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464 papers

Design of an artificial intelligence model to screen spontaneous speech to detect Alzheimer's Disease.

Madden KM et al. · Jun 25, 2026

There is a shortage of physicians trained in the specialized care of Alzheimer's disease (AD). One possible solution is to use machine learning (ML)/artificial intelligence (AI) techniques to screen for the effects of AD on speech patterns, a technique that has the potential for automation. Our objective was to evaluate the ability of various language processing/artificial intelligence (AI) techniques to classify subjects into AD and controls. Our study used the Pitt dataset (n = 549), from DementiaBank, a shared dataset of audio files of spontaneous speech using the standardized Cookie Theft Picture Description task. The dataset was divided into training (n = 337), development (n = 115) and test (n = 97) datasets. A series of language processing techniques were tested on their ability to classify subjects into AD and controls, including classical (Tfidf, Term Frequency-Inverse Document Frequency), hybrid (Tfidf + text embeddings), neural classification and large language models. The hybrid model (Tfidf + text embeddings) was the best performing one, with accuracy and recall of 0.92 and 0.93 respectively on the test dataset. However, when tested on an independently collected validation dataset it only achieved 0.70 accuracy and 0.44 recall, performing well in identifying controls but missing some true AD cases. The model also demonstrated similar performance in identifying controls in a dataset that included a high proportion of diverse cognitive conditions, similar to referrals to a specialized memory clinic. AI techniques have demonstrated some utility for the classification of spontaneous speech audio files into those with AD and controls although these techniques could benefit from having enlarged datasets.

Medicine

Evaluating a Dual Digital Cognitive Behavioral Therapy and Health and Wellness Coaching Intervention for Anxiety and Depression: Single-Arm Pilot Study.

Kirk A et al. · Jun 25, 2026

Background Anxiety and depressive disorders remain highly prevalent and insufficiently treated, with many individuals experiencing persistent or untreated symptoms, limited access to evidence-based care, or insufficient support between clinical encounters. Adults with disabilities represent a particularly underserved subpopulation, often facing compounded barriers to mental health care and higher rates of anxiety and depression. Digital therapeutics offer a scalable opportunity to address these gaps by extending structured, evidence-based interventions beyond traditional care settings. Objective This pilot study evaluated Rauha, a novel digital therapeutic created by Toivoa Inc, that integrates cognitive behavioral therapy (CBT)-based modules with live weekly sessions led by a National Board-Certified Health and Wellness Coach (NBC-HWC), delivering structured, smartphone-based psychoeducation and interactive therapeutic exercises combined with personalized mental health coaching to support behavior change. Methods Thirteen adults with mobility and/or hearing disabilities and clinically elevated anxiety and/or depression were enrolled in a single-arm, within-participants design. Participants completed 8 weeks of CBT modules delivered via smartphone, accompanied by synchronous virtual mental health coaching. Anxiety and depression were assessed using the Hamilton Anxiety and Hamilton Depression Rating Scales, respectively, at baseline, post treatment, and at the 4-week follow-up. Results Mean reductions were significant for both anxiety (-13.05, SD 2.51; P Conclusions The findings suggest that a combined digital CBT and NBC-HWC approach can yield clinically meaningful and durable symptom reductions in depression and anxiety, coupled with high user acceptability and engagement, for adults with disabilities. These findings provide preliminary evidence supporting Rauha as a scalable, evidence-informed mental health intervention with the strong potential to improve access and address key barriers to care.

Psychology

Controlling the synchronization and symmetry breaking of coupled bacterial pili on active biofilm carpets.

Altın B et al. · Jun 25, 2026

In the low Reynolds number regime, active biological systems utilize nonreciprocal cyclic activities to achieve motility, as seen in the spinning of bacterial flagella and the beating of cilia. Coupling among these active mechanical components leads to synchronization and emergence of metachronal waves. Here, we report that biofilms of Pseudomonas nitroreducens form active carpet-like surfaces textured with diverse topological defects, generating Mexican-wave-like collective behavior in which bacteria periodically lift up. On these active surfaces, non-reciprocally coupled extension and retraction activities of bacterial pili drive these collective oscillations. Surprisingly, this collective behavior exhibits left-right asymmetry across the biofilm driving unidirectionally propagating waves. We discover that this directionality is primarily governed by an aging-related frequency gradient across the biofilm. Leveraging these insights, we further demonstrate the ability to control the collective dynamics of these waves, including symmetry breaking, transitions from spiral waves into target and propagating plane waves by manipulating the elastic properties of biofilms. Overall, our findings illuminate the fundamental role of nonreciprocally interacting active components in regulating synchronization, collective dynamics, and symmetry-breaking phenomena in biological systems.

