Photosynthesis sustains life on Earth by converting light to chemical energy through the coordinated action of photosystem I (PSI) and photosystem II (PSII) within thylakoid membranes1-4. Although structures of isolated photosystems are available, their native organization in chloroplasts remains unknown. Here, using in situ cryo-electron microscopy, we directly imaged Oryza sativa (rice) chloroplasts and determined structures of photosystem supercomplexes in their native membrane environment. We resolved a C2S2M2L4-type PSII-light harvesting complex II (LHCII) supercomplex, including four LHCII antenna trimers that were not retained in purified preparations. Excitation energy transfer calculations based on this architecture closely reproduce in vivo measurements, indicating its physiological relevance. We also resolved asymmetric PSII-LHCII dimers, including side-by-side, trans-lumenal and trans-stromal architectures, and higher-order assemblies of trimers and tetramers. On the basis of these observations, we propose that PSII forms a trans-lumenal and trans-stromal 'skeleton' that shapes thylakoid morphology and supports grana stacking. In addition, we obtained high-resolution structures of PSI-LHCI-LHCII and PSI-LHCI supercomplexes. Together, these structures reveal extensive networks of lipids, pigments and cofactors, providing the first molecular framework for understanding how the native architecture of plant photosystem supports the exceptional photon-to-electron efficiency of photosynthesis.
Mistreatment of trainees in graduate medical education (GME) persists despite Accreditation College of Graduate Medical Education (ACGME) standards. Mistreatment disproportionately affects minoritized trainees and undermines their well-being and abilities to provide empathic patient care. The authors conducted a scoping review to identify existing structures-education/trainings and programs/policies-to mitigate harm from and address perpetrators of mistreatment, and to map gaps to guide practice and research. They searched PubMed and Embase for US-based, English-language studies (January 2015-July 2025). References were screened independently and in duplicate. Included studies described educational/training interventions or programs/policies, or proposed a structural approach focused on addressing mistreatment of trainees. Of 856 records, 71 studies (41 articles, 30 abstracts) were included: 56 education/trainings and 15 programs/policies. Trainings reached 3909 learners, were predominantly single-session, and commonly used case-based discussion, role-play, and simulation. Assessments relied largely on immediate self-report of knowledge, skills, or attitudes; few used objective measures or longitudinal follow-up. Programs and policies encompassed real-time reporting tools, communication campaigns, co-created protocols, and task forces all focused on addressing mistreatment after the fact. Outcomes included increased reporting volume of mistreatment, characterization of perpetrators, and identification of concentrated areas of mistreatment within the health system, trainee perceptions, and feedback loops. Mapping of the literature revealed many education/training interventions and fewer programs/policies. A significant gap remains because too strong a focus exists on teaching trainees-the targets of mistreatment-to manage the mistreatment after the fact, rather than implementing trainings and programs to proactively prevent learner mistreatment. The authors suggest opportunities including perpetrator-focused, non-punitive trainings, longitudinal skills reinforcement in the clinical learning environment, transparent measurement, and a continuous quality improvement approach to both preventing and recovering from mistreatment. Addressing mistreatment will require institutional policies and comprehensive, equity-informed structures with objective assessment, shifting focus from resilience after harm to prevention at its source.
Poxviruses are a family of large, complex double-stranded DNA viruses that includes human pathogens such as variola-the cause of smallpox-and monkeypox. Recent outbreaks of mpox underscore the need for a better understanding of poxvirus biology1,2. Poxvirus assembly is a conserved process that involves the formation of a biconcave core inside the membrane of the maturing virus3,4. Here we use cryo-electron tomography combined with subtomogram averaging and structure prediction to determine the structure and composition of the portal complex-a pore that spans the core wall-in vaccinia virus, the prototypical poxvirus. The hexameric complex consists of the E8, E6 and L3 proteins, which are conserved across poxviruses and essential for mRNA release during the establishment of infection5-7. E6, which is also required for virus assembly8-10, forms the central chamber of the portal and interacts with the surrounding core wall. A hexamer of E8 attaches to the exterior side of E6. L3, a target of TRIM5α-mediated restriction11, binds as a hexamer of dimers to the interior side. Furthermore, the viral helicase D5, which is required for genome release from cores12, associates with cytoplasmic cores during infection by docking onto the exterior E8 rim of the portal complex. We propose that the portal complex represents an attractive target for the development of anti-poxvirus therapeutics.
