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Objective: Growth differentiation factor 15 (GDF15) acts on the receptor dimer of GDNF family receptor alpha-like (GFRAL) and Rearranged during transfection (RET). While Gfral-expressing cells are known to be present in the area postrema and nucleus of the solitary tract (AP/NTS) located in the brainstem, the presence of Gfral-expressing cells in other sites within the central nervous system and peripheral tissues is not been fully addressed. Our objective was to thoroughly investigate whether GFRAL is expressed in peripheral tissues and in brain sites different from the brainstem. Methods: From Gfral:eGFP mice we collected tissue from 12 different tissues, including brain, and used single molecule in-situ hybridizations to identify cells within those tissues expressing Gfral. We then contrasted the results with human Gfral-expression by analyzing publicly available single-cell RNA sequencing data. Results: In mice we found readably detectable Gfral mRNA within the AP/NTS but not within other brain sites. Within peripheral tissues, we failed to detect any Gfral-labelled cells in the vast majority of examined tissues and when present, were extremely rare. Single cell sequencing of human tissues confirmed GFRAL-expressing cells are detectable in some sites outside the AP/NTS in an extremely sparse manner. Importantly, across the utilized methodologies, smFISH, genetic Gfral reporter mice and scRNA-Seq, we failed to detect Gfral-labelled cells with all three. Conclusions: Through highly sensitive and selective technologies we show Gfral expression is overwhelmingly restricted to the brainstem and expect that GDF15 and GFRAL-based therapies in development for cancer cachexia will specifically target AP/NTS cells.

BackgroundEnsuring access to accurate and verified information is essential for effective patient treatment and diagnosis. Although health workers rely on the internet for clinical data, there is a need for a more streamlined approach. ObjectiveThis systematic review aims to assess the current state of artificial intelligence (AI) and natural language processing (NLP) techniques in health care to identify their potential use in electronic health records and automated information searches. MethodsA search was conducted in the PubMed, Embase, ScienceDirect, Scopus, and Web of Science online databases for articles published between January 2000 and April 2023. The only inclusion criteria were (1) original research articles and studies on the application of AI-based medical clinical decision support using NLP techniques and (2) publications in English. A Critical Appraisal Skills Programme tool was used to assess the quality of the studies. ResultsThe search yielded 707 articles, from which 26 studies were included (24 original articles and 2 systematic reviews). Of the evaluated articles, 21 (81%) explained the use of NLP as a source of data collection, 18 (69%) used electronic health records as a data source, and a further 8 (31%) were based on clinical data. Only 5 (19%) of the articles showed the use of combined strategies for NLP to obtain clinical data. In total, 16 (62%) articles presented stand-alone data review algorithms. Other studies (n=9, 35%) showed that the clinical decision support system alternative was also a way of displaying the information obtained for immediate clinical use. ConclusionsThe use of NLP engines can effectively improve clinical decision systems’ accuracy, while biphasic tools combining AI algorithms and human criteria may optimize clinical diagnosis and treatment flows. Trial RegistrationPROSPERO CRD42022373386; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=373386

IntroductionExosomes produced by the protozoan parasite Leishmania (LeishEXO) are well-established drivers of virulence, though mechanisms underlying their exacerbation of experimental leishmaniasis remain elusive. Expression of Annexin A1 (ANXA1), a protein implicated in exosome-mediated pathologies and viral internalization, has been shown to correlate with cutaneous leishmaniasis severity. Given ANXA1’s regulation of myeloid cells – the canonical hosts for Leishmania – we studied the potential role of ANXA1 and its receptors FPR1/2 in exerting LeishEXO’s effects.MethodsMurine and in vitro ANXA1-/- models were used to study the generation of protective TH1 responses during experimental L. major infection with and without LeishEXO. Recruitment of inflammatory cells was assessed using a peritoneal cell recruitment assay and immunophenotyping, and production of inflammatory mediators was measured using a cytokine and chemokine array. Treatment of experimental models with FPR2 antagonist WRW4 and FPR1/2 agonist WKYMVm was used to delineate the role of the FPR/ANXA1 axis in LeishEXO-mediated hyperpathogenesis.ResultsWe established that ANXA1 deficiency prohibits LeishEXO-mediated pathogenesis and myeloid cell infection, with minimal alterations to adaptive and innate immune phenotypes. FPR2 blockade with WRW4 similarly inhibited leishmanial hyperpathogenesis, while direct activation of FPRs with WKYMVm enhanced infection and recapitulated the LeishEXO-mediated phenotype. This research describes LeishEXO’s utilization of the ANXA1/FPR axis to facilitate parasitic internalization and pathogenesis, which may be leveraged in the development of therapeutics for leishmaniasis.

