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This collaborative work by over 180 researchers from 40+ countries addresses the challenges posed by "phantom agents"-putative pathogenic agents named in literature without supporting data on their existence. Those agents remain on regulatory lists, creating barriers in trade and plant certification. Historically identified based solely on symptoms, these agents lack isolates or sequence data, making reliable detection or risk assessment impossible. After reviewing over 120 such agents across 10 key plant genera, we recommend their removal from regulatory lists and call for revised standards aligned with modern diagnostics. This effort seeks to streamline germplasm exchange, benefiting global agriculture by removing the constraints imposed by phantoms., Competing Interests: The author(s) declare no conflict of interest.

Competing Interests: Conflict of interest: none declared.

Virus-induced gene silencing (VIGS) represents a particularly relevant tool in agricultural species for studying gene functionality. This study presents a novel approach for utilizing viruses belonging to the 30K family of movement proteins (MPs) as VIGS vectors. The method described here employs smaller inserts (54 bp or less) than those commonly used (100-500 bp). The developed strategy involves modifying 30K family MPs to introduce heterologous sequences of the gene of interest into their coding sequence. This approach enabled the successful induction of gene silencing in Nicotiana tabacum and Nicotiana benthamiana. Three representative viruses of the MP 30K family, alfalfa mosaic virus (AMV), cucumber mosaic virus (CMV), and tobacco mosaic virus (TMV) were employed. The capacity to induce gene silencing of small inserts (18-54 bp) was investigated, enabling to establish a correlation between insert size and silencing efficacy. This allowed the system to be calibrated to achieve partial silencing levels. The relationship between viral encapsidation and the level of gene silencing was also investigated, revealing that a high efficiency of viral encapsidation results in a reduction in the level of gene silencing achieved. Considering these findings, it can be concluded that the approach carried out with AMV, CMV, and TMV could be applied to other members of the MP 30K family. The MP 30K family comprises 20 viral genera and over 500 viral species, which can infect all agronomically significant plant species. Consequently, the strategy presented in this work could be applied to a wide range of relevant hosts., (© 2024 The Author(s). Biotechnology Journal published by Wiley‐VCH GmbH.)

The interaction of viral proteins with host factors represents a crucial aspect of the infection process in plants. In this work, we developed a strategy to identify host factors in Nicotiana tabacum that interact with movement proteins (MPs) of the 30K family, a group of viral proteins around 30 kDa related to the MP of tobacco mosaic virus, which enables virus movement between plant cells. Using the alfalfa mosaic virus (AMV) MP as a model, we incorporated tags into its coding sequence, without affecting its functionality, enabling the identification of 121 potential interactors through in vivo immunoprecipitation of the tagged MP. Further analysis of five selected candidates (histone 2B (H2B), actin, 14-3-3A protein, eukaryotic initiation factor 4A (elF4A), and a peroxidase-POX-) were conducted using bimolecular fluorescence complementation (BiFC). The interactions between these factors were also studied, revealing that some form part of protein complexes associated with AMV MP. Moreover, H2B, actin, 14-3-3, and eIF4A interacted with other MPs of the 30K family. This observation suggests that, beyond functional and structural features, 30K family MPs may share common interactors. Our results demonstrate that tagging 30K family MPs is an effective strategy to identify host factors associated with these proteins during viral infection.

Pathogenic microorganisms can adhere to solid surfaces, leading to the formation of biofilms, thus building a physical barrier hindering the penetration and diffusion of antimicrobial compounds. In this context, the use of natural antimicrobial compounds, such as essential oil components, as substitutes for common synthetic antimicrobials in the fight to prevent antimicrobial resistance is explored. As stainless steel is one of the most widely used surfaces in different industries, we have developed an innovative antimicrobial treatment for stainless steel surfaces based on a multi-step functionalization process, in which the stainless steel surface is coated with a silica layer to which a vanillin derivative is covalently attached. The surface was analyzed by microscopy studies, indicating the correct immobilization on the surfaces. Antimicrobial studies (viability and bacterial adhesion assays) were performed against the bacteria Staphylococcus epidermidis , which is one of the most frequent causes of nosocomial infections. The results of the microbiological studies showed that vanillin-functionalized stainless steel surfaces reduce the bacteria viability by 100% and the biofilm formation on the stainless steel surface by 75% compared with non-functionalized surfaces, highlighting the contact-killing and adhesion resistance properties of the developed surface. Additional cycles using the functionalized surfaces showed good maintenance of the antimicrobial coating efficacy. Moreover, the surfaces coated with an intermediate silica layer demonstrated much greater antimicrobial activity than surfaces in which the active molecule was directly functionalized on the stainless steel surface.

