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Abstract Myocarditis is a serious cardiovascular ailment that can lead to severe consequences if not promptly treated. It is triggered by viral infections and presents symptoms such as chest pain and heart dysfunction. Early detection is crucial for successful treatment, and cardiac magnetic resonance imaging (CMR) is a valuable tool for identifying this condition. However, the detection of myocarditis using CMR images can be challenging due to low contrast, variable noise, and the presence of multiple high CMR slices per patient. To overcome these challenges, the approach proposed incorporates advanced techniques such as convolutional neural networks (CNNs), an improved differential evolution (DE) algorithm for pre‐training, and a reinforcement learning (RL)‐based model for training. Developing this method presented a significant challenge due to the imbalanced classification of the Z‐Alizadeh Sani myocarditis dataset from Omid Hospital in Tehran. To address this, the training process is framed as a sequential decision‐making process, where the agent receives higher rewards/penalties for correctly/incorrectly classifying the minority/majority class. Additionally, the authors suggest an enhanced DE algorithm to initiate the backpropagation (BP) process, overcoming the initialisation sensitivity issue of gradient‐based methods like back‐propagation during the training phase. The effectiveness of the proposed model in diagnosing myocarditis is demonstrated through experimental results based on standard performance metrics. Overall, this method shows promise in expediting the triage of CMR images for automatic screening, facilitating early detection and successful treatment of myocarditis.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, characterized by late diagnosis and poor treatment response. Surgery is the only curative approach, only available to early‐diagnosed patients. Current therapies have limited effects, cause severe toxicities, and minimally improve overall survival. Understanding of splicing machinery alterations in PDAC remains incomplete. Here, we comprehensively examined 59 splicing machinery components, uncovering dysregulation in pre‐mRNA processing factor 8 (PRPF8) and RNA‐binding motif protein X‐linked (RBMX). Their downregulated expression was linked to poor prognosis and malignancy features, including tumor stage, invasion and metastasis, and associated with poorer survival and the mutation of key PDAC genes. Experimental modulation of these splicing factors in pancreatic cancer cell lines reverted their expression to non‐tumor levels and resulted in decreased key tumor‐related features. These results provide evidence that the splicing machinery is altered in PDAC, wherein PRPF8 and RBMX emerge as candidate actionable therapeutic targets.

Abstract Counting high‐density objects quickly and accurately is a popular area of research. Crowd counting has significant social and economic value and is a major focus in artificial intelligence. Despite many advancements in this field, many of them are not widely known, especially in terms of research data. The authors proposed a three‐tier standardised dataset taxonomy (TSDT). The Taxonomy divides datasets into small‐scale, large‐scale and hyper‐scale, according to different application scenarios. This theory can help researchers make more efficient use of datasets and improve the performance of AI algorithms in specific fields. Additionally, the authors proposed a new evaluation index for the clarity of the dataset: average pixel occupied by each object (APO). This new evaluation index is more suitable for evaluating the clarity of the dataset in the object counting task than the image resolution. Moreover, the authors classified the crowd counting methods from a data‐driven perspective: multi‐scale networks, single‐column networks, multi‐column networks, multi‐task networks, attention networks and weak‐supervised networks and introduced the classic crowd counting methods of each class. The authors classified the existing 36 datasets according to the theory of three‐tier standardised dataset taxonomy and discussed and evaluated these datasets. The authors evaluated the performance of more than 100 methods in the past five years on different levels of popular datasets. Recently, progress in research on small‐scale datasets has slowed down. There are few new datasets and algorithms on small‐scale datasets. The studies focused on large or hyper‐scale datasets appear to be reaching a saturation point. The combined use of multiple approaches began to be a major research direction. The authors discussed the theoretical and practical challenges of crowd counting from the perspective of data, algorithms and computing resources. The field of crowd counting is moving towards combining multiple methods and requires fresh, targeted datasets. Despite advancements, the field still faces challenges such as handling real‐world scenarios and processing large crowds in real‐time. Researchers are exploring transfer learning to overcome the limitations of small datasets. The development of effective algorithms for crowd counting remains a challenging and important task in computer vision and AI, with many opportunities for future research.

ABSTRACT The Sierra Madre Oriental (SMO) is a significant mountain range and one of Mexico's 14 biogeographical provinces. Its delimitation has been debated. This study aims to analyze the distribution of plants, beetles, odonates, amphibians, reptiles, and mammals using an endemicity analysis to identify endemism areas and confirm the SMO's biogeographical units. Georeferenced data for 326 species distributed in the Sierra Madre Oriental were compiled using QGIS software, and an endemicity analysis (EA) was carried out with NDM‐VNDM to evaluate taxon distribution congruence in predefined grids. Different grid sizes and specific parameters were used to identify areas of endemism, with an Endemicity Index (EI) assigned to measure the consistency of these areas. Six main areas of endemism (EA) were identified: two in the northern region and four in the southern region of the SMO. These areas are supported by several taxa, except mammals, which did not significantly contribute to the identified AEs. The study suggests new boundaries within the SMO, establishing the Rio Verde as the natural barrier in the north rather than the Moctezuma River. The multi‐taxonomic analysis supports dividing the SMO into two subprovinces, proposing a new delimitation based on the distribution of species with different dispersal capacities. This new regionalization can be useful for prioritizing conservation areas and designing more effective strategies. Future research should include more distribution data of mammals and birds to strengthen these results and better define the subprovinces and biogeographical districts of the SMO.