PurposeRenal replacement therapy (RRT) is used in hyperammonemia to reduce the concentration of ammonia in the blood. In the case of plasma hyperosmolarity, RRT can also rapidly decrease plasma osmolarity, which may increase cerebral edema in these patients and favor the occurrence of brain herniation.MethodsWe conducted a retrospective clinical study in a tertiary care university-affiliated hospital. All patients admitted in a Pediatric Intensive Care Unit (PICU), less than 18 years old with ammonemia >150 µmol/L and who underwent RRT between January 2015 and June 2023 were included. We collected data on plasma osmolarity levels, osmolar gap and blood ammonia levels before and during RRT.ResultsEleven patients were included (10 with acute liver failure and 1 with a urea cycle disorders). Their mean age was 36.2 months. Before RRT, the median highest measured osmolarity was 320 (305–324) mOsm/L, whereas the median calculated osmolarity was 303 (293–314) mOsm/L, corresponding to an osmolar gap of 14 mOsm/L. Ammonia blood level over 400 µmol/L are significantly associated with higher plasma osmolarity (P-Value

Ocean beaches are a major recreational attraction in many coastal cities, requiring accurate visitor counts for infrastructure planning and value estimation. We developed a novel method to assess beach usage on the Gold Coast, Australia, using 507 drone surveys across 24 beaches. The surveys covered 30 km of coastline, accounting for different seasons, times of day, and environmental conditions. Two AI models were employed: one for counting people on land and in water (91–95% accuracy), and another for identifying usage types (85–92% accuracy). Using drone data, we estimated annual beach usage at 34 million people in 2022/23, with 55% on land and 45% in water—approximately double the most recent estimate from lifeguard counts, which are spatially limited and prone to human error. When applying similar restrictions as lifeguard surveys, drone data estimated 15 million visits, aligning closely with lifeguard counts (within 9%). Temporal (time of day, day of the week, season) and spatial (beach location) factors were the strongest predictors of beach usage, with additional patterns explained by weather variables. Our method, combining drones with AI, enhances the coverage, accuracy, and granularity of beach monitoring, offering a scalable, cost-effective solution for long-term usage assessment.

Agriculture in the Andean region is mainly small-scale and rainfed, especially in Peru where almost 80% of its population depends on agriculture-related activities. Climate change in addition to social factors threatens the food security of this region. The forecast of more frequent dry spells would especially affect potato crops, domesticated centuries ago in the Andes, where there remains a great genetic diversity. This study aimed to characterize the response to drought stress of 79 potato landraces traditionally grown in the Central Andes of Peru (Pasco region) as a first selection for future breeding evaluations. The used indices were mean productivity (MP), geometric mean productivity (GMP), stress tolerance (STI), stress susceptibility (SSI), and tolerance index (TOL), and a scoring methodology that integrates all of them into a single descriptor in a simple and fast way. The varied responses showed a wide genetic diversity within the assessed landraces, where at least nine of them own high resilience and productivity qualities, and many others are highly vulnerable to drought. It is recommended to complement these studies with physiological and molecular evaluations in stress situations, especially in those with tolerance qualities highlighted in this study, and thus promote the conservation of the biodiversity of this region.

Foxp3+ TREG cells have been at the focus of intense investigation for their recognized roles in preventing autoimmunity, facilitating tissue recuperation following injury, and orchestrating a tolerance to innocuous non-self-antigens. To perform these critical tasks, TREG cells undergo deep epigenetic, transcriptional, and post-transcriptional changes that allow them to adapt to conditions found in tissues both at steady-state and during inflammation. The path leading TREG cells to express these tissue-specialized phenotypes begins during thymic development, and is further driven by epigenetic and transcriptional modifications following TCR engagement and polarizing signals in the periphery. However, this process is highly regulated and requires TREG cells to adopt strategies to avoid losing their regulatory program altogether. Here, we review the origins of tissue-resident TREG cells, from their thymic and peripheral development to the transcriptional regulators involved in their tissue residency program. In addition, we discuss the distinct signalling pathways that engage the inflammatory adaptation of tissue-resident TREG cells, and how they relate to their ability to recognize tissue and pathogen-derived danger signals.

