Retroperitoneal soft tissue sarcomas: Predictive factors for incomplete resection.

INTRODUCTION: Curative management of retroperitoneal sarcoma relies on surgery, and complete monoblock resection is one of the main prognostic factors. The goal of this study was to search predictive factors for incomplete resection. METHODS: All patients undergoing surgery for retroperitoneal sarcoma in two University hospitals between 2010 and 202 were included. The main endpoint was incomplete resection (R1 ad R2) after surgery. Secondary analysis was performed where marginal R0 resection was considered as complete. Univariate and multivariable analysis of demographics, radiological, surgical and pathologic criteria were performed. Overall survival, local and distant recurrence were evaluated. RESULTS: Fifty-eight patients were included in the study. Fifty patients had incomplete resection, of which seven had marginal R0 resection. In multivariable analysis, none of the factors analyzed were associated with incomplete resection. In secondary analysis, undifferentiated liposarcoma histology (OR 12.3, 95% CI [1.416-107.303], P=0.023) was statistically significantly associated with incomplete resection. Low grade (grade I) histology was predictive of complete resection (OR 0.24, 95% CI [0.060-0.959], P=0.043). Median follow-up duration was 27 months. Local and distant recurrence rates at three years were 37% and 22.4%, respectively. CONCLUSION: In this study, we highlighted several predictive factors for incomplete resection. These factors enable us to define target populations that could most benefit from complementary therapy along with surgery.

Intermolecular Anionic Mixed-Valence and π-Dimer Complexes of ortho-Pentannulated Bisazacoronene Diimide.

This study reports the serendipitous discovery of intermolecular anionic mixed-valence (MV) and π-dimer species in ortho-pentannulated BisAzaCoroneneDiimides (BACDs) during their electrochemical reduction in a non-aqueous solvent. A library of nitrogen-containing extended PDIs was synthesized via an aza-benzannulation reaction followed by a Pd-catalysed ortho-pentannulation reaction. Ortho-pentannulated BACDs revealed strong aggregation abilities in solution. Concentration-dependent UV/Vis absorption spectra, variable temperature 1H NMR experiments, and atomic force microscopy coupled to molecular dynamics support their self-assembly into columnar aggregates. Cyclic voltammetry experiments in dichloromethane reveal prominent splitting of the first reduction wave, attributed to the formation of unprecedented intermolecular anionic MV and π-dimers in organic solvent. These species were thoroughly characterized by real-time spectroelectrochemistry, electrochemical simulations and theoretical calculations. Remarkably, this work underscores the tuneable nature of AzaBenzannulatedPerylene Diimides (AzaBPDIs) and BACDs, emphasizing their potential as a promising scaffold for designing supramolecular materials with long-range radical anion delocalization. The observation of this phenomenon provides insights into the fundamental behaviour of supramolecular organic semiconductors, thereby paving the way for the development of novel electronic devices and electron-deficient materials.

High-Resolution Mass Spectrometry for Human Exposomics: Expanding Chemical Space Coverage.

In the modern "omics" era, measurement of the human exposome is a critical missing link between genetic drivers and disease outcomes. High-resolution mass spectrometry (HRMS), routinely used in proteomics and metabolomics, has emerged as a leading technology to broadly profile chemical exposure agents and related biomolecules for accurate mass measurement, high sensitivity, rapid data acquisition, and increased resolution of chemical space. Non-targeted approaches are increasingly accessible, supporting a shift from conventional hypothesis-driven, quantitation-centric targeted analyses toward data-driven, hypothesis-generating chemical exposome-wide profiling. However, HRMS-based exposomics encounters unique challenges. New analytical and computational infrastructures are needed to expand the analysis coverage through streamlined, scalable, and harmonized workflows and data pipelines that permit longitudinal chemical exposome tracking, retrospective validation, and multi-omics integration for meaningful health-oriented inferences. In this article, we survey the literature on state-of-the-art HRMS-based technologies, review current analytical workflows and informatic pipelines, and provide an up-to-date reference on exposomic approaches for chemists, toxicologists, epidemiologists, care providers, and stakeholders in health sciences and medicine. We propose efforts to benchmark fit-for-purpose platforms for expanding coverage of chemical space, including gas/liquid chromatography-HRMS (GC-HRMS and LC-HRMS), and discuss opportunities, challenges, and strategies to advance the burgeoning field of the exposome.

