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Abstract We report the clinical case of a patient with acute myocardial infarction due to coronary stent compression as first manifestation of a large thymoma. The patient underwent a coronarography and thrombus aspiration + plain old balloon angioplasty restoring the stent patency. The mass resection was performed through left robotic‐assisted thoracic surgery (RATS), resulting in a type A thymoma pT1a, IIb Masaoka‐Koga. An uncommon presentation led to early diagnosis and treatment of a thymoma with both oncological and functional significance.

Abstract Objective The aim of this study is to describe the pre‐ and post‐operative developmental and intellectual functions in a cohort of patients who underwent surgery for drug‐resistant epilepsy (DRE) before the age of 5 years. Method We retrospectively reviewed the medical records and neurodevelopmental assessments of a cohort of 80 surgically treated pediatric patients with DRE. We included patients if they had at least one pre‐ and one post‐surgical neuropsychological assessments; 27 met the inclusion criteria. We evaluated Developmental Quotient (DQ) and Intelligence Quotient (IQ) before and after surgery. We identified two groups based on psychological evaluation outcome: Group 1, with stable or improved developmental and intellectual functions, and Group 2, experiencing developmental and intellectual loss. Results The mean age at seizure onset was 1.2 ± 1.0 years, and the mean age at surgery was 2.9 ± 1.2 years. At the last follow‐up (mean 4 years, SD ± 2), 19/27 (70%) patients were seizure‐ and drug‐free; 18/27 patients (67%) fit in Group 1, and 9/27 (33%) fit in Group 2. The mean age at surgery was 2.6 years (SD ± 1.1; range 1.2–5.1) in Group 1 and 3.4 years in Group 2 (SD ± 1.1; range 1.6–5.0). Group 1 had a lower pre‐operative DQ/IQ total score than Group 2 (median DQ/IQ respectively 82 vs 108, p = 0.05). Between pre‐ and post‐assessments, we found that in Group 1, Performance scores improved (82.7 vs 102, p = 0.001), while in Group 2, the Total and Verbal scores worsened (respectively 108 vs 75, p = 0.008, and 100 vs 76, p = 0.021). Significance Our study's results emphasize the positive impact of surgery before the age of 5 years on developmental and intellectual outcomes. Despite limitations such as a small sample size, lack of a control group, and diverse etiologies, our findings support the crucial role of early intervention in preserving or enhancing developmental and intellectual functions in young patients with DRE. Plain Language Summary This retrospective study, conducted at the Bambino Gesù Children Hospital in Italy, reports neuropsychological and developmental and/or cognitive data for children undergoing early epilepsy surgery (before the age of 5). It found that children with lower developmental or cognitive profiles gained the highest scores on post‐operative neuropsychological evaluations. This study provides information on the potential benefits of early surgery in shortening the duration of epilepsy, preventing or arresting deterioration, and enhancing plasticity and recovery.

Abstract Objective Lennox–Gastaut syndrome (LGS) is a severe form of epilepsy characterized by difficult‐to‐control seizures and cognitive dysfunction. Previous studies mainly focused on pediatric populations, and little is known about the long‐term cognitive outcome in adult patients with LGS. The objective of this study was to investigate the long‐term functional and adaptive behavior in adult patients with LGS. Methods This cross‐sectional study enrolled adult patients diagnosed with LGS according to the recently published International League Against Epilepsy (ILAE) diagnostic criteria. The adaptive behavior of participants was assessed using the Vineland Adaptive Behavior Scales, Survey Interview, Second Edition (VABS‐II). Demographic, clinical, electroencephalography (EEG), and antiseizure medication (ASM) data were also collected at different timepoints, to investigate their association with VABS‐II scores. Results The study included 38 adult patients with LGS. A low score on the Adaptive Behavior Composite Scale was found in all patients. When considering single VABS‐II domains, particularly low scores were found in daily living skills and socialization, whereas slightly higher performances were observed in communication. An earlier age at LGS diagnosis was identified as the most significant predictor of worse adaptive outcomes in adult life. At the time of study evaluation, high seizure frequency, higher EEG background slowing, and multifocal EEG epileptiform abnormalities were significantly associated with lower VABS‐II raw scores. Furthermore, in an exploratory correlation analysis with ASM regimen at the study visit, treatment with cannabidiol was associated with higher adaptive behavior scores, whereas benzodiazepine intake correlated with lower scores. Significance This study provides relevant insights into the long‐term challenges faced by adults with Lennox–Gastaut syndrome (LGS), highlighting significant impairments in adaptive behavior as well as the associated clinical and electroencephalography features. Additionally, this study provides a more specific neuropsychological profile in adults with LGS and underscores the importance of comprehensive care approaches that go beyond seizure control in this population. Plain Language Summary This study examined adults with Lennox–Gastaut syndrome (LGS), a severe type of epilepsy, to understand their long‐term abilities to perform daily tasks and adapt socially. We found that these adults have significant difficulties with daily living and social skills, although not all areas were equally affected. They performed somewhat better in communication, particularly in understanding others (receptive communication). Importantly, the younger the age at which LGS was diagnosed, the worse their outcomes were as adults. This study highlights the need for research and treatment approaches that focus not only on controlling seizures but also on improving daily life skills.

Abstract Introduction Atrial fibrillation (AF) represents the most common arrhythmia in the postoperative setting. We aimed to investigate the incidence of postoperative AF (POAF) and determine its predictors, with a specific focus on inflammation markers. Methods We performed a retrospective single tertiary center cohort study including consecutive adult patients who underwent a major surgical procedure between January 2016 and January 2020. Patients were divided into four subgroups according to the type of surgery. Results Among 53,387 included patients (79.4% male, age 64.5 ± 9.5 years), POAF occurred in 570 (1.1%) with a mean latency after surgery of 3.4 ± 2.6 days. Ninety patients died (0.17%) after a mean of 13.7 ± 8.4 days. The 28‐day arrhythmia‐free survival was lower in patients undergoing lung and cardiovascular surgery (p

