Large-scale brain connectivity changes following the administration of lysergic acid diethylamide, d-amphetamine, and 3,4-methylenedioxyamphetamine.

Psychedelics have recently attracted significant attention for their potential to mitigate symptoms associated with various psychiatric disorders. However, the precise neurobiological mechanisms responsible for these effects remain incompletely understood. A valuable approach to gaining insights into the specific mechanisms of action involves comparing psychedelics with substances that have partially overlapping neurophysiological effects, i.e., modulating the same neurotransmitter systems. Imaging data were obtained from the clinical trial NCT03019822, which explored the acute effects of lysergic acid diethylamide (LSD), d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) in 28 healthy volunteers. The clinical trial employed a double-blind, placebo-controlled, crossover design. Herein, various resting-state connectivity measures were examined, including within-network connectivity (integrity), between-network connectivity (segregation), seed-based connectivity of resting-state networks, and global connectivity. Differences between placebo and the active conditions were assessed using repeated-measures ANOVA, followed by post-hoc pairwise t-tests. Changes in voxel-wise seed-based connectivity were correlated with serotonin 2 A receptor density maps. Compared to placebo, all substances reduced integrity in several networks, indicating both common and unique effects. While LSD uniquely reduced integrity in the default-mode network (DMN), the amphetamines, in contrast to our expectations, reduced integrity in more networks than LSD. However, LSD exhibited more pronounced segregation effects, characterized solely by decreases, in contrast to the amphetamines, which also induced increases. Across all substances, seed-based connectivity mostly increased between networks, with LSD demonstrating more pronounced effects than both amphetamines. Finally, while all substances decreased global connectivity in visual areas, compared to placebo, LSD specifically increased global connectivity in the basal ganglia and thalamus. These findings advance our understanding of the distinctive neurobiological effects of psychedelics, prompting further exploration of their therapeutic potential.

Pharmacological and non-pharmacological predictors of the LSD experience in healthy participants.

The pharmacodynamic effects of lysergic acid diethylamide (LSD) are diverse and different in different individuals. Effects of other psychoactive substances have been shown to be critically influenced by non-pharmacological factors such as personality traits and mood states. The aim of this study was to determine pharmacological and psychological predictors of the LSD effects in healthy human subjects. This analysis is based on nine double-blind, placebo-controlled, cross-over studies with a total of 213 healthy subjects receiving between 25-200 µg LSD. The influence of sex, age, dose, body weight, pharmacogenetic, drug experience, personality, setting, and mood before drug intake on the peak autonomic and total subjective responses to LSD was investigated using multiple linear mixed effects models and Least Absolute Shrinkage and Selection Operator regression. Results were adjusted for LSD dose and corrected for multiple testing. LSD dose emerged as the most influential predictor, exhibiting a positive correlation with most response variables. Pre-drug mental states such as "Well-Being", "Emotional Excitability", and "Anxiety" were also important predictor for a range of subjective effects but also heart rate and body temperature. The trait "Openness to Experiences" was positively correlated with elevated ratings in "Oceanic Boundlessness" and mystical-type effects. Previous experiences with hallucinogens have been negatively associated with the overall altered state of consciousness and particularly with "Anxious Ego Dissolution". Acute anxiety negatively correlated with the genetically determined functionality of the Cytochrome 2D6 enzyme. In summary, besides the amount of drug consumed, non-pharmacological factors such as personal traits and current mood also significantly predicted the subjective drug experience. Sex and body weight were not significant factors in influencing the drug experience.

Using AI to Identify Unremarkable Chest Radiographs for Automatic Reporting.