Curved Nanographenes as Stoppers in a [2]Rotaxane with Two-Photon Excited Emission.

Heptagon-containing distorted nanographenes are used as stoppers for the capping of a [2]rotaxane through a Michael-type addition reaction to vinyl sulfone groups. These curved aromatics are bulky enough to prevent the disassembly of the rotaxane but also give emissive and nonlinear (two-photon absorption and emission) optical properties to the structure.

Combining Immune Checkpoint Inhibitors with Loco-Regional Treatments in Hepatocellular Carcinoma: Ready for Prime Time?

Hepatocellular carcinoma (HCC) is a disease with a poor prognosis, often diagnosed at an advanced stage. Therapeutic options have developed considerably in recent years, particularly with trans-arterial treatments. Systemic treatments have also evolved significantly, with the rise of immune checkpoint inhibitors (ICI) as first-line treatment for advanced HCC. The combination of loco-regional treatments and ICI is opening up new prospects and is the subject of numerous clinical trials. Recently, two global phase 3 trials investigating ICI-based adjuvant combinations have demonstrated improvements in recurrence-free survival or progression-free survival in patients treated with resection, ablation, or trans-arterial chemoembolization. However, mature data and overall survival results are still awaited but will be difficult to interpret. We are at the start of a new era of combinations of loco-regional treatments and immunotherapy. The identification of the best therapeutic strategies and predictive biomarkers is a crucial issue for future standards in clinical practice.

Citizen science in environmental health research: A comparison with conventional approaches and creation of a guidance tool issued from the LILAS initiative.

CONTEXT: Public interest for citizen science (CS) in environmental health is growing. The goals of environmental health research projects are diverse, as are the methods used to reach these goals. Opportunities for greater implication of the civil society and related challenges differ at each step of such projects. These methodological aspects need to be widely shared and understood by all stakeholders. The LILAS initiative (acronym for "application of citizen science approaches such as LIving LAbS to research on environmental exposures and chronic risks") aimed to 1) favor a mutual understanding of the main issues and research methods in environmental health, of their stakes for different actors, but also of the requirements, strengths and limitations of these methods and to 2) identify expected benefits and points of attention related to stronger degrees of participation as part of environmental health research projects. METHODS: The LILAS initiative gathered institutional researchers, academics and civil society representatives interested in environmental exposures. Five meetings allowed to collectively identify different types of environmental health research studies and reflect about the benefits, limitations, and methodological issues related to the introduction of growing citizen participation as part of such studies. An analytic table matrix summarizing these aspects was co-created and filled by participants, as a tool devoted to help stakeholders with the definition of future CS research projects in environmental health. RESULTS: For different fields of research (e.g.: studies for assessment of environmental exposures, interventions on these exposures, quantitative risk assessment, epidemiological studies), the matrix lists expected benefits for various stakeholders, the fundamental principles of research methods and related practical constraints, but also advantages and limitations related to the use of CS or conventional research approaches. CONCLUSION: The LILAS initiative allowed to develop a tool which provides consolidated grounds for the co-creation of research projects on environmental exposures involving CS.

Host response during unresolved urinary tract infection alters female mammary tissue homeostasis through collagen deposition and TIMP1.