Clinical practice guidelines (CPGs) are tools developed to support evidence-based decision making in healthcare. However, despite the availability of CPGs for the surgical management of female stress urinary incontinence (FSUI), their methodological quality has not been evaluated. The aim of this study was to assess the methodological quality of published guidelines for the surgical management of FSUI using the AGREE II tool. A systematic search of CPGs published between 2017 and 2023 was performed in databases including MEDLINE/PubMed, LILACS, Scopus, and Trip Medical Database. Data extraction and guideline selection were performed independently by two reviewers, as was the assessment using the AGREE II instrument. Of 1459 initial records, six guidelines met the eligibility criteria. The scores for each domain evaluated were as follows: scope and purpose (45.83%; SD: 22.69), stakeholder participation (30.56%; SD: 29.03), development (48.56%; SD: 30.42), presentation clarity (58.80%; SD: 22.25), applicability (24.04%; SD: 26.36), and editorial independence (44.87%; SD: 32.88). One of the six included CPGs was rated as high quality and recommended for clinical practice. Three CPGs with modifications were recommended because there were still areas that needed improvement to enhance their quality, and two CPGs were not recommended for clinical practice because the six domains evaluated scored below 60%. According to these findings, it is essential that new CPGs developed for the surgical management of FSUI adhere to greater methodological rigor to ensure that recommendations are based on the best available evidence. Furthermore, guidelines should take into account patient values and clinical expertise to improve and facilitate effective healthcare decision making.

Abstract In accordance with Article 6 of Regulation (EC) No 396/2005, the original evaluating Member State (EMS), the United Kingdom, received an application from Bayer CropScience to set an import tolerance for the non‐approved active substance ethiprole in rice. In the framework of the assessment process, the application was re‐allocated to the Netherlands and the purpose of the application was changed to only set European residue definitions and toxicological reference values for the active substance ethiprole. Based on the assessment of the available toxicological data, an acceptable daily intake of 0.002 mg/kg bw per day and an acute reference dose of 0.005 mg/kg bw were derived. The data submitted in support of the request were found to be sufficient to derive residue definitions in primary crops and in processed commodities. The residue definition for enforcement was derived as ‘ethiprole’. Adequate analytical methods for enforcement are available to control the residues of ethiprole in dry commodities at the validated LOQ of 0.002 mg/kg. A residue definition for risk assessment was derived as the ‘sum of ethiprole, ethiprole‐sulfone (RPA097973) and ethiprole‐amide (RPA112916), expressed as ethiprole’. This residue definition is applicable for foliar treatment in all primary crops, for both foliar and soil treatments in cereals crops, and is also valid for processed commodities.

Abstract Immune cells in the lungs are important for maintaining lung function. The importance of immune cells in defending against lung diseases and infections is increasingly recognized. However, a primary knowledge gaps in current studies of lung immune cells is the understanding of their subtypes and functional heterogeneity. Increasing evidence supports the existence of novel immune cell subtypes that engage in the complex crosstalk between lung‐resident immune cells, recruited immune cells, and epithelial cells. Therefore, further studies on how immune cells respond to perturbations in the pulmonary microenvironment are warranted. This review explores the processes behind the formation of the immune cell niche during lung development, and the characteristics and cell interaction modes of several major lung‐resident immune cells. It indicates that distinct lung microenvironments or inflammatory niches can mediate the formation of different cell subtypes. These findings summarize and clarify paths to identify new cell subtypes that originate from resident progenitor cells and recruited peripheral cells, which are remodeled by the pulmonary microenvironment. The development of new techniques combining transcriptome analysis and location information is essential for identifying new immune cell subtypes and their relative immune niches, as well as for uncovering the molecular mechanisms of immune cell‐mediated lung homeostasis.

Abstract Aims Compensatory mechanisms in heart failure (HF) are triggered to maintain adequate cardiac output. Among them, hyperactivation of the sympathetic nervous system (SNS) is one of the main ones and carries a worse prognosis. The pupillary reflex depends on the SNS, and we can evaluate it through pupillometry. The aim of the study was to compare the differences in pupillary reflex between patients with acute HF and controls and to analyse whether these differences in pupillary reflex may offer a new and easy prognostic factor in such patients. Methods and results We prospectively and consecutively included 107 patients admitted with decompensated HF. Quantitative pupillometry was performed with the NeuroOptics pupillometry during the first 24 h after admission and prior to discharge. The results were compared with those of a group of 100 healthy volunteers who also underwent pupillometry. The maximum baseline pupil size (MBPS) and the minimum pupil diameter (MPD) were measured. Patients with decompensated HF have a higher MBPS (3.64 ± 0.81) and higher MPD (2.60 ± 0.58) than HF patients at discharge and in the control group (P‐value = 0.01 and 0.01, respectively). Also, HF patients presented an improvement in pupillometric values at discharge [MBPS (3.47 ± 0.79) and MPD (2.51 ± 0.58)] and showed no differences compared with the control group [MBPS (3.34 ± 0.82) and MPD (2.40 ± 0.53)] (P‐value = 0.19 and 0.14, respectively). In addition, MBPS provides a good independent predictor of in‐hospital and 1 month mortality in patients admitted with HF. Six patients (5.61%) died during hospital admission, and 11 patients (10.2%) died in the first month after discharge. Also, four patients (3.74%) were readmitted within 1 month of discharge. The receiver operating characteristic (ROC) curve for predicting in‐hospital mortality through MBPS was 0.823. No patient with an MBPS