Docetaxel (DTX) is a recommended treatment in patients with metastasic prostate cancer (PCa), despite its therapeutic efficacy is limited by strong systemic toxicity. However, in localized PCa, intratumoral (IT) administration of DTX could be an alternative to consider that may help to overcome the disadvantages of conventional intravenous (IV) therapy. In this context, we here present the first in vivo preclinical study of PCa therapy with nanomedicines of mesoporous silica nanoparticles (MSN) and DTX by IT injection over a xenograft mouse model bearing human prostate adenocarcinoma tumors. The efficacy and tolerability, the biodistribution and the histopathology after therapy have been investigated for the DTX nanomedicine and the free drug, and compared with the IV administration of DTX. The obtained results demonstrate that IT injection of DTX and DTX nanomedicines allows precise and selective therapy of non-metastatic PCa and minimize systemic diffusion of the drug, showing superior activity than IV route. This allows reducing the therapeutic dose by one order and widens substantially the therapeutic window for this drug. Furthermore, the use of DTX nanomedicines as IT injection promotes strong antitumor efficacy and drug accumulation at the tumor site, improving the results obtained with the free drug by the same route., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Pablo Botella Asuncion reports financial support was provided by State Agency of Research. Pablo Botella Asuncion reports financial support was provided by Government of Valencia. Pablo Botella Asuncion has patent #WO2021/099662 issued to Universitat Politècnica de Valencia-Consejo Superior de Investigaciones Cientificas. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The escalating concern over poor air quality, particularly nitrogen dioxide (NO 2 ), poses a critical public health challenge, especially for vulnerable populations, such as children, older adults, and those with chronic diseases. This study aimed to analyze air quality in areas with vulnerable populations through a geospatial analysis of NO 2 concentration measured by the passive dosimetry method in 2022. The results reveal high vulnerability caused by areas with over-centralized facilities and high concentrations of nitrogen dioxide, often coinciding with busy avenues. The study emphasizes the urgent need to address air quality disparities, providing crucial insights for public decision-makers to allocate resources effectively and reduce environmental inequalities in the city, ultimately safeguarding the health of at-risk communities.

Antimicrobial resistance poses a major threat to global health and food security and is primarily driven by antimicrobial use in human and veterinary medicine. Understanding its epidemiology at farm level is crucial for effective control measures. Despite the significant reduction in antibiotic use in conventional livestock production, the swine sector traditionally has a higher level of antibiotic use in veterinary medicine. Consequently, multidrug resistance (MDR) among microbial isolates of swine origin has been relatively frequent. The aim of this study was to assess the presence of multidrug-resistant (MDR) bacteria, enteric pathogens and resistance genes to the main antibiotics used in clinical practice, both within the environment and in animals across pig farms characterized by varying degrees of sanitary status. A total of 274 samples were collected. Of these, 34 samples were collected from the environment (wall swabs, slat swabs and slurry pit), and 240 samples were collected from animals (sows' and piglets' rectal faeces). All samples were analysed for MDR bacteria and enteric pathogens. The study revealed a high frequency of extended-spectrum beta-lactamases (ESBL)-producing Enterobacterales and Campylobacter spp., with ESBL-producing Enterobacterales predominating in high health status farms (environment and animals) and Campylobacter spp. in both high health status and low health status environments. Additionally, a high percentage of methicillin-resistant Staphylococcus aureus (MRSA) was found, mainly in environmental samples from high health status farms, and Clostridioides difficile was distributed ubiquitously among farms and samples. Furthermore, though less frequently, vancomycin-resistant Enterococcus faecium (VRE) was isolated only in high health status farms, and Gram-negative bacilli resistant to carbapenems were isolated only in environmental samples of high health status and low health status farms. This study underscores the importance of surveillance for MDR bacteria in farm animals and their environment, including their waste. Such ecosystems serve as crucial reservoirs of bacteria, requiring national-level surveillance to promote responsible antibiotic use and pandemic control.