Background Radiology practices have a high volume of unremarkable chest radiographs and artificial intelligence (AI) could possibly improve workflow by providing an automatic report. Purpose To estimate the proportion of unremarkable chest radiographs, where AI can correctly exclude pathology (ie, specificity) without increasing diagnostic errors. Materials and Methods In this retrospective study, consecutive chest radiographs in unique adult patients (≥18 years of age) were obtained January 1-12, 2020, at four Danish hospitals. Exclusion criteria included insufficient radiology reports or AI output error. Two thoracic radiologists, who were blinded to AI output, labeled chest radiographs as "remarkable" or "unremarkable" based on predefined unremarkable findings (reference standard). Radiology reports were classified similarly. A commercial AI tool was adapted to output a chest radiograph "remarkableness" probability, which was used to calculate specificity at different AI sensitivities. Chest radiographs with missed findings by AI and/or the radiology report were graded by one thoracic radiologist as critical, clinically significant, or clinically insignificant. Paired proportions were compared using the McNemar test. Results A total of 1961 patients were included (median age, 72 years [IQR, 58-81 years]; 993 female), with one chest radiograph per patient. The reference standard labeled 1231 of 1961 chest radiographs (62.8%) as remarkable and 730 of 1961 (37.2%) as unremarkable. At 99.9%, 99.0%, and 98.0% sensitivity, the AI had a specificity of 24.5% (179 of 730 radiographs [95% CI: 21, 28]), 47.1% (344 of 730 radiographs [95% CI: 43, 51]), and 52.7% (385 of 730 radiographs [95% CI: 49, 56]), respectively. With the AI fixed to have a similar sensitivity as radiology reports (87.2%), the missed findings of AI and reports had 2.2% (27 of 1231 radiographs) and 1.1% (14 of 1231 radiographs) classified as critical (P = .01), 4.1% (51 of 1231 radiographs) and 3.6% (44 of 1231 radiographs) classified as clinically significant (P = .46), and 6.5% (80 of 1231) and 8.1% (100 of 1231) classified as clinically insignificant (P = .11), respectively. At sensitivities greater than or equal to 95.4%, the AI tool exhibited less than or equal to 1.1% critical misses. Conclusion A commercial AI tool used off-label could correctly exclude pathology in 24.5%-52.7% of all unremarkable chest radiographs at greater than or equal to 98% sensitivity. The AI had equal or lower rates of critical misses than radiology reports at sensitivities greater than or equal to 95.4%. These results should be confirmed in a prospective study. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Yoon and Hwang in this issue.

Rethinking Urban Water Management Through Drivers-Pressures-States-Impacts-Responses Framework Application in Chennai, India.

Cities suffering water scarcity are projected to increase in the following decades. However, the application of standardized indicator frameworks for assessing urban water resource management problems is on an early stage. India is expected to have the highest urban population facing water scarcity in the world by 2050. In this study, the authors assess how the Drivers-Pressures-States-Impacts-Responses framework, a causal framework adopted by the European Environment Agency, can contribute to evaluate water management challenges in cities and apply it to Chennai, India´s fourth-largest urban agglomeration. The framework proved to be a helpful tool for the evaluation of water management challenges in cities by disentangling relationships between environmental indicators and structuring dispersed data that allows a better understanding for policymakers. The main drivers identified in Chennai were population growth and economic development which generated impacts such as loss of aquatic ecosystems, low water table, low water quality, and reduction of biodiversity and human health. As a response, better urban planning, projects for new water infrastructure, and water bodies restoration have been implemented. Nevertheless, Chennai keeps facing difficulties to achieve proper water management. The severe hit of the COVID-19 pandemic on the Indian economy and its future management will be key for achievements related to water management.

Interobserver Agreement and Performance of Concurrent AI Assistance for Radiographic Evaluation of Knee Osteoarthritis.