Abstract The paper explores the use of the magnetic control strategy for the output power regulation of an LCC‐S compensated inductive wireless power transfer system. The magnetic control is implemented through a controlled variable inductor whose magnetization state is actively regulated by an auxiliary DC–DC converter. The principles for the design and regulation of the system are discussed, and the experimental setup for the validation of the regulation method is implemented. Several measurement results highlight the effectiveness and potential improvements of the magnetic control strategy for inductive wireless power transfer systems.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of Lentilactobacillus buchneri DSM 32651 when used as a technological additive to improve ensiling of fresh plant material. The additive is intended for use in all fresh material for all animal species at a proposed minimum concentration of 1 × 108 colony forming units (CFU)/kg fresh plant material. The bacterial species L. buchneri is considered by EFSA to be suitable for the qualified presumption of safety approach to safety assessment. The identity of the strain was established and no acquired antimicrobial resistance genes of concern were detected. Therefore, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the use of the strain as a silage additive is considered safe for all the animal species, for consumers of products from animals fed the treated silage and for the environment. Regarding user safety, the additive should be considered as a potential skin and respiratory sensitiser, and any exposure through skin and respiratory tract is considered a risk. The additive is not an eye irritant. The FEEDAP Panel concluded that the additive consisting of L. buchneri DSM 32651 at a minimum concentration of 1 × 108 CFU/kg fresh material may extend the aerobic stability of silage prepared from fresh plant material with a DM range of 28%–45%.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of the feed additive consisting of l‐arginine produced by fermentation with a genetically modified strain of Escherichia coli (CGMCC 7.401). The additive is intended to be used in feed and water for drinking for all animal species and categories. The genetic modifications introduced do not raise safety concerns. No viable cells or DNA of the production strain were detected in the final product. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive does not pose any safety concern with regard to the production strain. l‐Arginine produced with E. coli CGMCC 7.401 is safe for the target species when supplemented in appropriate amounts to the diet according to the nutritional needs of the target species. The FEEDAP Panel has concerns on the use of amino acids in water for drinking for hygienic reasons, and due to the risk of imbalances when administered simultaneously via feed and water. The use of l‐arginine produced with E. coli CGMCC 7.401 in animal nutrition is considered safe for the consumers and for the environment. The endotoxin activity of the additive does not represent a hazard for persons handling the additive. In the absence of data, the FEEDAP Panel cannot conclude on the potential of the additive to be irritant to skin and/or eyes, or to be a dermal or respiratory sensitiser. The additive l‐arginine produced with E. coli CGMCC 7.401 is regarded as an efficacious source of the essential amino acid l‐arginine for non‐ruminant species. For supplemental l‐arginine to be as efficacious in ruminants as in non‐ruminant species, it requires protection against degradation in the rumen.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of an essential oil from the flowering tops of Thymbra capitata (L.) Cav. (Spanish type origanum oil) when used as a sensory additive in feed and in water for drinking for all animal species. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive under assessment is considered safe up to the maximum use level in complete feed of 15 mg/kg for poultry species, 30 mg/kg for pigs and horses, 20 mg/kg for ruminants, 25 mg/kg for rabbits, dogs, cats and ornamental fish, and 125 mg/kg for salmonids. These conclusions were extrapolated to other physiologically related species. For any other species, the additive is safe at 15 mg/kg complete feed. The FEEDAP Panel considered that the use level in water for drinking is safe provided that the total daily intake of the additive does not exceed the daily amount that is considered safe when consumed via feed. The use of the additive in animal feed under the proposed conditions of use is safe for the consumer and the environment. Regarding user safety, the essential oil under assessment should be considered as an irritant to skin and eyes and as a dermal and respiratory sensitiser. Since T. capitata and its preparations were recognised to flavour food and its function in feed would be essentially the same as that in food, no further demonstration of efficacy was considered necessary.