The development of a holistic theoretical framework that can predict the corrosion inhibition efficiency and evaluate the anti-corrosion potentials of novel materials has been a challenging one. This work aimed to address this challenge by integrating machine learning-based Quantitative Structure-Property Relationship (QSPR) models with computational simulation techniques. 25 descriptors derived from density functional theory (DFT) results for 130 triazole derivatives on mild and carbon steels in hydrochloric acid (HCl) solutions were used to develop predictive models. Random Forest, K-Nearest Neighbor, Gradient Boosting, Support Vector Regression, and Stacked Regression. Key features influencing the model's predicted outcomes were identified through Recursive Feature Elimination (RFE) and Shapley Additive ExPlanation (SHAP) analyses. The models demonstrated competitive performance with Stacked Regression being more pronounced, as indicated by results of some statistical metrics, including Mean Squared Error (60.50-64.90), Root Mean Squared Error (7.740-8.056), Mean Absolute Error (6.179-6.340), Mean Absolute Percentage Error (7.17-7.37), and a concordance correlation coefficient (0.30-0.31). Among the novel triazoles evaluated, T1 emerged as the most effective inhibitor, exhibiting corrosion inhibition efficiencies (CIEs) ranging from 89.66 to 93.17%, followed by T2 (88.76-94.38%) and T3 (85.76-92.43%) across the models. Further analysis using Mulliken population, Frontier Molecular Orbital (FMO), and Radial Distribution Function (RDF) revealed molecular/atomistic interactions between the inhibitor molecules and the metal, indicating effective chemical adsorption characterized by high adsorption energies from - 143.56 kcal/mol to - 175.79 kcal/mol and favorable orientations for spontaneous and robust interactions. This research underscores the effectiveness of combining machine learning with computational simulations in corrosion science.
Bipolar disorder and depression are associated with structural and functional changes in the retina, including a thinner retinal nerve fibre layer (RNFL). Lithium is widely considered the most effective treatment for bipolar disorder, but its mechanism of action is not fully understood. We assessed research looking at the effect of lithium on structural or functional retinal outcomes in humans. Searches using the terms 'Lithium' AND 'retina' were carried out to identify peer reviewed studies assessing the impact of lithium on retinal structure or function. These included those with or without a control group comparison, pre- and post- lithium comparisons and observational studies. There were no exclusions based on the quantity or preparation of lithium administered, or the length of administration. Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tool for Analytical Cross Sectional Studies, and a narrative synthesis and tabulated summary of the included studies was completed. Seven studies assessing structural outcomes and 10 reporting functional ones were identified, all highly heterogenous and with multiple limitations. Structural outcomes were derived exclusively from optical coherence tomography (OCT) with retinal nerve fibre layer (RNFL) being the most common measurement. There was no evidence of differences in the RNFL between participants with bipolar disorder taking lithium and healthy controls in two larger studies. In six studies looking at differences in those with bipolar disorder taking lithium and those taking valproate, two showed no signs of difference and four showed evidence of thicker RNFL in the lithium group. Studies reporting functional outcomes reported a statistically significant effect of lithium on at least one functional measure, derived from electrooculography, electroretinography, and dark adaptation thresholds. Current evidence suggests that lithium is likely to have an effect on the retina but limitations in all studies mean better designed and adequately powered prospective studies are required. PROSPERO database (Number-CRD42024516635).
Two-stage models of grammatical encoding posit that sentence production unfolds in two sequential steps: the construction of a hierarchical syntactic structure, followed by its linearization into a sequence suitable for articulation. While widely accepted in psycho- and neurolinguistics, such models lack formal computational implementations. Here, we introduce a novel multinomial processing tree (MPT) model that operationalizes this two-stage framework to explain syntactic error patterns in individuals with aphasia. Drawing on discourse samples annotated for distinct error types, we fit an MPT model to estimate individual abilities at each processing stage. These ability estimates correlated with observed error rates and localized to distinct neural substrates: hierarchical encoding ability was linked to the posterior superior temporal sulcus and parietal cortex, linearization to posterior inferior frontal regions, and omission-related processes to more dorsal frontal regions and the underlying white matter. Our findings support a neurocomputational dissociation between hierarchical and linear stages of grammatical encoding, aligning with prior lesion-symptom mapping and theoretical accounts of expressive agrammatism and paragrammatism. This work represents the first computational instantiation of a two-stage model of syntactic production, bridging formal modeling and lesion analysis to advance our understanding of the architecture and breakdown of grammatical encoding.