Background Due to conflicting findings in the literature, there are concerns about a lack of objectivity in grading knee osteoarthritis (KOA) on radiographs. Purpose To examine how artificial intelligence (AI) assistance affects the performance and interobserver agreement of radiologists and orthopedists of various experience levels when evaluating KOA on radiographs according to the established Kellgren-Lawrence (KL) grading system. Materials and Methods In this retrospective observer performance study, consecutive standing knee radiographs from patients with suspected KOA were collected from three participating European centers between April 2019 and May 2022. Each center recruited four readers across radiology and orthopedic surgery at in-training and board-certified experience levels. KL grading (KL-0 = no KOA, KL-4 = severe KOA) on the frontal view was assessed by readers with and without assistance from a commercial AI tool. The majority vote of three musculoskeletal radiology consultants established the reference standard. The ordinal receiver operating characteristic method was used to estimate grading performance. Light kappa was used to estimate interrater agreement, and bootstrapped t statistics were used to compare groups. Results Seventy-five studies were included from each center, totaling 225 studies (mean patient age, 55 years ± 15 [SD]; 113 female patients). The KL grades were KL-0, 24.0% (n = 54); KL-1, 28.0% (n = 63); KL-2, 21.8% (n = 49); KL-3, 18.7% (n = 42); and KL-4, 7.6% (n = 17). Eleven readers completed their readings. Three of the six junior readers showed higher KL grading performance with versus without AI assistance (area under the receiver operating characteristic curve, 0.81 ± 0.017 [SEM] vs 0.88 ± 0.011 [P < .001]; 0.76 ± 0.018 vs 0.86 ± 0.013 [P < .001]; and 0.89 ± 0.011 vs 0.91 ± 0.009 [P = .008]). Interobserver agreement for KL grading among all readers was higher with versus without AI assistance (κ = 0.77 ± 0.018 [SEM] vs 0.85 ± 0.013; P < .001). Board-certified radiologists achieved almost perfect agreement for KL grading when assisted by AI (κ = 0.90 ± 0.01), which was higher than that achieved by the reference readers independently (κ = 0.84 ± 0.017; P = .01). Conclusion AI assistance increased junior readers' radiographic KOA grading performance and increased interobserver agreement for osteoarthritis grading across all readers and experience levels. Published under a CC BY 4.0 license. Supplemental material is available for this article.

Pharmacological Properties of Psychedelics with a Special Focus on Potential Harms.

Psychedelics are a group of substances within the heterogeneous class of hallucinogenic drugs. Via binding to the serotonin (5-HT) 2A receptor, psychedelics exert profound alterations in various mental domains, including sensation, cognition, emotions, and self-perception. Psychedelics comprise phenethylamines (e.g., mescaline), tryptamines (e.g., psilocybin), and ergolines (e.g., LSD). These drugs have been used recreationally for decades but have also regained attention as potential treatments for various psychiatric as well as neurological illnesses. While psychedelics are generally considered to be relatively safe from a physiological standpoint, especially when compared to other recreational drugs, they are not without risks. The main safety concerns are lasting psychological adverse reactions such as persisting anxiety, dissociation, or flashbacks.This chapter provides a comprehensive overview of the pharmacology of classic psychedelics, including their origins, psychological and autonomic effects, interactions, and potential risks and side effects. Furthermore, the origin, dosing, and consumption methods are discussed. It differentiates psychedelics from other psychoactive drugs, such as MDMA and ketamine, and elaborates on their distinct receptor profiles. Overall, this chapter provides an overview of the pharmacological underpinnings necessary for understanding the harms caused by psychedelic drugs.

LSD-assisted therapy in patients with anxiety: open-label prospective 12-month follow-up.

BACKGROUND: Anxiety disorders are a major public health burden with limited treatment options. AIMS: We investigated the long-term safety and efficacy of lysergic acid diethylamide (LSD)-assisted therapy in patients with anxiety with or without life-threatening illness. METHOD: This study was an a priori-planned long-term follow-up of an investigator-initiated, two-centre trial that used a double-blind, placebo-controlled, two-period, random-order, crossover design with two sessions with either oral LSD (200 µg) or placebo per period. Participants (n = 39) were followed up 1 year after the end-of-study visit to assess symptoms of anxiety, depression and long-term effects of psychedelics using Spielberger's State-Trait Anxiety Inventory-Global (STAI-G), the Beck Depression Inventory (BDI), the Persisting Effects Questionnaire and measures of personality traits using the NEO-Five-Factor Inventory. RESULTS: Participants reported a sustained reduction of STAI-G scores compared with baseline (least square means (95% CI) = -21.6 (-32.7, -10.4), d = 1.04, P < 0.001, for those who received LSD in the first period (94 weeks after the last LSD treatment) and -16.5 (-26.2, -6.8), d = 1.02, P < 0.05, for those who received LSD in the second period (68 weeks after the last LSD treatment)). Similar effects were observed for comorbid depression with change from baseline BDI scores of -8.1 (-13.2, -3.1), d = 0.71, P < 0.01, and -8.9 (-12.9, -4.9), d = 1.21, P < 0.01, for the LSD-first and placebo-first groups, respectively. Personality trait neuroticism decreased (P < 0.0001) and trait extraversion increased (P < 0.01) compared with study inclusion. Individuals attributed positive long-term effects to the psychedelic experience. CONCLUSIONS: Patients reported sustained long-term effects of LSD-assisted therapy for anxiety.