The effects of porcine circovirus type 2b (PCV2b) and porcine reproductive and respiratory syndrome virus (PRRSV) co-infection in epithelial cells of the swine respiratory tract is unknown. In the present study, the newborn pig trachea cell line NPTr-CD163, which is permissive to both viruses, was persistently infected with PCV2b and then with PRRSV. Viral replication, cell viability, cytokines’ mRNA expression, and modulation of cellular genes expression were evaluated in infected cells. In NPTr-CD163 co-infection model, PCV2b replication was enhanced while PRRSV replication was suppressed. Cell viability was significantly decreased during PCV2b single infection and co-infection compared to mock-infected and PRRSV single infected cells. However, no difference was observed in cell viability between PCV2b and PCV2b/PRRSV infected cells. The IL6, IL8 and IL10 mRNA expression was significantly higher in co-infected cells compared to PCV2b and PRRSV single infected cells. Moreover, the IFN-α/β expression was significantly reduced in co-infected cells compared to PCV2b infected cells whereas it remained higher compared to PRRSV infected cells. The differential gene expression analysis revealed that the mRNA expression level of the cellular gene DUSP1 was significantly higher in all PRRSV infection models compared to PCV2b single infected cells. Knockdown of DUSP1 expression in co-infected cells significantly reduced PCV2b replication, suggesting a role for DUSP1 in PCV2b/PRRSV pathogenesis.

Introduction Non-alcoholic fatty liver disease (NAFLD) is increasingly prevalent in obese adolescents. Increased systemic inflammation and decreased gut microbial diversity linked to obesity affect the liver and are also associated with cardiovascular diseases in adulthood. However, NAFLD and vascular alterations are reversible.Methods and analysis This pilot study evaluated the feasibility of a prospective open-label randomised controlled trial evaluating the effects of polyphenols on NAFLD and vascular parameters in obese adolescents. Children aged 12–18 years with hepatic steatosis (n=60) will be recruited. The participants will be randomised with a 1:1 allocation ratio to receive polyphenol supplementation one time per day for 8 weeks along with the clinician-prescribed treatment (group B, n=30) or to continue the prescribed treatment without taking any polyphenols (group A, n=30). The outcome measures will be collected from both the groups at day 1 before starting polyphenol supplementation, at day 60 after 8 weeks of supplementation and at day 120, that is, 60 days after supplementation. The changes in hepatic steatosis and vascular parameters will be measured using liver and vascular imaging. Furthermore, anthropometric measures, blood tests and stool samples for gut microbiome analysis will be collected. After evaluating the study’s feasibility, we hypothesise that, as a secondary outcome, compared with group A, the adolescents in group B will have improved NAFLD, vascular parameters, systemic inflammation and gut microbiome.Ethics and dissemination This study is approved by Health Canada and the hospital ethics. Participants and their parents/tutors will both provide consent. Trial results will be communicated to the collaborating gastroenterologists who follow the enrolled participants. Abstracts and scientific articles will be submitted to high-impact radiological societies and journals. ClinicalTrials.gov ID: NCT03994029. Health Canada authorisation referral number: 250 811. Protocole version 13, 2 June 2023.Trial registration number NCT03994029.

IntroductionEbola virus (EBOV) is an RNA virus of the Filoviridae family that is responsible for outbreaks of hemorrhagic fevers in primates with a lethality rate as high as 90%. EBOV primarily targets host macrophages leading to cell activation and systemic cytokine storm, and fatal infection is associated with an inhibited interferon response, and lymphopenia. The EBOV surface glycoprotein (GP) has been shown to directly induce T cell depletion and can be secreted outside the virion via extracellular vesicles (EVs), though most studies are limited to epithelial cells and underlying mechanisms remain poorly elucidated.MethodsTo assess the role of GP on EBOV-induced dysregulation of host immunity, we first utilized EBOV virus-like particles (VLPs) expressing VP40 and NP either alone (Bald-VLP) or in conjunction with GP (VLP-GP) to investigate early inflammatory responses in THP-1 macrophages and in a murine model. We then sought to decipher the role of non-classical inflammatory mediators such as EVs over the course of EBOV infection in two EBOV-infected rhesus macaques by isolating and characterizing circulatory EVs throughout disease progression using size exclusion chromatography, nanoparticle tracking-analysis, and LC-MS/MS.ResultsWhile all VLPs could induce inflammatory mediators and recruit small peritoneal macrophages, pro-inflammatory cytokine and chemokine gene expression was exacerbated by the presence of GP. Further, quantification of EVs isolated from infected rhesus macaques revealed that the concentration of vesicles peaked in circulation at the terminal stage, at which time EBOV GP could be detected in host-derived exosomes. Moreover, comparative proteomics conducted across EV populations isolated from serum at various time points before and after infection revealed differences in host-derived protein content that were most significantly pronounced at the endpoint of infection, including significant expression of mediators of TLR4 signaling.DiscussionThese results suggest a dynamic role for EVs in the modification of disease states in the context of EBOV. Overall, our work highlights the importance of viral factors, such as the GP, and host derived EVs in the inflammatory cascade and pathogenesis of EBOV, which can be collectively further exploited for novel antiviral development.