Physics and Astronomy

A microprotein encoded by FERMT3 modulates endothelial cell protein catabolism and induces cell cycle arrest and senescence.

Raheja M et al. · Jun 25, 2026

Background Endothelial cells express numerous microproteins (miPs) encoded by small open reading frames (smORFs), yet the biological function of most remains unknown. This study set out to characterize a novel 69 amino acid miP encoded within the FERM domain containing kindlin-3 transcript (miP-FERMT3), which is upregulated under inflammatory conditions. Methods Confocal microscopy was used to determine miP-FERMT3 localization, and its interaction partners were determined by mass spectrometry and immunoblotting. RNA sequencing and quantitative mass spectrometry were performed to assess transcriptional and proteomic alterations. Cell proliferation and cell cycle progression were examined by live cell imaging, EdU incorporation and flow cytometry, while senescence was determined by β-galactosidase staining, live cell imaging and RT-qPCR-based analysis of telomere length. Results In endothelial cells, miP-FERMT3 localized mainly to centriole subdistal appendages, where it colocalized with ninein and CEP170 and induced centrosome amplification. The expression of miP-FERMT3 caused cell cycle arrest and DNA damage, evidenced by γ-H2AX foci and nuclear p53 accumulation. Consistent with this, miP-FERMT3-expressing endothelial cells exhibited downregulation of genes required for cell-cycle progression and upregulation of genes involved in cell cycle inhibition and senescence. However, canonical p53 target genes were not induced and cell cycle arrest occurred independently of p53. Mechanistically, miP-FERMT3 interacted with proteins involved in ubiquitin/proteasome-dependent protein catabolism, including PSMD9, CUL2 and TRIM8, and its expression increased protein ubiquitination, centrosomal neddylation and proteasomal activity. Notably, enhanced proteasomal turnover of p21 in miP-FERMT3-expressing endothelial cells resulted in replication stress, as evidenced by increased CHK1 phosphorylation. These alterations culminated in rapid induction of cellular senescence, characterized by enlarged cell size, β-galactosidase activity, telomere shortening and a paracrine pro-inflammatory activation of naïve endothelial cells. Analyses of independent murine and human transcriptomic and proteomic aging datasets further revealed that FERMT3 expression and protein abundance increase with age. Conclusions miP-FERMT3 is a novel regulator of protein catabolism that promotes p21 degradation, replication stress and p53-independent cell cycle arrest and senescence in endothelial cells. Given the aging-associated upregulation of FERMT3 in mouse and human endothelial cells, increased miP-FERMT3 expression may contribute to the onset of vascular senescence as a hallmark of aging.

Medicine

Preclinical evaluation of cysteine protease-inhibitor aloxistatin (E64d) for heart failure therapy.

Jordan M et al. · Jun 25, 2026

Heart failure (HF) affects over 64 million people worldwide causally linked to fibrotic scarring. None of the available cardiac drugs target fibrosis directly, underlining unmet clinical need for novel therapies. This study aimed to explore the therapeutic potential of the cysteine protease inhibitor aloxistatin as a repurposed drug candidate to combat fibrotic progression in predictive HF models. Aloxistatin reduced migratory and proliferative capacities of human cardiac fibroblasts (HCFs) derived from various HF backgrounds. Mechanistically, aloxistatin attenuated TGFβ1-induced pro-fibrotic signaling in cardiomyopathy-derived HCFs by inhibiting extracellular matrix organization-related gene expression and secretion of MMP2 und FN1, partially mediated through CAPN2 inhibition. Transcriptomic analysis of rat ex vivo myocardial slices revealed a pronounced suppression of inflammatory pathways. Anti-inflammatory effects of aloxistatin were further confirmed by reduced NFκB activity in reporter cells and inhibited HLA-DR expression in human iPSC-derived macrophages. Application of diverse preclinical cardiac HF models arguably underlined aloxistatin as a potential drug repurposing strategy by simultaneously counteracting myocardial inflammatory signaling and pro-fibrotic mechanisms. This preclinical study suggests aloxistatin therapy for translational use to attenuate cardiac remodeling and progression of heart failure.