[Unclear cause of unilateral blindness with normal inflammation parameters]. / Unklare Ursache einseitiger Erblindung bei normwertigen Entzündungsparametern.

A 70-year-old female patient presented with unilateral blindness of the right eye. As C­reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were inconspicuous, a nonarteritic embolic occlusion was assumed; however, after detailed anamnesis large vessel vasculitis (LVV) appeared more likely, which was confirmed by the subsequent imaging diagnostics. This rare case of LVV without an increase in one of the inflammatory parameters CRP or ESR highlights the importance of the medical history and targeted diagnostic procedures.

Structured feedback and operative video debriefing with critical view of safety annotation in training of laparoscopic cholecystectomy: a randomized controlled study.

BACKGROUND: The learning curve in minimally invasive surgery (MIS) is lengthened compared to open surgery. It has been reported that structured feedback and training in teams of two trainees improves MIS training and MIS performance. Annotation of surgical images and videos may prove beneficial for surgical training. This study investigated whether structured feedback and video debriefing, including annotation of critical view of safety (CVS), have beneficial learning effects in a predefined, multi-modal MIS training curriculum in teams of two trainees. METHODS: This randomized-controlled single-center study included medical students without MIS experience (n = 80). The participants first completed a standardized and structured multi-modal MIS training curriculum. They were then randomly divided into two groups (n = 40 each), and four laparoscopic cholecystectomies (LCs) were performed on ex-vivo porcine livers each. Students in the intervention group received structured feedback after each LC, consisting of LC performance evaluations through tutor-trainee joint video debriefing and CVS video annotation. Performance was evaluated using global and LC-specific Objective Structured Assessments of Technical Skills (OSATS) and Global Operative Assessment of Laparoscopic Skills (GOALS) scores. RESULTS: The participants in the intervention group had higher global and LC-specific OSATS as well as global and LC-specific GOALS scores than the participants in the control group (25.5 ± 7.3 vs. 23.4 ± 5.1, p = 0.003; 47.6 ± 12.9 vs. 36 ± 12.8, p < 0.001; 17.5 ± 4.4 vs. 16 ± 3.8, p < 0.001; 6.6 ± 2.3 vs. 5.9 ± 2.1, p = 0.005). The intervention group achieved CVS more often than the control group (1. LC: 20 vs. 10 participants, p = 0.037, 2. LC: 24 vs. 8, p = 0.001, 3. LC: 31 vs. 8, p < 0.001, 4. LC: 31 vs. 10, p < 0.001). CONCLUSIONS: Structured feedback and video debriefing with CVS annotation improves CVS achievement and ex-vivo porcine LC training performance based on OSATS and GOALS scores.

RNA-Templated Peptide Bond Formation Promotes L-Homochirality.

The world in which we live is homochiral. The ribose units that form the backbone of DNA and RNA are all D-configured and the encoded amino acids that comprise the proteins of all living species feature an all-L-configuration at the α-carbon atoms. The homochirality of α-amino acids is essential for folding of the peptides into well-defined and functional 3D structures and the homochirality of D-ribose is crucial for helix formation and base-pairing. The question of why nature uses only encoded L-α-amino acids is not understood. Herein, we show that an RNA-peptide world, in which peptides grow on RNAs constructed from D-ribose, leads to the self-selection of homo-L-peptides, which provides a possible explanation for the homo-D-ribose and homo-L-amino acid combination seen in nature.

