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Microbial communities serve as vital indicators of ecosystem health and play a crucial role in facilitating the restoration of degraded soil ecosystems, acting as key participants in soil nutrient cycling. However, the interaction mechanisms between microbial communities and plants in different soil zones under varying restoration approaches remain unclear. This study focused on a restoration area of a decommissioned open-pit coal mine in an alpine region, comparing the microbial community structure and nutrient characteristics of rhizosphere and bulk soils under two restoration methods: herbaceous vegetation restoration and sea-buckthorn shrub restoration. The aim is to reveal the impact of different restoration measures on the soil-microorganism interactions. The results demonstrated that soil organic carbon (SOC), total nitrogen (TN), available nitrogen (AN), total potassium (TK), and available potassium (AK) contents were significantly higher in the herbaceous restoration area (O) than in the seabuckthorn area (S), by 51.7%, 88.6%, 38.2%, 13.1%, and 4.7%, respectively. Compared to bulk soil, rhizosphere soil exhibited higher microbial community diversity and richness. Furthermore, seabuckthorn rhizosphere microbial diversity surpassed that of herbaceous rhizosphere. Different restoration areas (DRE) significantly (p&#x2009;<&#x2009;0.05) influenced the relative abundances of Actinobacteria, Proteobacteria, Chloroflexi, and Acidobacteria. The seabuckthorn area showed higher proportions of Proteobacteria (26.48&#x2009;-&#x2009;42.86%) and Actinobacteria (28.26&#x2009;-&#x2009;45.19%) compared to the herbaceous area. Functional gene prediction revealed that the seabuckthorn area expressed significantly higher abundances of core metabolic functional genes related to energy production and conversion (C), amino acid transport and metabolism (E), carbohydrate metabolism (G), and lipid metabolism (I) than the herbaceous area. Additionally, a symbiotic functional guild comprising animal pathogens, endophytes, lichen parasites, plant pathogens, and wood saprotrophs was formed in the seabuckthorn area. Redundancy analysis (RDA) indicated significant positive correlations (p&#x2009;<&#x2009;0.05) between Acidobacteria, Chloroflexi, Actinobacteria, and Ascomycota and the contents of SOC, TN, and total phosphorus (TP). Bacterial networks formed with Actinobacteria as the core hub, comprising 300 edges connecting 50 nodes, while fungal networks were dominated by Ascomycota. Based on these findings, this study proposes a synergistic restoration strategy characterized by "herbaceous-induced short-term priming" coupled with "seabuckthorn-driven long-term stability." This strategy provides a theoretical foundation for the targeted microbial regulation of ecological restoration in mining areas.

Parkinson's disease (PD) is characterized by progressive loss of nigral dopaminergic neurons, resulting in disabling motor symptoms. Intracerebral transplantation of stem cell-derived dopaminergic progenitors to replace lost endogenous dopaminergic neurons offers a new potentially restorative therapeutic approach for PD. Here we report the 12-month primary safety end point and interim efficacy outcomes from a phase 1/2, open-label, multicenter trial evaluating STEM-PD, a cryopreserved, off-the-shelf dopaminergic progenitor product derived from human pluripotent stem cells. Eight individuals with moderate PD underwent bilateral intraputaminal transplantation at two escalating doses (n&#x2009;=&#x2009;4 per cohort), followed by 12&#x2009;months of immunosuppression. Seven participants completed 12-month follow-up; one participant died from a pulmonary infection. No serious adverse events were attributed to the cell product, no graft-induced dyskinesias were observed and serial magnetic resonance imaging showed no evidence of tumor formation. These findings support the feasibility and favorable safety profile of human pluripotent stem cell-derived dopaminergic progenitor transplantation in this early-phase study, with risks primarily associated with the immunosuppression regimen. Ongoing follow-up to 36&#x2009;months will further evaluate durability, clinical outcomes and graft function. ClinicalTrials.gov identifier: NCT05635409 .