Abstract The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the initial competent authorities of the rapporteur Member State, the United Kingdom, and co‐rapporteur Member State, Ireland, for the pesticide active substance mecoprop‐P are reported. Due to the UK leaving the EU, the renewal of approval dossier on mecoprop‐P was reallocated to Ireland, as RMS. 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 mecoprop‐P as a herbicide on winter and spring wheat (including durum and spelt), barley, rye, oats and triticale. The conclusions were updated following the request from the European Commission to review the risk assessment as regards non‐dietary exposure and the endocrine‐disrupting properties of mecoprop‐P. 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.

Summary: Recent publications have explored intranasal (i.n.) adenovirus-based (Ad) vaccines as an effective strategy for SARS-CoV-2 in pre-clinical models. However, the effects of prior immunizations and infections have yet to be considered. Here, we investigate the immunomodulatory effects of Mycobacterium bovis BCG pre-immunization followed by vaccination with an S-protein-expressing i.n. Ad, termed Ad(Spike). While i.n. Ad(Spike) retains some protective effect after 6 months, a single administration of BCG-Danish prior to Ad(Spike) potentiates its ability to control viral replication of the B.1.351 SARS-CoV-2 variant within the respiratory tract. Though BCG-Danish did not affect Ad(Spike)-generated humoral immunity, it promoted the generation of cytotoxic/Th1 responses over suppressive FoxP3+ TREG cells in the lungs of infected mice. Thus, this vaccination strategy may prove useful in limiting future pandemics by potentiating the long-term efficacy of mucosal vaccines within the context of the widely distributed BCG vaccine.

Abstract The conclusions of 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 Greece for the pesticide active substance hydrolysed proteins 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 hydrolysed proteins as an insect attractant on olive tree, deciduous fruit tree, stone fruit tree, pome fruit tree, walnut tree, citrus tree, fig tree, persimmon tree, kiwi and blueberry crops. 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 EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State The Netherlands and co‐rapporteur Member State Germany for the pesticide active substance dimethomorph 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 dimethomorph as a fungicide applied via foliar spraying on field strawberry and grapevine crops and permanent greenhouse lettuce crops; via drenching on field and permanent greenhouse strawberry crops and via dripping on permanent greenhouse strawberry crops. The peer review also provided considerations on whether exposure to humans and the environment from the representative uses of dimethomorph can be considered negligible, taking into account the European Commission's draft guidance on this topic. MRLs were assessed in potatoes, other root and tuber vegetables (except radishes), stem vegetables (except celery, leeks, globe artichokes, sugar beet, cereal forage and straw). 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. The 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, the Netherlands, and co‐rapporteur Member State, the United Kingdom, for the pesticide active substance flutolanil, 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 flutolanil as a fungicide on potatoes, tulips and iris (field uses). MRLs were assessed for a potato in‐furrow treatment. 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 authorities of the rapporteur Member State, Lithuania, and co‐rapporteur Member State, Latvia, for the pesticide active substance trinexapac 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 use of trinexapac as a plant growth regulator on barley (winter and spring) and wheat (winter). MRLs were assessed in rye. The conclusions were updated with regard to the endocrine‐disrupting properties following a mandate received from the European Commission in January 2019.The reliable end points, appropriate for use in regulatory risk assessment and the proposed MRLs, are presented. The confirmatory data following the review of existing MRLs according to Article 12 of Regulation (EC) No 396/2005 were also assessed under this conclusion. 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 Latvia and co‐rapporteur Member State Slovakia for the pesticide active substance metrafenone 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 metrafenone as a fungicide on wheat, rye, triticale, oats, barley and 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 where identified.