Viral load of SARS-CoV-2 in surgical smoke in minimally invasive and open surgery: a single-center prospective clinical trial.

At the beginning of the COVID-19 pandemic, it was assumed that SARS-CoV-2 could be transmitted through surgical smoke generated by electrocauterization. Minimally invasive surgery (MIS) was targeted due to potentially higher concentrations of the SARS-CoV-2 particles in the pneumoperitoneum. Some surgical societies even recommended open surgery instead of MIS to prevent the potential spread of SARS-CoV-2 from the pneumoperitoneum. This study aimed to detect SARS-CoV-2 in surgical smoke during open and MIS. Patients with SARS-CoV-2 infection who underwent open surgery or MIS at Heidelberg University Hospital were included in the study. A control group of patients without SARS-CoV-2 infection undergoing MIS or open surgery was included for comparison. The trial was approved by the Ethics Committee of Heidelberg University Medical School (S-098/2021). The following samples were collected: nasopharyngeal and intraabdominal swabs, blood, urine, surgical smoke, and air samples from the operating room. An SKC BioSampler was used to sample the surgical smoke from the pneumoperitoneum during MIS and the approximate surgical field during open surgery in 15 ml of sterilized phosphate-buffered saline. An RT-PCR test was performed on all collected samples to detect SARS-CoV-2 viral particles. Twelve patients with proven SARS-CoV-2 infection underwent open abdominal surgery. Two SARS-CoV-2-positive patients underwent an MIS procedure. The control group included 24 patients: 12 underwent open surgery and 12 MIS. One intraabdominal swab in a patient with SARS-CoV-2 infection was positive for SARS-CoV-2. However, during both open surgery and MIS, none of the surgical smoke samples showed any detectable viral particles of SARS-CoV-2. The air samples collected at the end of the surgical procedure showed no viral particles of SARS-CoV-2. Major complications (CD ≥ IIIa) were more often observed in SARS-CoV-2 positive patients (10 vs. 4, p = 0.001). This study showed no detectable viral particles of SARS-CoV-2 in surgical smoke sampled during MIS and open surgery. Thus, the discussed risk of transmission of SARS-CoV-2 via surgical smoke could not be confirmed in the present study.

Autoantibodies against the chemokine receptor 3 predict cardiovascular risk.

BACKGROUND AND AIMS: Chronic inflammation and autoimmunity contribute to cardiovascular (CV) disease. Recently, autoantibodies (aAbs) against the CXC-motif-chemokine receptor 3 (CXCR3), a G protein-coupled receptor with a key role in atherosclerosis, have been identified. The role of anti-CXCR3 aAbs for CV risk and disease is unclear. METHODS: Anti-CXCR3 aAbs were quantified by a commercially available enzyme-linked immunosorbent assay in 5000 participants (availability: 97.1%) of the population-based Gutenberg Health Study with extensive clinical phenotyping. Regression analyses were carried out to identify determinants of anti-CXCR3 aAbs and relevance for clinical outcome (i.e. all-cause mortality, cardiac death, heart failure, and major adverse cardiac events comprising incident coronary artery disease, myocardial infarction, and cardiac death). Last, immunization with CXCR3 and passive transfer of aAbs were performed in ApoE(-/-) mice for preclinical validation. RESULTS: The analysis sample included 4195 individuals (48% female, mean age 55.5 ± 11 years) after exclusion of individuals with autoimmune disease, immunomodulatory medication, acute infection, and history of cancer. Independent of age, sex, renal function, and traditional CV risk factors, increasing concentrations of anti-CXCR3 aAbs translated into higher intima-media thickness, left ventricular mass, and N-terminal pro-B-type natriuretic peptide. Adjusted for age and sex, anti-CXCR3 aAbs above the 75th percentile predicted all-cause death [hazard ratio (HR) (95% confidence interval) 1.25 (1.02, 1.52), P = .029], driven by excess cardiac mortality [HR 2.51 (1.21, 5.22), P = .014]. A trend towards a higher risk for major adverse cardiac events [HR 1.42 (1.0, 2.0), P = .05] along with increased risk of incident heart failure [HR per standard deviation increase of anti-CXCR3 aAbs: 1.26 (1.02, 1.56), P = .03] may contribute to this observation. Targeted proteomics revealed a molecular signature of anti-CXCR3 aAbs reflecting immune cell activation and cytokine-cytokine receptor interactions associated with an ongoing T helper cell 1 response. Finally, ApoE(-/-) mice immunized against CXCR3 displayed increased anti-CXCR3 aAbs and exhibited a higher burden of atherosclerosis compared to non-immunized controls, correlating with concentrations of anti-CXCR3 aAbs in the passive transfer model. CONCLUSIONS: In individuals free of autoimmune disease, anti-CXCR3 aAbs were abundant, related to CV end-organ damage, and predicted all-cause death as well as cardiac morbidity and mortality in conjunction with the acceleration of experimental atherosclerosis.