Exposure to pathogens throughout a lifetime influences immunity and organ function. Here, we explore how the systemic host-response to bacterial urinary tract infection (UTI) induces tissue-specific alterations to the mammary gland. Utilizing a combination of histological tissue analysis, single cell transcriptomics, and flow cytometry, we identify that mammary tissue from UTI-bearing mice displays collagen deposition, enlarged ductal structures, ductal hyperplasia with atypical epithelial transcriptomes and altered immune composition. Bacterial cells are absent in the mammary tissue and blood of UTI-bearing mice, therefore, alterations to the distal mammary tissue are mediated by the systemic host response to local infection. Furthermore, broad spectrum antibiotic treatment resolves the infection and restores mammary cellular and tissue homeostasis. Systemically, unresolved UTI correlates with increased plasma levels of the metalloproteinase inhibitor, TIMP1, which controls extracellular matrix remodeling and neutrophil function. Treatment of nulliparous and post-lactation UTI-bearing female mice with a TIMP1 neutralizing antibody, restores mammary tissue normal homeostasis, thus providing evidence for a link between the systemic host response during UTI and mammary gland alterations.

Innovative analytical methodologies for characterizing chemical exposure with a view to next-generation risk assessment.

The chemical burden on the environment and human population is increasing. Consequently, regulatory risk assessment must keep pace to manage, reduce, and prevent adverse impacts on human and environmental health associated with hazardous chemicals. Surveillance of chemicals of known, emerging, or potential future concern, entering the environment-food-human continuum is needed to document the reality of risks posed by chemicals on ecosystem and human health from a one health perspective, feed into early warning systems and support public policies for exposure mitigation provisions and safe and sustainable by design strategies. The use of less-conventional sampling strategies and integration of full-scan, high-resolution mass spectrometry and effect-directed analysis in environmental and human monitoring programmes have the potential to enhance the screening and identification of a wider range of chemicals of known, emerging or potential future concern. Here, we outline the key needs and recommendations identified within the European Partnership for Assessment of Risks from Chemicals (PARC) project for leveraging these innovative methodologies to support the development of next-generation chemical risk assessment.

Human biomonitoring and toxicokinetics as key building blocks for next generation risk assessment.

Human health risk assessment is historically built upon animal testing, often following Organisation for Economic Co-operation and Development (OECD) test guidelines and exposure assessments. Using combinations of human relevant in vitro models, chemical analysis and computational (in silico) approaches bring advantages compared to animal studies. These include a greater focus on the human species and on molecular mechanisms and kinetics, identification of Adverse Outcome Pathways and downstream Key Events as well as the possibility of addressing susceptible populations and additional endpoints. Much of the advancement and progress made in the Next Generation Risk Assessment (NGRA) have been primarily focused on new approach methodologies (NAMs) and physiologically based kinetic (PBK) modelling without incorporating human biomonitoring (HBM). The integration of toxicokinetics (TK) and PBK modelling is an essential component of NGRA. PBK models are essential for describing in quantitative terms the TK processes with a focus on the effective dose at the expected target site. Furthermore, the need for PBK models is amplified by the increasing scientific and regulatory interest in aggregate and cumulative exposure as well as interactions of chemicals in mixtures. Since incorporating HBM data strengthens approaches and reduces uncertainties in risk assessment, here we elaborate on the integrated use of TK, PBK modelling and HBM in chemical risk assessment highlighting opportunities as well as challenges and limitations. Examples are provided where HBM and TK/PBK modelling can be used in both exposure assessment and hazard characterization shifting from external exposure and animal dose/response assays to animal-free, internal exposure-based NGRA.

Supramolecular Large Nanosheets Assembled at Air/Water Interfaces and in Solution from Amphiphilic Heptagon-Containing Nanographenes.

We report the synthesis of a new set of amphiphilic saddle-shaped heptagon-containing polycyclic aromatic hydrocarbons (PAHs) functionalized with tetraethylene glycol chains and their self-assembly into large two-dimensional (2D) polymers. An in-depth analysis of the self-assembly mechanism at the air/water interface has been carried out, and the proposed arrangement models are in good agreement with the molecular dynamics simulations. Quite remarkably, the number and disposition of the tetraethylene glycol chains significantly influence the disposition of the PAHs at the interface and conditionate their packing under pressure. For the three compounds studied, we observed three different behaviors in which the aromatic core is parallel, perpendicular, and tilted with respect to the water surface. We also show that these curved PAHs are able to self-assemble in solution into remarkably large sheets of up to 150 µm2. These results show the relationship, within a family of curved nanographenes, between the monomer configuration and their self-assembly capacity in air/water interfaces and organic-water mixtures.