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In the implant-prosthesis complex, material choice and prosthetic design directly affect stress distribution and load transmission. This study aimed to compare the effects of different prosthetic framework materials on stress distribution in implant-supported fixed prostheses, using titanium and zirconia abutments, through three-dimensional finite element stress analysis. In this study, two titanium implants (4.1 mm × 10 mm) with one titanium and one zirconia abutment were modeled. Three-dimensional finite element models of implant-supported fixed prostheses were created using six framework materials and four veneering types, forming ten groups in total. After meshing bone and restorative structures, material properties (Poisson's ratio and Young's modulus) were assigned. A 178 N load was applied vertically and at 45° to the palatal surfaces of the maxillary central incisor and canine, and von Mises and tensile stresses were analyzed in the implants, abutments, peri-implant bone, and superstructures. Under both loading conditions, the highest stresses occurred in the polyetheretherketone (PEEK) (implants, abutments) and fiber-reinforced composite (FRC) (superstructures) groups, while the lowest were found in the monolithic zirconia group. In cortical bone, stress was highest in the FRC group under oblique loading and in the PEEK group under vertical loading, whereas the Co-Cr group showed the lowest abutment stress under oblique loading. The study demonstrated that different framework materials significantly affect stress distribution within the implant, abutment, peri-implant bone, and prosthetic superstructure. Framework materials with lower elastic modulus were found to induce higher stress accumulation in the surrounding bone tissue, implant components, and crown structures.
To investigate the abnormal knee hyperextension and coupled external rotation, varus, and anterior translation that occurs using sequential ligament and capsular sectioning in multiligamentous injuries. A six-degree-of-freedom robotic system measured knee hyperextension and coupled external rotation, varus, and anterior-posterior translation with selective tissue cutting in 23 cadaveric knees. Tests were performed up to 25 Nm hyperextension load before and after cutting 6 structures: oblique popliteal ligament (OPL), posterolateral capsule with the fabellofibular ligament (PLC+FFL), posteromedial capsule with posterior oblique ligament (PMC+POL), lateral collateral ligament and popliteus tendon (LCL+POP), and the anterior cruciate ligament (ACL). Sequence 1 sectioned the posterior capsular structures (OPL, PLC+FFL, and PMC+POL) followed by the LCL+POP and ACL. Sequence 2 simulated a posterolateral injury (LCL+POP) and ACL injury followed by the posterior capsular injuries (OPL, PLC+FFL, and PMC+POL). In sequence 1, sectioning the posterior capsule caused statistically significant increases to hyperextension (2.5° ± 0.9°; P = .02). Additional injury of the LCL+POP and ACL significantly increased hyperextension to 7.6°± 4.4° (P < .01), external rotation to 2.7° ± 2.8° (P < .01), and varus rotation to 3.2°± 3.9° (P < .01). In sequence 2, sectioning the LCL+POP significantly increased hyperextension (1.4° ± 0.6°; P < .01) and additional ACL sectioning significantly increased hyperextension (2.1° ± 1.0°; P < .01). Further sectioning the posterior capsule significantly increased hyperextension to 6.9° ± 1.7° (P < .01), external rotation to 2.9° ± 2.3° (P < .01), and varus rotation to 2.5° ± 1.4° (P < .01). Posterolateral injuries (LCL+POP and PLC+FFL) resulted in small increases in knee hyperextension, external tibial rotation, and varus rotation. Sectioning the entire posterior capsular structures (PLC+FFL, PMC+POL, and OPL) is necessary for major increases in knee hyperextension. Posterolateral ligament injuries may not result in a positive external rotation recurvatum test as only modest increases in external rotation and varus occur with knee hyperextension. Other ligament tests including the dial test for external tibial rotation and varus loading for lateral joint opening in knee flexion are recommended.
Melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm primarily affecting the craniofacial skeleton in infants. Management can be challenging in unresectable, multiply recurrent, or metastatic cases. Diagnosis requires local imaging assessment with magnetic resonance imaging (MRI) and computed tomography (CT) and histopathological confirmation. Surgery is the mainstay of treatment, achieving 80%-90% cure rates. Chemotherapy may be considered for advanced disease, whereas radiotherapy is generally avoided in young children. These recommendations were developed within European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) and European Reference Network Paediatric Cancer (ERN PaedCan) using a structured consensus process based on focused literature review and expert agreement. Multidisciplinary, risk-adapted management, and structured follow-up are essential.
Herbal medicine has emerged as an important area of investigation in gastrointestinal cancers owing to its multitarget therapeutic potential and growing integration with modern oncology. However, the rapid expansion of the literature has resulted in a fragmented understanding of the field's knowledge structure, research evolution, and emerging directions. A bibliometric analysis was performed using publications retrieved from the Web of Science Core Collection between 2016 and 2025. Bibliometrix, VOSviewer, and CiteSpace were employed to evaluate publication trends, collaboration networks, thematic evolution, and knowledge foundations. To further assess the biological relevance of major research themes, representative molecular markers associated with apoptosis, cell-cycle regulation, and epithelial biology were examined using transcriptomic data integrated from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project through the Gene Expression Profiling Interactive Analysis (GEPIA) platform. A total of 1,985 publications were included. Research activity increased substantially over the study period, particularly after 2020. Bibliometric analyses revealed a progressive transition from traditional investigations of apoptosis, proliferation, and metastasis toward emerging themes involving tumor microenvironment regulation, ferroptosis, gut microbiota interactions, network pharmacology, and molecular docking. Knowledge structure analyses demonstrated increasing integration of experimental oncology, bioinformatics, and traditional Chinese medicine research. China dominated global publication output, while the United States exhibited the strongest international collaborative profile. Exploratory transcriptomic validation showed that representative molecular markers (BCL2, CCND1, and CDH1) exhibited differential expression patterns across multiple gastrointestinal malignancies, supporting the biological relevance of the dominant research themes identified through bibliometric analyses. Research on herbal medicine for gastrointestinal cancers is transitioning from descriptive pharmacological investigations toward mechanism-oriented, data-driven, and translational research. By integrating bibliometric visualization with exploratory pan-gastrointestinal-cancer transcriptomic validation, this study provides a comprehensive overview of the field's evolution and offers a complementary framework linking knowledge mapping with molecular-level evidence. These findings provide biological context for emerging research priorities and may facilitate future biomarker discovery and precision-oriented herbal medicine research for gastrointestinal cancers.
Vaping is increasingly prevalent among young adults at age for starting families. Thirdhand e-cigarette aerosols (THEA) are persistent residues that adhere to indoor surfaces and can resuspend in air. Since lung development continues after birth, infants from homes with adults who vape, are vulnerable to THEA exposures. Neonate mice were exposed to THEA with nicotine or nicotine + tobacco-flavoring from terrycloth and carpet for the first 21 days of life. We assessed broncho-alveolar lavage cytology, lung morphometry, gene expression, and intestinal microbiomes at 21 days. At 10 weeks, we evaluated lung function. We showed that exposures to THEA during alveologenesis, a critical window of lung development, induced sex-specific alterations in pulmonary inflammatory and developmental trajectories. Females exhibited acute pulmonary neutrophilic inflammation with a resolving cytokine profile. In contrast, males exhibited upregulation of genes associated with pulmonary inflammation and epithelial mesenchymal transition, plus delayed lung development, leading to lung dysfunction in adulthood. Male gut microbiomes showed reduced abundance of taxa associated with xenobiotic biotransformation, suggesting host-microbial detoxification capacity as a target of THEA exposure. Low-level of THEA exposures in early life can alter lung inflammation, structure, and function, increasing susceptibility to respiratory dysfunction later in life. Early-life exposures to nicotine and carbonyls from thirdhand e-cigarette aerosols (THEA) may induce alterations in lung alveologenesis and augment susceptibility to lung conditions later in life. Using a preclinical model of pediatric airways, we showed that THEA exposures caused neutrophilic inflammation in neonate female mice. In neonate male mice, THEA exposures led to alterations in lung structure, gene expression, and gut microbiome dysbiosis. Adult male mice exposed to THEA as neonates exhibited decline in lung function characteristic of obstructive pulmonary physiology.
