Clinical and Imaging Characteristics, Care Pathways, and Outcomes of Traumatic Epidural Hematomas: A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study.

BACKGROUND AND OBJECTIVES: Guideline recommendations for surgical management of traumatic epidural hematomas (EDHs) do not directly address EDHs that co-occur with other intracranial hematomas; the relative rates of isolated vs nonisolated EDHs and guideline adherence are unknown. We describe characteristics of a contemporary cohort of patients with EDHs and identify factors influencing acute surgery. METHODS: This research was conducted within the longitudinal, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury cohort study which prospectively enrolled patients with traumatic brain injury from 65 hospitals in 18 European countries from 2014 to 2017. All patients with EDH on the first scan were included. We describe clinical, imaging, management, and outcome characteristics and assess associations between site and baseline characteristics and acute EDH surgery, using regression modeling. RESULTS: In 461 patients with EDH, median age was 41 years (IQR 24-56), 76% were male, and median EDH volume was 5 cm3 (IQR 2-20). Concomitant acute subdural hematomas (ASDHs) and/or intraparenchymal hemorrhages were present in 328/461 patients (71%). Acute surgery was performed in 99/461 patients (21%), including 70/86 with EDH volume ≥30 cm3 (81%). Larger EDH volumes (odds ratio [OR] 1.19 [95% CI 1.14-1.24] per cm3 below 30 cm3), smaller ASDH volumes (OR 0.93 [95% CI 0.88-0.97] per cm3), and midline shift (OR 6.63 [95% CI 1.99-22.15]) were associated with acute surgery; between-site variation was observed (median OR 2.08 [95% CI 1.01-3.48]). Six-month Glasgow Outcome Scale-Extended scores ≥5 occurred in 289/389 patients (74%); 41/389 (11%) died. CONCLUSION: Isolated EDHs are relatively infrequent, and two-thirds of patients harbor concomitant ASDHs and/or intraparenchymal hemorrhages. EDHs ≥30 cm3 are generally evacuated early, adhering to Brain Trauma Foundation guidelines. For heterogeneous intracranial pathology, surgical decision-making is related to clinical status and overall lesion burden. Further research should examine the optimal surgical management of EDH with concomitant lesions in traumatic brain injury, to inform updated guidelines.

Association of preprocedural antiplatelet use with decreased thromboembolic complications for intracranial aneurysms undergoing intrasaccular flow disruption.

OBJECTIVE: This study was conducted to investigate the impact of antiplatelet administration in the periprocedural period on the occurrence of thromboembolic complications (TECs) in patients undergoing treatment using the Woven EndoBridge (WEB) device for intracranial wide-necked bifurcation aneurysms. The primary objective was to assess whether the use of antiplatelets in the pre- and postprocedural phases reduces the likelihood of developing TECs, considering various covariates. METHODS: A retrospective multicenter observational study was conducted within the WorldWideWEB Consortium and comprised 38 academic centers with endovascular treatment capabilities. Univariable and multivariable logistic regression analyses were performed to determine the association between antiplatelet use and TECs, adjusting for covariates. Missing predictor data were addressed using multiple imputation. RESULTS: The study comprised two cohorts: one addressing general thromboembolic events and consisting of 1412 patients, among whom 103 experienced TECs, and another focusing on symptomatic thromboembolic events and comprising 1395 patients, of whom 50 experienced symptomatic TECs. Preprocedural antiplatelet use was associated with a reduced likelihood of overall TECs (OR 0.32, 95% CI 0.19-0.53, p < 0.001) and symptomatic TECs (OR 0.49, 95% CI 0.25-0.95, p = 0.036), whereas postprocedural antiplatelet use showed no significant association with TECs. The study also revealed additional predictors of TECs, including stent use (overall: OR 4.96, 95% CI 2.38-10.3, p < 0.001; symptomatic: OR 3.24, 95% CI 1.26-8.36, p = 0.015), WEB single-layer sphere (SLS) type (overall: OR 0.18, 95% CI 0.04-0.74, p = 0.017), and posterior circulation aneurysm location (symptomatic: OR 18.43, 95% CI 1.48-230, p = 0.024). CONCLUSIONS: The findings of this study suggest that the preprocedural administration of antiplatelets is associated with a reduced likelihood of TECs in patients undergoing treatment with the WEB device for wide-necked bifurcation aneurysms. However, postprocedural antiplatelet use did not show a significant impact on TEC occurrence.

