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The Panel considers that taking into account the composition of the NF and the proposed conditions of use, consumption of the NF is not nutritionally disadvantageous. No toxicological studies with the NF were provided by the applicant; however, the Panel considers that no toxicological studies are required for this NF. The NF has the potential capacity to sensitise individuals or to induce allergic reactions in individuals allergic to pea, rice and Shiitake mushroom. However, this risk is expected not to be higher than that resulting from the normal consumption of pea, rice or the fruiting body of the Shiitake mushroom. The Panel considers that the NF is safe at the proposed conditions of use.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.Equine herpesvirus-1 (EHV-1) can affect the entire equine sector in EU, and the large outbreak reported in 2021 in Spain drew attention to the needs of the European Commission for scientific advice for the assessment of EHV-1 infection within the framework of Animal Health Law. EHV-1 is considered endemic in the EU; its main risk is linked to the characteristic of producing latent life-long infections. These can reactivate producing clinical disease, which can include respiratory, abortive and possibly fatal neurological forms. From the epidemiological and genomic viewpoint, there are no specific neuropathogenic EHV-1 strains; the respiratory, reproductive and neurological signs are not found to be strain-specific. This was also the case of the virus that caused the outbreak in Valencia (Spain) in 2021, which was genetically closely related to other viruses circulating before in Europe, and did not present the so-called neuropathogenic genotype. The outbreak reported in Valencia was followed by wide geographic spread of the virus possibly due to a delay in diagnosis and late application of biosecurity measures. The recommended and most sensitive diagnostic test for detecting EHV-1 is PCR performed on swabs collected according to the type of clinical signs. Serological assays on paired blood samples can help to detect a recent infection, while no diagnostic methods are available to detect EHV-1 latent infections. Safe movements of horses can be ensured at premovement phase by testing and issuing health certificates, and by isolating animals upon arrival at new premises with regular health monitoring. In case of suspicion, movements should be forbidden and EHV-1 infection early detected/confirmed by validated diagnostic tools. During outbreaks, no movements should be allowed until 21 days after the detection of the last case. In general, vaccination against EHV-1 should be promoted, although this offers limited protection against the neurological form of the disease.Wildlife tourism could be a conservation tool; however, it may disrupt the natural behaviors of wild animals. We examined how wildlife tourism affects Lowe's monkeys (Cercopithecus lowei) at the Boabeng-Fiema Monkey Sanctuary, central Ghana. We examined and compared the time budget, aggression patterns, home range size and strata use of two C. lowei groups-one with a high level of provisioning by visitors/tour guides (HP group) versus one with a low level of provisioning by visitors/tour guides (LP group). We found evidence that the HP group fed less and rested more than the LP group. The HP group significantly increased the time spent feeding and decreased their time resting, but no significant differences were recorded for moving or socializing either in the presence of small or big groups of visitors (i.e., 1-10 visitors or > 10 visitors). In the presence of one to ten visitors, the HP group monkeys increased the use of ground by 22.10% and decreased the use of medium and high tree strata by 15.43% and 11.6%, respectively. Agonistic behaviors (i.e., threat, chase, and attack) were three times higher in the HP group (e.g., open-jawed gaze gesture or head-bobbing). In the presence of visitors, aggression in the HP group increased from 12.81% to 30.18%. The home range size of the C. lowei HP group was smaller (4.68 ha) compared to the LP group (14.25 ha) (i.e., 50.56% difference). The LP group spent significantly less time socializing and more time moving. They fed more on fruits and insects. On average, the daily travel of LP group was 0.58 km more than the HP group (i.e., 22.80% difference), and the former group also spent significantly more time in the mid strata of the canopy. Our results showed that continued provisioning of the monkeys with human foods is detrimental to their natural behavior of the monkeys and could have negative long-term effects on the conservation efforts for the species.Interspecific interactions of commensal non-native species such as domestic dogs and livestock with native wildlife are evident issues in protected areas (PAs). We studied spatiotemporal interactions by combining camera trap photographic sampling over three years. We used a generic multiseason occupancy and co-occurrence analysis and kernel density estimates of temporal activity. We accumulated a total of 1,305 and 1,557 independent photo-captures respectively for non-native and carnivore species during 26,216 trap nights. We found that non-native and carnivore species did not show substantial changes in occupancy rate over time. Yet both kinds of species were frequently detected. Carnivores had lower values of occupancy equilibrium than non-native