Two-dimensional atomic crystals (2DACs), which feature non-bonding van der Waals (vdW) gaps between crystalline atomic layers, allow selected atoms or molecules to intercalate. When confined within these vdW gaps, the intercalants can self-assemble into ordered interlayers between adjacent 2D atomic lattices, forming well-defined intercalated superlattices. These structures combine the intrinsic properties of solid-state 2DACs with the chemically programmable electronic, optical and magnetic functionalities of self-assembled atomic or molecular interlayers. As a result, they can integrate disparate quantum and collective phenomena, enabling device functionalities beyond the reach of conventional heterostructures. However, the synthesis of intercalated superlattices with specific functions is more complex than arbitrarily combining 2DACs with functional intercalants. Electronically, optically or magnetically active interlayers are inherently more reactive than passive species and are often incompatible with conventional chemical or electrochemical intercalation strategies. In this Review, we classify the functional building blocks used to construct functional intercalated superlattices and examine the key challenges and emerging strategies for their synthesis and assembly. Our goal is to establish guiding principles for the modular design and synthesis of chemically programmable intercalated superlattices with tailored electronic, optical, magnetic and quantum functionalities.
Numerous geometric earthworks have been found in southwestern Amazonia, evidence of a monument-building precolonial civilization1-3. This knowledge has contributed to the discussion about the deep history and the precolonial urbanism of Amazonia, its sociocultural contexts and its environmental legacy2,4-8. Estimates of the geographical extent and population size of the forest civilization have remained weak, because the detection of earthworks has been almost exclusively limited to deforested areas where vegetation does not completely hide the structures. Here we used canopy-penetrating LiDAR data over 4,430 km of flight to define the geographical distribution and quantity of earthworks in this region better. On the basis of both existing data and our LiDAR documentation, we show that this cultural area alone contains as many earthworks as previously estimated for the whole of Amazonia. We also propose that the total human population of the area in 100-300 AD was 1.25-3 million people. If similar results are found elsewhere in Amazonia, the total precolonial population density and its effect on the current Amazonian soil and forest structure, biodiversity and even some modelling of the global climate should be re-evaluated.
The development of highly active and stable non-noble metal oxide catalysts to replace iridium-based materials for efficient acidic water electrolysis is crucial1-3. However, traditional spinel cobalt oxide suffers from intrinsic performance limitations from coexistence of inactive tetrahedral (Td) and highly active octahedral (Oh) coordination sites4,5. Here we report a new trigonal-phase Co3O4 (Tri-Co3O4) produced by a vacuum-mediated molten-alkali mechanochemical method, which shows edge-shared [CoO6] octahedral coordination with the space group P-3m1 (164). The three-layer compact structure provides Co2+ and Co3+ located in octahedral coordination in the ratio 1:2. Tri-Co3O4 achieves a low overpotential of 269 millivolts (mV) at the current density of 10 mA cm-2 in the acidic oxygen evolution reaction (OER), 181 mV less than spinel-type Co3O4. It also achieves a current density exceeding 1,800 mA cm-2 at a cell voltage of 1.80 V in proton-exchange membrane water electrolysis (PEMWE) devices. The catalytic mechanism shows that the 2D layered structure with edge-shared octahedral coordination can effectively optimize the adsorption of intermediates and reduce the dissolution of Co, thereby substantially improving the activity and stability of the non-noble metal catalysts.
