The escalating energy consumption of existing artificial intelligence hardware has become a serious global issue that demands immediate action. Neuromorphic computing offers promises to drastically reduce this footprint. Here, we introduce multicomponent p-type Hf(Sr,Ti)O2 thin films for energy-efficient, resistive switching–based neuromorphic devices. We demonstrate interfacial memristors with ultralow switching currents (≤~10−8 A), exceptional cycle-to-cycle and device-to-device uniformities, and retention >105 s. They reveal hundreds of ultralow conductance levels with a modulation range of >50 (without reaching any saturation) and reproducibly satisfy unsupervised learning rules. This performance originates from incorporating a self-assembled p-n heterointerface between p-type Hf(Sr,Ti)O2 and n-type TiOxNy, resulting in a fully depleted space-charge layer asymmetrically extended into Hf(Sr,Ti)O2, a large built-in potential, and extremely low saturation current density under reverse bias. Ultralow conductance modulation is controlled by tuning p-n heterointerface’s energy-barrier height through electro-ionic charge migration. This materials-engineering strategy addresses energy consumption and variability in existing memristors, opening a pathway toward energy-efficient neuromorphic computing systems.

Borderline personality disorder (BPD) is a significant cause of morbidity with no approved pharmacological treatment. We assessed treatment trajectories of patients with BPD in real-world clinical practice to help identify treatment gaps. This retrospective, observational, cohort study used de-identified MindLinc electronic health records data from the Holmusk NeuroBlu database (Version 21R2) to analyse the treatment journey of patients with BPD (aged ≥ 12 years with ≥1 diagnosis of BPD) that were prescribed pharmacological treatment within 14 days of diagnosis (baseline) and had treatment data for ≥12 months. Of those prescribed pharmacological treatment at baseline, 1461 patients (16.1%) had 12 months of follow-up data. Antidepressants were the most frequently prescribed medication at baseline (80.4%) either alone or in combination with other medication classes, followed by second-generation antipsychotics (SGAs), anxiolytics and mood stabilisers. In the 12 months post-baseline, the most frequently recorded treatment pathway was a switch from 1 antidepressant to another. Sertraline (5.5%), fluoxetine (5%), and citalopram (5%) were the most-prescribed antidepressants; lamotrigine (24.9%), gabapentin (15.4%), and valproate (7.1%) were the most prescribed mood stabilisers; and quetiapine (22.1%) and aripiprazole (19.0%) were the most prescribed SGAs. Polypharmacy (defined as the prescription of ≥ 1 psychotropic medication) was observed in 83.1% of patients at baseline and increased with follow-up time and age. The high rates of polypharmacy observed suggest that current clinical practices may not fully align with treatment guidelines for BPD, and that patients with BPD experience a considerable treatment burden. Limitations of this study include the absence of psychotherapy data and the use of prescription records without information on treatment adherence. Nonetheless, the diversity of treatment patterns observed reflects the complex symptomatology of BPD and highlights the need to deepen our understanding of its neurobiology to improve pharmacological treatment strategies and translate to meaningful patient outcomes. Not applicable.

Mazviita Chirimuuta’s The Brain Abstracted (2024) is a fascinating intervention into the philosophy of mind and neuroscience, containing deeply interesting ideas and arguments. Our aim is to critically probe whether Haptic Realism is neutral on some substantive issues which Chirimuuta would like it to be neutral on. Firstly, it is unclear whether Haptic Realism is compatible with Chirimuuta’s metaphysical neutrality. Causal notions feature heavily in Haptic Realism, including construction and interaction, without which it is unclear what the haptic component of Haptic Realism amounts to. We argue that the interpretation of these causal notions forces a choice that jeopardises metaphysical neutrality, since it is doubtful that there are any relevantly neutral theories of causation. Secondly, we ask the question ‘Do all brains have neurons?’ Haptic Realism trades on the idea of ideal patterns, patterns that are coaxed into existence by the interaction between practitioners and the world. If ideal patterns only exist within the confines of the lab, and neurons are idealizations, then brains out in the wild do not have neurons. Worryingly, this commitment of Haptic Realism undermines our ability to project neurological knowledge that we gain from studying particular brains to what is happening inside the everyday human beings.

Methods to detect circulating tumor DNA (ctDNA) enable minimally invasive responsive monitoring of cancer dynamics. However, sensitive and cost-effective methods are still lacking. Current methods for detecting cancer signals in shallow whole-genome sequencing (sWGS) data from cell-free DNA (cfDNA) via copy number aberration (CNA) analysis typically have a limit of detection of approximately 3% tumor fraction (TF). We developed informCNA, a bioinformatics method that leverages CNA information from sWGS of tumor or pre-treatment plasma samples with high TF as references, enabling ctDNA detection down to 0.2% TF across multiple cancer types. In 177 serial plasma samples from 18 patients with ovarian cancer, informCNA showed high concordance with the standard serum protein marker CA-125 and identified recurrence a median of 3.7 months earlier than CA-125 test. These results demonstrate the potential of personalized CNA analysis through sWGS for estimating ctDNA burden, enabling precise and cost-effective disease monitoring and early detection of relapse.