Diagnostic test accuracy study of a commercially available deep learning algorithm for ischemic lesion detection on brain MRIs in suspected stroke patients from a non-comprehensive stroke center.

PURPOSE: To estimate the ability of a commercially available artificial intelligence (AI) tool to detect acute brain ischemia on Magnetic Resonance Imaging (MRI), compared to an experienced neuroradiologist. METHODS: We retrospectively included 1030 patients with brain MRI, suspected of stroke from January 6th, 2020 to 1st of April 2022, based on these criteria: Age ≥ 18 years, symptoms within four weeks before the scan. The neuroradiologist reinterpreted the MRI scans and subclassified ischemic lesions for reference. We excluded scans with interpretation difficulties due to artifacts or missing sequences. Four MRI scanner models from the same vendor were used. The first 800 patients were included consecutively, remaining enriched for less frequent lesions. The index test was a CE-approved AI tool (Apollo version 2.1.1 by Cerebriu). RESULTS: The final analysis cohort comprised 995 patients (mean age 69 years, 53 % female). A case-based analysis for detecting acute ischemic lesions showed a sensitivity of 89 % (95 % CI: 85 %-91 %) and specificity of 90 % (95 % CI: 87 %-92 %). We found no significant difference in sensitivity or specificity based on sex, age, or comorbidities. Specificity was reduced in cases with DWI artifacts. Multivariate analysis showed that increasing ischemic lesion size and fragmented lesions were independently associated with higher sensitivity, while non-acute lesion ages lowered sensitivity. CONCLUSIONS: The AI tool exhibits high sensitivity and specificity in detecting acute ischemic lesions on MRI compared to an experienced neuroradiologist. While sensitivity depends on the ischemic lesions' characteristics, specificity depends on the image quality.

AutoCore: A network-based definition of the core module of human autoimmunity and autoinflammation.

Although research on rare autoimmune and autoinflammatory diseases has enabled definition of nonredundant regulators of homeostasis in human immunity, because of the single gene-single disease nature of many of these diseases, contributing factors were mostly unveiled in sequential and noncoordinated individual studies. We used a network-based approach for integrating a set of 186 inborn errors of immunity with predominant autoimmunity/autoinflammation into a comprehensive map of human immune dysregulation, which we termed "AutoCore." The AutoCore is located centrally within the interactome of all protein-protein interactions, connecting and pinpointing multidisease markers for a range of common, polygenic autoimmune/autoinflammatory diseases. The AutoCore can be subdivided into 19 endotypes that correspond to molecularly and phenotypically cohesive disease subgroups, providing a molecular mechanism-based disease classification and rationale toward systematic targeting for therapeutic purposes. Our study provides a proof of concept for using network-based methods to systematically investigate the molecular relationships between individual rare diseases and address a range of conceptual, diagnostic, and therapeutic challenges.

The Entropy of Entropy: Are We Talking about the Same Thing?