We sought to determine whether the endoscopic grade of gastric atrophy (according to Kimura-Takemoto) affects the likelihood of successful first-line H. pylori eradication. We conducted a retrospective analysis of consecutive patients hospitalized at Wuhan Fourth Hospital between November 2021 and November 2025. Eligible individuals had a positive urea breath test confirming H. pylori infection, were diagnosed with chronic atrophic gastritis via gastroscopy, received a bismuth-containing quadruple regimen as first-line therapy, and returned for a follow-up breath test at least 4 weeks post-treatment. Prior to therapy (within 28 days), each patient underwent high-definition white-light gastroscopy. Two independent endoscopists, unaware of patient allocation, retrospectively reviewed all images to grade atrophy using the Kimura-Takemoto system. Patients were assigned to either the closed-type (C-type) or open-type (O-type) atrophy group. The primary endpoint was eradication failure, defined as a positive follow-up breath test. Logistic regression (univariate and multivariate) was used to identify factors independently linked to treatment failure. A total of 154 patients completed follow-up and were included. The overall eradication rate was 76.6% (118/154). In the open-type atrophy group (n = 26), the eradication rate was only 42.3% (11/26), significantly lower than the 83.6% (107/128) observed in the closed-type group (P < 0.001). After adjusting for confounders such as body weight and age, multivariate analysis revealed that endoscopic open-type atrophy was independently associated with eradication failure (OR = 8.287, 95% CI: 3.150-21.804, P < 0.001). The extent of endoscopic gastric mucosal atrophy independently predicts a lower efficacy of first-line H. pylori eradication. For patients with Kimura-Takemoto open-type atrophy, clarithromycin-containing quadruple regimens should be used cautiously. Alternative clarithromycin-free regimens (e.g., tetracycline-, metronidazole-, or levofloxacin-based therapies, or high-dose amoxicillin with PPI/vonoprazan) or susceptibility-guided individualized therapy are recommended in clinical practice.

Psychosis prevention relies on early detection of individuals at clinical high risk for psychosis (CHR-P). The effectiveness of the CHR-P state is constrained, in part, due to clinical assessments requiring specialist interpretation of narrative interviews, limiting scalability. Here, we evaluate whether large language models (LLMs; deep learning models trained on large text corpora to process and generate language) can extract clinically meaningful information from such interviews to support psychosis risk assessment. We assessed 11 open-weight LLMs on 678 partial PSYCHS interview transcripts from 373 participants (77.7% CHR-P). Models inferred CHR-P status and estimated severity and frequency across 15 symptom domains, benchmarked against researcher-rated scores. Larger models achieved the strongest classification performance (Llama-3.3-70B: accuracy = 0.80, sensitivity = 0.93, specificity = 0.58). LLM-generated symptom scores showed good correlations with researcher-rated scores (ICCsev = 0.74, ICCfreq = 0.75). Performance disparities were minimal across most demographic groups but varied across sites. Generated summaries were largely faithful to source transcripts, with low rates of clinically relevant confabulation (3%). Errors primarily reflected over-pathologisation of non-clinical experiences. While accuracy scaled with model size, smaller models achieved competitive performance with substantially lower computational cost. These findings demonstrate that open-weight LLMs have the potential to assess psychosis risk from psychometric interview transcripts, supporting scalable, human-in-the-loop approaches to early detection.

Transition-metal oxide/layered double hydroxide (LDH) electrodes often suffer from insufficient utilization of active sites, sluggish electron/ion transport, and limited cycling stability at high rates. Here, La-doped ZnCo2O4/MnCo-LDH nanoflowers serve as the positive electrode and Ti-supported Sb-doped SnO2 (Ti/Sb-SnO2) serves as the negative electrode for constructing an asymmetric supercapacitor. A stepwise hydrothermal route, La-doping regulation, and ethylenediamine-assisted morphology control transform stacked nanosheets into open porous nanoflowers with a specific surface area of 382.5 m2 g-1, thereby exposing more electroactive sites and shortening OH- diffusion pathways. La3+-induced lattice distortion and defect-related oxygen species further tune the electronic structure and improve interfacial charge-transfer kinetics. The optimized La-ZnCo2O4/MnCo-LDH electrode delivers 2130 F g-1 at 1 A g-1 and retains 1993 F g-1 after 10,000 cycles at 3 A g-1. The Ti/Sb-SnO2 negative electrode provides 673 F g-1 at 1 A g-1 and 302 F g-1 at 15 A g-1. The assembled device operates stably from 0 to 1.8 V in 2 M KOH and achieves 69 Wh kg-1 and 13,500 W kg-1.