This review synthesizes recent empirical and theoretical studies from 2024 to 2025 that examine the psychological effects of war, displacement, and siege on Palestinian children in the Gaza Strip. It focuses on the interconnected issues of death anxiety, post-traumatic stress disorder (PTSD), grief, and resilience, aiming to frame mental health outcomes within structural and political contexts rather than within individual pathology. Studies indicate that between 70 and 90% of children in the Gaza Strip meet criteria for PTSD or exhibit significant symptoms of depression and anxiety. Continuous traumatic stress stems from prolonged bombardment, displacement, and loss, exacerbated by the collapse of mental health services. Qualitative evidence reveals widespread death anxiety, anticipatory grief, and moral injury. However, resilience rooted in family cohesion, faith, education, and Sumud (steadfastness) remains a key protective factor. Community-based interventions show potential but lack sustainability amid systemic destruction. Decolonial scholarship further challenges Western trauma models, treating children’s stories as acts of agency and epistemic resistance. The psychological impact of the military siege and sustained attacks in the Gaza Strip on children is profound and enduring. Effective responses should integrate psychosocial, educational, and justice-oriented approaches to rebuild community systems and explicitly acknowledge the political conditions that shape children’s lives. Future research should employ longitudinal, participatory, and culturally grounded methods that link psychological recovery to social reconstruction and the restoration of dignity.

Celcomen leverages a mathematical causality framework to disentangle intra- and inter-cellular gene regulation programs in spatial transcriptomics data through a generative graph neural network. It is a first step towards perturbation models of Virtual Tissues and can generate post-perturbation counterfactual spatial transcriptomics, thereby offering access to experimentally inaccessible samples. We validated its disentanglement, identifiability of causal structure, and counterfactual prediction capabilities through simulations and in clinically relevant human glioblastoma, human fetal spleen, and mouse lung cancer samples. Celcomen provides the means to model disease- and therapy-induced changes allowing for new insights into single-cell spatially resolved tissue responses.

Synthesizer is a fast, flexible, modular, and extensible Python package that empowers astronomers to turn theoretical galaxy models into realistic synthetic observations-including spectra, photometry, images, and spectral cubes-with a focus on interchangeable modelling assumptions.By offloading computationally intensive tasks to threaded C++ extensions, Synthesizer delivers both simplicity and speed, enabling rapid forward-modelling workflows without requiring users to manage low-level data processing and computational details.

Parkinson's disease (PD) is a debilitating neurodegenerative condition that results in a loss of mobility and muscle control. A neuropathological hallmark of PD is the presence of aberrant inclusions, known as Lewy pathology, of which α-synuclein (α-Syn) is a major component. The accumulation of α-Syn may be due to an imbalance in the proteostasis system regulating α-Syn. To investigate this hypothesis, we delineated the proteostasis network (PN) of α-Syn in the human substantia nigra at the proteomic and transcriptomic level. We then defined an α-Syn proteostasis activity score (PAS) that quantifiably describes the relative activity of the α-Syn PN in promoting or inhibiting α-Syn aggregation. We report a corresponding PAS signature indicative of disease state, age-of-death in PD patients, and brain regional vulnerability to α-Syn aggregation in PD and healthy brains. After establishing the relevance of our network to PD, we developed a transcriptome-derived network model as an operational digital twin of the α-Syn PN in human substantia nigra cells from single-cell data and used it to prioritize candidate targets for PD. We then further showed the application of the α-Syn PN toward facilitating drug repurposing. Overall, this proof-of-concept study illustrates how our computational framework can identify and prioritize putative therapeutic targets and repurposing candidates for PD, providing testable hypotheses for experimental validation.

SUMMARYModification by ubiquitination governs the half-lives of thousands of proteins that are fated for elimination by either the proteasome or autophagy pathways, depending on the intricate architectures of ubiquitin modification. This system mediates quality control for individual proteins, protein complexes, and organelles, as well as myriad purely regulatory functions. Here we provide a comprehensive survey of the ubiquitin-proteasome system (UPS), the scope of which is at present poorly defined. The UPS, with the inclusion of pathways involving ubiquitin-like modifiers, comprises in our estimate over 1400 distinct proteins in humans, a vast set of activities whose collective impact on the biology of the cell is pervasive. The UPS is an integral component of the proteostasis network (PN), the remainder of which we have also surveyed in recent studies. With the addition of molecular chaperones, proteins from autophagy-lysosome pathway, and related activities, the PN includes in total over 3100 components by our estimates. Comprehensive and systematic definition of these pathways should support a range of ongoing investigations in the areas of genomics, proteomics, biochemistry, cell biology, and disease research.