In the last few decades, the number of published papers that include search terms such as thermodynamics, entropy, ecology, and ecosystems has grown rapidly. Recently, background research carried out during the development of a paper on "thermodynamics in ecology" revealed huge variation in the understanding of the meaning and the use of some of the central terms in this field-in particular, entropy. This variation seems to be based primarily on the differing educational and scientific backgrounds of the researchers responsible for contributions to this field. Secondly, some ecological subdisciplines also seem to be better suited and applicable to certain interpretations of the concept than others. The most well-known seems to be the use of the Boltzmann-Gibbs equation in the guise of the Shannon-Weaver/Wiener index when applied to the estimation of biodiversity in ecology. Thirdly, this tendency also revealed that the use of entropy-like functions could be diverted into an area of statistical and distributional analyses as opposed to real thermodynamic approaches, which explicitly aim to describe and account for the energy fluxes and dissipations in the systems. Fourthly, these different ways of usage contribute to an increased confusion in discussions about efficiency and possible telos in nature, whether at the developmental level of the organism, a population, or an entire ecosystem. All the papers, in general, suffer from a lack of clear definitions of the thermodynamic functions used, and we, therefore, recommend that future publications in this area endeavor to achieve a more precise use of language. Only by increasing such efforts it is possible to understand and resolve some of the significant and possibly misleading discussions in this area.

Commercially Available Chest Radiograph AI Tools for Detecting Airspace Disease, Pneumothorax, and Pleural Effusion.

Background Commercially available artificial intelligence (AI) tools can assist radiologists in interpreting chest radiographs, but their real-life diagnostic accuracy remains unclear. Purpose To evaluate the diagnostic accuracy of four commercially available AI tools for detection of airspace disease, pneumothorax, and pleural effusion on chest radiographs. Materials and Methods This retrospective study included consecutive adult patients who underwent chest radiography at one of four Danish hospitals in January 2020. Two thoracic radiologists (or three, in cases of disagreement) who had access to all previous and future imaging labeled chest radiographs independently for the reference standard. Area under the receiver operating characteristic curve, sensitivity, and specificity were calculated. Sensitivity and specificity were additionally stratified according to the severity of findings, number of findings on chest radiographs, and radiographic projection. The χ2 and McNemar tests were used for comparisons. Results The data set comprised 2040 patients (median age, 72 years [IQR, 58-81 years]; 1033 female), of whom 669 (32.8%) had target findings. The AI tools demonstrated areas under the receiver operating characteristic curve ranging 0.83-0.88 for airspace disease, 0.89-0.97 for pneumothorax, and 0.94-0.97 for pleural effusion. Sensitivities ranged 72%-91% for airspace disease, 63%-90% for pneumothorax, and 62%-95% for pleural effusion. Negative predictive values ranged 92%-100% for all target findings. In airspace disease, pneumothorax, and pleural effusion, specificity was high for chest radiographs with normal or single findings (range, 85%-96%, 99%-100%, and 95%-100%, respectively) and markedly lower for chest radiographs with four or more findings (range, 27%-69%, 96%-99%, 65%-92%, respectively) (P < .001). AI sensitivity was lower for vague airspace disease (range, 33%-61%) and small pneumothorax or pleural effusion (range, 9%-94%) compared with larger findings (range, 81%-100%; P value range, > .99 to < .001). Conclusion Current-generation AI tools showed moderate to high sensitivity for detecting airspace disease, pneumothorax, and pleural effusion on chest radiographs. However, they produced more false-positive findings than radiology reports, and their performance decreased for smaller-sized target findings and when multiple findings were present. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Yanagawa and Tomiyama in this issue.

Effective Connectivity of Thalamocortical Interactions Following d-Amphetamine, LSD, and MDMA Administration.