Progression toward Vertebral Collapse of Vertebral Metastases Treated with Percutaneous Vertebroplasty: Rate and Risk Factors.

PURPOSE: To evaluate of the rate of and risks for progression toward collapse in vertebral metastases (VMs) treated with percutaneous vertebroplasty (PV). MATERIALS AND METHODS: A total of 151 PVs were performed in 81 patients with vertebral metastases and were retrospectively analyzed. Follow-up imaging was performed at 12 months to measure vertebral body height and to report vertebral collapse at the level of the treated vertebrae. Vertebral characteristics (spine instability neoplastic score [SINS], number of lysed cortices, and prior radiotherapy) and procedural parameters (Saliou score, cortical contact with cement, and intradiscal cement leakage) were compared between the group of patients with and without collapse of the treated vertebrae. RESULTS: Of the vertebrae treated with PV, 41 of 151 (27%) progressed toward collapse. Vertebral collapse was influenced by a high SINS (odds ratio [OR] = 1.27, P = .004), SINS value > 9 (OR = 2.96, P = .004), intradiscal cement leakage (OR = 2.18, P = .048), pre-existing spinal deformity (OR = 2.65, P = .020), and pre-existing vertebral fracture (OR = 3.93, P = .045). A high Saliou score (OR = 0.82, P = .011), more than 3 cortices in contact with the cement (OR = 0.38, P = .014), and preserved spinal alignment (OR = 0.38, P = .020) were associated with a lower incidence of collapse. CONCLUSIONS: Rate of vertebral collapse despite PV was influenced by vertebra-specific characteristics and by cement injection quality. Vertebrae with a SINS of ≤9 and with homogeneous cement filling had a lower incidence of collapse.

Scannotation: A Suspect Screening Tool for the Rapid Pre-Annotation of the Human LC-HRMS-Based Chemical Exposome.

In an increasingly chemically polluted environment, rapidly characterizing the human chemical exposome (i.e., chemical mixtures accumulating in humans) at the population scale is critical to understand its impact on health. High-resolution mass spectrometry (HRMS) profiling of complex biological matrices can theoretically provide a comprehensive picture of chemical exposures. However, annotating the detected chemical features, particularly low-abundant ones, remains a significant obstacle to implementing such approaches at a large scale. We present Scannotation (https://github.com/scannotation/Scannotation_software), an automated and user-friendly suspect screening tool for the rapid pre-annotation of HRMS preprocessed data sets. This software tool combines several MS1 chemical predictors, i.e., m/z, experimental and predicted retention times, isotopic patterns, and neutral loss patterns, to score the proximity between features and suspects, thus efficiently prioritizing tentative annotations to verify. Scannotation and MS-DIAL4 were used to annotate blood serum samples of 75 Breton adolescents. Scannotation's combination of MS1-based chemical predictors allowed us to annotate 89 chemically diverse environmental compounds with high confidence (confirmed by MS2 when available). These compounds included 62% of emerging molecules, for which no toxicological or human biomonitoring data are reported in the literature. The complementarity observed with MS-DIAL4 results demonstrates the relevance of Scannotation for the efficient pre-annotation of large-scale exposomics data sets.

High-resolution mass spectrometry identifies delayed biomarkers for improved precision in acetaminophen/paracetamol human biomonitoring.

