, with a concomitant 75% decrease in urine oxalate levels. We also evaluated in vivo targeting in rhesus macaques injected with AAV expressing two different versions of the HAO1 meganuclease. Dose-dependent editing of hepatic DNA and RNA was achieved, and serum glycolate levels changed in a manner consistent with successful liver editing; additionally, the treatment was well tolerated. Our results indicate that AAV-delivered meganucleases can effectively target HAO1 in mice and nonhuman primates to achieve high levels of HAO1 gene editing. Moreover, increased glycolate levels in serum indicate that this intervention significantly impacts the HAO1-mediated glycolate-to-glyoxylate pathway. These data suggest that this approach may represent an effective treatment for PH1.

Hyperoxaluria, Primary↗

PubMed2026

Artificial intelligence for anticancer drug discovery from natural products of macroalgae and sponges: A systematic review.

Marine natural products (MNPs) from macroalgae and marine sponges have inspired clinically important anticancer agents, including the cytarabine pharmacophore and the eribulin scaffold, while cyanobacterial dolastatin chemistry supplies the auristatin payloads of several marine-inspired antibody-drug conjugates (ADCs) such as brentuximab vedotin. Artificial intelligence (AI) methods, encompassing both classical machine learning (ML) with hand-engineered features and modern deep learning (DL) with many-layered neural networks, are increasingly supporting key decisions in natural-product anticancer drug discovery, including bioactivity prediction, target identification, absorption, distribution, metabolism, excretion and toxicity (ADMET) filtering, generative analogue design, and the selection of preclinical candidates. DL architectures relevant to this field include graph neural networks, transformer-based molecular generators, diffusion models for protein-ligand docking, and convolutional networks for mass spectrometry, while classical ML contributes interpretable fingerprint-based bioactivity models and molecular networking for dereplication. This review follows a systematic literature review methodology to organize the landscape of AI methods now applied to MNP anticancer discovery, distinguishing ML and DL approaches where relevant, situating them within the chemical context of macroalgal and sponge-derived oncology leads, and critically examining published case studies, including validation level (computational, in vitro, in vivo, clinical). The principal bottleneck for medical translation has shifted partly from algorithmic capability toward data infrastructure and experimental validation. Sparse, heterogeneous, and taxonomically biased bioactivity records limit what current models can learn and reduce the reliability of AI-prioritized candidates entering the preclinical pipeline. A roadmap is proposed that prioritizes open MNP-specific benchmarks, symbiont-aware modeling, and active learning loops with synthesizability and ADMET constraints. These AI workflows may accelerate the prioritization of marine-derived anticancer leads and support earlier, more evidence-based translational decisions in oncology drug development.

Biological Products↗

PubMed2026

Does future-oriented imagery rescripting increase willingness to carry out a social anxiety-related behavioral experiment? An extended replication.

BACKGROUND AND OBJECTIVES: Mental images of threat are common in social anxiety disorder and could impede exposure to fear-relevant situations. Landkroon et al. (2022) found that imagery rescripting of anticipated future threat, compared to no-task, increases willingness of non-clinical individuals to conduct a social anxiety-related behavioral experiment. The aim of this two-day preregistered extended replication study was to examine whether the effects persist beyond the intervention session by scheduling the behavioral experiment 1-7 days after the intervention. METHODS: On Day 1, 60 pre-screened participants were asked to design a behavioral experiment to test an idiosyncratic negative belief about a feared social situation. They were then randomly assigned to imagery rescripting (focused on their worst feared outcome of the behavioral experiment) or no-task. Participants' willingness to do the behavioral experiment and their threat beliefs was measured. On Day 2, they were asked to carry out the behavioral experiment. RESULTS: The imagery rescripting group, compared to the control group, did not show increased willingness or compliance to do the behavioral experiment on Day 1 or 2. Furthermore, the imagery rescripting did not lead to greater reductions in threat beliefs on either day. LIMITATIONS: The quality of the imagery rescripting intervention was not assessed, and given the brief nature of the intervention, any effects may have dissipated before participants decided whether to carry out the behavioral experiment. CONCLUSIONS: There was no evidence that imagery rescripting leads to changes in willingness or compliance to do a fear-relevant behavioral experiment. More research is needed to examine interventions that can enhance exposure in socially anxious people.

Humans↗