The increasing use of antibiotics in livestock farming raises concerns about environmental impacts. This study examined the effects of three commonly used veterinary antibiotics - Tylosin, Enrofloxacin, and Oxytetracycline - on manure greenhouse gas (GHG) emissions and fertilizer quality during solid manure storage. Aliquots of fresh cattle manure (10&#x202f;kg) were either spiked with high or low concentrations of each antibiotic, or left untreated as Control, then incubated in open buckets for 110 days to simulate manure heaping. Emissions of CO2, CH4, and N2O were measured using a static chamber with a laser spectrometer. Tylosin (High and Low) treatments and High-dose Enrofloxacin significantly increased manure N2O emissions (2.1&#x202f;&#xb1;&#x202f;0.2 to 2.5&#x202f;&#xb1;&#x202f;0.4&#x202f;%), exceeding the IPCC default values of 1&#x202f;% manure-N. All antibiotic treatments increased CH4 emission factors (6.4&#x202f;&#xb1;&#x202f;0.7 to 14.2&#x202f;&#xb1;&#x202f;1.1&#x202f;g CH4 kg-1 VS) compared to the Control (2.2&#x202f;&#xb1;&#x202f;0.5&#x202f;g CH4 kg-1 VS) and the IPCC default value (4.44&#x202f;g CH4 kg-1 VS). Overall, antibiotic residues increased the global warming potential (GWP) of stored solid manure by 218&#x202f;% compared to the Control. Despite the slightly greater nitrogen losses from increased N2O emissions, the final fertilizer quality of the manure remained unaffected by the antibiotic treatments. Besides health concerns related to antimicrobial resistance, our findings on environmental impacts call for a One Health approach to promote sustainable antibiotic use in livestock production.

MXenes are a rapidly expanding family of two-dimensional transition-metal carbides, nitrides, and carbonitrides whose physicochemical behavior in aqueous and biological environments is dominated by their surface terminations (e.g., -O, -OH, and -F), rendering them intrinsically active solid-liquid interfaces. These terminations regulate interfacial charge distribution, hydration structure, adsorption equilibria, and colloidal stability, positioning MXenes as dynamic interfacial systems rather than passive nanomaterials. Rational control of surface termination chemistry therefore represents a central strategy for governing MXene interactions with electrolytes, proteins, and biological media. This review provides a comprehensive and critical analysis of recent advances in MXene surface-termination engineering from the perspective of interfacial and colloidal science, with emphasis on etching routes, post-synthetic modification, dimensional tailoring (2D, 3D, and emerging 4D architectures), and characterization approaches relevant to interfacial behavior. We examine how termination chemistry controls key interfacial properties, including zeta potential, dispersion stability in physiological electrolytes, hydration-mediated wetting, and protein corona formation, and how these interfacial factors collectively shape biological responses such as cytotoxicity, inflammatory signaling, antibacterial activity, and reactive oxygen species generation. Particular attention is devoted to termination-driven charge regulation and coordination chemistry at solid-liquid interfaces, which govern adsorption-desorption dynamics, molecular loading, and stimulus-responsive release, as well as the modulation of optical and magnetic responses. By critically comparing reported systems and explicitly addressing unresolved challenges related to termination heterogeneity, interfacial aging, and scalability, this review clarifies structure-interface-function relationships that underpin MXene performance in complex environments. Finally, we identify emerging strategies and open questions for designing surface-terminated MXenes with predictable and controllable interfacial behavior, highlighting their broader relevance as model systems for dynamic solid-liquid interfaces with bio-functional implications.

This debate addresses the choice of placebo versus active comparator in randomized controlled trials (RCTs) for chronic migraine (CM), a disabling condition with high global burden. Placebo-controlled designs have traditionally been considered the gold standard for new treatments, allowing quantification of placebo and pharmacological effects, ensuring internal validity, smaller sample sizes, and regulatory acceptance. Yet, ethical concerns arise from the possibility that participants may be denied effective treatments. The emergence of migraine-specific therapies targeting the calcitonin gene-related peptide (CGRP) pathway has prompted calls for active comparator designs. Such trials may enhance clinical relevance, support recruitment, and better mirror clinical practice compared with placebo-controlled RCTs. However, defining a universal standard of care may be challenging given global disparities in access, cost, and treatment preferences, limiting the feasibility of RCTs with active comparators. Placebo-controlled trials remain valuable, but alternative strategies, including short placebo phases with open-label extensions, add-on designs, or three-arm trials (investigational treatment, placebo, active comparator) may reconcile scientific rigor with ethical considerations. Ultimately, the optimal trial design depends on the research question, regulatory requirements, and evolving definitions of standard care in CM prevention.