Quantifying dysmorphologies of the neurocranium using artificial neural networks.

BACKGROUND: Craniosynostosis, a congenital condition characterized by the premature fusion of cranial sutures, necessitates objective methods for evaluating cranial morphology to enhance patient treatment. Current subjective assessments often lead to inconsistent outcomes. This study introduces a novel, quantitative approach to classify craniosynostosis and measure its severity. METHODS: An artificial neural network was trained to classify normocephalic, trigonocephalic, and scaphocephalic head shapes based on a publicly available dataset of synthetic 3D head models. Each 3D model was converted into a low-dimensional shape representation based on the distribution of normal vectors, which served as the input for the neural network, ensuring complete patient anonymity and invariance to geometric size and orientation. Explainable AI methods were utilized to highlight significant features when making predictions. Additionally, the Feature Prominence (FP) score was introduced, a novel metric that captures the prominence of distinct shape characteristics associated with a given class. Its relationship with clinical severity scores was examined using the Spearman Rank Correlation Coefficient. RESULTS: The final model achieved excellent test accuracy in classifying the different cranial shapes from their low-dimensional representation. Attention maps indicated that the network's attention was predominantly directed toward the parietal and temporal regions, as well as toward the region signifying vertex depression in scaphocephaly. In trigonocephaly, features around the temples were most pronounced. The FP score showed a strong positive monotonic relationship with clinical severity scores in both scaphocephalic (ρ = 0.83, p < 0.001) and trigonocephalic (ρ = 0.64, p < 0.001) models. Visual assessments further confirmed that as FP values rose, phenotypic severity became increasingly evident. CONCLUSION: This study presents an innovative and accessible AI-based method for quantifying cranial shape that mitigates the need for adjustments due to age-specific size variations or differences in the spatial orientation of the 3D images, while ensuring complete patient privacy. The proposed FP score strongly correlates with clinical severity scores and has the potential to aid in clinical decision-making and facilitate multi-center collaborations. Future work will focus on validating the model with larger patient datasets and exploring the potential of the FP score for broader applications. The publicly available source code facilitates easy implementation, aiming to advance craniofacial care and research.

Machine Learning-Based Prediction of Stroke in Emergency Departments.

Background: Stroke misdiagnosis, associated with poor outcomes, is estimated to occur in 9% of all stroke patients. Objectives: We hypothesized that machine learning (ML) could assist in the diagnosis of ischemic stroke in emergency departments (EDs). Design: The study was conducted and reported according to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines. We performed model development and prospective temporal validation, using data from pre- and post-COVID periods; we also performed a case study on a small cohort of previously misdiagnosed stroke patients. Methods: We used structured and unstructured electronic health records (EHRs) of 56,452 patient encounters from 13 hospitals in Pennsylvania, from September 2003 to January 2021. ML pipelines, including natural language processing, were created using pre-event clinical data and provider notes in the EDs. Results: Using pre-event information, our model's area under the receiver operating characteristics curve (AUROC) ranged from 0.88 to 0.92 with a similar range accuracy (0.87-0.90). Using provider notes, we identified five models that reached a balanced performance in terms of AUROC, sensitivity, and specificity. Model AUROC ranged from 0.93 to 0.99. Model sensitivity and specificity reached 0.90 and 0.99, respectively. Four of the top five performing models were based on the post-COVID provider notes; however, no performance difference between models tested on pre- and post-COVID was observed. Conclusion: This study leveraged pre-event and at-encounter level EHR for stroke prediction. The results indicate that available clinical information can be used for building EHR-based stroke prediction models and ED stroke alert systems.