The promotion of food from underutilized plants can help combat biodiversity loss, foster cultural preservation, and empower farmers in the face of market pressures and sustainable production conditions. The nutritional and aromatic characterization of two undervalued types of Sorbus domestica fruits, differentiated by their apple and pear shapes, has been carried out. Official Association of Analytical Communities methods have been used for proximate composition and mineral analysis determinations, and gas chromatography was used for the analysis of volatile components in three states of ripeness and compared with the aromas of fresh apple and quince jam. S. domestica fruits are a good source of K, Ca, Fe, and fiber and are an important source of antioxidants in the human diet. S. domestica fruits have proven to be very distinctive in the aromatic fraction. 1-hexanol, hexyl 1,3-octanediol, phenylacetaldehyde, nonanal, hexanal, and α-farnesene are the most potent odor compounds in the overripening stage of the fruits. The aroma profiles of immature S. domestica fruits were dominated by aldehydes, while in the overripe stage, the fruit accumulated abundant esters, alcohols, and sesquiterpenoids. S. domestica fruits could be introduced as an alternative to seasonal fruit consumption and could generate sustainable production and consumption alternatives while recovering cultural and food heritage.

Femtosecond fluorescence upconversion experiments were combined with CASPT2 and time dependent DFT calculations to characterize the excited state dynamics of the mutagenic etheno adduct 1,N 2 -etheno-2'-deoxyguanosine (ϵdG). This endogenously formed lesion is attracting great interest because of its ubiquity in human tissues and its highly mutagenic properties. The ϵdG fluorescence is strongly modified with respect to that of the canonical nucleoside dG, notably by an about 6-fold increase in fluorescence lifetime and quantum yield at neutral pH. In addition, femtosecond fluorescence upconversion experiments reveal the presence of two emission bands with maxima at 335 nm for the shorter-lived and 425 nm for the longer-lived. Quantum mechanical calculations rationalize these findings and provide absorption and fluorescence spectral shapes similar to the experimental ones. Two different bright minima are located on the potential energy surface of the lowest energy singlet excited state. One planar minimum, slightly more stable, is associated with the emission at 335 nm, whereas the other one, with a bent etheno ring, is associated with the red-shifted emission., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Background: Anxiety and depression are highly prevalent disorders among individuals undergoing chronic haemodialysis. For patients with kidney disease, the haemodialysis process often exacerbates these conditions. This study aims to investigate the effects of listening to live classical music on anxiety and depression scales during haemodialysis sessions., Methods: A randomised clinical trial was conducted with a group of patients who listened to live classical music during haemodialysis sessions, while the control group received treatment as usual. Anxiety and depression levels were assessed at baseline and after 4 weeks of listening to live music. The study comprised 90 patients., Results: The results demonstrated a significant decrease in anxiety and depression among the intervention group, who listened to music, compared to the control group, who did not receive this intervention. Specifically, the intervention group, presented a decrease in score on the anxiety scale of -5.35 (p < 0.001) points on average and a decrease in score on the depression scale of -5.88 (p < 0.001) points on average, while in the control group the levels worsened with the progression of time., Conclusion: It is concluded that listening to live classical music during haemodialysis sessions reduces anxiety and depression levels in HD patients. This conclusion adds value to listening to live music in the hospital context, specifically in this case, in haemodialysis rooms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Soliva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The integration of Artificial Intelligence (AI) in healthcare signifies a substantial shift, offering benefits to patients and healthcare systems while also introducing new risks. The emphasis on patient safety and performance standards is pivotal, especially with the European Union's strides towards regulating AI through the AI Act. This act focuses on classifying AI systems based on risk levels, mandating stringent requirements for high-risk AI, enhancing transparency, and ensuring ethics in AI applications. The concept of an "AI passport" is introduced as a living document detailing the AI system's purpose, ethical declarations, training, evaluation, and potential biases. This passport aims to enhance transparency and safety in medical AI applications, serving as a comprehensive record for patients, clinicians, and stakeholders. The AI passport, structured in JSON format, encapsulates key information about the AI system as a mechanism for continuous performance evaluation and transparency. This initiative may represent a significant step towards mitigating the risks associated with AI in healthcare, emphasizing the importance of accountability, transparency, and patient safety in the development and application of AI technologies.