Abstract Ammonium propionate is authorised as a liquid preparation of ≥ 19% ammonium propionate, ≤ 80% propionic acid and ≤ 30% water. The applicant requested for the renewal of the authorisation of ammonium propionate when used as a feed additive for all terrestrial animal species. The applicant has provided evidence that the additive in the market complies with the conditions of the authorisation. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP Panel) confirms that the use of ammonium propionate under the current authorised conditions of use is safe for the target species, the consumers and the environment. Concerning the user safety, the additive is corrosive to skin and eyes. Any exposure is considered a risk. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of tea tree oil obtained from leaves and terminal branchlets of Melaleuca alternifolia (Maiden & Betche) Cheel when used as a sensory additive for all animal species. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that tea tree oil was very unlikely to be of safety concern for long‐living and reproductive animals and is of no concern for target species for fattening at the following concentrations in complete feed: 1.1 mg/kg for chickens for fattening, 1.5 mg/kg for turkeys for fattening, 1.7 mg/kg for laying hens, 2.0 mg/kg for piglets, 2.4 mg/kg for pigs for fattening, 3.1 mg/kg for sows, 5.0 mg/kg for veal calves (milk replacer) and salmonids, 4.4 mg/kg for cattle for fattening, sheep/goats and horses, 2.9 mg/kg for dairy cows, 1.8 mg/kg for rabbits, 0.9 mg/kg for cats, 5.3 mg/kg for dogs, 6.6 for crustaceans and 15 mg/kg for ornamental fish. These conclusions were extrapolated to other physiologically related species. For any other species, the additive is very unlikely to be of safety concern at 1.1 mg/kg complete feed. No concerns for consumers and the environment were identified following the use of the additive up to the highest safe use level in feed. Regarding user safety, tea tree oil should be considered as an irritant to skin and eyes and as a dermal and respiratory sensitiser. It is classified as a reprotoxic substance (category 1B) following CLP criteria and should be handled accordingly. Since M. alternifolia and its preparations were recognised to flavour food and its function in feed would be essentially the same as that in food, no further demonstration of efficacy was considered necessary.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of Spanish sage oil from the leaves of Salvia officinalis ssp. lavandulifolia (Vahl) Gams (Spanish sage oil) when used as a sensory additive in feed and in water for drinking for all animal species. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive under assessment is considered safe up to the maximum use level of 14 mg/kg complete feed for all animal species. The FEEDAP Panel considered that the use of Spanish sage oil in water for drinking is safe provided that the total daily intake of the additive does not exceed the daily amount that is considered safe when consumed via feed. The use of Spanish sage oil in animal feed under the proposed conditions of use is safe for the consumer and the environment. Regarding user safety, the essential oil under assessment should be considered as an irritant to skin and eyes and as a dermal and respiratory sensitiser. Since the oil of the leaves of S. officinalis ssp. lavandulifolia (Vahl) Gams is recognised to flavour food and its function in feed would be essentially the same as that in food, no further demonstration of efficacy was considered necessary.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of tartrazine as sensory additive (functional group: (a) colourants: (i) substances that add or restore colour in feedingstuffs). Tartrazine is intended to be incorporated in fishing baits up to a maximum of 30 mg/kg in complementary feed in order to colour them and attract fish in freshwater (ponds, rivers), for both recreational and competitive fishing. The additive is not intended for use in aquaculture. Tartrazine is already authorised for use with cats and dogs, ornamental fish, grain‐eating ornamental birds and small rodents. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the use of tartrazine in the preparation of baits for freshwater fish under the proposed conditions of use is of no concern for the target animals. The use of tartrazine as a feed additive under the proposed conditions of use is considered safe for the consumer and the environment. Regarding the user safety, the additive should be considered a dermal and respiratory sensitiser. Inhalation and dermal exposure are considered a risk. The FEEDAP Panel could not conclude on the irritation potential of the additive. In absence of data, no conclusion can be reached on the efficacy of tartrazine in freshwater fish baits.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of l‐valine produced by fermentation with a genetically modified strain of Escherichia coli (CGMCC 22721) as a nutritional additive for all animal species. The production strain and its DNA were not detected in the final additive. Therefore, the final product does not give raise to any safety concern regarding the genetic modification of the production strain. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concludes that l‐valine produced using E. coli CGMCC 22721 is safe for the target species when supplemented in appropriate amounts to the diet according to the nutritional needs of the target species. The FEEDAP Panel has concerns on the use of amino acids in water for drinking for hygienic reasons, and due to the risk of imbalances when administered simultaneously via feed. The use of l‐valine produced using E. coli CGMCC 22721 in animal nutrition is considered safe for the consumers and for the environment. The FEEDAP Panel cannot conclude on the potential of l‐valine produced using E. coli CGMCC 22721 to irritant to the skin or eyes, a dermal or respiratory sensitiser due to the lack of data. The endotoxin activity of the additive does not represent a hazard for users handling the additive when exposed by inhalation. The additive l‐valine produced by fermentation using E. coli CGMCC 22721 is regarded as an efficacious source of the essential amino acid l‐valine for non‐ruminant nutrition. For the supplemental l‐valine to be as efficacious in ruminants as in non‐ruminant species, it requires protection against degradation in the rumen.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of a product containing endo‐1,4‐β‐xylanase (ECONASE® XT) as a zootechnical feed additive (digestibility enhancer) for pigs for fattening, laying hens and minor poultry species. ECONASE® XT is available in two liquid and three solid forms and is produced with a genetically modified strain of Trichoderma reesei (CBS 114044). The FEEDAP Panel concluded that the genetic modification of the production strain does not raise any safety concerns, and viable cells of the production strain and its DNA were not detected in the final products. The Panel also concluded that ECONASE® XT is safe for pigs for fattening, laying hens and minor poultry species at the proposed conditions of use. The use of the additive raises no safety concerns for the consumers of products derived from animals fed with the additive or for the environment. The liquid and solid forms of ECONASE® XT are non‐irritant to the skin, but only the liquid forms were confirmed as non‐irritant to the eyes and not dermal sensitisers. The Panel could not conclude on the irritation potential to the eyes and the dermal sensitisation potential for the solid forms. Due to the proteinaceous nature of the active substance, the additive is considered to be a respiratory sensitiser. The additive has the potential to be efficacious in pigs for fattening at 20,000 BXU/kg complete feed, in all laying poultry species at 12,000 BXU/kg complete feed and in minor poultry species other than laying birds at 8000 BXU/kg complete feed.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for the renewal of authorisation of a preparation containing a smoke flavouring extract for cats and dogs. The applicant provided data demonstrating that the additive currently on the market does not fully comply with the conditions of authorisation, but with newly proposed specifications based on different analytical methods. Considering that the additive under assessment contains benzofuran and styrene, for which a potential concern for genotoxicity has been identified, and that the whole mixture raises a potential concern for genotoxicity, additional data would be needed to complete the assessment. Therefore, the FEEDAP Panel is not in the position to conclude on the safety for cats and dogs. The additive is authorised for use in feed for cats and dogs, and therefore, there is no need to perform an assessment of the safety for the consumer and the environment. Regarding user safety, the additive should be considered as irritant to skin and eyes, and as a dermal and respiratory sensitiser. When handling the additive, exposure of unprotected users to potential genotoxic substances may occur. Therefore, to reduce the risk, the exposure of the users should be minimised. There was no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of Saccharomyces cerevisiae NCYC R618 as a zootechnical feed additive (functional group: gut flora stabiliser) for chickens for fattening and other poultry species for fattening and reared for laying. The additive has never been authorised. The strain under assessment S. cerevisiae (NCYC R618) qualifies for the qualified presumption of safety (QPS) and, consequently, the FEEDAP Panel concluded that the product is safe for the target species, the consumers and the environment. The FEEDAP Panel could not conclude on the skin and eye irritation or skin sensitisation potential of the additive. The additive should be considered a respiratory sensitiser. Due to the lack of sufficient data, the Panel cannot conclude on the efficacy of the additive under the proposed conditions of use.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety of the feed additive consisting of 3‐phytase produced with a genetically modified strain of Komagataella phaffii (CECT 13171). The additive is intended to be used as a zootechnical additive for poultry species, pigs for fattening and minor porcine species for fattening. In a previous opinion, the EFSA Panel on Additives and Products or Substance used in Animal Feed (FEEDAP) Panel could not conclude on the taxonomic identification of the production strain. Moreover, the presence of viable cells of the production strain in the final formulations of the product could not be excluded. Therefore, no conclusions could be drawn on the safety for the target species, consumers, users and environment. In the present submission, the applicant provided supplementary information regarding the characterisation of the production strain and the absence of its viable cells in the final product. Based on the data provided, the identification of CECT 13171 as K. phaffii was confirmed and no viable cells of the production strain were detected in the final formulations of the additive. The FEEDAP Panel concluded that the 3‐phytase produced with the genetically modified strain K. phaffii CECT 13171 does not give rise to any safety concern as regard to the production strain. Consequently, the additive, in both its liquid and solid formulations, is safe for the target species, consumers, users and environment.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for the renewal of the authorisation of fumaric acid as a technological and sensory additive (functional groups: preservative and flavouring compounds, respectively) and for a new use of the additive as a technological additive (functional group: acidity regulator) for all animal species. The applicant provided evidence that the additive currently in the market complies with the existing conditions of authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that fumaric acid remains safe under the authorised conditions of use for the terrestrial animals, consumers and the environment. However, the Panel cannot conclude on the safety for the aquatic animals under all authorised condition of use. Fumaric acid is irritant to skin, eyes and respiratory tract, and should be considered a skin and respiratory sensitiser due to the presence of nickel. The Panel also considers that the new use of the additive as an acidity regulator under proposed conditions of use would not introduce risks not already considered. There is no need to assess the efficacy of the additive in the context of the renewal of the authorisation (for its use as preservative and flavouring compound). The Panel is not in the position to conclude on the efficacy of fumaric acid as an acidity regulator in feed.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of a Camellia oleifera C.Abel seed extract (Cosap®) as technological feed additive for all animal species except fin fish. In the absence of adequate tolerance studies in the target species or toxicological studies with the additive under assessment, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) could not conclude on the safety of C. oleifera extract for the target species. The use of the additive in animal nutrition is not expected to cause concern for consumer safety. The additive is considered as irritant to the eyes and mucous membranes. No conclusions can be reached on the potential of the additive to be irritant to the skin or to be a dermal sensitiser. The use of the additive under the proposed conditions of use is considered safe for the terrestrial compartment. However, no conclusion can be reached on the safety of the additive for the environment when used in feed of aquatic animals other than fin fish. The Panel concluded that the additive has the potential to be efficacious as an emulsifier when used according to proposed conditions of use.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of lutein‐rich extract of Tagetes erecta L. as sensory additive (functional group: Colourants (ii) substances which, when fed to animals, add colours to food of animal origin) for turkeys for fattening. The additive is already authorised for use in feed for chickens for fattening and minor poultry for fattening and laying hens and minor poultry for laying. The FEEDAP Panel concluded that the use of lutein‐rich extract of T. erecta is safe for turkeys for fattening when used up to the maximum proposed use level of 80 mg total carotenoids/kg complete feed. The Panel concluded that the use of lutein‐rich extract of T. erecta in feed for turkeys for fattening under the proposed conditions of use would not be of concern for the consumer, considering also its use in other poultry for fattening and for laying hens. Regarding user safety, the lutein‐rich extract of T. erecta extract is irritant to skin and eyes and any exposure is considered a risk. The conclusions on user safety reached for the lutein‐rich extract of T. erecta would, in principle, apply to preparations made with it. The use of the additive in feed for turkeys for fattening under the proposed conditions of use is safe for the environment. The FEEDAP Panel concluded that the additive has the potential to colour the skin of turkeys for fattening at the proposed conditions of use.