Abstract Objective This study aimed to explore the impact of co‐antiseizure medication (co‐ASM) optimization on the effectiveness and tolerability of adjunctive cenobamate (CNB) in patients with drug‐resistant epilepsy in a real‐world setting. Methods This unicentric, retrospective, observational study included adults with focal‐onset seizures who had received ≥2 previous ASMs. The main effectiveness endpoints included responder rates and seizure frequency reduction at 3, 6, and 12‐month visits. The number of co‐ASMs and defined daily dose (DDD) were analyzed at every visit. Safety endpoints included adverse drug reactions (ADRs). Results Thirty‐four patients with a median epilepsy duration of 22 years and a median of 15.5 seizures/month were analyzed. The median number of prior ASMs was 12, and the mean number of co‐ASMs was 2.9 (SD 1). There was a reduction in seizure frequency/month from baseline to the last visit (p

Abstract Objective Endovascular thrombectomy (EVT) in patients with large infarct volume remains controversial. The aim of this study is to compare clinical outcomes between EVT and medical management in acute large vessel occlusion with infarct volumes larger than 70 mL on diffusion‐weighted magnetic resonance imaging (DWI). Methods A prospective observational cohort study was conducted, including patients with anterior cerebral circulation occlusion due to ischemic stroke with infarct volumes larger than 70 mL within 24 h of onset between July 2018 and June 2023. Eligible patients were divided into two groups: the EVT group and the medical management (non‐EVT) group. The main outcomes were functional independence and mortality at 90 days. To assess clinical endpoints, we selected variables including age, NIHSS score, infarct volume, and occlusion location for 1:1 propensity score (PS) matching and PS adjustment using inverse probability of treatment weighting (IPTW). Results Among the 131 identified patients (mean [SD] age, 69.9 [13.7] years; 58 female), the median infarct volume was 123.6 mL. Of these patients, 75 (57.3%) underwent EVT. After PS adjustment, EVT was not associated with functional independence (10.9% vs. 10.9%; p = 1.000) or mortality (43.5% vs. 47.8%; p = 0.675). Additionally, after PS adjustment using IPTW, EVT was also not associated with a functional independence (15.8% vs. 13.7%; p = 0.767) or mortality (46.8% vs. 44.0%; p = 0.762). Conclusion This study provides real‐world evidence regarding infarct volumes larger than 70 mL, indicating that EVT does not provide benefits compared to medical management alone when considering age, NIHSS score, infarct volume, and occlusion location.

Abstract Myocarditis is a significant public health concern because of its potential to cause heart failure and sudden death. The standard invasive diagnostic method, endomyocardial biopsy, is typically reserved for cases with severe complications, limiting its widespread use. Conversely, non‐invasive cardiac magnetic resonance (CMR) imaging presents a promising alternative for detecting and monitoring myocarditis, because of its high signal contrast that reveals myocardial involvement. To assist medical professionals via artificial intelligence, the authors introduce generative adversarial networks ‐ multi discriminator (GAN‐MD), a deep learning model that uses binary classification to diagnose myocarditis from CMR images. Their approach employs a series of convolutional neural networks (CNNs) that extract and combine feature vectors for accurate diagnosis. The authors suggest a novel technique for improving the classification precision of CNNs. Using generative adversarial networks (GANs) to create synthetic images for data augmentation, the authors address challenges such as mode collapse and unstable training. Incorporating a reconstruction loss into the GAN loss function requires the generator to produce images reflecting the discriminator features, thus enhancing the generated images' quality to more accurately replicate authentic data patterns. Moreover, combining this loss function with other regularisation methods, such as gradient penalty, has proven to further improve the performance of diverse GAN models. A significant challenge in myocarditis diagnosis is the imbalance of classification, where one class dominates over the other. To mitigate this, the authors introduce a focal loss‐based training method that effectively trains the model on the minority class samples. The GAN‐MD approach, evaluated on the Z‐Alizadeh Sani myocarditis dataset, achieves superior results (F‐measure 86.2%; geometric mean 91.0%) compared with other deep learning models and traditional machine learning methods.

Abstract Cancer is one of the leading causes of death in the world, with radiotherapy as one of the treatment options. Radiotherapy planning starts with delineating the affected area from healthy organs, called organs at risk (OAR). A new approach to automatic OAR segmentation in the chest cavity in Computed Tomography (CT) images is presented. The proposed approach is based on the modified U‐Net architecture with the ResNet‐34 encoder, which is the baseline adopted in this work. The new two‐branch CS‐SA U‐Net architecture is proposed, which consists of two parallel U‐Net models in which self‐attention blocks with cosine similarity as query‐key similarity function (CS‐SA) blocks are inserted between the encoder and decoder, which enabled the use of consistency regularisation. The proposed solution demonstrates state‐of‐the‐art performance for the problem of OAR segmentation in CT images on the publicly available SegTHOR benchmark dataset in terms of a Dice coefficient (oesophagus—0.8714, heart—0.9516, trachea—0.9286, aorta—0.9510) and Hausdorff distance (oesophagus—0.2541, heart—0.1514, trachea—0.1722, aorta—0.1114) and significantly outperforms the baseline. The current approach is demonstrated to be viable for improving the quality of OAR segmentation for radiotherapy planning.

Abstract The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State Slovenia and co‐rapporteur Member State Slovakia for the pesticide active substance gibberellins (GA4/GA7) and the considerations as regards the inclusion of the substance in Annex IV of Regulation (EC) No 396/2005 are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of gibberellins (GA4/GA7) as a plant growth regulator on apple and pear (field use). The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported when identified.

Abstract The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State Slovenia and co‐rapporteur Member State Slovakia for the pesticide active substance gibberellic acid and the considerations as regards the inclusion of the substance in Annex IV of Regulation (EC) No 396/2005 are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative use of gibberellic acid as a plant growth regulator on seedless grapes (field use). The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported when identified.