Nanoactuator for Neuronal Optoporation.

Light-driven modulation of neuronal activity at high spatial-temporal resolution is becoming of high interest in neuroscience. In addition to optogenetics, nongenetic membrane-targeted nanomachines that alter the electrical state of the neuronal membranes are in demand. Here, we engineered and characterized a photoswitchable conjugated compound (BV-1) that spontaneously partitions into the neuronal membrane and undergoes a charge transfer upon light stimulation. The activity of primary neurons is not affected in the dark, whereas millisecond light pulses of cyan light induce a progressive decrease in membrane resistance and an increase in inward current matched to a progressive depolarization and action potential firing. We found that illumination of BV-1 induces oxidation of membrane phospholipids, which is necessary for the electrophysiological effects and is associated with decreased membrane tension and increased membrane fluidity. Time-resolved atomic force microscopy and molecular dynamics simulations performed on planar lipid bilayers revealed that the underlying mechanism is a light-driven formation of pore-like structures across the plasma membrane. Such a phenomenon decreases membrane resistance and increases permeability to monovalent cations, namely, Na+, mimicking the effects of antifungal polyenes. The same effect on membrane resistance was also observed in nonexcitable cells. When sustained light stimulations are applied, neuronal swelling and death occur. The light-controlled pore-forming properties of BV-1 allow performing "on-demand" light-induced membrane poration to rapidly shift from cell-attached to perforated whole-cell patch-clamp configuration. Administration of BV-1 to ex vivo retinal explants or in vivo primary visual cortex elicited neuronal firing in response to short trains of light stimuli, followed by activity silencing upon prolonged light stimulations. BV-1 represents a versatile molecular nanomachine whose properties can be exploited to induce either photostimulation or space-specific cell death, depending on the pattern and duration of light stimulation.

Cognition and health-related quality of life in long-term survivors of high-grade glioma: an interactive perspective from patient and caregiver.

BACKGROUND: The health-related quality of life (HRQoL) and cognition are important indicators for the quality of survival in patients with high-grade glioma (HGG). However, data on long-term survivors and their caregivers are scarce. We aim to investigate the interaction between cognition and HRQoL in long-term survivors, their caregivers' evaluations, and the effect on caregiver strain and burden. METHODS: 21 long-term HGG (8 WHO grade III and 13 WHO grade IV) survivors (survival ≥ 5 years) and 15 caregivers were included. Cognition (verbal memory, attention, executive functioning, and language), HRQoL, anxiety and depression, caregiver strain, and caregiver burden were assessed with standardized measures. Questionnaires were completed by patients and/or their caregivers. RESULTS: Mean survival was 12 years (grade III) and 8 years (grade IV). Cognition was significantly impaired with a large individual variety. Patients' general HRQoL was not impaired but all functioning scales were deviant. Patient-proxy agreement was found in most HRQoL subscales. Three patients (14%) showed indications of anxiety or depression. One-third of the caregivers reported a high caregiver strain or a high burden. Test scores for attention, executive functioning, language, and/or verbal memory were correlated with perceived global health status, cognitive functioning, and/or communication deficits. Caregiver burden was not related to cognitive deficits. CONCLUSIONS: In long-term HGG survivors maintained HRQoL seems possible even when cognition is impaired in a large variety at the individual level. A tailored approach is therefore recommended to investigate the cognitive impairments and HRQoL in patients and the need for patient and caregiver support.

Focused update to guidelines for endovascular therapy for emergent large vessel occlusion: basilar artery occlusion patients.