Paracetamol/acetaminophen (N-acetyl-p-aminophenol, APAP) is a top selling analgesic used in more than 600 prescription and non-prescription pharmaceuticals. To study efficiently some of the potential undesirable effects associated with increasing APAP consumption (e.g., developmental disorders, drug-induced liver injury), there is a need to improve current APAP biomonitoring methods that are limited by APAP short half-life. Here, we demonstrate using high-resolution mass spectrometry (HRMS) in several human studies that APAP thiomethyl metabolite conjugates (S-methyl-3-thioacetaminophen sulfate and S-methyl-3-thioacetaminophen sulphoxide sulfate) are stable biomarkers with delayed excretion rates compared to conventional APAP metabolites, that could provide a more reliable history of APAP ingestion in epidemiological studies. We also show that these biomarkers could serve as relevant clinical markers to diagnose APAP acute intoxication in overdosed patients, when free APAP have nearly disappeared from blood. Using in vitro liver models (HepaRG cells and primary human hepatocytes), we then confirm that these thiomethyl metabolites are directly linked to the toxic N-acetyl-p-benzoquinone imine (NAPQI) elimination, and produced via an overlooked pathway called the thiomethyl shunt pathway. Further studies will be needed to determine whether the production of the reactive hepatotoxic NAPQI metabolites is currently underestimated in human. Nevertheless, these biomarkers could already serve to improve APAP human biomonitoring, and investigate, for instance, inter-individual variability in NAPQI production to study underlying causes involved in APAP-induced hepatotoxicity. Overall, our findings demonstrate the potential of exposomics-based HRMS approach to advance towards a better precision for human biomonitoring.

What is in the fish? Collaborative trial in suspect and non-target screening of organic micropollutants using LC- and GC-HRMS.

A collaborative trial involving 16 participants from nine European countries was conducted within the NORMAN network in efforts to harmonise suspect and non-target screening of environmental contaminants in whole fish samples of bream (Abramis brama). Participants were provided with freeze-dried, homogenised fish samples from a contaminated and a reference site, extracts (spiked and non-spiked) and reference sample preparation protocols for liquid chromatography (LC) and gas chromatography (GC) coupled to high resolution mass spectrometry (HRMS). Participants extracted fish samples using their in-house sample preparation method and/or the protocol provided. Participants correctly identified 9-69 % of spiked compounds using LC-HRMS and 20-60 % of spiked compounds using GC-HRMS. From the contaminated site, suspect screening with participants' own suspect lists led to putative identification of on average ∼145 and ∼20 unique features per participant using LC-HRMS and GC-HRMS, respectively, while non-target screening identified on average ∼42 and ∼56 unique features per participant using LC-HRMS and GC-HRMS, respectively. Within the same sub-group of sample preparation method, only a few features were identified by at least two participants in suspect screening (16 features using LC-HRMS, 0 features using GC-HRMS) and non-target screening (0 features using LC-HRMS, 2 features using GC-HRMS). The compounds identified had log octanol/water partition coefficient (KOW) values from -9.9 to 16 and mass-to-charge ratios (m/z) of 68 to 761 (LC-HRMS and GC-HRMS). A significant linear trend was found between log KOW and m/z for the GC-HRMS data. Overall, these findings indicate that differences in screening results are mainly due to the data analysis workflows used by different participants. Further work is needed to harmonise the results obtained when applying suspect and non-target screening approaches to environmental biota samples.

Efficacy and safety of cryoablation for localized renal tumor as an alternative approach to partial nephrectomy.

Introduction: Renal cryoablation displays a profile of high tolerance, including in a frail population. Cryoablation appears as a validated alternative treatment to surgery for renal tumors smaller than 4 cm. However, evidence is lacking for larger tumors, despite encouraging data for tumors up to 7 cm. Material and methods: This retrospective descriptive study of a population with a stage T1b renal tumor treated by cryoablation was conducted at the Nantes University Hospital between January 2009 and July 2021. Primary endpoint was 3-year rate of local recurrence. Secondary endpoints included technical efficacy, overall and cancer-specific survivals, and safety assessment. Results: A total of 63 patients were analyzed. Three-year rate of local recurrence was 11.1%. Primary and secondary technical efficacies were achieved in 88.9% and 96.8% of patients, respectively, and 3-year overall and cancer-specific survival were 87.3% and 95.2%, respectively. Most patients (73%) experienced no complications, 13% of patients had minor (CIRSE grades 1 or 2) adverse effects, and 13% had severe but non-lethal (CIRSE grade 3) adverse effects. One patient died following cryoablation due to colic perforation. The most common AE (all grades) was hemorrhage (9.5%). Discussion: This study showed a good efficacy and safety of cryoablation for renal tumors up to 7 cm (T1b). Our results were consistent with a rather sparse literature and contributed to guide future recommendations about cryoablation as an alternative to surgery for T1b renal tumors.