Abstract The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State Austria and co‐rapporteur Member State Finland for the pesticide active substance fenoxaprop‐P‐ethyl are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of fenoxaprop‐P‐ethyl as a post‐emergence herbicide in wheat, durum wheat, rye, triticale and barley to control annual monocotyledonous weeds. The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified.

Abstract Simulations based on physical models of the thermosphere‐ionosphere system suggest that the ionosphere will sink as the thermosphere cools and contracts in response to increasing greenhouse gas concentrations. As a consequence, long‐term trends can be expected in ionospheric parameters such as: total electron content (TEC), the critical frequency of the F2 layer, foF2, and its peak height, hmF2. Since early 1990s, foF2 and hmF2, though to a lesser extent, have been widely analyzed to find these trends. This study shows long‐term TEC trends for the period 1999–2023 from available global International GNSS service TEC maps. Using F30, F10.7 or MgII as proxies to filter out the effect of solar EUV, the trends are negative, not only for the mean global value but also for most regions with very few exceptions. This would align with the greenhouse effect hypothesis, even though our results show higher negative trend values than expected theoretically.

Key Clinical Message Closed‐loop bowel obstruction and contained perforation secondary to acute on chronic jejunal diverticulitis is rare and should be included in the differential diagnosis of acute abdomen. The association between polymyalgia rheumatica and diverticular disease requires further research but may prompt clinicians to consider appropriate therapies in patients with both diseases. Abstract Jejunal diverticulosis is a sac‐like outpouching of the intestinal wall that can cause complications such as diverticulitis, obstruction, abscess, perforation, or fistula formation. Complicated jejunal diverticulosis may present with acute abdomen and nonspecific symptoms which can lead to misdiagnosis and delayed treatment. A 76‐year‐old male with a remote history of polymyalgia rheumatica (PMR) presented with sudden onset abdominal pain, fever, nausea, vomiting, and inability to pass flatus. Physical exam revealed a distended and diffusely tender abdomen with signs of peritonitis. Laboratory test results were significant for neutrophil‐dominant leukocytosis and elevated inflammatory markers. CT scan of the abdomen with IV contrast revealed a contained perforation and a closed‐loop small bowel obstruction in the mid‐abdomen. The patient underwent emergent exploratory laparotomy and resection of 100 cm of mid‐jejunum which was found to have numerous diverticula surrounding the closed‐loop obstruction and contained perforation. Pathology findings showed evidence of acute on chronic jejunal diverticulitis. Jejunal diverticulosis with complications may present with an acute abdomen and peritonitis. Closed‐loop bowel obstruction and contained perforation secondary to acute on chronic jejunal diverticulitis is uncommonly thought of and should be considered in the differential diagnosis. Additionally, the association between PMR and diverticular disease is notable. While the patient had a remote history but no active PMR on presentation, studies suggest a possible association between gut inflammation and rheumatologic disease. This association should prompt clinicians to consider appropriate therapies and bear in mind the potential risk for diverticular perforation if glucocorticoids are given to treat PMR. Jejunal diverticulosis with multiple complications such as closed‐loop bowel obstruction and contained perforation secondary to acute on chronic jejunal diverticulitis is rare and may present with an acute abdomen and nonspecific symptoms. Including rare pathologies as such in the differential diagnosis may prevent misdiagnosis and delayed treatment. While further investigation is needed, the association between diverticulosis and PMR is noteworthy as patients who present with both diseases would require mindful management due to the potential risk of diverticular perforation after treatment with steroids.

Abstract The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Italy, and co‐rapporteur Member State, Poland, for the pesticide active substance penoxsulam are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of penoxsulam as a herbicide on rice and chicory. The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Abstract The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State Austria for the pesticide active substance elemental iron and the considerations as regards the inclusion of the substance in Annex IV of Regulation (EC) No 396/2005 are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions were reached on the basis of the evaluation of the representative uses of elemental iron in field and greenhouses (permanent and non‐permanent structures) via granule application by spreading on all edible and non‐edible crops, ornamental plants and amenity grassland to control molluscs. The reliable endpoints, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed.

Abstract The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State, The Netherlands for the pesticide active substance bixlozone are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions were reached on the basis of the evaluation of the representative uses of bixlozone as an herbicide on winter cereals (wheat and barley), winter oilseed rape and maize via soil broadcast spray application in field. The reliable endpoints, appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified.

Abstract The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Finland, and co‐rapporteur Member State, Croatia, for the pesticide active substance amidosulfuron and the assessment of confirmatory data following the Article 12 MRL review are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of amidosulfuron as a post‐emergence herbicide on winter cereals, spring cereals, flax and grass/pasture (all field uses). The reliable end points, appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

The conservation of hydrological resources involves continuously monitoring their contamination. A multiagent system composed of autonomous surface vehicles is proposed herein to efficiently monitor the water quality. To achieve a safe control of the fleet, the fleet policy should be able to act based on measurements and fleet state. It is proposed to use local Gaussian processes and deep reinforcement learning to jointly obtain effective monitoring policies. Local Gaussian processes, unlike classical global Gaussian processes, can accurately model the information in a dissimilar spatial correlation which captures more accurately the water quality information. A deep convolutional policy is proposed, that bases the decisions on the observation on the mean and variance of this model, by means of an information gain reward. Using a double deep Q‐learning algorithm, agents are trained to minimize the estimation error in a safe manner thanks to a Consensus‐based heuristic. Simulation results indicate an improvement of up to 24% in terms of the mean absolute error with the proposed models. Also, training results with 1–3 agents indicate that our proposed approach returns 20% and 24% smaller average estimation errors for, respectively, monitoring water quality variables and monitoring algae blooms, as compared to state‐of‐the‐art approaches.