Medicine

Surgical strategies and long-term survival for third ventricle chordoid gliomas: a systematic review and clinical algorithm.

Alomari O et al. · Jun 25, 2026

Chordoid gliomas are rare World Health Organization Grade II neoplasms of the third ventricle. While Gross Total Resection (GTR) has traditionally been the primary surgical objective, the intimate adherence to the hypothalamus and optic apparatus of these tumors creates a therapeutic dilemma for balancing oncological control against the risk of severe neurological and endocrine morbidity. This study aims to guide optimal management by bridging the evidence gap with the largest systematic review to date, analyzing clinical characteristics, surgical outcomes, and survival data. A systematic review was conducted according to PRISMA 2020 guidelines, searching Web of Science, PubMed, Scopus, and Embase for studies from database inception to November 2025. Data included patient demographics, clinical presentation, radiological phenotypes, surgical techniques, molecular profiles, and follow-up outcomes. Kaplan-Meier survival estimates and log-rank tests were used to assess survival outcomes by extent of resection. All analyses were performed using R-software (version 4.3.1). The cohort (N = 198; mean age 41.8 years; female-to-male ratio 2:1) predominantly presented with headache (51.3%), visual disturbances (37.5%), and cognitive deficits (24.4%). GTR was achieved in 56% of patients, while 32% underwent Subtotal Resection (STR), and 10% biopsy only. Kaplan-Meier analysis revealed a significant survival advantage for GTR, with a stable 5-year survival rate of 91.9% compared to 54.7% for STR (p = 0.0089). Molecular profiling identified PRKCA D463H as the predominant driver mutation, with BRAF V600E observed in a minority of cases. GTR is associated with superior long-term survival in the literature and may be considered when anatomically feasible. However, because this association may be confounded by tumor adherence and surgical selection, resection strategies must be strictly individualized to balance tumor control against hypothalamic morbidity.

Medicine

Thermally modulated resonant quantum transport in asymmetric nanoscale junctions for optimal bias and power generation analysis.

Aly AH. · Jun 25, 2026

A phenomenological effective transport model inspired by Landauer-type resonant transport concepts is presented to investigate thermally modulated transport behavior in an asymmetric nanoscale junction under combined electrical and thermal driving. The proposed framework incorporates resonance alignment, thermal resonance modulation, finite-bias activation, damping effects, and structural asymmetry within a computationally efficient formulation. The transport response is systematically analyzed as functions of bias voltage, asymmetry strength, temperature, and resonance energy. The results show that increasing structural asymmetry reduces the magnitudes of the heat-current proxy, charge-current magnitude, and electrical power magnitude due to weaker effective transport coupling. However, the optimal bias voltage associated with the maximum electrical power magnitude remains only weakly affected within the investigated parameter range because the asymmetry factor primarily scales the transport amplitude while weakly modifying the resonance-alignment condition. The simulations further demonstrate that the maximum electrical power magnitude increases with temperature, whereas the thermal sensitivity gradually decreases at elevated temperatures. In addition, the optimal operating bias increases with resonance energy according to the resonance-alignment condition included in the model. A two-dimensional operating map identifies a stable high-performance transport region near 4-4.5 mV. All numerical parameters used in the simulations are explicitly reported to support reproducibility. The proposed framework provides a simplified and physically interpretable platform for analyzing resonance-dominated transport trends in asymmetric nanoscale systems and may serve as a useful basis for future microscopic or experimentally calibrated studies.

Engineering

The structural chemistry and biosynthesis of chlorophylls.

Hunter CN et al. · Jun 25, 2026

Chlorophylls (Chls) harvest the solar energy that drives photosynthesis, which underpins most of the food chains on our planet. Starting from protoporphyrin IX, just seven biosynthetic reactions culminate in the synthesis of Chl a , the major light-absorbing pigment on Earth. Other such pigments, Chls b , c , d and f , widen the absorption range in the visible and red regions of the spectrum, and several bacteriochlorophylls (BChls), BChls a , b and g in particular, open new spectral windows allowing organisms to harvest near infra-red light. This perspective surveys the structural features of porphyrins, chlorins and bacteriochlorins that impart their characteristic absorption features, then presents a similar analysis of the biosynthetic intermediates leading to Chls a , b , c , d and f . The interlinked Chl and BChl biosynthetic pathways are summarised, then the rest of the perspective focusses on the enzymes that synthesise Chls a , b , c , d and f . AlphaFold 3 was used to model a complete set of structures for Chl biosynthesis enzymes, predicting intersubunit associations and the arrangements of cofactors and bound substrates, and providing insights into catalytic mechanisms. A new scheme for binding substrates and transferring products between pathway enzymes suggests how synthetic biology approaches can assemble hybrid Chl and BChl pathways to expand the spectral range for harvesting and using solar energy.