BACKGROUND: Endovascular therapy (EVT) dramatically improves clinical outcomes for patients with anterior circulation emergent large vessel occlusion (ELVO) strokes. With recent publication of two randomized controlled trials in favor of EVT for basilar artery occlusions, the Society of NeuroInterventional Surgery (SNIS) Standards and Guidelines Committee provides this focused update for the existing SNIS guideline, 'Current endovascular strategies for posterior circulation large vessel occlusion stroke.' METHODS: A structured literature review and analysis of studies related to posterior circulation large vessel occlusion (basilar or vertebral artery) strokes treated by EVT was performed. Based on the strength and quality of the evidence, recommendations were made by consensus of the writing committee, with additional input from the full SNIS Standards and Guidelines Committee and the SNIS Board of Directors. RESULTS: Based on the results of the most recent randomized, controlled trials on EVT for basilar or vertebral artery occlusion, the expert panel agreed on the following recommendations. For patients presenting with an acute ischemic stroke due to an acute basilar or vertebral artery occlusion confirmed on CT angiography, National Institutes of Health Stroke Scale (NIHSS) score of ≥6, posterior circulation Alberta Stroke Program Early CT Score (PC-ASPECTS) ≥6, and age 18-89 years: (1) thrombectomy is indicated within 12 hours since last known well (class I, level B-R); (2) thrombectomy is reasonable within 12-24 hours from the last known well (class IIa, level B-R); (3) thrombectomy may be considered on a case by case basis for patients presenting beyond 24 hours since last known well (class IIb, level C-EO). In addition, thrombectomy may be considered on a case by case basis for patients aged <18 years or >89 years on a case by case basis (class IIb, level C-EO). CONCLUSIONS: The indications for EVT of ELVO strokes continue to expand and now include patients with basilar artery occlusion. Further prospective, randomized controlled trials are warranted to elucidate the efficacy and safety of EVT in populations not included in this set of recommendations, and to confirm long term outcomes.

3D Analysis of the Cranial and Facial Shape in Craniosynostosis Patients: A Systematic Review.

With increasing interest in 3D photogrammetry, diverse methods have been developed for craniofacial shape analysis in craniosynostosis patients. This review provides an overview of these methods and offers recommendations for future studies. A systematic literature search was used to identify publications on 3D photogrammetry analyses in craniosynostosis patients until August 2023. Inclusion criteria were original research reporting on 3D photogrammetry analyses in patients with craniosynostosis and written in English. Sixty-three publications that had reproducible methods for measuring cranial, forehead, or facial shape were included in the systematic review. Cranial shape changes were commonly assessed using heat maps and curvature analyses. Publications assessing the forehead utilized volumetric measurements, angles, ratios, and mirroring techniques. Mirroring techniques were frequently used to determine facial asymmetry. Although 3D photogrammetry shows promise, methods vary widely between standardized and less conventional measurements. A standardized protocol for the selection and documentation of landmarks, planes, and measurements across the cranium, forehead, and face is essential for consistent clinical and research applications.

An autologous ex vivo model for exploring patient-specific responses to viro-immunotherapy in glioblastoma.

Oncolytic virus (OV) clinical trials have demonstrated remarkable efficacy in subsets of patients with glioblastoma (GBM). However, the lack of tools to predict this response hinders the advancement of a more personalized application of OV therapy. In this study, we characterize an ex vivo co-culture system designed to examine the immune response to OV infection of patient-derived GBM neurospheres in the presence of autologous peripheral blood mononuclear cells (PBMCs). Co-culture conditions were optimized to retain viability and functionality of both tumor cells and PBMCs, effectively recapitulating the well-recognized immunosuppressive effects of GBM. Following OV infection, we observed elevated secretion of pro-inflammatory cytokines and chemokines, including interferon γ, tumor necrosis factor α, CXCL9, and CXCL10, and marked changes in immune cell activation markers. Importantly, OV treatment induced unique patient-specific immune responses. In summary, our co-culture platform presents an avenue for personalized screening of viro-immunotherapies in GBM, offering promise as a potential tool for future patient stratification in OV therapy.

The influence of socioeconomic status and gender on incidence and survival in bladder cancer: a longitudinal study based on the Hamburg Cancer Registry.