Recognition of foreign molecules inside cells is critical for immunity across all domains of life. Proteins of the STAND NTPase superfamily1,2, including eukaryotic NOD-like receptors, play a central role in this process3,4. In bacteria and archaea, although several STAND families sense phage proteins5-9, their functional diversity remains largely unexplored. Here we conduct a systematic phylogenetic analysis of prokaryotic STAND NTPases and identify at least 90 structurally distinct families associated with antiviral defence. We first show that the uncharacterized Avs7 family recognizes the major capsid protein (MCP) of tailed phages. Three cryogenic electron microscopy structures of Salmonella enterica Avs7 reveal an asymmetric, butterfly-shaped tetramer that assembles stepwise through large, MCP-induced conformational changes, incorporating bacterial elongation factor Tu (EF-Tu) as a structural component that enhances defence. Using genetic screens with a library of 687 phage genes, we further show that 13 additional STAND families sense 13 conserved phage proteins, encompassing most of the core structural and replicative components of tailed phages. These include 2 distinct MCP-sensing families (Avs8 and Avs10) and 11 others (Avs11-21), which recognize the portal, portal adaptor, tail nozzle, head-tail connector, tail terminator, tail tube protein, tail assembly chaperone, tape measure protein, DNA polymerase, helicase/RecA-type ATPase and single-stranded DNA annealing protein, respectively. Together, our findings reveal a mechanism of host-factor repurposing and establish structure-based pattern recognition as a fundamental strategy of bacterial immunity.
Aging populations, multimorbidity, and rapid medical progress have expanded treatment options in old age, but also intensified ethical and organizational challenges in everyday care. Little is known about how nurses, as key frontline professionals, experience these structural developments specifically in the context of medical and nursing care for older adults in Germany. Therefore, this study aimed to examine how nursing staff perceive structural conditions in the German healthcare system and their effects on medical and nursing care for older patients. This study employed a qualitative analysis of five focus group discussions with 28 nurses from hospitals, nursing homes, and home-based nursing services in Germany. Participants with diverse qualifications and work settings were purposively and conveniently sampled, and discussions were stimulated by case vignettes on elective surgery and life-prolonging interventions in very old age. Data were analyzed using Kuckartz's Qualitative Content Analysis. Nurses described medical progress as simultaneously enabling better symptom control, mobility, and end-of-life care, while also prolonging phases of frail survival with high care dependence. They reported strong treatment pressures and financially driven incentive structures that foster overtreatment and can conflict with older patients' wishes and perceived quality of life. Chronic staff shortages and time constraints led to "shortcuts" such as tube feeding or increased use of psychotropic medication, which were experienced as undermining person-centered care and professional ethics. Across settings, nurses highlighted a loss of professional influence in medical decision-making, feelings of powerlessness, and moral distress linked to implementing decisions they had not shaped but were responsible for carrying out. From a nursing perspective, good medical care in old age depends not only on technological advances and geriatric expertise but also on structural reforms of financing, staffing, and decision-making processes. Strengthening nurses' autonomy, involvement in treatment decisions, and ethical support within interprofessional teams may help align medical interventions more closely with older people's concepts of a good life and a good death. DRKS00027076, 05/11/2021. https://www.drks.de/search/de/trial/DRKS00027076/details .
Children of parents with depression, hereafter referred to as high-risk youth, are at elevated risk for mental illness, yet the mechanisms underlying this vulnerability remain unclear. Biased interpretation of ambiguous information and altered stress responses in this population have been proposed as potential pathways. As no previous study has examined these factors together, we investigated interpretation bias and endocrinological and affective stress responses as potential markers of depression vulnerability in high-risk children. We hypothesised that children of parents with depression would show more negative interpretation bias, altered cortisol stress responses and greater affective reactivity and prolonged recovery compared to children of parents with no mental illness. Across the sample, associations between interpretation bias and stress responses were expected. Participants were 80 high-risk (parental depression) and 77 low-risk (no parental mental illness) youth aged 10 to 14 years. Mental health was assessed using structured clinical interviews. Interpretation bias was measured using the Scrambled Sentences Task, and stress reactivity and recovery were indexed by salivary cortisol and self-reported affect across six time points. Group differences were tested with t-tests and analyses of covariance. Regressions examined the unique contribution of familial risk status beyond other relevant factors, including depression, anxiety, childhood trauma, pubertal status, and sex. Correlations examined associations between interpretation bias and cortisol and affective stress indices. Groups did not differ in interpretation bias, or cortisol or affective stress responses. Children's own symptoms of psychopathology (depression slightly more so than anxiety) positively predicted their interpretation bias but not their cortisol or affective stress responses. Exploratory moderation analyses showed that higher baseline cortisol strengthened the relationship between depression and interpretation bias. Interpretation bias correlated with cortisol reactivity and recovery within the high-risk but not the low-risk group. Contrary to theoretical accounts, high-risk youth did not exhibit cognitive, affective, or endocrinological vulnerabilities relative to low-risk peers. Interpretation bias was found to be a promising target, robustly linked to clinical outcomes and tentatively to cortisol stress responses, though its absence in high-risk youth is in support of a more selective intervention approach. The study was preregistered under the Deutsches Register Klinischer Studien DRKS00028842 on August 19, 2022.