This work describes a comprehensive assessment of operating parameters of a bench-scale electrodialysis (ED) plant for nutrient concentration from an Anaerobic Membrane BioReactor (AnMBR) effluent. The ED bench-scale plant serves a dual purpose. Firstly, to generate a concentrated stream with a high nutrient content, and secondly, to produce high-quality reclaimed water in the diluted stream, both sourced from real wastewater coming from the effluent of an AnMBR. Two sets of experiments were conducted: 1) short-term experiments to study the effect of some parameters such as the applied current and the type of anionic exchange membrane (AEM), among others, and 2) a long-term experiment to verify the feasibility of the process using the selected parameters. The results showed that ED produced concentrated ammonium and phosphate streams using a 10-cell pair stack with 64 cm 2 of unitary effective membrane area, working in galvanostatic mode at 0.24 A, and operating with an Acid-100-OT anionic exchange membrane. Concentrations up to 740 mg/L and 50 mg/L for NH 4 -N and PO 4 -P, respectively, were achieved in the concentrated stream along with removal efficiencies of 70% for ammonium and 60% for phosphate in the diluted stream. The average energy consumption was around 0.47 kWh·m -3 ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Flowers, and hence, fruits and seeds, are produced by the activity of the inflorescence meristem after the floral transition. In plants with indeterminate inflorescences, the final number of flowers produced by the inflorescence meristem is determined by the length of the flowering period, which ends with inflorescence arrest. Inflorescence arrest depends on many different factors, such as the presence of seeds, the influence of the environment, or endogenous factors such as phytohormone levels and age, which modulate inflorescence meristem activity. The FRUITFULL-APETALA2 (FUL-AP2) pathway plays a major role in regulating the end of flowering, likely integrating both endogenous cues and those related to seed formation. Among AP2 targets, HOMEOBOX PROTEIN21 (HB21) has been identified as a putative mediator of AP2 function in the control of inflorescence arrest. HB21 is a homeodomain leucine zipper transcription factor involved in establishing axillary bud dormancy. Here, we characterized the role of HB21 in the control of the inflorescence arrest at the end of flowering in Arabidopsis (Arabidopsis thaliana). HB21, together with HB40 and HB53, are upregulated in the inflorescence apex at the end of flowering, promoting floral bud arrest. We also show that abscisic acid (ABA) accumulation occurs in the inflorescence apex in an HB-dependent manner. Our work suggests a physiological role of ABA in floral bud arrest at the end of flowering, pointing to ABA as a regulator of inflorescence arrest downstream of the HB21/40/53 genes., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Introduction: Stringent regulations in pig farming, such as antibiotic control and the ban on certain additives and disinfectants, complicate disease control efforts. Despite the evolution of microbial communities inside the house environment, they maintain stability over the years, exhibiting characteristics specific to each type of production and, in some cases, unique to a particular company or farm production type. In addition, some infectious diseases are recurrent in specific farms, while other farms never present these diseases, suggesting a connection between the presence of these microorganisms in animals or their environment. Therefore, the aim of this study was to characterise environmental microbiomes of farms with high and low sanitary status, establishing the relationships between both, health status, environmental microbial ecology and its functionality., Methods: For this purpose, 6 pig farms were environmentally sampled. Farms were affiliated with a production company that handle the majority of the pigs slaughtered in Spain. This study investigated the relationship among high health and low health status farms using high throughput 16S rRNA gene sequencing. In addition, to identify ecologically relevant functions and potential pathogens based on the 16S rRNA gene sequences obtained, functional Annotation with PROkaryotic TAXa (FAPROTAX) was performed., Results and Discussion: This study reveals notable differences in microbial communities between farms with persistent health issues and those with good health outcomes, suggesting a need for protocols tailored to address specific challenges. The variation in microbial populations among farms underscores the need for specific and eco-friendly cleaning and disinfection protocols. These measures are key to enhancing the sustainability of livestock farming, ensuring safer products and boosting competitive edge in the market., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Marin, Migura-García, Rodríguez, Ventero, Pérez-Gracia, Vega, Tort-Miró, Marco-Fuertes, Lorenzo-Rebenaque and Montoro-Dasi.)