Abstract Background Epidermolysis bullosa (EB) comprises a group of rare types of genodermatoses characterized by extreme mucocutaneous fragility, leading to blistering and/or erosions, even with minimal trauma. Continuous care through wound management is an integral part of daily life for the families and individuals affected. The aim of this study was to assess the social reality and impacts on families of having minor members diagnosed with EB in Spain. Methods A qualitative methodology was employed, utilizing four focus groups entailing participation by 24 parents (19 mothers and five fathers) of minors diagnosed with EB in Spain. Results Negative impacts on the family nucleus were evident in four priority areas of analysis: sociorelational, economic‐labour, physical and psychoemotional, with significant differences observed based on the severity of the symptoms. Conclusion Impacts on the family nucleus are noticeable from birth, influencing all other daily life routines and complicating family planning and organization. There is an imperative need to enhance the availability of sociohealth resources and to adopt an interdisciplinary approach to address their biopsychosocial needs. Patient or Public Contribution The active participation of relatives of minors diagnosed with Epidermolysis Bullosa (EB) is invaluable to sociohealth professionals, legislators and researchers. A team member conducts their professional activities at DEBRA España (national patient association dedicated to enhancing the quality of life for individuals with EB and their families), actively engaging in all study phases.

Abstract The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State The Netherlands for the pesticide active substance 1‐methylcyclopropene are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council for an amendment in approval conditions. The current approval of 1‐methylcyclopropene includes the specific provision ‘Only uses as plant growth regulator for post‐harvest storage in sealable warehouse may be authorised’. The applicant AgroFresh Holding France SAS submitted, in accordance with Article 7 of Reg. (EC) 1107/2009, an application to remove this specific provision in order to allow member states to authorise the use of products containing 1‐methylcyclopropene on outdoor crops pre‐harvest. The conclusions were reached on the basis of the evaluation of the representative use(s) of 1‐methylcyclopropene as a plant growth regulator via spray application on pome fruit. The reliable endpoints, appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Abstract The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State Poland and co‐rapporteur Member State Hungary for the pesticide active substance triclopyr (variant triclopyr‐butotyl) and the assessment of applications for maximum residue levels (MRLs) are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of triclopyr (variant triclopyr‐butotyl) as a herbicide on established pasture and non‐recreational amenity grassland (field use). MRLs were assessed in rice. The reliable end points, appropriate for use in regulatory risk assessment and the proposed MRLs, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Abstract The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Belgium, and co‐rapporteur Member State, Austria, for the pesticide active substance lenacil are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of lenacil as a herbicide on sugar and fodder beet (field use). The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Abstract The conclusions of the EFSA following the peer review of the initial risk assessment carried out by the competent authority of the rapporteur Member State, Spain, for the pesticide active substance difenoconazole are reported. The context of the peer review was that requested by the European Commission following the submission and evaluation of confirmatory information with regard to the consumer risk assessment. The conclusions were reached on the basis of the evaluation of the representative uses of difenoconazole as a fungicide on pome fruit, carrot, wheat, barley, triticale, rye and oats. The reliable endpoints concluded as being appropriate for use in regulatory risk assessment, derived from the available studies and/or literature in the dossier peer reviewed, are presented. Concerns were not identified.

Abstract The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Finland, and co‐rapporteur Member State, Estonia, for the pesticide active substance mepiquat (evaluated variant mepiquat chloride) are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of mepiquat chloride as a plant growth regulator on cereals and grass (field uses). The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified.

Abstract The trade in high‐value natural resources, particularly exotic plants and animals (henceforth biocommerce), can lead to both positive and negative impacts on wild populations. The exotic plant and animal hobbies are highly organized with internal cultures that are often poorly understood by non‐members; however, understanding them is of central importance for biocommerce with both direct and indirect consequences for the conservation of wild populations. Growing international demands for exotic species leaves simple questions related to the economics of biocommerce unexplored. The long‐term success of biocommerce businesses requires constant income, meaning they obtain and retain significant market proportions. Some biocommerce products can be reproduced by hobbyists and undercut business efforts based on sustainably produced exports. We analyse a test case in Neotropical poison frogs where sustainable biocommerce is burgeoning, yet (export‐based) businesses face direct market competition from the offspring produced within the countries, which receive their exports, and therefore are forced to rely on fervent customer support. Solution: We survey customers' behaviours where we find different classes of consumers, which differ in where they place higher values within the hobby. By taking into account these different classes, we gain insights and potential solutions to promote the stability of this unique type of biocommerce.