BACKGROUND: To investigate the influence of socioeconomic status (SES) and gender on the incidence and survival of patients with bladder cancer on a small scale within the city of Hamburg, Germany. METHODS: Patients documented in the Hamburg Cancer Registry aged ≥ 18 years with primary bladder carcinoma (ICD-10: C67, D09.0), diagnosed in the period 2004-2020 (follow-up until 31.12.2021), and residing in Hamburg were included. The patients were divided into three groups (low, intermediate, and high SES) based on the socioeconomic situation at the district level, defined by the proportion of unemployed individuals, social housing, benefit recipients according to law, etc. Relative survival in the years 2004-2020 was calculated using a period approach. RESULTS: Among the 10,659 patients included, age-standardized 5-year relative survival (5YRS) in 2004-2020 correlated with SES. The age-standardized 5YRS differed significantly between patients with high and intermediate SES vs low SES. Women with low SES had the worst 5YRS at 58.2%, while men with high SES presented the best relative 5YRS at 73.5%. This effect remained after stratification by UICC stages. Concerning incidence, there is an indication that women with low SES were more often diagnosed in higher UICC stages III or IV than women with high SES (18.3% versus 12.6%). CONCLUSIONS: The socioeconomic situation at the time of diagnosis, as well as gender, has a substantial impact on the incidence and cancer survival rates in patients with bladder cancer. Further research, including the study of patient care, is needed to better understand and address these inequalities.

Dual Layer vs Single Layer Woven EndoBridge Device in the Treatment of Intracranial Aneurysms: A Propensity Score-Matched Analysis.

BACKGROUND: The Woven EndoBridge (WEB) devices have been used for treating wide neck bifurcation aneurysms (WNBAs) with several generational enhancements to improve clinical outcomes. The original device dual-layer (WEB DL) was replaced by a single-layer (WEB SL) device in 2013. This study aimed to compare the effectiveness and safety of these devices in managing intracranial aneurysms. METHODS: A multicenter cohort study was conducted, and data from 1,289 patients with intracranial aneurysms treated with either the WEB SL or WEB DL devices were retrospectively analyzed. Propensity score matching was utilized to balance the baseline characteristics between the two groups. Outcomes assessed included immediate occlusion rate, complete occlusion at last follow-up, retreatment rate, device compaction, and aneurysmal rupture. RESULTS: Before propensity score matching, patients treated with the WEB SL had a significantly higher rate of complete occlusion at the last follow-up and a lower rate of retreatment. After matching, there was no significant difference in immediate occlusion rate, retreatment rate, or device compaction between the WEB SL and DL groups. However, the SL group maintained a higher rate of complete occlusion at the final follow-up. Regression analysis showed that SL was associated with higher rates of complete occlusion (OR: 0.19; CI: 0.04 to 0.8, p = 0.029) and lower rates of retreatment (OR: 0.12; CI: 0 to 4.12, p = 0.23). CONCLUSION: The WEB SL and DL devices demonstrated similar performances in immediate occlusion rates and retreatment requirements for intracranial aneurysms. The SL device showed a higher rate of complete occlusion at the final follow-up.

Endovascular therapy for anterior circulation emergent large vessel occlusion stroke in patients with large ischemic cores: a report of the SNIS Standards and Guidelines Committee.