species in seasons one and two. Domestic dogs directly occurred with native carnivores (except with leopards in season one), while the human and livestock presence displayed direct (Species Interaction Factors > 1) and indirect (Species Interaction Factors close to 1) co-occurrence, respectively, with the leopard and two mesocarnivores. The leopard cat was the least spatially influenced carnivore by the non-native species interactions. Furthermore, the leopard had higher temporal overlap (high Δ4) with all non-native species than the leopard cat and red fox (low Δ4). Our study exposes the negative impact of free-ranging non-native species across this protected area on native carnivore occupancy. An evaluation of the interconnections among non-native and carnivore species across diverse PA management regimes is crucial to develop robust landscape-scale conservation strategies.CD155 serves an important role in tumor progression by promoting cell proliferation and migration. CD155 is also involved in the immune evasion of tumor cells, which may cause the development and progression of tumors. Accordingly, CD155 has emerged as a novel target in cancer immunotherapy; however, its expression in lung cancer remains unclear. To assess CD155 expression and its prognostic significance, 96 patients with completely resected pathologic stage I adenocarcinoma of the lung were retrospectively reviewed. Immunohistochemical staining was performed to evaluate CD155 expression on tumor cells. Expression levels of programmed death-ligand 1 (PD-L1), another molecule participating in immune evasion, were also evaluated immunohistochemically. CD155 expression was positive in 37 patients (38.5%). CD155-positivity was associated with aggressive tumor behavior, such as pleural invasion and vascular invasion. In addition, CD155-positivity was a significant factor to predict a poor prognosis (5-year overall survival (OS) rate, 63.3% for CD155-positive patients vs. 93.1% for CD155-negative patients; P less then 0.001). Patients harboring tumors with positive CD155 and PD-L1 expression showed the poorest prognosis (5-year OS rate, 44.4% for both-positive patients vs. 85.4% for the other patients; P less then 0.001). The positive expression status of both CD155 and PD-L1 was a significant and independent unfavorable prognostic factor (hazard ratio, 3.86; 95% confidence interval, 1.51-9.89; P=0.004; in a multivariate analysis). In conclusion, CD155-positivity was associated with aggressive tumor behavior, and was a factor to predict a poor prognosis. Its prognostic impact was enhanced when combined with PD-L1 expression status. These results should be validated in a large-scale study.Acquired resistance to tyrosine kinase inhibitors (TKIs) limits the duration of antitumor effects and impairs the survival of patients with oncogene-driven non-small cell lung cancer (NSCLC). 8-Cyclopentyl-1,3-dimethylxanthine supplier At present, little is known about the immunomodulatory ability of TKIs during the entire treatment period, including the drug-sensitive and drug-resistant periods. The present review aimed to comprehensively explore the dynamic changes in the tumor microenvironment (TME) during TKI treatment in NSCLC. Previous clinical and preclinical studies from medical and health databases related to NSCLC are reviewed. During the response period, cytotoxic immune cells accumulate in the TME and contribute to the formation of an inflammatory microenvironment. During the resistance period, the number of immunosuppressive cells increases, as does the expression of immune checkpoint proteins, which are critical mechanisms for tumor progression. The combination of targeted therapy and immunotherapy has been explored in multiple studies, and preliminary data showed controversial results. Extensive studies are needed to confirm the criteria of the selected patient subgroups and the toxicity profiles of EGFR TKIs and immune checkpoint inhibitors (ICIs). At present, the reagents targeting other immune cells, cytokines and related pathways remain underexplored compared with the revolutionary effect of ICIs in lung cancer. In the future, the precisely selected regimens for combination treatment should be further investigated in carefully designed xenograft models and clinical trials.Adenylate kinase 4 pseudogene 1 (AK4P1) is a processed pseudogene whose function in cancer biology remains largely underexplored. Bioinformatics analysis suggested an association between the expression levels of adenylate kinase 4 (AK4) gene and AK4P1, as well as a clinical significance in relation to the increased transcription levels of AK4P1 in pancreatic adenocarcinoma (PAAD). In the present study, the expression levels of AK4P1 and AK4 were compared by RT-qPCR and western blotting between PAAD tissue and paired adjacent tissue. The level of AK4P1 transcript was compared between the circulating exosomes derived from patients with PAAD and those derived from healthy donors. Overall survival of the patients with PAAD with high or low expression levels of AK4P1 or AK4 was compared. AK4 gene expression level, in vitro cell viability and gemcitabine-induced apoptosis in PAAD cells with or without AK4P1 overexpression were also assessed using Cell Counting Kit-8 and TUNEL assays. It was identified that the transcription level of AK4P1 and the expression level of AK4 in PAAD tissue were significantly higher compared with those in paired non-cancerous tissue specimens.