Flowering plants adjust their reproductive period to maximize the success of the offspring. Monocarpic plants, those with a single reproductive cycle that precedes plant senescence and death, tightly regulate both flowering initiation and flowering cessation. The end of the flowering period involves the arrest of the inflorescence meristem activity, known as proliferative arrest, in what has been interpreted as an evolutionary adaptation to maximize the allocation of resources to seed production and the viability of the progeny. Factors influencing proliferative arrest were described for several monocarpic plant species many decades ago, but only in the last few years studies performed in Arabidopsis have allowed to approach proliferative arrest regulation in a comprehensive manner by studying the physiology, hormone dynamics, and genetic factors involved in its regulation. However, these studies remain restricted to Arabidopsis and there is a need to expand our knowledge to other monocarpic species to propose general mechanisms controlling the process. In this work, we have characterized proliferative arrest in Pisum sativum, trying to parallel available studies in Arabidopsis to maximize this comparative framework. We have assessed quantitatively the role of fruits/seeds in the process, the influence of the positional effect of these fruits/seeds in the behavior of the inflorescence meristem, and the transcriptomic changes in the inflorescence associated with the arrested state of the meristem. Our results support a high conservation of the factors triggering arrest in pea and Arabidopsis, but also reveal differences reinforcing the need to perform similar studies in other species., (© 2024 The Author(s). Physiologia Plantarum published by John Wiley & Sons Ltd on behalf of Scandinavian Plant Physiology Society.)

Background: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy., Objective: To determine which factors influence compliance with treatment., Methods: A systematic prospective non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance., Results: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p < 0.001). Differences in non-adherence in the three most frequent first-line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non-compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p < 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2-7.7]; p < 0.001)., Conclusions: Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue-treatment, prolonged treatment regimens, the presence of adverse events, and the use of non-bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Hydrogels are of great importance in biomedical engineering. They possess the ability to mimic bodily soft tissues, and this allows exciting possibilities for applications such as tissue engineering, drug delivery and wound healing, however much work remains on stability and mechanical robustness to allow for translation to clinical applications. The work herein describes the synthesis and analysis of a biocompatible, versatile hydrogel that has tailorable swelling, high stability when swollen and thermal stability. The synthesis methods used produce a hydrogel with high elasticity, good mechanical properties and rapid crosslinking whilst displaying biocompatibility, adhesion, and conductivity. It has been shown that cell viability in the samples is above 80 % in all cases, a Young's Modulus of up to 85 kPa and high swelling degrees were achieved. These materials show potential for use in numerous applications such as adhesive sensors, skin grafts and drug delivery systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: KRAS-mutant non-small cell lung cancer (NSCLC) shows a relatively low response rate to chemotherapy, immunotherapy and KRAS-G12C selective inhibitors, leading to short median progression-free survival, and overall survival. The MET receptor tyrosine kinase (c-MET), the cognate receptor of hepatocyte growth factor (HGF), was reported to be overexpressed in KRAS-mutant lung cancer cells leading to tumor-growth in anchorage-independent conditions., Methods: Cell viability assay and synergy analysis were carried out in native, sotorasib and trametinib-resistant KRAS-mutant NSCLC cell lines. Colony formation assays and Western blot analysis were also performed. RNA isolation from tumors of KRAS-mutant NSCLC patients was performed and KRAS and MET mRNA expression was determined by real-time RT-qPCR. In vivo studies were conducted in NSCLC (NCI-H358) cell-derived tumor xenograft model., Results: Our research has shown promising activity of omeprazole, a V-ATPase-driven proton pump inhibitor with potential anti-cancer properties, in combination with the MET inhibitor tepotinib in KRAS-mutant G12C and non-G12C NSCLC cell lines, as well as in G12C inhibitor (AMG510, sotorasib) and MEK inhibitor (trametinib)-resistant cell lines. Moreover, in a xenograft mouse model, combination of omeprazole plus tepotinib caused tumor growth regression. We observed that the combination of these two drugs downregulates phosphorylation of the glycolytic enzyme enolase 1 (ENO1) and the low-density lipoprotein receptor-related protein (LRP) 5/6 in the H358 KRAS G12C cell line, but not in the H358 sotorasib resistant, indicating that the effect of the combination could be independent of ENO1. In addition, we examined the probability of recurrence-free survival and overall survival in 40 early lung adenocarcinoma patients with KRAS G12C mutation stratified by KRAS and MET mRNA levels. Significant differences were observed in recurrence-free survival according to high levels of KRAS mRNA expression. Hazard ratio (HR) of recurrence-free survival was 7.291 (p = 0.014) for high levels of KRAS mRNA expression and 3.742 (p = 0.052) for high MET mRNA expression., Conclusions: We posit that the combination of the V-ATPase inhibitor omeprazole plus tepotinib warrants further assessment in KRAS-mutant G12C and non G12C cell lines, including those resistant to the covalent KRAS G12C inhibitors., (© 2024. The Author(s).)