Efficient separation of carbon monoxide (CO) from nitrogen (N&#x2082;) is vital for recycling steel industry by-product gases and advancing carbon-neutral chemical production. However, current Cu(I)-based &#x3c0;-complexation adsorbents suffer from excessive binding strength and low working capacity. Here we report thermally-dispersed open metal sites (OMS) with two-coordinated Cu(I) units, (&#x2009;&#x2261;&#x2009;C-O)CuCl, anchored onto zeolite imidazolate frameworks (ZIFs) derived oxygen-containing porous carbons (ZPC), where the Cu&#xb7;&#xb7;&#xb7;CO interaction strength is precisely moderated. The optimized adsorbent, 15Cu(I)/ZPC-1, with 15&#x2009;mmol&#x2009;g&#x207b;&#xb9; Cu(I) dispersed in 10-30&#x2009;&#xc5; pores, delivers a high CO working capacity of 3.21&#x2009;mmol&#x2009;g&#x207b;&#xb9; (0.1-1&#x2009;bar, 298&#x2009;K), the highest among reported recyclable Cu(I)-based adsorbents. The analyses reveal that a low-symmetric trigonal (&#x2009;&#x2261;&#x2009;C-O)CuCl&#xb7;&#xb7;&#xb7;CO coordination geometry weakens &#x3c0;-backbonding, enhances working capacity. Process simulations predict that 15Cu(I)/ZPC-1 enables high productivity and low energy consumption. This work establishes OMS regulation in porous carbon as an effective strategy for efficient CO/N&#x2082; separation.

Infants are vulnerable to meningococcal disease. In this open-label phase III study (NCT03632720; registered 13/8/2018), infants were randomised to quadrivalent ACWY conjugated vaccine, MenACYW-TT, at 3 and 12-13 months and four-component meningococcus group B vaccine (4CMenB) at 2, 4, and 12-13 months (Group 1), MenACYW-TT at 3 and 12-13 months and 4CMenB at 2 and 4 months (Group 2), or 4CMenB at 2, 4, and 12-13 months (Group 3). Routine vaccines were also administered per UK schedule. Primary outcome of non-inferiority of seroprotection rates against the four capsular groups (A, C, W, and Y) in Group 1 versus Group 2 at day 30 after the second vaccine dose was demonstrated with seroprotection rates &#x2265;99% against all capsular groups in both groups. In Group 3, cross-reactivity was observed, with hSBA titres against capsular groups A and C increasing >10-fold after the third 4CMenB dose. Reactogenicity was consistent with the known profiles of both vaccines; one case of anaphylaxis related to MenACYW-TT was reported and resolved without sequelae. No new safety concerns were identified.

To describe the epidemiological characteristics of children and young people presenting to the emergency department (ED) with acute severe behavioural disturbance (ASBD) who were deemed to require oral sedative medication. Secondary analysis of a randomised controlled open-label multi-centre trial of oral olanzapine versus oral diazepam for the management of ASBD in children and young people aged nine to 17&#x2009;years for whom epidemiological data were recorded. There were 348 participants enrolled in the randomised controlled trial (RCT). The majority were female (215/348, 62%) with a mean age of 14.6&#x2009;years (standard deviation 2.2). The most common pre-existing medical or mental health condition was anxiety (122/299, 35%) followed by attention deficit hyperactivity disorder and autism spectrum disorder (33% and 32%, respectively). Two-thirds of the study population (216/348, 62%) had previously attended the ED for ASBD management and 61% (212/348) reported previous intentional self-harm. Nearly three-quarters (247/348, 71%) were accessing psychiatric care in the community prior to their ED presentation. Half of the study population (178/348, 52%) presented to the ED with emergency services (e.g., ambulance, police). The median length of stay in the ED was 5.7&#x2009;h (interquartile range 3.9-10.2&#x2009;h) and 28% (98/348) of study participants required admission to hospital. For children and young people presenting to the ED with ASBD who were deemed to require oral sedative medication to assist with behavioural containment, pre-existing mental health disorders were common. There is a need for focussed management procedures for more targeted, trauma-focussed care for children and young people presenting to the ED with ASBD and for support and education in the pre-hospital setting. The primary study (PEAChY-O) was registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12621001236886) prior to commencement.