BACKGROUND: Early clinical trials validating endovascular therapy (EVT) for emergent large vessel occlusion (ELVO) ischemic stroke in the anterior circulation initially focused on patients with small or absent completed infarctions (ischemic cores) to maximize the probability of detecting a clinically meaningful and statistically significant benefit of EVT. Subsequently, real-world experience suggested that patients with large core ischemic strokes (LCS) at presentation may also benefit from EVT. Several large, retrospective, and prospective randomized clinical trials have recently been published that further validate this approach. These guidelines aim to provide an update for endovascular treatment of LCS. METHODS: A structured literature review of LCS studies available since 2019 and grading the strength and quality of the evidence was performed. Recommendations were made based on these new data by consensus of the authors, with additional input from the full SNIS Standards and Guidelines Committee and the SNIS Board of Directors. RESULTS: The management of ELVO strokes with large ischemic cores continues to evolve. The expert panel agreed on several recommendations: Recommendation 1: In patients with anterior circulation ELVO who present within 24 hours of last known normal with large infarct core (70-149 mL or ASPECTS 3-5) and meet other criteria of RESCUE-Japan LIMIT, SELECT2, ANGEL-ASPECT, TESLA, TENSION, or LASTE trials, thrombectomy is indicated (Class I, Level A). Recommendations 2-7 flow directly from recommendation 1. Recommendation 2: EVT in patients with LCS aged 18-85 years is beneficial (Class I, Level A). Recommendation 3: EVT in patients with LCS >85 years of age may be beneficial (Class I, Level B-R). Recommendation 4: Patients with LCS and NIHSS score 6-30 benefit from EVT in LCS (Class I, Level A). Recommendation 5: Patients with LCS and NIHSS score <6 and >30 may benefit from EVT in LCS (Class IIa, Level A). Recommendation 6: Patients with LCS and low baseline mRS (0-1) benefit from EVT (Class I, Level A). Recommendation 7: Patients with LCS and time of last known well 0-24 hours benefit from EVT (Class I, Level A). Recommendation 8: It is recommended that patients with ELVO LCS who also meet the criteria for on-label or guideline-directed use of IV thrombolysis receive IV thrombolysis, irrespective of whether endovascular treatments are being considered (Class I, Level B-NR). CONCLUSIONS: The indications for endovascular treatment of ELVO strokes continue to expand and now include patients with large ischemic cores on presentation. Further prospective randomized studies, including follow-up to assess the population-based efficacy of treating patients with LCS, are warranted.

Factors Affecting Selection of TraineE for Neurointervention (FASTEN).

BACKGROUND AND IMPORTANCE: Neurointervention is a very competitive specialty in the United States due to the limited number of training spots and the larger pool of applicants. The training standards are continuously updated to ensure solid training experiences. Factors affecting candidate(s) selection have not been fully established yet. Our study aims to investigate the factors influencing the selection process. METHODS: A 52-question survey was distributed to 93 program directors (PDs). The survey consisted of six categories: (a) Program characteristics, (b) Candidate demographics, (c) Educational credentials, (d) Personal traits, (e) Research and extracurricular activities, and (f) Overall final set of characteristics. The response rate was 59.1%. As per the programs' characteristics, neurosurgery was the most involved specialty in running the training programs (69%). Regarding demographics, the need for visa sponsorship held the greatest prominence with a mean score of 5.9 [standard deviation (SD) 2.9]. For the educational credentials, being a graduate from a neurosurgical residency and the institution where the candidate's residency training is/was scored the highest [5.4 (SD = 2.9), 5.4 (SD = 2.5), respectively]. Regarding the personal traits, assessment by faculty members achieved the highest score [8.9 (SD = 1)]. In terms of research/extracurricular activities, fluency in English had the highest score [7.2 (SD = 1.9)] followed by peer-reviewed/PubMed-indexed publications [6.4 (SD = 2.2)]. CONCLUSION: Our survey investigated the factors influencing the final decision when choosing the future neurointerventional trainee, including demographic, educational, research, and extracurricular activities, which might serve as valuable guidance for both applicants and programs to refine the selection process.

Measuring the Four Higher-Order Values in Schwartz's Theory: Validation of a 17-Item Inventory.