Abstract Propionic acid is currently authorised as a technological additive (functional group: silage additives) for all animal species. The applicants requested for the renewal of the authorisation of propionic acid when used as a feed additive for all terrestrial animal species. The applicants have provided evidence that the additive in the market complies with the conditions of the authorisation. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP Panel) confirms that the use of propionic acid under the current authorised conditions of use is safe for the target species, the consumers and the environment. Regarding user safety, the additive is corrosive to the skin and any exposure to users is considered a risk. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of an essential oil from the fresh flowering tops of Lavandula angustifolia Mill. (lavender oil) when used as a sensory additive in feed and in water for drinking for all animal species. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive under assessment is considered safe up to the maximum proposed use levels in complete feed of 30 mg/kg for dogs and ornamental fish. For the other target species, the calculated safe concentrations were 9 mg/kg for chickens for fattening, 13 mg/kg for laying hens, 12 mg/kg for turkeys for fattening, 19 mg/kg for pigs for fattening, 16 mg/kg for piglets, 23 mg/kg for sows, 39 mg/kg for veal calves (milk replacer) and salmonids, 35 mg/kg for cattle for fattening, sheep/goats and horses, 22 mg/kg for dairy cows, 14 mg/kg for rabbits and 7 mg/kg for cats. These conclusions were extrapolated to other physiologically related species. For any other species, the additive is safe at 7 mg/kg complete feed. The use of lavender oil in water for drinking was considered safe provided that the total daily intake does not exceed the daily amount considered safe when consumed via feed. The use of lavender oil in animal feed under the proposed conditions of use is safe for the consumer and the environment. Regarding user safety, the essential oil under assessment should be considered as an irritant to skin and eyes and as a dermal and respiratory sensitiser. Since the oil of the flowering tops of L. angustifolia is recognised to flavour food and its function in feed would be essentially the same as that in food, no further demonstration of efficacy was considered necessary.

Key Clinical Message Posterior glottic lesions resembling granulomas unresponsive to conservative treatment should raise suspicion of a neoplastic condition. Although surgery is rarely recommended for arytenoid granulomas due to their high recurrence rate, histological evaluation is mandatory in cases of uncertain diagnosis. Clinicians should be aware that, although very rare, a laryngeal neuroendocrine tumor occurring in the posterior glottis can mimic the appearance of an idiopathic granuloma, presenting a diagnostic challenge.

Abstract Introduction In addition to produce biogas, the anaerobic digestion process releases a significant quantity of solid digestate (DG), a C‐rich byproduct suitable both as a soil improver and as a biosorbent of organic and inorganic pollutants. This study considered a mixed biowaste DG and two aerobic DG‐derivatives such as compost (CP) and vermicompost (VC). Materials and Methods A multianalytical approach was adopted to comprehensively characterize DG, CP and VC. Elemental composition was determined by total reflection X‐ray fluorescence (TXRF) spectroscopy; micromorphological features, surface elements and surface area were evaluated by scanning electron microscopy coupled with energy dispersive X‐ray (SEM‐EDX) technique and Brunauer–Emmett–Teller (BET) analysis; functional properties were investigated by attenuated total reflectance‐Fourier transform infrared (FTIR‐ATR) spectroscopy and Raman spectroscopy. Results TXRF analysis showed that DG had the highest K content (~8.9 g kg−1), while VC had the maximum P, S and Ca contents, and appreciable levels of essential plant micronutrients, such as Mn, Fe, Cu and Zn. SEM‐EDX technique evidenced heterogeneous surfaces and low porosity of all materials. BET analysis showed relevant specific surface areas of DG, CP and, especially, VC (~1.6 m2 g−1). FTIR‐ATR and Raman spectroscopy allowed to identify various aliphatic and aromatic functional groups of the materials and provided information on their major molecular classes, such as lignocellulosic moieties and inorganic components. The latter techniques also contributed to understand the chemical transformations of the DG after the aerobic treatments. Conclusion The overall results obtained confirmed the valuable potential of these materials in improving the physical and chemical fertility of the soil and in retaining pollutants, with consequent benefits for mantaining soil productivity and preserving ecosystem health.

Abstract Despite increasing knowledge about small extracellular vesicle (sEV) composition and functions in cell–cell communication, the mechanism behind their biogenesis remains unclear. Here, we reveal for the first time that sEV biogenesis and release into the microenvironment are tightly connected with another important organelle, Lipid Droplets (LDs). The correlation was observed in several human cancer cell lines as well as patient‐derived colorectal cancer stem cells (CR‐CSCs). Our results demonstrated that external stimuli such as radiation, pH, hypoxia or lipid‐interfering drugs, known to affect the number of LDs/cell, similarly influenced sEV secretion. Importantly, through multiple omics data, at both mRNA and protein levels, we revealed RAB5C as a potential important molecular player behind this organelle connection. Altogether, the potential to fine‐tune sEV biogenesis by targeting LDs could significantly impact the amount, cargos and properties of these sEVs, opening new clinical perspectives.

Background Higher cardiac troponin is associated with worse outcomes in patients with acute heart failure. The significance of repeat measurements over hours remains unclear. We assessed whether a repeat measurement and the Δ between measurements of high‐sensitivity cardiac troponin I (hs‐cTnI) were associated with outcomes in hypervolemic patients with acute heart failure without acute coronary syndrome. Methods and Results We analyzed 582 individuals from AKINESIS (Acute Kidney Injury Neutrophil Gelatinase‐Associated Lipocalin Evaluation of Symptomatic Heart Failure Study) with hs‐cTnI measured ≤12 hours from admission and repeated ≤6 hours thereafter. Associations between hs‐cTnI levels and their Δ with short‐term (death, intensive care unit admission, receipt of inotropes, or positive pressure ventilation during hospitalization) and long‐term (death or heart failure readmission within 1 year) outcomes were assessed. The average age was 69±13 years, 62% were men, 65% were White, 46% had coronary artery disease, and 22% had chest pain. Median hs‐cTnI levels were 27 (interquartile range [IQR], 13–62) ng/L initially and 28 (IQR, 14–68) ng/L subsequently, with a Δ of 0 [IQR, −2 to 4] ng/L over 3.4±1 hours. Only the second measurement was associated with short‐term outcomes (odds ratio, 1.14 per 2‐fold higher [95% CI, 1.02–1.28]). Both individual measurements and the Δ were associated with long‐term outcomes (hazard ratios, 1.09, 1.12, and 1.16 for first, second, and Δ, respectively). Associated risk for the first and second measurements were not constant over the year but highest early after being measured and decreased over 1 year. Conclusions Repeat measurements of hs‐cTnI over hours can identify individuals with acute heart failure without acute coronary syndrome at risk for short‐ and long‐term outcomes.