Summary: CD4+ T cells are critical for adaptive immunity, differentiating into distinct effector and regulatory subsets. Although the transcriptional programs underlying their differentiation are known, recent research has highlighted the importance of mRNA translation in determining protein abundance. We previously conducted genome-wide analysis of translation in CD4+ T cells revealing distinct translational signatures distinguishing these subsets, identifying eIF4E as a central differentially translated transcript. As eIF4E is vital for eukaryotic translation, we examined how altered eIF4E activity affected T cell function using mice lacking eIF4E-binding proteins (BP-/-). BP-/- effector T cells showed elevated Th1 responses ex vivo and upon viral challenge with enhanced Th1 differentiation observed in vitro. This was accompanied by increased TCR activation and elevated glycolytic activity. This study highlights how regulating T cell-intrinsic eIF4E activity can influence T cell activation and differentiation, suggesting the eIF4EBP-eIF4E axis as a potential therapeutic target for controlling aberrant T cell responses.

Abstract The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State France and co‐rapporteur Member State Slovenia for the pesticide active substance sulfur 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 sulfur as a fungicide and acaricide on grapevine and cereals (wheat, barley, oat, rye, triticale). 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 authorities of the rapporteur Member State, the Netherlands and co‐rapporteur Member State, the United Kingdom, for the pesticide active substance ethephon 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 ethephon as a plant growth regulator on cereals (winter and spring barley, winter and spring wheat, winter rye, winter triticale, spelt, durum wheat). 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 authority of the rapporteur Member State, the Netherlands, for the pesticide active substance (3E)‐dec‐3‐en‐2‐one 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 post‐harvest use of (3E)‐dec‐3‐en‐2‐one on potato as a sprouting inhibitor applied by hot fogging in potato storage rooms. 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 EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State Germany and co‐rapporteur Member State the Netherlands for the pesticide active substance Cydia pomonella granulovirus (CpGV) 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 CpGV as an insecticide on pome fruit (apple, pear, quince, nashi pears, medlars), stone fruit (peach, apricot, nectarine, almond, plum trees), walnut trees (field foliar spray applications, professional and non‐professional 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.

Abstract The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State Greece and co‐rapporteur Member State France for the pesticide active substance aluminium silicate calcined (kaolin calcined) and the considerations as regards the Article 12 MRL review 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 aluminium silicate calcined (kaolin calcined) as an insect repellent via broadcast spray application on grapevine, apricot tree, almond tree, cherry tree, hazel tree, walnut tree, peach tree, apple tree, pear tree, quince tree, nashi tree, plum tree, citrus tree, lavender, lavandin and olive tree, as proposed by the applicants. 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 EFSA following the peer review of the initial risk assessment carried out by the competent authority of the rapporteur Member State Belgium, for the pesticide active substance flutianil, 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 endocrine disruption potential of the substance. The conclusions were reached on the basis of the evaluation of the representative uses of flutianil as a fungicide on grapevine and ornamental crops. Assessments not finalised, together with the missing information identified as being required by the regulatory framework, are listed.

Abstract Background The native Andean potatoes, despite their low yield, have a large diversity that is conserved by subsistence farmers in Peru, due to their culinary characteristics and other qualities. However, this diversity is threatened by the impacts of climate change, which would directly affect the food security of these people, and eventually ours. Among its qualities of resistance to pests and diseases, there could be a genetic source of resistance to late blight, one of the most damaging diseases of the potato crop in the world. In this assay, 103 native landraces collected from local farmers in the Pasco region of Peru were subjected to natural infection conditions with Phytophthora infestans to identify potential resistant landraces within them. Results The 103 landraces assessed showed a broad variety of responses and were classified as “resistant” (22%), “moderately resistant” (57%), and “susceptible landraces” (21%). A relative effect of the disease in the yield is also shown, which is already low for commercial intentions. Conclusion Within this representative sample of the native potato diversity of the Pasco region, at least 23 local varieties grown by subsistence farmers have resistance qualities against eventual late blight disease.