Purpose: High-mobility group box 1 protein (HMGB1) is subject to exportin 1 (XPO1)-dependent nuclear export, and it is involved in functions implicated in resistance to immunotherapy. We investigated whether HMGB1 mRNA expression was associated with response to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC)., Patients and Methods: RNA was isolated from pretreatment biopsies of patients with advanced NSCLC treated with ICI. Gene expression analysis of several genes, including HMGB1, was conducted using the NanoString Counter analysis system (PanCancer Immune Profiling Panel). Western blotting analysis and cell viability assays in EGFR and KRAS mutant cell lines were carried out. Evaluation of the antitumoral effect of ICI in combination with XPO1 blocker (selinexor) and trametinib was determined in a murine Lewis lung carcinoma model., Results: HMGB1 mRNA levels in NSCLC patients treated with ICI correlated with progression-free survival (PFS) (median PFS 9.0 versus 18.0 months, P=0.008, hazard ratio=0.30 in high versus low HMGB1). After TNF-α stimulation, HMGB1 accumulates in the cytoplasm of PC9 cells, but this accumulation can be prevented by using selinexor or antiretroviral drugs. Erlotinib or osimertinib with selinexor in EGFR-mutant cells and trametinib plus selinexor in KRAS mutant abolish tumor cell proliferation. Selinexor with a PD-1 inhibitor with or without trametinib abrogates the tumor growth in the murine Lewis lung cancer model., Conclusion: An in-depth exploration of the functions of HMGB1 mRNA and protein is expected to uncover new potential targets and provide a basis for treating metastatic NSCLC in combination with ICI., Competing Interests: Dr Andrés Aguilar reports personal fee and/or non-financial support for congress, travel and/or speaker honoraria from MERCK SHARP and DOHME, Janssen-Cilag S.A., ROCHE-FARMA SA, TAKEDA ONCOLOGY, Bristol-Myers Squibb, outside the submitted work. The authors declare that they have no other known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 González-Cao et al.)

Background: Uterine leiomyosarcomas (uLMS) are aggressive tumours with poor prognosis and limited treatment options. Although immune checkpoint blockade (ICB) has proven effective in some 'challenging-to-treat' cancers, clinical trials showed that uLMS do not respond to ICB. Emerging evidence suggests that aberrant PI3K/mTOR signalling can drive resistance to ICB. We therefore explored the relevance of the PI3K/mTOR pathway for ICB treatment in uLMS and explored pharmacological inhibition of this pathway to sensitise these tumours to ICB., Methods: We performed an integrated multiomics analysis based on TCGA data to explore the correlation between PI3K/mTOR dysregulation and immune infiltration in 101 LMS. We assessed response to PI3K/mTOR inhibitors in immunodeficient and humanized uLMS patient-derived xenografts (PDXs) by evaluating tumour microenvironment modulation using multiplex immunofluorescence. We explored response to single-agent and a combination of PI3K/mTOR inhibitors with PD-1 blockade in humanized uLMS PDXs. We mapped intratumoural dynamics using single-cell RNA/TCR sequencing of serially collected biopsies., Results: PI3K/mTOR over-activation (pS6 high ) associated with lymphocyte depletion and wound healing immune landscapes in (u)LMS, suggesting it contributes to immune evasion. In contrast, PI3K/mTOR inhibition induced profound tumour microenvironment remodelling in an ICB-resistant humanized uLMS PDX model, fostering adaptive anti-tumour immune responses. Indeed, PI3K/mTOR inhibition induced macrophage repolarisation towards an anti-tumourigenic phenotype and increased antigen presentation on dendritic and tumour cells, but also promoted infiltration of PD-1+ T cells displaying an exhausted phenotype. When combined with anti-PD-1, PI3K/mTOR inhibition led to partial or complete tumour responses, whereas no response to single-agent anti-PD-1 was observed. Combination therapy reinvigorated exhausted T cells and induced clonal hyper-expansion of a cytotoxic CD8+ T-cell population supported by a CD4+ T h 1 niche., Conclusions: Our findings indicate that aberrant PI3K/mTOR pathway activation contributes to immune escape in uLMS and provides a rationale for combining PI3K/mTOR inhibition with ICB for the treatment of this patient population., (© 2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Photodynamic Therapy is a therapy based on combining a non-toxic compound, known as photosensitizer (PS), and irradiation with light of the appropriate wavelength to excite the PS molecule. The photon absorption by the PS leads to reactive oxygen species generation and a subsequent oxidative burst that causes cell damage and death. In this work, we report an antimicrobial nanodevice that uses the activity of curcumin (Cur) as a PS for antimicrobial Photodynamic Therapy (aPDT), based on mesoporous silica nanoparticles in which the action of the classical antibiotic PMB is synergistically