Abstract Surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) are options in severe aortic valve stenosis (AVS). Cardiovascular (CV) and cerebrovascular (CBV) control markers, derived from variability of heart period, systolic arterial pressure, mean cerebral blood velocity and mean arterial pressure, were acquired in 19 AVS patients (age: 76.8 ± 3.1 yrs, eight males) scheduled for SAVR and in 19 AVS patients (age: 79.9 + 6.5 yrs, 11 males) scheduled for TAVI before (PRE) and after intervention (POST,

Abstract Heart failure with preserved ejection fraction (HFpEF) has a high prevalence, affecting more than 50% of patients with heart failure. HFpEF is associated with multiple comorbidities, and obesity is one of the most common. A distinct phenotype has been proposed for obese patients with HFpEF. Recent data show the beneficial role of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) for weight loss in diabetic and non‐diabetic patients with obesity or overweight when given as adjunctive therapy to diet and exercise. The mechanisms of action are related to paracrine and endocrine signalling pathways within the gastrointestinal tract, pancreas, and central nervous system that delay gastric emptying, decrease appetite, augment pancreatic beta‐cell insulin secretion, and suppress pancreatic glucagon release. These drugs are therefore potentially indicated for treatment of patients with HFpEF and obesity or overweight. Efficacy and safety need to be shown by clinical trials with a first one, Semaglutide Treatment Effect in People with obesity and heart failure with preserved ejection fraction (STEP HFpEF), recently concluded. The aim of the present review is to provide the pathophysiological and pharmacological rationale for GLP‐1 RA administration to obese patients with HFpEF.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application of renewal of Levilactobacillus brevis DSM 16680 as a technological feed additive (functional group: silage additives) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing terms of the authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive remains safe for all animal species, consumers and the environment. Regarding user safety, the additive should be considered as an eye irritant and a skin and respiratory sensitiser. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Abstract Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the feed additive consisting of endo‐1,4‐beta‐xylanase (produced with Trichoderma reesei MUCL 49755) and endo‐1,3(4)‐beta‐glucanase (produced with T. reesei MUCL 49754) (AveMix® XG 10/AveMix® XG 10 L) for the renewal of its authorisation as zootechnical feed additive for pigs for fattening, minor porcine species for fattening and turkeys for fattening. The applicant declared a change in the carrier material used in AveMix® XG 10 from soybean meal to calcium carbonate + wheat flour or calcium carbonate + sepiolite. The applicant provided evidence that the additive Avemix® XG 10 with calcium carbonate + wheat flour and Avemix® XG 10 L comply with the conditions of the authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) noted that no data were submitted to support compliance of the formulation of Avemix® XG 10 with calcium carbonate + sepiolite with the conditions of the authorisation. The FEEDAP Panel concluded that both forms of the additive remain safe for pigs for fattening, minor porcine species for fattening and turkeys for fattening, consumers and the environment. Regarding the safety for the user, Avemix® XG 10 formulated with calcium carbonate + sepiolite and Avemix® XG 10 L are not irritant to skin and eyes. No conclusions on the irritation potential of Avemix® XG 10 formulated with calcium carbonate + wheat flour could be drawn. The additive in all its formulations is considered a respiratory and skin sensitiser. There was no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Abstract Sodium propionate is authorised containing at least 98.5% of sodium propionate. The applicants requested for the renewal of the authorisation of sodium propionate when used as a feed additive for all terrestrial animal species. The applicant has provided evidence that the additive in the market complies with the conditions of the authorisation. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP Panel) confirms that the use of sodium propionate under the current authorised conditions of use is safe for the target species, the consumers and the environment. Considering the user safety, the additive is corrosive to skin, eyes and respiratory tract, but is not a skin sensitiser. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Additive manufacturing technologies increasingly revolutionize current production techniques for object manufacturing. Particularly, fused deposition modeling (FDM) strongly impacts production processes by enabling the cost‐effective and efficient creation of structures with complex designs and innovative geometries. The use of conductive filaments in FDM printing is paving the way for the advancement of entirely printed sensors and circuits, although this domain is still in its early stages. In this article, the design and production of bilayer deformable pressure sensors fabricated using conductive thermoplastic polyurethane are investigated. The potential to vary the mechanical and electrical characteristics of FDM‐printed components by adjusting printing parameters is explored. The influence of different levels of material infill (20%, 50%, and 100%) and different contact geometries between layers (domes, pyramids, and cylinders) is studied. Electromechanical tests are carried out to characterize the sensor, applying pressures up to 22 kPa. The 3D‐printed pressure sensors demonstrate tunable mechanical and electrical sensitivities at different infill values, with the highest value of −6.3 kPa−1 achieved by using a pyramid layer at 100% infill. Sensor outputs registered during cyclic tests show reproducible responses with a wide range of sensitivity, paving the way for applicability in recording both static and periodic pressure changes.

Abstract The European Commission asked EFSA to update its 2011 risk assessment on tetrabromobisphenol A (TBBPA) and five derivatives in food. Neurotoxicity and carcinogenicity were considered as the critical effects of TBBPA in rodent studies. The available evidence indicates that the carcinogenicity of TBBPA occurs via non‐genotoxic mechanisms. Taking into account the new data, the CONTAM Panel considered it appropriate to set a tolerable daily intake (TDI). Based on decreased interest in social interaction in male mice, a lowest observed adverse effect level (LOAEL) of 0.2 mg/kg body weight (bw) per day was identified and selected as the reference point for the risk characterisation. Applying the default uncertainty factor of 100 for inter‐ and intraspecies variability, and a factor of 3 to extrapolate from the LOAEL to NOAEL, a TDI for TBBPA of 0.7 μg/kg bw per day was established. Around 2100 analytical results for TBBPA in food were used to estimate dietary exposure for the European population. The most important contributors to the chronic dietary LB exposure to TBBPA were fish and seafood, meat and meat products and milk and dairy products. The exposure estimates to TBBPA were all below the TDI, including those estimated for breastfed and formula‐fed infants. Accounting for the uncertainties affecting the assessment, the CONTAM Panel concluded with 90%–95% certainty that the current dietary exposure to TBBPA does not raise a health concern for any of the population groups considered. There were insufficient data on the toxicity of any of the TBBPA derivatives to derive reference points, or to allow a comparison with TBBPA that would support assignment to an assessment group for the purposes of combined risk assessment.