A Critical Review on the Opportunity to Use Placenta and Innovative Biomonitoring Methods to Characterize the Prenatal Chemical Exposome.

Adverse effects associated with chemical exposures during pregnancy include several developmental and reproductive disorders. However, considering the tens of thousands of chemicals present on the market, the effects of chemical mixtures on the developing fetus is still likely underestimated. In this critical review, we discuss the potential to apply innovative biomonitoring methods using high-resolution mass spectrometry (HRMS) on placenta to improve the monitoring of chemical exposure during pregnancy. The physiology of the placenta and its relevance as a matrix for monitoring chemical exposures and their effects on fetal health is first outlined. We then identify several key parameters that require further investigations before placenta can be used for large-scale monitoring in a robust manner. Most critical is the need for standardization of placental sampling. Placenta is a highly heterogeneous organ, and knowledge of the intraplacenta variability of chemical composition is required to ensure unbiased and robust interindividual comparisons. Other important variables include the time of collection, the sex of the fetus, and mode of delivery. Finally, we discuss the first applications of HRMS methods on the placenta to decipher the chemical exposome and describe how the use of placenta can complement biofluids collected on the mother or the fetus.

A computationally designed antigen eliciting broad humoral responses against SARS-CoV-2 and related sarbecoviruses.

The threat of spillovers of coronaviruses associated with the severe acute respiratory syndrome (SARS) from animals to humans necessitates vaccines that offer broader protection from sarbecoviruses. By leveraging a viral-genome-informed computational method for selecting immune-optimized and structurally engineered antigens, here we show that a single antigen based on the receptor binding domain of the spike protein of sarbecoviruses elicits broad humoral responses against SARS-CoV-1, SARS-CoV-2, WIV16 and RaTG13 in mice, rabbits and guinea pigs. When administered as a DNA immunogen or by a vector based on a modified vaccinia virus Ankara, the optimized antigen induced vaccine protection from the Delta variant of SARS-CoV-2 in mice genetically engineered to express angiotensin-converting enzyme 2 and primed by a viral-vector vaccine (AZD1222) against SARS-CoV-2. A vaccine formulation incorporating mRNA coding for the optimized antigen further validated its broad immunogenicity. Vaccines that elicit broad immune responses across subgroups of coronaviruses may counteract the threat of zoonotic spillovers of betacoronaviruses.

Endovascular Thrombectomy for Acute Iliofemoral Deep Venous Thrombosis Through a Jugular Approach with a Rotational Device.

PURPOSE: To report the effectiveness of pharmacomechanical catheter-directed thrombolysis (PCDT) in the management of acute iliofemoral deep venous thrombosis (DVT) via the jugular vein using a slow rotation and large-tip device (SRD) in a large cohort of patients. MATERIAL AND METHODS: From 2011 to 2021, 277 patients (mean age 45 years, 59.2% women) were treated in 6 centres with PCDT for ilio-fémoral DVT. PCDT was performed via the jugular vein and consisted of one session of fragmentation-fibrinolysis, aspiration and, if needed, angioplasty with stenting. The aim of PCDT was to achieve complete clearance of the venous thrombosis and to restore iliofemoral patency. Residual thrombotic load was assessed by angiography, venous patency by duplex ultrasound and clinical effectiveness by the rate of post-thrombotic syndrome (Villalta score > 4). RESULTS: All patients were treated via the jugular vein using an SRD, and all but one were treated with fibrinolysis. Angioplasty with stenting was performed in 84.1% of patients. After the procedure, the residual thrombotic load at the ilio-fémoral region was < 10% in 96.1% of patients. The rate of major complications was 1.8% (n = 5), the rate of minor complications was 4% (n = 11), and one patient died from pulmonary embolism (0.4%) At a median follow-up of 24 months, primary and secondary iliofemoral patency was 89.6% and 95.8%, respectively. The rate of PTS was 13.8% at 12 months. CONCLUSION: PCDT via the jugular vein using an SRD is an efficient treatment for acute iliofemoral DVT and results in high long-term venous patency and low PTS rates. Level of evidence Level 4, Case series.