The freshwater shrimp genus Cryphiops Dana, 1852 has a disjunct distribution in North (Mexico) and South (Brazil, Chile) America, and is composed of only six species. The current classification of genera in the Palaemonidae is controversial, based on variable morphological characters, and still far from a clear definition. Cryphiops differs from the speciose genus Macrobrachium Spence Bate, 1868 only by the absence of the hepatic spines on the carapace. Previous studies with a limited dataset suggested the necessity to link morphology and phylogeny to create an internal rearrangement in the genus to resolve the paraphyletic status. Through a molecular phylogenetic approach, the evolutionary relationships are inferred based on four (mitochondrial and nuclear) genes, among all recognized species of Cryphiops and, in combination with a taxonomic revision, a rearrangement in the systematics of the genus is suggested. The absence of hepatic spines on the carapace, the only character used to separate the genus Cryphiops, is subjective and should be considered as a homoplasy. This implies that Cryphiops and Macrobrachium are subjective synonyms and, because the latter genus is much more diverse and widely known, with several economically important species, to avoid confusion and disturbance in nomenclatural stability and keep universality, a proposal for the priority of the older synonym (Cryphiops) to be partially suppressed in favor of maintaining the prevailing use of the younger synonym (Macrobrachium) is presented. As the species of Cryphiops should be accommodated in the genus Macrobrachium, new names to replace three preoccupied specific names that, by this action, resulted to be secondary homonyms are offered.

Two types of autoimmune hepatitis (AIH) are recognized; AIH-1 is characterized by the presence of anti-nuclear and/or anti-smooth muscle autoantibodies, while AIH-2 is associated with the presence of anti-Liver kidney microsome and/or anti-Liver Cytosol antibodies. The autoantigens targeted by AIH-2 autoantibodies are the cytochrome P450 2D6 and Formiminotransferase-cyclodeaminase for anti-LKM1 and anti-LC1 respectively. Both autoantigens are expressed in hepatocytes at higher levels than in any other cell type. Therefore, compared to AIH-1, the autoantigens targeted in AIH-2 are predominantly tissue-specific. Distinct clinical features are specific to AIH-2 compared to AIH-1, including diagnosis in younger patients (mean age 6.6 years), onset as fulminant hepatitis in very young patients (3 years of age or less), higher frequency in children than in adults and is frequently associated with extrahepatic T cell-mediated autoimmune diseases. AIH-2 is also often diagnosed in patients with primary immunodeficiency. AIH-2 is associated with specific HLA class II susceptibility alleles; DQB1*0201 is considered the main determinant of susceptibility while DRB1*07/DRB1*03 is associated with the type of autoantibody present. HLA DQB1*0201 is in strong linkage disequilibrium with both HLA DRB1*03 and DRB1*07. Interestingly, as in humans, MHC and non-MHC genes strongly influence the development of the disease in an animal model of AIH-2. Altogether, these findings suggest that AIH-2 incidence is likely dependent on specific genetic susceptibility factors combined with distinct environmental triggers.

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, Norway, and co‐rapporteur Member State, the Netherlands, for the pesticide active substance benfluralin 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 benfluralin as a herbicide on chicory and lettuce and updated following the request from Commission to review the risk assessment as regards birds and mammals and aquatic organisms. 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 conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Latvia, and co‐rapporteur Member State, Romania, for the pesticide active substance quartz sand 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 field uses of quartz sand as a game repellent on deciduous and coniferous trees (professional use and non‐professional use), orchards, ornamental shrubs and trees in forestry (professional use and non‐professional use) and seedlings of conifer and deciduous trees in forestry (professional 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. No concerns are 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, Slovenia, and co‐rapporteur Member State, Finland, for the pesticide active substance rimsulfuron 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 rimsulfuron as an herbicide on maize, potato and tomato and updated following the request to update the risk assessment of rimsulfuron in view of the renewal process under Commission Implementing Regulation (EU) No 844/2012. 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 urgent need to address the global sustainability issues that modern society is currently facing requires the development of micro and nanotechnologies, which rely largely on functional materials. Beyond studies focused solely on low-dimensional materials, broader research related to multifunctionality has shown that the major efforts to meet these criteria for new electronic, photonic, and optoelectronic concepts, particularly to achieve high-performance devices, are still challenging. By exploiting their unique properties, a comprehensive understanding of the implications of research for the synthesis and discovery of novel materials is obtained. The present article encompasses innovation research as an alternative optimization and design for sustainable energy development, bridging the scaling gap in atomically controlled growth in terms of surface heterogeneity and interfacial engineering. In addition, the corresponding research topics are widely regarded as a scientometric analysis and visualization for the evaluation of scientific contributions into the early 20 years of the 21st century. In this perspective, a brief overview of the global trends and current challenges toward high-throughput fabrication followed by a scenario-based future for hybrid integration and emerging structural standards of scalable control design and growth profiles are emphasized. Finally, these opportunities are unprecedented to overcome current limitations, creating numerous combinations and triggering new functionalities and unparalleled properties for disruptive innovations of Frontier technologies.