Mitochondrial reactive oxygen species (mtROS) have been implicated in aging and disease for decades and are typically viewed as a unitary, non-specific oxidative burden on cells and tissues. However, recent studies have identified at least eleven individual sources of mitochondrial ROS (ISOMRs) and revealed that ISOMRs have distinct, dynamic, and often reversible roles in diverse physiological and pathological processes, including neurodegenerative diseases, immune and metabolic dysregulation, and ischemia-reperfusion injury. This review describes the upstream molecular events that control ISOMR activity, recently developed tools for studying mtROS in general and ISOMRs more specifically, and the evolving perspectives on ISOMR roles in context-specific cell signaling. Future studies to define predictive principles of ISOMR regulation are necessary to open frontiers of redox biology and identify therapeutic strategies for selective modulation of ISOMR-dependent mechanisms in aging and disease.

Aqueous zinc-ion batteries (AZIBs) possess distinct benefits in cost and safety, but bilateral interfacial failures on Zn anodes and MnO2 cathodes constrain their practical applications. Inspired by zymogen-to-enzyme activation, this work proposes a biomimetic, intelligent electrolyte additive strategy that enables on-demand protection on both electrodes. This strategy employs an inert additive, 1,4-butane sultone (BS), which preferentially adsorbs on the electrode surfaces. Upon water attack and localized pH increase, BS can be activated, generating open-ring derivatives (OBS) to facilitate the in situ construction of bilateral protective interphases with organic-inorganic composite components. Concurrently, it optimizes Zn2+ solvation structures to lower the desolvation energy barrier. Residual BS further traps SO4 2- and H2O and sustains the OBS formation for preventing interfacial alkalization. Consequently, the BS-modified Zn//Zn cell delivers a lifespan exceeding 4000&#xa0;h, and the Zn//Cu cell attains an ultrahigh initial Coulombic efficiency of 97.62%. Zn//MnO2 full cells maintain capacity retention of 92.7% and 80.5% after 100 cycles at 0.2 A g-1 and 8000 cycles at 6 A g-1, respectively. Such a strategy not only delivers a high-performance electrolyte additive for AZIBs but also offers biomimetic inspiration for the development of electrolytes in other metal-based battery systems.

Background/Objectives: Resistant pathogenic bacteria and fungi are a growing problem worldwide; therefore, the discovery of new active ingredients is an important challenge for which the functionalization of natural terpenes with biologically active heterocycles can provide a basis. To reach this goal, a series of 1,4-disubstituted-1,2,3-triazole conjugates was designed and synthesized starting from commercially available &#x3b1;-santonin. Methods: The key azido derivative intermediate was prepared according to literature procedures via Michael addition between dehydrosantonin and the TMSN3/AcOH/Et3N system at its highly reactive &#x3b1;-methylene-&#x3b3;-lactone motif. Subsequently, the obtained azide was applied to regioselective Huisgen 1,3-dipolar cycloaddition reaction with a wide range of terminal alkynes bearing N-, S- and O-heterocycles. These include pyridine, pyrimidine, purine, quinoline, indol, or coumarin to afford the sesquiterpene-heterocycle chimaeras. All triazole conjugates were screened for in vitro antiproliferative activity by MTT assay against HeLa, MDA-MB231, SiHa, MCF-7 and A2780 human cancer cell lines compared with fibroblast cells (NIH/3T3) to check their cytotoxicity and antimicrobial effects on two Gram-positive (B. subtilis, S. aureus) pathogenic bacteria, two Gram-negative (E. coli and P. aeruginosa) pathogenic bacteria, and two yeasts (C. krusei and C. albicans). Results: The results indicated that most of the examined compounds expressed weak activity against human cell lines, while some of them showed moderate activity against S. aureus (up to 99% inhibition at 100 &#xb5;g/mL conc.), C. krusei (up to 51% inhibition at 10 &#xb5;g/mL conc.) and C. albicans (up to 52% inhibition at 10 &#xb5;g/mL conc.). Conclusions: Further structural modification of the best, selective antibacterial and antifungal compounds may open the possibility to the development of effective natural sesquiterpene-based selective antimicrobial agents.