Biochemistry, Genetics and Molecular Biology

Pharmacovigilance Signal Detection and Mutually Exclusive Driver Mutations of the PI3K/AKT Pathway in Breast Cancer Treated With Capivasertib.

Luo Z et al. · Jun 25, 2026

Background and objective This study is aimed at comprehensively evaluating the real-world safety profile and underlying molecular mechanisms of the AKT inhibitor capivasertib by integrating pharmacovigilance data, computational biology, and multiomics analyses. Methods Adverse event (AE) reports from the FAERS database were analyzed using disproportionality algorithms (ROR, PRR, BCPNN, EBGM) to detect significant safety signals. To elucidate potential toxicological mechanisms, we employed network toxicology and molecular docking, further validated by 100 ns molecular dynamics (MD) simulations. Additionally, bulk genomic cohorts (e.g., TCGA, METABRIC) and single-cell RNA sequencing (scRNA-seq) datasets were utilized to assess mutation patterns and delineate key targets within the tumor microenvironment (TME). Results Analysis of 22,143 AE reports yielded 133 significant safety signals, predominantly involving metabolism (e.g., hyperglycemia), the gastrointestinal system (e.g., nausea, stomatitis), and dermatological conditions (e.g., rash). Pathway enrichment highlighted the PI3K-AKT, HIF-1, and EGFR signaling networks. Integrative analyses identified critical toxicity-related modulators, notably AKT1, IGF1, PTEN, TP53, and GSK3B. Crucially, MD simulations robustly confirmed the thermodynamic stability of the capivasertib-GSK3B complex. Genomic profiling revealed pronounced mutual exclusivity among PIK3CA, AKT1, and PTEN alterations. Furthermore, scRNA-seq analysis demonstrated that GSK3B overexpression defines a highly aggressive, proliferative malignant subpopulation that profoundly reshapes intercellular communication with stromal fibroblasts. Conclusion By seamlessly bridging real-world pharmacovigilance with advanced structural biology and single-cell transcriptomics, this study delineates the comprehensive safety landscape of capivasertib. Our findings provide crucial clinical alerts for AE monitoring and offer deep mechanistic insights to optimize personalized therapeutic management in breast cancer.

Medicine

Narrative Review of Lithium Disilicate Veneers in Esthetic Dentistry: Current Perspectives and Clinical Case Report.

Rojas-Ruedas S et al. · Jun 25, 2026

Objectives To provide a focused, evidence-based overview of lithium disilicate (LDS) veneers, with particular emphasis on indications, material properties, adhesive protocols, and clinical performance, supported by illustrative clinical cases. Methods A narrative review of the literature was conducted to summarize current evidence on the mechanical, optical, and adhesive characteristics of LDS ceramics in veneer applications. The review emphasizes enamel preservation, adhesive reliability, and reported clinical outcomes, without undertaking a systematic comparison of study designs. In addition, two clinical case reports are presented to illustrate the clinical workflow for esthetic rehabilitation using pressed LDS veneers. Results LDS veneers demonstrate high flexural strength (~360-400 MPa), favorable optical properties, and reliable adhesive performance when enamel is preserved and appropriate adhesive protocols are applied. Reported survival rates exceeding 95% at up to 10 years have been documented in selected patient populations. Clinical success is closely associated with appropriate case selection, conservative tooth preparation, precise adhesive procedures, and patient compliance. Common complications, including debonding, fracture, and marginal discoloration, are more frequently reported when enamel is limited or occlusal risk factors are not adequately managed. Conclusions When applied under appropriate clinical conditions, LDS veneers represent a predictable and esthetically effective treatment option in contemporary restorative dentistry. Their long-term success depends on meticulous technique, patient-specific risk assessment, and adherence to evidence-based adhesive and occlusal management principles.

Dentistry