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 States, the United Kingdom (former) and France (after withdrawal of the United Kingdom from the EU), for the pesticide active substance isoflucypram. 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 use of isoflucypram as a fungicide on wheat, rye, triticale, barley and oats (field use). 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 EFSA following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State Czech Republic for the pesticide active substance limestone powder (calcium carbonate) 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 use of limestone powder in paste form as a repellent in forest plantations and forest tree nurseries (field uses). The reliable endpoints, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. No concerns are 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, France, and co‐rapporteur Member State, Denmark, for the pesticide active substance triflusulfuron‐methyl 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 triflusulfuron‐methyl as a herbicide on sugar beet, fodder beet, red beet, chicory and witloof (field uses). The peer review also provided considerations on whether exposure to humans and the environment from the representative uses of triflusulfuron‐methyl can be considered negligible, taking into account the European Commission’s draft guidance on this topic. 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. An evaluation of data concerning the necessity of triflusulfuron‐methyl as herbicide to control a serious danger to plant health which cannot be contained by other available means, including non‐chemical methods is also presented.

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, Italy, and co‐rapporteur Member State, France, for the pesticide active substance oxamyl 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 oxamyl as a nematicide on potato and tobacco (field use), on tomato (permanent greenhouse), on cucurbits (edible and inedible peel), pepper, aubergine and plants nurseries of the above‐mentioned crops on soil bed preparation (permanent greenhouse). 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 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, Ireland, and co‐rapporteur Member State, Portugal, for the pesticide active substance aluminium ammonium sulfate 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 aluminium ammonium sulfate as a repellent on row crops (salad, brassica, carrots and other vegetable crops), combinable crops (grains, pulses and oilseed rape), grassland (primarily amenity and sports turf), orchards and forestry, amenity and ornamentals including use on hard surfaces. The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework and assessments not finalised are 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, France, for the pesticide active substance Trichoderma atroviride strain AT10 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 use of Trichoderma atroviride strain AT10 as a fungicide on lettuce (field use). 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 Background Evaluation of renal replacement therapy with haemodialysis is essential for its improvement. Remarkably, outcomes vary across centres. In addition, the methods used have important epistemological limitations, such as ignoring significant features (e.g., quality of life) or no relevance given to the patient’s perspective in the indicator’s selection. The present study aimed to determine the opinions and preferences of stakeholders (patients, clinicians, and managers) and establish their relative importance, considering the complexity of their interactions, to facilitate a comprehensive evaluation of haemodialysis centres. Methods Successive working groups (WGs) were established using a multicriteria methodology. WG1 created a draft of criteria and sub-criteria, WG2 agreed, using a qualitative structured analysis with pre-established criteria, and WG3 was composed of three face-to-face subgroups (WG3-A, WG3-B, and WG3-C) that weighted them using two methodologies: weighted sum (WS) and analytic hierarchy process (AHP). Subsequently, they determined a preference for the WS or AHP results. Finally, via the Internet, WG4 weighted the criteria and sub-criteria by the method preferred by WG3, and WG5 analysed the results. Results WG1 and WG2 identified and agreed on the following evaluation criteria: evidence-based variables (EBVs), annual morbidity, annual mortality, patient-reported outcome measures (PROMs), and patient-reported experience measures (PREMs). The EBVs consisted of five sub-criteria: type of vascular access, dialysis dose, haemoglobin concentration, ratio of catheter bacteraemia, and bone mineral disease. The patients rated the PROMs with greater weight than the other stakeholders in both face-to-face WG3 (WS and AHP) and WG4 via the Internet. The type of vascular access was the most valued sub-criterion. A performance matrix of each criterion and sub-criterion is presented as a reference for assessing the results based on the preferences of the stakeholders. Conclusions The use of a multicriteria methodology allows the relative importance of the indicators to be determined, reflecting the values of the different stakeholders. In a performance matrix, the inclusion of values and intangible aspects in the evaluation could help in making clinical and organizational decisions.