Abstract Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of liquid l‐lysine base produced with a genetically modified strain of Corynebacterium glutamicum as a nutritional feed additive for all animal species. The l‐lysine base liquid produced with C. glutamicum NRRL B‐67535 and NRRL B‐67439 is currently authorised as a nutritional additive for all animal species. The present application is aimed at modifying the current authorisation to include C. glutamicum NRRL B‐68248 as a production strain. The new production strain qualifies for the qualified presumption of safety approach when used for production purposes. It was unambiguously identified as C. glutamicum and was shown not to harbour acquired antimicrobial resistance determinants for antibiotics of human and veterinary importance. All the introduced sequences or mutations were considered to be safe, and no viable cells or DNA of the NRRL B‐68248 strain was detected in the final product. Therefore, the final product does not pose any safety concern associated with the production strain. l‐Lysine base produced using C. glutamicum NRRL B‐68248 does not represent a risk for the target species, the consumer or the environment. The additive was considered to be neither irritant to skin or the eyes, nor a dermal sensitiser. l‐Lysine base produced with C. glutamicum NRRL B‐68248 is considered to be an efficacious source of the essential amino acid l‐lysine for non‐ruminant animal species. For the supplemental l‐lysine to be as efficacious in ruminants as in non‐ruminant species, it would require protection against degradation in the rumen.

Abstract The European Commission asked EFSA for a risk assessment on small organoarsenic species in food. For monomethylarsonic acid MMA(V), decreased body weight resulting from diarrhoea in rats was identified as the critical endpoint and a BMDL10 of 18.2 mg MMA(V)/kg body weight (bw) per day (equivalent to 9.7 mg As/kg bw per day) was calculated as a reference point (RP). For dimethylarsinic acid DMA(V), increased incidence in urinary bladder tumours in rats was identified as the critical endpoint. A BMDL10 of 1.1 mg DMA(V)/kg bw per day (equivalent to 0.6 mg As/kg bw per day) was calculated as an RP. For other small organoarsenic species, the toxicological data are insufficient to identify critical effects and RPs, and they could not be included in the risk assessment. For both MMA(V) and DMA(V), the toxicological database is incomplete and a margin of exposure (MOE) approach was applied for risk characterisation. The highest chronic dietary exposure to DMA(V) was estimated in ‘Toddlers’, with rice and fish meat as the main contributors across population groups. For MMA(V), the highest chronic dietary exposures were estimated for high consumers of fish meat and processed/preserved fish in ‘Infants’ and ‘Elderly’ age class, respectively. For MMA(V), an MOE of ≥ 500 was identified not to raise a health concern. For MMA(V), all MOEs were well above 500 for average and high consumers and thus do not raise a health concern. For DMA(V), an MOE of 10,000 was identified as of low health concern as it is genotoxic and carcinogenic, although the mechanisms of genotoxicity and its role in carcinogenicity of DMA(V) are not fully elucidated. For DMA(V), MOEs were below 10,000 in many cases across dietary surveys and age groups, in particular for some 95th percentile exposures. The Panel considers that this would raise a health concern.

Abstract Objective Radiographs are an integral part of detecting proximal caries. The aim of this study was to evaluate the effect of contrast, brightness, noise, sharpness, and γ adjustment of digital intraoral radiographs on the diagnosis of proximal caries. Materials and methods In this in vitro study, 40 extracted teeth including 20 premolars and 20 molars with enamel lesions (white spot or dentin discoloration seen through the enamel) were mounted together in groups of eight inside the skull. Bitewing radiographic images of each dental group were obtained by a photostimulable phosphor plate sensor with exposure conditions of 8 mA, 70 kV, and 0.2 s. The images were reconstructed by the built‐in software and examined by two oral and maxillofacial radiologists in various settings of contrast, brightness, sharpness, noise, and γ. The teeth were then cut mesiodistally and the presence or absence of caries was confirmed by an oral and maxillofacial pathologist using a stereomicroscope. The data were then analyzed using the κ agreement coefficient, sensitivity, specificity, and accuracy (α = .05). Results Adjustment of brightness and contrast led to higher diagnostic performance with an accuracy of 82.5% and 83.8 (for observers 1 and 2, respectively) and 82.5% (for both observers), respectively. Noise adjustment was the least helpful approach for diagnosis of proximal dental caries among other adjustments, with an accuracy of 78.8% and 77.5% for observers 1 and 2, respectively. Conclusion Brightness and contrast setting was more efficient in improving the diagnostic potential of bitewing radiographs compared to other adjustments.

Abstract According to the CDC, both Pfizer and Moderna COVID‐19 vaccines contain nucleoside‐modified messenger RNA (mRNA) encoding the viral spike glycoprotein of severe acute respiratory syndrome caused by corona virus (SARS‐CoV‐2), administered via intramuscular injections. Despite their worldwide use, very little is known about how nucleoside modifications in mRNA sequences affect their breakdown, transcription and protein synthesis. It was hoped that resident and circulating immune cells attracted to the injection site make copies of the spike protein while the injected mRNA degrades within a few days. It was also originally estimated that recombinant spike proteins generated by mRNA vaccines would persist in the body for a few weeks. In reality, clinical studies now report that modified SARS‐CoV‐2 mRNA routinely persist up to a month from injection and can be detected in cardiac and skeletal muscle at sites of inflammation and fibrosis, while the recombinant spike protein may persist a little over half a year in blood. Vaccination with 1‐methylΨ (pseudouridine enriched) mRNA can elicit cellular immunity to peptide antigens produced by +1 ribosomal frameshifting in major histocompatibility complex‐diverse people. The translation of 1‐methylΨ mRNA using liquid chromatography tandem mass spectrometry identified nine peptides derived from the mRNA +1 frame. These products impact on off‐target host T cell immunity that include increased production of new B cell antigens with far reaching clinical consequences. As an example, a highly significant increase in heart muscle 18‐flourodeoxyglucose uptake was detected in vaccinated patients up to half a year (180 days). This review article focuses on medical biochemistry, proteomics and deutenomics principles that explain the persisting spike phenomenon in circulation with organ‐related functional damage even in asymptomatic individuals. Proline and hydroxyproline residues emerge as prominent deuterium (heavy hydrogen) binding sites in structural proteins with robust isotopic stability that resists not only enzymatic breakdown, but virtually all (non)‐enzymatic cleavage mechanisms known in chemistry.