Abstract Baroreflex activation therapy (BAT) is a possible adjuvant treatment for patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal medical therapy and may be an alternative therapy in patients with contraindications or drug intolerance. Our aim was to evaluate the efficacy and safety of BAT in patients with HFrEF. The protocol for this study was registered with PROSPERO (CRD42022349175). Searches were conducted using MEDLINE, preMedLine (via PubMed), EMBASE, Cochrane Library, Web of Science, Trip Medical Database, WHO International Clinical Trials Registry, and ClinicalTrials.gov. We included randomized controlled trials that compared the effects of BAT with pharmacological treatment. We assessed the risk of bias of each study using the Cochrane RoB2 tool and the certainty of the results using the GRADE approach. We performed a meta‐analysis of treatment effects using a fixed‐effects or random‐effects model, depending on the heterogeneity observed. Two studies were included in the meta‐analysis (HOPE4HF and BeAT‐HF). The results showed that BAT led to statistically significant improvements in New York Heart Association functional class (relative risk 2.13; 95% confidence interval [CI, 1.65 to 2.76]), quality of life (difference in means −16.97; 95% CI [−21.87 to −12.07]), 6 min walk test (difference in means 56.54; 95% CI [55.67 to 57.41]) and N‐terminal probrain natriuretic peptide (difference in means −120.02; 95% CI [−193.58 to −46.45]). The system‐ and procedure‐related complication event‐free rate varied from 85.9% to 97%. The results show that BAT is safe and improves functional class, quality of life and congestion in selected patients with HFrEF. Further studies and long‐term follow‐up are needed to assess efficacy in reducing cardiovascular events and mortality.

Abstract Background Ellis‐van Creveld syndrome (EvCS) is a chondroectodermal dysplasia caused by germline pathogenic variants in ciliary complex subunit 1 and 2 genes (EVC, EVC2) on chromosome 4p16.2. This disease has a broad phenotype, and there are few described phenotype–genotype correlations. Methods Ethical Compliance: Written informed consent was obtained from the parents. Here, we report a genetically confirmed Mexican patient with EvCS having two inherited pathogenic variants in trans in EVC2: c.[1195C>T];[2161delC]. Results This patient allowed a genotypic–phenotypic comparison with another Mexican subject who presented a more attenuated phenotype; furthermore, our patient also presented cleft palate, a rarely reported feature. Conclusion Our case shows the importance of comparing functional hemizygosity between patient's phenotypes when they share a variant, and our case also supports the association of alterations in the palate as part of the EvCS phenotype.

Abstract Macrophages regulate essential aspects of innate immunity against pathogens. In response to microbial components, macrophages activate primary and secondary inflammatory gene programs crucial for host defense. The liver X receptors (LXRα, LXRβ) are ligand‐dependent nuclear receptors that direct gene expression important for cholesterol metabolism and inflammation, but little is known about the individual roles of LXRα and LXRβ in antimicrobial responses. Here, the results demonstrate that induction of LXRα transcription by prolonged exposure to lipopolysaccharide (LPS) supports inflammatory gene expression in macrophages. LXRα transcription is induced by NF‐κB and type‐I interferon downstream of TLR4 activation. Moreover, LPS triggers a reprogramming of the LXRα cistrome that promotes cytokine and chemokine gene expression through direct LXRα binding to DNA consensus sequences within cis‐regulatory regions including enhancers. LXRα‐deficient macrophages present fewer binding of p65 NF‐κB and reduced histone H3K27 acetylation at enhancers of secondary inflammatory response genes. Mice lacking LXRα in the hematopoietic compartment show impaired responses to bacterial endotoxin in peritonitis models, exhibiting reduced neutrophil infiltration and decreased expansion and inflammatory activation of recruited F4/80lo‐MHC‐IIhi peritoneal macrophages. Together, these results uncover a previously unrecognized function for LXRα‐dependent transcriptional cis‐activation of secondary inflammatory gene expression in macrophages and the host response to microbial ligands.

Abstract The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State, Malta, for the pesticide active substance clove oil are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions for the amendment of approval were reached on the basis of the evaluation of the representative use of clove oil as a preharvest nematicide on tomatoes and cucumbers (permanent greenhouse use). The representative use evaluated for the renewal of approval of clove oil was as post‐harvest fungicide and bactericide on apples, pears and peaches (indoor uses). The reliable endpoints appropriate for use in regulatory risk assessment are presented. Endpoints not relevant to the scope of the proposed amendment of approval conditions will be addressed in the context of the renewal of approval procedure of clove oil running in parallel (AIR IV, EFSA Q‐2016‐00809). Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Abstract Relapsed/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) outcomes remain poor. A targeted cluster of differentiation (CD)33 × CD3 bispecific antibody, JNJ‐67571244, was assessed to identify the maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety and tolerability, and preliminary clinical activity in patients with r/rAML or r/rMDS. This first‐in‐human, open‐label, phase I, dose‐escalation/dose‐expansion study included patients with r/rAML or r/rMDS who were ineligible for or had exhausted standard therapeutic options. JNJ‐67571244 was administered intravenously or subcutaneously using step‐up dosing until ≥1 discontinuation condition was met. Outcomes included safety/tolerability, preliminary clinical activity, and systemic pharmacokinetics and pharmacodynamics. The study was terminated after evaluating 10 dose‐escalation cohorts (n = 68) and before starting dose‐expansion. Overall, 11 (16.2%) patients experienced ≥1 dose‐limiting toxicity; all experienced ≥1 treatment‐emergent adverse event (TEAE; treatment related: 60 [88.2%]); and 64 (94.1%) experienced ≥1 TEAE of Grade ≥3 toxicity (treatment related: 28 [41.2%]). Although some patients had temporary disease burden reductions, no responses were seen. JNJ‐67571244 administration increased multiple cytokines, which coincided with incidence of cytokine release syndrome, infusion‐related reactions, and elevated liver function tests. A prolonged step‐up strategy was tested to improve tolerability, though this approach did not prevent hepatotoxicity. T‐cell activation following treatment suggested target engagement but did not correlate with clinical activity. Safely reaching the projected exposure level for JNJ‐67571244 efficacy was not achieved, thus MTD and RP2D were not determined.