combined with the aPDT properties of curcumin to combat bacteria. The synergistic effect of the designed gated device in combination with irradiation with blue LED light (470 nm) is evaluated against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus epidermidis. The results show that the nanodevice exhibits a noteworthy antibacterial activity against these microorganisms, a much more significant effect than free Cur and PMB at equivalent concentrations. Thus, 0.1 µg/mL of MSNs-Cur-PMB eliminates a bacterial concentration of about 10 5 CFU/mL of E. coli, while 1 µg/mL of MSNs-Cur-PMB is required for P. aeruginosa and S. epidermidis. In addition, antibiofilm activity against the selected bacteria was also tested. We found that 0.1 mg/mL of MSNs-Cur-PMB inhibited 99 % biofilm formation for E. coli, and 1 mg/mL of MSNs-Cur-PMB achieved 90 % and 100 % inhibition of biofilm formation for S. epidermidis and P. aeruginosa, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Recent research suggests that children born after suspected preterm labor may observe a potential cluster with different attention deficit hyperactivity disorder features, depending on the time of birth. However, the evolution of symptoms and their predictors remain unknown in this population., Objective: This study aimed to examine the trajectories of attention deficit hyperactivity disorder symptoms of children born after suspected preterm labor, between ages 2 and 6 years, considering prematurity condition and comparing with controls. In addition, this study aimed to find potential modifiable predictors of evolution to enhance prognosis., Study Design: In this prospective cohort study, 119 mother-child pairs who experienced suspected preterm labor and 60 controls were included. Patients were divided according to prematurity condition in full term (n=27), late preterm (n=55), and very preterm (n=37). Attention deficit hyperactivity disorder symptoms were assessed at ages 2 and 6 years. The association between potential modifying factors (group, time of assessment, sex, birthweight percentile, maternal history of trauma, maternal anxiety at diagnosis, and maternal anxiety during the children's assessments) and disorder trajectories was assessed by adjusting the Bayesian mixed linear models. All analyses were performed in R (version 4.3.0; R Foundation for Statistical Computing, Vienna, Austria)., Results: An interaction emerged between time and group, with late-preterm neonates born after suspected preterm labor being the only group to improve from ages 2 to 6 years (-2.26 points in Conners scale per percentile decrease and 0.98 probability of effect). Another interaction between time and maternal anxiety at postnatal time assessments intensified over time (0.07 and 0.84). Predictors of symptom severity included lower weight percentile at birth (-0.2 and 0.96), male sex (-2.99 and <0.99), higher maternal anxiety at diagnosis (+0.08 and 0.99), and maternal history of trauma (+0.23 and 0.98)., Conclusion: Unlike very-preterm and full-term children, those born late preterm showed an improvement over time, probably because late-preterm children do not carry the sequelae derived from severe prematurity but benefit from close monitoring. As maternal psychopathology emerged as a determinant modifier of course and severity, it is crucial to develop targeted psychological interventions for pregnant individuals and reevaluate monitoring programs for their offspring, regardless of prematurity., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Most total disc replacements provide excessive mobility and not reproduce spinal kinematics, inducing zygapophyseal joint arthritic changes and chronic back pain. In cadaveric lumbosacral spines, we studied if a new lumbar disc prosthesis kinematics mimics the intact intervertebral disc., Methods: In eight cold preserved cadaveric lumbosacral spines, we registered the movement ranges in flexion, extension, right and left lateral bending, and rotation in the intact status, post-discectomy, and after our prosthesis implantation, comparing them for each specimen., Findings: Comparing the intact lumbosacral spine with the L 4 -L 5 prosthesis implanted specimens, we saw statistically significant differences in lateral bending and right rotation but not in the full range of rotation. Analyzing segments, we also noticed statistically significant differences at L 4 -L 5 in flexion-extension and rotation. On the other hand, the L 4 -L 5 discectomy, compared to the baseline spine condition, showed a statistically significant mobility increase in flexion, extension, lateral bending, and axial rotation, with an abnormal instantaneous center of rotation, which destabilizes the segment partly due to anterior annulus surgical removal. Disc prosthesis implantation reversed these changes in instantaneous center of rotation, but the prosthesis failed to restore the initial range of motion due to the destabilization of the ligaments in