Real-world data (RWD) in unstructured electronic health records (EHRs) is crucial for understanding complex diseases like cancer, but extracting structured information is challenging due to linguistic variability, semantic complexity, and privacy concerns. This study evaluates the performance of four small, locally deployable language models for information extraction from Italian EHRs. We examine three prompting strategies (zero-shot, few-shot, and annotated few-shot) across English and Italian, involving clinicians with varying expertise to assess the impact of prompt design on accuracy. We evaluate the performance of four open-source small language models (SLMs) for clinical information extraction from Italian electronic health records (EHRs) in the APOLLO 11 trial on non-small cell lung cancer (NSCLC). The extraction protocol involves four steps: problem definition, data preprocessing, Large Language Model (LLM)-based information extraction, and output evaluation. We show that general-purpose models (e.g., LLaMA 3.1 8B) outperform biomedical models in most tasks, particularly in extracting binary features. Multiclass variables such as TNM (Tumor, Node, Metastasis) staging, PD-L1 (Programmed death-ligand 1), and ECOG-PS (Eastern Cooperative Oncology Group-Performance Status) are more difficult due to implicit language and lack of standardization. Few-shot prompting and native-language inputs significantly improve performance and reduced hallucinations. Clinical expertise enhances consistency in the extraction, particularly among students using annotated examples. The study confirms that privacy-preserving SLMs can be deployed locally for efficient and secure cancer data extraction. Findings highlight the need for hybrid systems combining SLMs with expert input and underline the importance of aligning clinical documentation practices with SLM capabilities. This is the first study to benchmark SLMs on Italian EHRs and investigate the role of clinical expertise in prompt engineering, offering valuable insights for the future integration of SLMs into real-world clinical workflows. This study aimed to explore how a type of computational models called small language models (SLMs) can help extract important information from patients&#x2019; medical records. We tested four different models, three different ways to prompt the models to analyse the medical records and records in English and Italian. We found some models were better at extracting information than others. As far as we are aware, this is the first study to benchmark SLMs on Italian EHRs and investigate the role of clinical expertise in prompt engineering, offering valuable insights for the future integration of SLMs into real-world clinical workflows.

Foslevodopa/foscarbidopa continuous subcutaneous infusion (LDp/CDp CSI) has emerged as an effective and well-tolerated therapy for reducing OFF and increasing non-troublesome ON in advanced Parkinson's disease (PD). Neuropsychiatric adverse events (AEs) have been reported in both clinical trials and real-world studies, with some real-world cohorts suggesting higher rates among patients with prior hallucinations or cognitive impairment. The present study aimed to determine the incidence and risk factors of neuropsychiatric AEs in a large prospective real-world cohort. We analyzed data from the DATs-PD GETM Spanish Registry, an observational, prospective, multicenter, open-label study. 214 patients treated with LDp/CDp CSI were included. Median age was 69&#x2009;years, and median disease duration was 12&#x2009;years. At baseline, 35% had cognitive impairment, 25.7% hallucinations/psychosis, and 26.2% impulse control disorders (ICDs). During follow-up after initiation (median 163&#x2009;days), 19.2% developed at least one neuropsychiatric AE, mostly mild-moderate, and only 2.3% required device removal. Most events occurred more than 1&#x2009;month after treatment initiation. In adjusted Cox, none of the evaluated variables were associated with the development of hallucinations/psychosis/confusion. The presence of ICD at baseline was associated with an increased risk of ICD-related AEs. Neuropsychiatric AEs, mainly hallucinations/psychosis, occurred in a clinically relevant proportion of patients treated with LDp/CDp CSI. However, they were generally mild-to-moderate and rarely led to treatment discontinuation. Except for ICD, baseline cognitive and psychotic features were not associated with higher incidence. These findings support its use in appropriately selected patients while highlighting the importance of individualized careful clinical monitoring.