Abstract The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Ireland, and co‐rapporteur Member State, Poland, for the pesticide active substance dichlorprop‐P and the variant dichlorprop‐P‐2‐ethylhexyl and the assessment of applications for maximum residue levels (MRLs) are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. The conclusions were reached on the basis of the evaluation of the representative uses of dichlorprop‐P as a herbicide on cereals, grassland and grass seed crops and of the variant dichlorprop‐P‐2‐ethylhexyl as a plant growth regulator on citrus. MRLs were assessed in mandarin and lemon. The conclusions from 2018 were updated in 2024 following the request from the European Commission with regard to the endocrine‐disrupting properties. The reliable end points, appropriate for use in regulatory risk assessment and the proposed MRLs, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Abstract The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Spain, and co‐rapporteur Member State, the Netherlands, for the pesticide active substance quinolin‐8‐ol are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. The conclusions were reached on the basis of the evaluation of the representative use of quinolin‐8‐ol as a fungicide and bactericide against soil‐borne pathogens in tomato cultivation in permanent greenhouses applied by drip irrigation. The reliable end points, appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Abstract Aims Residual congestion at the time of hospital discharge is an important readmission risk factor, and its detection with physical examination and usual diagnostic techniques have strong limitations in overweight and obese patients. New tools like bioelectrical impedance analysis (BIA) could help to determine when euvolaemia is reached. The aim of this study was to investigate the usefulness of BIA in management of heart failure (HF) in overweight and obese patients. Methods and results Our study is a single‐centre, single‐blind, randomized controlled trial that included 48 overweight and obese patients admitted for acute HF. The study population was randomized into two arms: BIA‐guided group and standard care. Serum electrolytes, kidney function, and natriuretic peptides were followed up during their hospital stay and at 90 days after discharge. The primary endpoint was development of severe acute kidney injury (AKI) defined as an increase in serum creatinine by >0.5 mg/dL during hospitalization, and the main secondary endpoint was the reduction of N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels during hospitalization and within 90 days after discharge. The BIA‐guided group showed a remarkable lower incidence of severe AKI, although no significant differences were found (41.4% vs. 16.7%; P = 0.057). The proportion of patients who achieved levels of NT‐proBNP

Abstract Oncology treatments require continuous individual adjustment based on the measurement of multiple clinical parameters. Prediction tools exploiting the patterns present in the clinical data could be used to assist decision making and ease the burden associated to the interpretation of all these parameters. The goal of this study was to predict the evolution of patients with pancreatic cancer at their next visit using information routinely recorded in health records, providing a decision‐support system for clinicians. We selected hematological variables as the visit's clinical outcomes, under the assumption that they can be predictive of the evolution of the patient. Multivariate models based on regression trees were generated to predict next‐visit values for each of the clinical outcomes selected, based on the longitudinal clinical data as well as on molecular data sets streaming from in silico simulations of individual patient status at each visit. The models predict, with a mean prediction score (balanced accuracy) of 0.79, the evolution trends of eosinophils, leukocytes, monocytes, and platelets. Time span between visits and neutropenia were among the most common factors contributing to the predicted evolution. The inclusion of molecular variables from the systems‐biology in silico simulations provided a molecular background for the observed variations in the selected outcome variables, mostly in relation to the regulation of hematopoiesis. In spite of its limitations, this study serves as a proof of concept for the application of next‐visit prediction tools in real‐world settings, even when available data sets are small.

Abstract Aim The main aim of the present study is to examine the expectations and feelings of people awaiting lung transplantation. Background The assessment of the benefits of lung transplant should consider, among other things, the subjective perceptions of patients about the procedure, especially in relation to the context and to their values, goals and expectations. This is an issue that has not been studied in depth, especially in Spain. Design Exploratory qualitative study. Methods Data were collected through semi‐structured interviews during the period of being on the waiting list for transplantation. Thematic analysis of the data was supported by the Atlas.ti software. Results The study population comprised 16 patients awaiting lung transplant, a number sufficient to reach data saturation. Four categories were identified to describe patients' feelings and expectations: (1) reasons for undergoing the transplant, (2) expectations about life post‐transplant, (3) emotional state, and (4) relationship with the healthcare team. Conclusions Patients have high expectations of lung transplantation. They see it as offering them a second chance at life, although the future creates uncertainty. The healthcare professionals are identified as key actors, providing essential support and information throughout the various stages of the process. Future research should explore recipients' experiences of lung transplant at later stages. Relevance to clinical practice It is important to adapt care through all the lung transplant process, which is accompanied by intense and complex emotions since the beginning. Thus, providing social and psychological support from the beginning may contribute to their health status, helping them deal with all the emotions and feelings experienced, and find balance between expectations and reality. Patient or public contribution Sixteen patients awaiting lung transplant were interviewed. Interview transcripts were returned to participants to check for accuracy with their experiences.

Abstract Age‐related changes in pharmacokinetics and pharmacodynamics, multimorbidity, frailty, and cognitive impairment represent challenges for drug treatments. Moreover, older adults are commonly exposed to polypharmacy, leading to increased risk of drug interactions and related adverse events, and higher costs for the healthcare systems. Thus, the complex task of prescribing medications to older polymedicated patients encourages the use of Clinical Decision Support Systems (CDSS). This paper evaluates the CDSS miniQ for identifying potentially inappropriate prescribing in poly‐medicated older adults and assesses the usability and acceptability of the system in health care professionals, patients, and caregivers. The results of the study demonstrate that the miniQ system was useful for Primary Care physicians in significantly improving prescription, thereby reducing potentially inappropriate medication prescriptions for elderly patients. Additionally, the system was found to be beneficial for patients and their caregivers in understanding their medications, as well as usable and acceptable among healthcare professionals, patients, and caregivers, highlighting the potential to improve the prescription process and reduce errors, and enhancing the quality of care for elderly patients with polypharmacy, reducing adverse drug events, and improving medication management.