BACKGROUND: While the exploration of serotonergic psychedelics as psychiatric medicines deepens, so does the pressure to better understand how these compounds act on the brain. METHODS: We used a double-blind, placebo-controlled, crossover design and administered lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), and d-amphetamine in 25 healthy participants. By using spectral dynamic causal modeling, we mapped substance-induced changes in effective connectivity between the thalamus and different cortex types (unimodal vs. transmodal) derived from a previous study with resting-state functional magnetic resonance imaging data. Due to the distinct pharmacological modes of action of the 3 substances, we were able to investigate specific effects mainly driven by different neurotransmitter systems on thalamocortical and corticothalamic interactions. RESULTS: Compared with placebo, all 3 substances increased the effective connectivity from the thalamus to specific unimodal cortices, whereas the influence of these cortices on the thalamus was reduced. These results indicate increased bottom-up and decreased top-down information flow between the thalamus and some unimodal cortices. However, for the amphetamines, we found the opposite effects when examining the effective connectivity with transmodal cortices, including parts of the salience network. Intriguingly, LSD increased the effective connectivity from the thalamus to both unimodal and transmodal cortices, indicating a breach in the hierarchical organization of ongoing brain activity. CONCLUSIONS: The results advance our knowledge about the action of psychedelics on the brain and refine current models aiming to explain the underlying neurobiological processes.

Telestration with augmented reality improves the performance of the first ten ex vivo porcine laparoscopic cholecystectomies: a randomized controlled study.

INTRODUCTION: The learning curve in minimally invasive surgery (MIS) is steep compared to open surgery. One of the reasons is that training in the operating room in MIS is mainly limited to verbal instructions. The iSurgeon telestration device with augmented reality (AR) enables visual instructions, guidance, and feedback during MIS. This study aims to compare the effects of the iSurgeon on the training of novices performing repeated laparoscopic cholecystectomy (LC) on a porcine liver compared to traditional verbal instruction methods. METHODS: Forty medical students were randomized into the iSurgeon and the control group. The iSurgeon group performed 10 LCs receiving interactive visual guidance. The control group performed 10 LCs receiving conventional verbal guidance. The performance assessment using Objective Structured Assessments of Technical Skills (OSATS) and Global Operative Assessment of Laparoscopic Skills (GOALS) scores, the total operating time, and complications were compared between the two groups. RESULTS: The iSurgeon group performed LCs significantly better (global GOALS 17.3 ± 2.6 vs. 16 ± 2.6, p ≤ 0.001, LC specific GOALS 7 ± 2 vs. 5.9 ± 2.1, p ≤ 0.001, global OSATS 25.3 ± 4.3 vs. 23.5 ± 3.9, p ≤ 0.001, LC specific OSATS scores 50.8 ± 11.1 vs. 41.2 ± 9.4, p ≤ 0.001) compared to the control group. The iSurgeon group had significantly fewer intraoperative complications in total (2.7 ± 2.0 vs. 3.6 ± 2.0, p ≤ 0.001) than the control group. There was no difference in operating time (79.6 ± 25.7 vs. 84.5 ± 33.2 min, p = 0.087). CONCLUSION: Visual guidance using the telestration device with AR, iSurgeon, improves performance and lowers the complication rates in LCs in novices compared to conventional verbal expert guidance.

Circulating Epithelial Cells in Patients with Intraductal Papillary Mucinous Neoplasm of the Pancreas.

Intraductal papillary mucinous neoplasm (IPMN) is the most common pancreatic cyst and a precursor of pancreatic cancer (PDAC). Since PDAC has a devastatingly high mortality rate, the early diagnosis and treatment of any precursor lesion are rational. The safety of the existing guidelines on the clinical management of IPMN has been criticized due to unsatisfactory sensitivity and specificity, showing the need for further markers. Blood obtained from patients with IPMN was therefore subjected to size-based isolation of circulating epithelial cells (CECs). We isolated CECs and evaluated their cytological characteristics. Additionally, we compared Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in CECs and the primary IPMN tissue, since KRAS mutations are very typical for PDAC. Samples from 27 IPMN patients were analyzed. In 10 (37%) patients, CECs were isolated and showed a hybrid pattern of surface markers involving both epithelial and mesenchymal markers, suggesting a possible EMT process of the cells. Especially, patients with high-grade dysplasia in the main specimen were all CEC-positive. KRAS mutations were also present in CECs but less common than in IPMN tissue. The existence of CEC in IPMN patients offers additional blood-based research possibilities for IMPN biology.