Schwartz's theory of basic human values is the dominant framework for assessing values. One of its strengths is that it allows for different levels of analysis. The 10 basic values can be reliably assigned to four higher-order dimensions: Openness to Change, Conservation, Self-Transcendence, and Self-Enhancement. In this paper, we examined the psychometric properties of the Higher-Order-Value Scale-17 (HOVS17), an inventory that economically assesses these higher-order values. We analyzed data from the GESIS Panel, an ongoing large-scale probability-based panel study that fields HOVS17 annually since 2013 and for which HOVS17 was originally developed. We found HOVS17 to have satisfactory psychometric properties. The 17 items were located in the two-dimensional multi-dimensional scaling (MDS) space as hypothesized. All four subscales were unidimensional, showed good fit when modeled as reflective latent variables, and had acceptable reliabilities as well as one-year test-retest stabilities (.65 to .69). The subscales correlated in theoretically plausible ways with a wide range of correlates and criteria, such as personality traits and well-being. This demonstrates that HOVS17 provides a sound basis for studying the development, precursors, and consequences of the higher-order values in the GESIS Panel and in future surveys that adopt HOVS17. We also discuss suggestions for further improvements of the inventory.

Observing Dynamic Conformational Changes within the Coiled-Coil Domain of Different Laminin Isoforms Using High-Speed Atomic Force Microscopy.

Laminins are trimeric glycoproteins with important roles in cell-matrix adhesion and tissue organization. The laminin α, ß, and γ-chains have short N-terminal arms, while their C-termini are connected via a triple coiled-coil domain, giving the laminin molecule a well-characterized cross-shaped morphology as a result. The C-terminus of laminin alpha chains contains additional globular laminin G-like (LG) domains with important roles in mediating cell adhesion. Dynamic conformational changes of different laminin domains have been implicated in regulating laminin function, but so far have not been analyzed at the single-molecule level. High-speed atomic force microscopy (HS-AFM) is a unique tool for visualizing such dynamic conformational changes under physiological conditions at sub-second temporal resolution. After optimizing surface immobilization and imaging conditions, we characterized the ultrastructure of laminin-111 and laminin-332 using HS-AFM timelapse imaging. While laminin-111 features a stable S-shaped coiled-coil domain displaying little conformational rearrangement, laminin-332 coiled-coil domains undergo rapid switching between straight and bent conformations around a defined central molecular hinge. Complementing the experimental AFM data with AlphaFold-based coiled-coil structure prediction enabled us to pinpoint the position of the hinge region, as well as to identify potential molecular rearrangement processes permitting hinge flexibility. Coarse-grained molecular dynamics simulations provide further support for a spatially defined kinking mechanism in the laminin-332 coiled-coil domain. Finally, we observed the dynamic rearrangement of the C-terminal LG domains of laminin-111 and laminin-332, switching them between compact and open conformations. Thus, HS-AFM can directly visualize molecular rearrangement processes within different laminin isoforms and provide dynamic structural insight not available from other microscopy techniques.

Measuring Global Character Dimensions: An Ant Colony Optimization Approach toward Three Core Strength Scales.

The Values in Action (VIA) framework encompasses 24 universally valued character strengths. Recent factor-analytic work has identified three global core strengths (metatraits) that proved to be well-interpretable and cross-culturally replicable: positivity, dependability, and mastery. However, there are no short scales to economically measure these core strengths that would encourage (large-scale) survey-based research on the global level of the VIA trait space. In the present study, we selected 18 items to measure the three metatraits from the 96-item IPIP-VIA-R inventory. To optimize the item selection while considering multiple psychometric criteria simultaneously, we made use of Ant Colony Optimization. Thereby, we obtained balanced-keyed scales that cover the heterogeneous constructs well, showed good model fit and reliability across six samples from Germany and the U.K. (total N = 2,754), and achieved scalar measurement invariance across countries. Furthermore, we demonstrated each scale's validity by locating the three core strengths in a nomological net with personality and value metatraits, life satisfaction, and behavioral criteria. Available in the public domain in English and German, these both valid and economical core strength scales may further stimulate integrative research on personality and values.

[Lichen sclerosus in clinically relevant phimosis: incidence, risk factors, and association with squamous cell carcinoma of the penis]. / Lichen sclerosus bei klinisch relevanter Phimose: Häufigkeit, Risikofaktoren und Assoziation mit Plattenepithelkarzinomen des Penis.