the operated disc., Interpretation: The ADDISC total disc replacement reproduces the intact disc kinematics and Instantaneous Center of Rotation, but the prosthesis fails to restore the initial range of motion due to ligament destabilization. More studies will be necessary to define a technique that restores the damaged ligaments when implanting the prosthesis., Competing Interests: Declaration of competing interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interests (such as honoraria; educational grants; participation in speaker's bureaus; membership, employment, consultancies, stock ownership, membership of a company board of directors, membership of an advisory board or committee for a company, and consultancy for or receipt of speaker's fees from a company or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interests (such as personal or professional relationships, affiliations, knowledge or belief(s) in the subject matter or materials discussed in this manuscript. The authors have no conflicts of interest to declare. ADDISC prosthesis, but the intellectual property belongs to the company ROA 14SL, La Pedrera, Gijón, Spain, which has not commercially manufactured the prosthesis yet. Professor V Vanaclocha has not received any honoraria or compensation for his work or invention., (Copyright © 2023. Published by Elsevier Ltd.)

Brevipalpus-transmitted viruses (BTVs) have a significant negative economic impact on the citrus industry in Central and South America. Until now, only a few studies have explored the intracellular distribution and interaction of BTVs-encoded proteins with host factors, particularly for cileviruses, the main BTV responsible for the Citrus Leprosis (CL) disease. This study describes the nuclear localization of citrus leprosis virus C (CiLV-C) capsid protein (p29) and its interaction with the fibrillarin (Fib2) within the nucleolar compartment and cell cytoplasm. Our results, obtained by computer predictions and laser scanning confocal microscopy analyses, including colocalization and bimolecular fluorescence complementation (BiFC) approaches, revealed that a fraction of the p29 is localized in the nucleus and colocalizes with the Fib2 in both the nucleolus and cytosol. The nuclear localization of p29 correlated with a smaller nucleus size. Furthermore, co-immunoprecipitation (Co-IP) assays confirmed the interactions between p29 and Fib2. The implications of these findings for the functionalities of the cilevirus capsid protein are discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The concept of backyard poultry historically encompassed "food-producing animals." Nevertheless, a recent shift in livestock production paradigms within developed countries is evident, as backyard poultry owners now raise their birds for purposes beyond self-consumption, raising animals in a familiar way, and fostering emotional bonds with them. Because backyard animals are frequently privately owned, and the resulting products are typically not marketed, very little information is available about the demographic profile of backyard owners and information on flocks' characteristics, husbandry, and welfare. Thus, this review aims to clarify the characteristics of backyard poultry, highlighting the prevalent infectious diseases and the zoonotic risk to which farmers are exposed. According to the FAO, there are different types of poultry production systems: intensive, sub-intensive, and extensive. The system conditions, requirements, and the resulting performance differ extensively due to the type of breed, feeding practices, prevalence of disease, prevention and control of diseases, flock management, and the interactions among all these factors. The presence and transmission of infectious diseases in avian species is a problem that affects both the animals themselves and public health. Bacterial (Escherichia coli, Salmonella, Campylobacter, and Mycoplasma), parasitic (helminths, louses, and mites), and viral (Avian influenza, Newcastle, Marek, Infectious Bronchitis, Gumboro, Infectious Laringotracheitis, and Fowlpox) are the most important pathogens involved in backyard poultry health. In addition, Avian influenza, Salmonella, Campylobacter, and E. coli, could be a risk for backyard farmers and/or backyard-derived products consumers. Thus, proper biosecurity implementation measures are mandatory to control them. While the principles and practices of on-farm biosecurity may be well-versed among commercial farmers, hobbyists, and backyard farmers might not be familiar with the necessary steps to protect their flocks from infectious diseases and curb their transmission. This sector represents the fourth category of poultry farming, characterized by the lowest biosecurity standards. Consequently, it is imperative to address the legal status of backyard poultry, educate owners about biosecurity measures, and promote proper veterinary care and disease control., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)