Abstract Tectonic plate motions are a prime constraint on lithosphere dynamics and on the torques acting upon plates. Researchers typically test hypotheses on the controlling torques via forward computer models, which allow accepting or rejecting hypotheses on the basis of the fit of model–output plate velocities to kinematic reconstructions. Such models typically require a significant amount of input information (e.g., tectonic boundaries, structure of the lithosphere, lateral variations of rheology, among others) to appropriately model the tectonic system, and obtain sufficiently–realistic realizations of plate motions. Alternatively, the inverse problem approach takes the difference between the plate torque–balance at two distinct moments in time. This results in an equation in which (a) torques that have not varied through time are canceled out and (b) torques that instead have varied through time are linked to the resulting plate–motion change through a term that accounts for the plate shape and the rheology of the underlying asthenosphere. This approach sacrifices the capability to describe the different individual forces/torques acting upon a plate. Instead, it focuses on determining torque temporal variations, which significantly reduces the amount of input knowledge required. In this technical note we introduce MYRIAM, an open–source software that implements such an inverse approach. MYRIAM takes plate–motion temporal changes, and outputs an estimate of the torque variation required upon a plate to generate the input kinematic change. MYRIAM is released as an open–source repository hosted at GitHub, complete with source code and executable files for Windows and Unix–based operating systems.

Abstract In compliance with Article 43 of Regulation (EC) No 396/2005, EFSA received from the European Commission in 2020 a mandate to provide its reasoned opinion on the toxicological properties and maximum residue levels (MRLs) for the benzimidazole substances carbendazim and thiophanate‐methyl. Specifically, EFSA was asked to assess whether thiophanate‐methyl or carbendazim has clastogenic potential and, in case clastogenic potential can be excluded, to derive toxicological reference values necessary for consumer risk assessment and assessment of maximum residue levels (MRLs). Although these active substances are no longer authorised within the European Union, MRLs were established by the Codex Alimentarius Commission (codex maximum residue limits; CXLs), and import tolerances are in place. Based on the assessment of the available data, toxicological reference values and MRL proposals were derived and a consumer risk assessment was carried out. Some information required by the regulatory framework was found to be missing and a possible acute risk to consumers was identified. Hence, the consumer risk assessment was considered indicative only and all MRL proposals derived by EFSA still require further consideration by risk managers. In October 2022, to ensure that MRLs derived by EFSA in its assessment of 2021 are safe for consumers also in view of endocrine‐disrupting properties, EFSA was requested to carry out a follow‐up assessment taking into account the scientific criteria for identifying endocrine disruptors (ED). Based on the outcome of the assessment, the experts agreed that the reference values are also covering the concern related to the identified hazards indicative of endocrine disruption for thiophanate‐methyl. No further considerations on the impact of the ED assessment on the current reference values were needed for carbendazim since the ED criteria are not met for this substance. Therefore, the risk assessment and the MRL recommendations derived in 2021 are confirmed.

Trans‐Saharan migrants often spend a large proportion of their annual cycle wintering in the Sahel. Advances in fieldwork and tracking technology have greatly enhanced our ability to study their ecology in these areas. Using GPS‐tracking we aimed to investigate the little known non‐breeding movements of the lesser kestrel Falco naumanni in sub‐Saharan Africa. We segment non‐breeding tracks (n = 79 tracks by 54 individuals) into staging events (131 ± 25 days per non‐breeding cycle), itinerant movements between staging sites (11 ± 10 days), and non‐directed exploratory movements (6 ± 5 days). We then describe timing and directionality of itinerant movements by male and female kestrels throughout the non‐breeding season. Regardless of sex, lesser kestrels spent on average 89% of the non‐breeding season staging at two (range = 1–4) sites in West Africa. At the end of September, kestrels arrived along a broad front throughout the northern Sahel. By December, however, they congregated into two distinct clusters in Senegal and along the Malian–Mauritanian border. The birds stayed for longer periods and showed greater daily activity in the latter areas, compared to their first and intermediate ones. Among 24 individuals tracked along multiple annual cycles, 20 individuals consistently used the Senegalese or Malian–Mauritanian cluster. The remaining four birds either used these clusters in the 2nd or 3rd year of tracking or alternated between them across different years. The eastward and westward itinerant movements of lesser kestrels during the non‐breeding season, coupled with their tendency to cluster geographically towards the end, differ from the southward movements of other insectivorous raptors in West Africa. While 31% of Spanish lesser kestrels converged in Senegal, where roosts of > 20 000 birds are known, 68% moved into the Malian‐Mauritanian border region where more groundwork is needed.

Root canal perforations are frequent but critical complications in endodontic treatments, which can pose a risk of irreversible damage to the affected tooth. These perforations typically occur during root canal preparation or endodontic post placement, presenting significant therapeutic challenges. The main objective in the management of such complications is to seal the perforation, thus preventing bacterial invasion and tooth loss. This report details the case of a 70-year-old patient with a perforation in the palatal wall of the middle root section of tooth #11. The treatment approach involved magnification techniques and the application of a bioactive material known as Biodentine. This case underscores the critical role of accurate radiographic evaluation and the use of biocompatible materials in the management of root perforations. Despite inherent challenges, proper diagnosis and planning, combined with appropriate techniques and materials, can lead to satisfactory results, effectively preserving the structure of the tooth.