BACKGROUND: Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory skin disease. It is frequently diagnosed following circumcision. Diabetes mellitus (DM) is a known risk factor in men. Malignant pathology is more common in patients with LSA. Data on LSA in men are very limited. OBJECTIVE: This study investigated the incidence of LSA in men who had undergone circumcision. Risk factors and likelihood of malignancy were captured. MATERIALS AND METHODS: Data of 215 patients were retrospectively analyzed. As potential risk factors, age, body mass index (BMI), DM, coronary heart disease (CHD) and arterial hypertension were identified. Data were analyzed and displayed graphically as spike histograms. Logistic regression was applied. Age and BMI were transformed using cubic spline function. RESULTS: Mean age of patients was 37 years (±â€¯22 years). Mean BMI was 26.4. In all, 24% of the patients had a BMI > 30. Of the patients, 11% had DM, 5.1% had CHD, and 19% had arterial hypertension. Pathology revealed LSA in 47% of patients. Malignant disease was apparent in 3.3% of patients (2.7% without concomitant LSA, 4% with concomitant LSA). Age (55 vs 20 years, odds ratio [OR]: 3.210 [1.421, 7.251]) was a significant risk factor for LSA. BMI (30 vs 22 kg/m2, OR 1.059 [0.614, 1.828]) and DM (OR: 0.42 [0.148, 1.192]) elevated the risk for LSA. CONCLUSION: We saw high rates of LSA in patients had undergone circumcision. Higher age represents a significant risk factor. In 3.3%, final pathology revealed squamous cell carcinoma of the penis. Therefore, pathologic work-up of circumcision specimen is mandatory.

AI Psychometrics: Assessing the Psychological Profiles of Large Language Models Through Psychometric Inventories.

We illustrate how standard psychometric inventories originally designed for assessing noncognitive human traits can be repurposed as diagnostic tools to evaluate analogous traits in large language models (LLMs). We start from the assumption that LLMs, inadvertently yet inevitably, acquire psychological traits (metaphorically speaking) from the vast text corpora on which they are trained. Such corpora contain sediments of the personalities, values, beliefs, and biases of the countless human authors of these texts, which LLMs learn through a complex training process. The traits that LLMs acquire in such a way can potentially influence their behavior, that is, their outputs in downstream tasks and applications in which they are employed, which in turn may have real-world consequences for individuals and social groups. By eliciting LLMs' responses to language-based psychometric inventories, we can bring their traits to light. Psychometric profiling enables researchers to study and compare LLMs in terms of noncognitive characteristics, thereby providing a window into the personalities, values, beliefs, and biases these models exhibit (or mimic). We discuss the history of similar ideas and outline possible psychometric approaches for LLMs. We demonstrate one promising approach, zero-shot classification, for several LLMs and psychometric inventories. We conclude by highlighting open challenges and future avenues of research for AI Psychometrics.

Structural heterogeneity of the ion and lipid channel TMEM16F.

Transmembrane protein 16 F (TMEM16F) is a Ca2+-activated homodimer which functions as an ion channel and a phospholipid scramblase. Despite the availability of several TMEM16F cryogenic electron microscopy (cryo-EM) structures, the mechanism of activation and substrate translocation remains controversial, possibly due to restrictions in the accessible protein conformational space. In this study, we use atomic force microscopy under physiological conditions to reveal a range of structurally and mechanically diverse TMEM16F assemblies, characterized by variable inter-subunit dimerization interfaces and protomer orientations, which have escaped prior cryo-EM studies. Furthermore, we find that Ca2+-induced activation is associated to stepwise changes in the pore region that affect the mechanical properties of transmembrane helices TM3, TM4 and TM6. Our direct observation of membrane remodelling in response to Ca2+ binding along with additional electrophysiological analysis, relate this structural multiplicity of TMEM16F to lipid and ion permeation processes. These results thus demonstrate how conformational heterogeneity of TMEM16F directly contributes to its diverse physiological functions.