Abstract Aims Patients with heart failure (HF) with reduced ejection fraction (EF) (HFrEF), mildly reduced EF (HFmrEF), and preserved EF (HFpEF) may all progress to advanced HF, but the impact of EF in the advanced setting is not well established. Our aim was to assess the prognostic impact of EF in patients with at least one ‘I NEED HELP’ marker for advanced HF. Methods and results Patients with HF and at least one high‐risk ‘I NEED HELP’ criterion from four centres were included in this analysis. Outcomes were assessed in patients with HFrEF (EF ≤ 40%), HFmrEF (EF 41–49%), and HFpEF (EF ≥ 50%) and with EF analysed as a continuous variable. The prognostic impact of medical therapy for HF in patients with EF 50% was also evaluated. All‐cause death was the primary endpoint, and cardiovascular death was a secondary endpoint. Among 1149 patients enrolled [mean age 75.1 ± 11.5 years, 67.3% males, 67.6% hospitalized, median follow‐up 260 days (inter‐quartile range 105–390 days)], HFrEF, HFmrEF, and HFpEF were observed in 699 (60.8%), 122 (10.6%), and 328 (28.6%) patients, and 1 year mortality was 28.3%, 26.2%, and 20.1, respectively (log‐rank P = 0.036). As compared with HFrEF patients, HFpEF patients had a lower risk of all‐cause death [adjusted hazard ratio (HRadj) 0.67, 95% confidence interval (CI) 0.48–0.94, P = 0.022], whereas no difference was noted for HFmrEF patients. After multivariable adjustment, a lower risk of all‐cause death (HRadj for 5% increase 0.94, 95% CI 0.89–0.99, P = 0.017) and cardiovascular death (HRadj for 5% increase 0.94, 95% CI 0.88–1.00, P = 0.049) was observed at higher EF values. Beta‐blockers and renin–angiotensin system inhibitors or sacubitril/valsartan were associated with lower mortality in both EF

Objective Systemic sclerosis (SSc) is an orphan disease that can lead to severe involvement of the gastrointestinal tract with a significant impact on patients' quality of life (QoL). The Mediterranean diet (MD) was consistently demonstrated to have beneficial effects on chronic diseases based on biological bases. We aimed to evaluate the adherence to the MD of Italian patients with SSc to preliminarily assess its association with gastrointestinal symptoms and other disease features, mood, and QoL. Methods In this cross‐sectional study, adherence to the MD was measured in 387 patients from four SSc Italian referral centers through the 14‐item Mediterranean Diet Adherence Screener (14‐MEDAS) questionnaire. We also registered patients’ reported outcomes related to the QoL and mood. Results Overall, an optimal adherence to MD was observed in 14.7% of patients with SSc, a moderate adherence in 71.3%, and a low adherence in 14.0%. In univariate analysis, poor adherence to the MD was associated with a more prominent depressive mood, time missed at work, and perception of more severe Raynaud's phenomenon and digital ulcers, whereas the 14‐MEDAS score inversely correlated with depression score and reflux. Conclusion In our cohort of patients with SSc, overall adherence to MD was moderate. Patients with lower adherence to MD also reported worse outcomes related to QoL and mood. Administration of the 14‐MEDAS could be a reasonable choice to assess adherence to the MD in patients with SSc. Future initiatives to study the role of MD in the management of patients with SSc are warranted.

Abstract Objective To investigate the risk factors for penile arterial insufficiency (PAI), which is a known cause of erectile dysfunction (ED). Methods Patients who attended our urology clinic complaining of ED for more than 6 months were prospectively enrolled in this study over 1‐year period. Patient consent was taken and ethical committee approval. Complete medical history and thorough general and local examination including body mass index (BMI), Peyronie's disease (PD) and penile size measurements (length and girth) were done for all of them. Laboratory tests included testosterone, lipid profile and glycated haemoglobin (HA1c). A penile duplex ultrasound study (PDU) was done for all patients after intracavernosal injection (ICI) with alprostadil. Peak systolic velocity (PSV) and end‐diastolic velocity (EDV) were measured after 15 min. Statistical analysis was done using SPSS. Results A total of 440 patients were enrolled in this analysis. The mean age was 48(23–81), and the mean BMI was 30 (18–51). Older patients had lower PSV (r = −0.361, P = 0.000) and higher EDV (r = 0.174, P = 0.001), and both correlations were highly statistically significant. Diabetics had lower PSV (r = −0.318, P = 0.000) and higher EDV (r = 0.139, P = 0.008), which were also highly statistically significant. Smokers had lower PSV (r = −0.140, P = 0.008) and higher EDV (r = 0.178, P = 0.001), which were highly statistically significant. Men with larger penises measured skin to tip had lower EDV (r = −0.119, P = 0.024), which was less significant. Interestingly, there was neither a significant correlation between BMI and PSV (0.16, P = 0.745) nor a significant correlation between testosterone and PSV (0.029, P = 0.552). Also, there was no correlation between PSV and both dyslipidaemia and penile PD. Conclusions Ageing, tobacco consumption, DM and hypertension seem to have a negative impact on penile haemodynamics, which was statistically significant. In our patients, there was no statistically significant effect on penile haemodynamics in patients with increased BMI, low testosterone or PD or according to the size of the penis.

Abstract Exposure‐response (E‐R) analyses are an integral component of understanding the benefit/risk profile of novel oncology therapeutics. These analyses are typically conducted using data from the treatment arm to characterize the relationship between drug exposure (low vs. high) and efficacy or safety outcomes. For example, outcomes of patients with lower exposure in the treatment arm (e.g., Q1) might be compared to outcomes of those with higher drug exposure (Q2, Q3, and Q4). Outcomes from the lowest exposure quartile may be also compared to the control arm to evaluate whether the Q1 subgroup derived clinical benefit. However, the sample size and the distribution of patient baseline characteristics and disease risk factors are not balanced in such a comparison (Q1 vs. control), which may bias the analysis and causal interpretation of clinical benefit in the Q1 subgroup. Herein, we report the use of case–control matching to account for this bias and better understand the E‐R relationship for avelumab in urothelial carcinoma, a PD‐L1 inhibitor approved for the treatment of several cancers. Data from JAVELIN‐100 was utilized which is a phase III study of avelumab in first‐line maintenance treatment in patients with urothelial carcinoma; this clinical study demonstrated superiority of avelumab versus best‐supportive care leading to approval in the United States, Europe, and other countries. A post hoc case‐control matching method was implemented to compare the efficacy outcome between Q1 avelumab subgroup and matched patients extracted from the control arm with similar baseline characteristics, which showed a clinically relevant difference in overall survival in favor of the Q1 avelumab subgroup. This analysis demonstrates the importance of accounting for imbalance in important baseline covariates when comparing efficacy outcomes between subgroups within the treatment arm versus the control arm.