Altered immune responses including increased neutrophils have been reported in Parkinson's disease (PD); however, the role of neutrophil extracellular traps (NETs) remains unclear. The aim of this study was to evaluate the contribution of NETs to the systemic immunity and central nervous system (CNS) in PD pathogenesis. Transcriptomic analysis from the Parkinson's Progression Markers Initiative (PPMI) cohort was performed. Serum NETs were measured by myeloperoxidase (MPO)-DNA and citrullinated histone H3 (CitH3)-DNA complexes using enzyme-linked immunosorbent assay (ELISA). In addition, NET structures in postmortem brains of individuals with PD and multiple system atrophy (MSA) were quantified using ELISA and visualized by confocal microscopy. Differential expression gene analysis showed significant systemic upregulation of PADI4 expression, which encodes the NET-priming enzyme peptidylarginine deiminase 4, in patients with PD compared with control subjects. In the regional cross-sectional cohort, serum MPO-DNA complexes were reduced in patients with PD compared with control subjects and showed a graded reduction with disease severity; this reduction was independently replicated using a CitH3-DNA ELISA. In contrast, NET structures were markedly increased in postmortem brain tissues from individuals with PD and MSA compared with control subjects. Confocal imaging further confirmed the presence of NETs in the PD brain cortex, with an increased density in the substantia nigra and in close proximity to Lewy bodies. These findings demonstrated systemic priming of NET-associated pathways accompanied by reduced circulating NET complexes in PD, alongside substantial NETs deposition within the CNS. Together, these observations identify the PADI4-NET axis as a candidate immune feature of PD that warrants further mechanistic investigation. © 2026 International Parkinson and Movement Disorder Society.
To explore the status of low-dose CT lung cancer screening (LCS) training practices, identify existing gaps, and define key competencies to be included in LCS educational curricula. As part of the European SOLACE project, a structured cross-sectional survey consisting of 11 closed- and open-ended items, developed based on relevant literature, international guidelines, and expert input to assess LCS current practices and training needs, was administered to a panel of European LCS experts. Participants were invited to individual Zoom interviews (May-November 2025). Data were analyzed using descriptive statistics. Twenty-five LCS experts were interviewed from 14 European countries, including 10 radiologists (40%), 8 pulmonologists (32%), 4 thoracic surgeons (16%), 1 project manager (4%), 1 smoking cessation specialist (4%), and 1 general practitioner (GP) (4%). Reported training activities ranged from established programmes (4/14 countries), to learning initiatives (6/14) and/or planned programmes (4/14). Radiologists (96%), pulmonologists (80%), and GPs (60%) were identified as the main target groups for training. On a 6-point Likert scale (0 = not important, 5 = extremely important), experts indicated limited awareness of training needs as the most relevant gap (mean 2.8 ± 2.2). Key educational areas to be strengthened included management of incidental findings (4.5 ± 0.6) and confident use of guidelines for nodule management (3.8 ± 1.8). Among essential competencies for professionals involved in LCS, the highest-rated were competence in managing incidental findings (4.7 ± 0.6), familiarity with guideline-based nodule management (4.7 ± 0.6), basic knowledge of AI tools (4.5 ± 0.8), and communication with LCS participants (4.5 ± 1.1). The findings suggest a heterogeneous LCS training landscape across European countries and underscore the importance of developing shared European curricula. Key priorities may include strengthening technical skills alongside structured communication training. Education and training of all stakeholders are essential for the successful implementation of LCS programmes. This survey assesses the current status of LCS training practices across Europe, identifies existing gaps, and defines key competencies to inform future curricula for health professionals involved in LCS. The European LCS training landscape is highly heterogeneous, with substantial variability in training activities, target professionals, and delivery modalities.