Development and validation of core entrustable professional activities for abdominal radiology.

OBJECTIVES: To develop and validate European entrustable professional activities (EPAs) for sub-specialised hepatobiliary and gastrointestinal (HB/GI) diagnostic imaging. MATERIALS AND METHODS: Both European Society of Radiology and national curricula in HB/GI diagnostic radiology were thoroughly reviewed, resulting in preliminary EPAs drafted by a pilot group of expert radiologists in 2 different countries. Each EPA was fully described with 7 components (Specification/limitations; Potential risks of failing; Relevant domains of competence; Required experience, knowledge, skills, attitude and behaviour; Assessment information sources to assess progress and ground a summative entrustment decision; Entrustment for which level of supervision is to be reached; and Expiration date). The modified Delphi method with 3 Delphi rounds was chosen for validation. Content validity index (CVI) and median values were used for validation. RESULTS: There were 15 preliminary EPAs, some of them divided according to 2 levels: resident and fellow level. The 37 members of the Delphi group were based in 2 different European countries with a background experience of 10 represented countries. Subsequent to the first Delphi round, 6 EPAs were accepted (CVI ≥ 0.8, median ≥ 4), 6 needed major revisions (CVI 0.7-0.79, median ≥ 4), 3 were rejected (CVI < 0.7) and 1 was added. After the second Delphi round, both the 6 revised EPAs and the additional one met the validation criteria (CVI ≥ 0.8, median ≥ 4). Finally, 13 EPAs were validated during the 3rd Delphi round with an agreement percentage of 95-100%. CONCLUSION: This study creates and validates EPAs for sub-specialised HB/GI diagnostic imaging. CRITICAL RELEVANCE STATEMENT: Thirteen EPAs for sub-specialised hepatobiliary and gastrointestinal diagnostic imaging were created with a strong methodology, and as a first example set in sub-specialised diagnostic imaging, they provide a template for others to be created. KEY POINTS: • The competence-based teaching in medical studies has recently been reintroduced through EPAs. • Thirteen EPAs have been developed for hepatobiliary and gastrointestinal sub-specialised diagnostic imaging. • These EPAs were validated using a Delphi modified method and provide a template for other to be created.

Exciplex Emission and Förster Resonance Energy Transfer in Polycyclic Aromatic Hydrocarbon-Based Bischromophoric Cyclophanes and Homo[2]catenanes.

Energy transfer and exciplex emission are not only crucial photophysical processes in many living organisms but also important for the development of smart photonic materials. We report, herein, the rationally designed synthesis and characterization of two highly charged bischromophoric homo[2]catenanes and one cyclophane incorporating a combination of polycyclic aromatic hydrocarbons, i.e., anthracene, pyrene, and perylene, which are intrinsically capable of supporting energy transfer and exciplex formation. The possible coconformations of the homo[2]catenanes, on account of their dynamic behavior, have been probed by Density Functional Theory calculations. The unique photophysical properties of these exotic molecules have been explored by steady-state and time-resolved absorption and fluorescence spectroscopies. The tetracationic pyrene-perylene cyclophane system exhibits emission emanating from a highly efficient Förster resonance energy transfer (FRET) mechanism which occurs in 48 ps, while the octacationic homo[2]catenane displays a weak exciplex photoluminescence following extremely fast (<0.3 ps) exciplex formation. The in-depth fundamental understanding of these photophysical processes involved in the fluorescence of bischromophoric cyclophanes and homo[2]catenanes paves the way for their use in future bioapplications and photonic devices.