Abstract Introduction Men who have sex with men (MSM), especially those living with HIV, are at an increased risk of anal cancer. The prevalence and incidence of its precursor, anal high‐grade squamous intraepithelial lesions (HSILs), among MSM who started antiretroviral therapy during acute HIV acquisition are yet to be explored. Methods Participants in an acute HIV acquisition cohort in Bangkok, Thailand, who agreed to take part in this study, were enrolled. All participants were diagnosed and started antiretroviral therapy during acute HIV acquisition. Human papillomavirus (HPV) genotyping and high‐resolution anoscopy, followed by anal biopsy as indicated, were done at baseline and 6‐monthly visits. Results A total of 89 MSM and four transgender women were included in the analyses. Median age at enrolment was 26 years. Baseline prevalence of histologic anal HSIL was 11.8%. With a total of 147.0 person‐years of follow‐up, the incidence of initial histologic anal HSIL was 19.7 per 100 person‐years. Factors associated with incident anal HSIL were anal HPV 16 (adjusted hazards ratio [aHR] 4.33, 95% CI 1.03–18.18), anal HPV 18/45 (aHR 6.82, 95% CI 1.57–29.51), other anal high‐risk HPV (aHR 4.23, 95% CI 1.27–14.14), syphilis infection (aHR 4.67, 95% CI 1.10–19.90) and CD4 count

Background Brugada syndrome (BrS) has been associated with sudden cardiac death in otherwise healthy subjects, and drug‐induced BrS accounts for 55% to 70% of all patients with BrS. This study aims to develop a deep convolutional neural network and evaluate its performance in recognizing and predicting BrS diagnosis. Methods and Results Consecutive patients who underwent ajmaline testing for BrS following a standardized protocol were included. ECG tracings from baseline and during ajmaline were transformed using wavelet analysis and a deep convolutional neural network was separately trained to (1) recognize and (2) predict BrS type I pattern. The resultant networks are referred to as BrS‐Net. A total of 1188 patients were included, of which 361 (30.3%) patients developed BrS type I pattern during ajmaline infusion. When trained and evaluated on ECG tracings during ajmaline, BrS‐Net recognized a BrS type I pattern with an AUC‐ROC of 0.945 (0.921–0.969) and an AUC‐PR of 0.892 (0.815–0.939). When trained and evaluated on ECG tracings at baseline, BrS‐Net predicted a BrS type I pattern during ajmaline with an AUC‐ROC of 0.805 (0.845–0.736) and an AUC‐PR of 0.605 (0.460–0.664). Conclusions BrS‐Net, a deep convolutional neural network, can identify BrS type I pattern with high performance. BrS‐Net can predict from baseline ECG the development of a BrS type I pattern after ajmaline with good performance in an unselected population.

Abstract Background Sleep disorders are often complained by cancer patients and can last years after the end of therapies, leading to different negative consequences. Non‐pharmacological strategies such as exercise interventions may be considered to counteract this phenomenon. The literature supports the beneficial effects of aerobic training (AT), while evidence on resistance training (RT) is scarce. Accordingly, our systematic review aims to investigate the potential novel effect of RT on sleep outcomes in cancer survivors. Methods The literature search was conducted on MEDLINE (Pubmed), Web of Science, Scopus, and Cochrane Central Register of Controlled Trials databases, including only randomized controlled trials (RCTs). The screening procedure was conducted using the web‐based software COVIDENCE. Sleep outcomes assessed through self‐reported questionnaires or objective sleep measurements were extracted from RCTs recruiting cancer survivors of any age and gender, on or off treatment. The risk of bias (RoB) for each study was assessed using the Cochrane RoB 2 tool for RCTs. Meta‐analytic syntheses were performed on sleep quality and insomnia. Results A total of 21 studies were included in the review. Considering the mean percentage differences of all studies combined, promising positive results were found after combined aerobic and resistance exercise program (COMB) for sleep quality (−19%) and sleep disturbance (−17.3%). The meta‐analysis results showed significant improvement for both sleep quality and insomnia (d = 0.28, SE: 0.11, Z = 2.51, p

Abstract Understanding the microscopic variability of impurities in glacier ice on a quantitative level has importance for assessing the preservation of paleoclimatic signals and enables the study of macroscopic deformational as well as dielectric ice properties. Two‐dimensional imaging via laser‐ablation‐inductively‐coupled‐plasma‐mass‐spectrometry (LA‐ICP‐MS) can provide key insight into the localization of impurities in the ice. So far, these findings are mostly qualitative and gaining quantitative insights remains challenging. Recent advances in LA‐ICP‐MS high‐resolution imaging now allow ice grains and grain boundaries to be resolved individually. These resolutions require new adequate quantification strategies and, consequently, accurate calibration with matrix‐matched standards. Here, we present three different quantification methods, which provide a high level of homogeneity at the scale of a few tens of microns and are dedicated to imaging applications of ice cores. One of the proposed methods has a second application, offering laboratory experiments to investigate the displacement of impurities by grain growth, with important future potential to study ice‐impurity interactions. Standards were analyzed to enable absolute quantification of impurities in selected ice core samples. Calibrated LA‐ICP‐MS maps indicate similar spatial distributions of impurities in all samples, while impurity levels vary distinctly: Higher concentrations were detected in glacial periods and Greenland, and lower levels in interglacial periods and samples from central Antarctica. These results are consistent with ranges from complementary meltwater analysis. Further comparison with cm‐scale melting techniques calls for a more sophisticated understanding of the ice chemistry across spatial scales, to which calibrated LA‐ICP‐MS maps now contribute quantitatively.

Key Clinical Message Neuropsychiatric symptoms, depression, and progressive mental confusion should not be overlooked as onset symptoms of multiple cerebral ischemic lesions due to cardiac embolization. Comprehensive clinical evaluation due to progressive anemia led to the diagnosis of poorly differentiated adenocarcinoma of the esophagogastric junction as cause of embolizing nonbacterial mitral endocarditis.

Abstract EFSA was asked for a scientific opinion on the risks for animal and human health related to the presence of polychlorinated naphthalenes (PCNs) in feed and food. The assessment focused on hexaCNs due to very limited data on other PCN congeners. For hexaCNs in feed, 217 analytical results were used to estimate dietary exposures for food‐producing and non‐food‐producing animals; however, a risk characterisation could not be performed because none of the toxicological studies allowed identification of reference points. The oral repeated dose toxicity studies performed in rats with a hexaCN mixture containing all 10 hexaCNs indicated that the critical target was the haematological system. A BMDL20 of 0.05 mg/kg body weight (bw) per day was identified for a considerable decrease in the platelet count. For hexaCNs in food, 2317 analytical results were used to estimate dietary exposures across dietary surveys and age groups. The highest exposure ranged from 0.91 to 29.8 pg/kg bw per day in general population and from 220 to 559 pg/kg bw per day for breast‐fed infants with the highest consumption of breast milk. Applying a margin of exposure (MOE) approach, the estimated MOEs for the high dietary exposures ranged from 1,700,000 to 55,000,000 for the general population and from 90,000 to 230,000 for breast‐fed infants with the highest consumption of breast milk. These MOEs are far above the minimum MOE of 2000 that does not raise a health concern. Taking account of the uncertainties affecting the assessment, the Panel concluded with at least 99% certainty that dietary exposure to hexaCNs does not raise a health concern for any of the population groups considered. Due to major limitations in the available data, no assessment was possible for genotoxic effects or for health risks of PCNs other than hexaCNs.