Reanalysis of genomic data in rare disease is highly effective in increasing diagnostic yields but remains limited by manual approaches. Automation and optimization for high specificity will be necessary to ensure scalability, adoption and sustainability of iterative reanalysis. We developed Talos, an open-source tool that automates variant prioritization by integrating dynamically updated gene-disease and variant-level evidence with inheritance-aware filtering and validated its performance using data from 1,089 individuals with rare disease. Trio-based analysis identified 90% of known diagnoses, returning 1.3 variants per case on average. Variant burden reduced to one variant per 200 cases on iterative monthly reanalysis. Application to an unselected cohort of 4,735 undiagnosed individuals identified 241 diagnoses (5.1% yield): 78 (32%) due to new gene-disease relationships, 54 (22%) due to new variant-level evidence and 109 (45%) due to improved analysis strategies. Our automated, iterative reanalysis model demonstrates the feasibility of delivering frequent, systematic reanalysis at scale.

Early detection of chronic kidney disease (CKD) is a critical public health priority. However, a gap exists for non-invasive tools to guide screening selection in the general adult population, leaving many at-risk individuals undiagnosed. We developed and validated MERWACS (Machineborne Early Renal Warning And Control System), a machine learning model designed to identify which individuals should be prioritized for definitive laboratory testing. We used 30 years of data from the U.S. National Health and Nutrition Examination Survey (NHANES; training set n&#x2009;=&#x2009;9,534) to train MERWACS using a final set of 12 non-invasive parameters derived from demographics, anthropometrics, and medical history. The model predicts a composite outcome of prevalent reduced kidney function, defined as a urine albumin-to-creatinine ratio&#x2009;&#x2265;&#x2009;30 mg/g or an estimated glomerular filtration rate (eGFR) below the age- and sex-specific 2.5th percentile, thereby accounting for the natural eGFR decline in healthy aging. To ensure robustness, we developed parallel models for three major eGFR equations. The final XGBoost-based model was validated on an internal test set (n&#x2009;=&#x2009;4,085) and a separate external dataset from the Korea NHANES (KNHANES; n&#x2009;=&#x2009;6,454). MERWACS demonstrated moderate and consistent discrimination across all three eGFR equation-based models, achieving ROCAUCs ranging from 0.68 to 0.70 on internal validation and 0.71 to 0.73 on external validation. MERWACS is a robust, externally validated, non-invasive tool that identifies adults and elderly individuals with a high probability of currently having reduced kidney health, helping prioritize them for definitive CKD screening. Its moderate performance is an intentional trade-off for accessibility, as it deliberately excludes laboratory data. By providing a personalized, numerical predicted probability through an open-access online application, MERWACS can empower individuals and support clinicians in identifying at-risk patients, prompting timely conversations and crucial evaluations to improve kidney health outcomes.

The development of efficient and stable photocatalysts for CO2 reduction remains a major challenge in solar fuel production. Herein, we report the synthesis and characterization of the novel bimetallic zirconium/cerium metal-organic framework [Zr5.96Ce0.04O4(OH)8(H2O)4(TTp)4] [H2TTp = (thieno)thiophene-2,5-dicarboxylic acid, Zr/Ce_TTp] used for CO2 reduction under UV-visible light irradiation. Crystal structure characterization confirms the formation of a mixed-metal framework of fcu topology with uniform element distribution. The material is porous (BET SSA = 1054 m2 g-1) and shows a good thermodynamic affinity for CO2 [Q st = 23.0 kJ mol-1]. Optical and electrochemical characterization studies reveal enhanced light-harvesting ability and superior charge separation properties compared to the monometallic analogues Zr_TTp and Ce_TTp. Under simulated solar irradiation, Zr/Ce_TTp displays significant photocatalytic activity for CO2 reduction to CO (5.8 &#xb5;mol g-1 h-1) with no need of auxiliary co-catalysts, while no activity is observed for the individual metal-based materials. The improved performance is attributed to the synergistic interaction between the redox-active Ce centers and the robust Zr nodes, as well as the light-absorbing capability of the H2TTp linker. Periodic DFT calculations support the experimental findings, highlighting the role of open CeIII sites in CO2 activation and the improved spatial separation of the frontier orbitals in the bimetallic framework that reduces e-h+ recombination with respect to its homometallic analogues. These results highlight the potential of heterometallic MOFs featuring &#x3c0;-conjugated heterocyclic linkers as promising platforms for solar-driven CO2 valorization.