Search

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.)

The storage root (SR) of cassava is the main staple food in sub-Saharan Africa, where it feeds over 500 million people. However, little is known about the genetic and molecular regulation underlying its development. Unraveling such regulation would pave the way for biotechnology approaches aimed at enhancing cassava productivity. Anatomical studies indicate that SR development relies on the massive accumulation of xylem parenchyma, a cell-type derived from the vascular cambium. The C3HDZ family of transcription factors regulate cambial cells proliferation and xylem differentiation in Arabidopsis and other species. We thus aimed at identifying C3HDZ proteins in cassava and determining whether any of them shows preferential activity in the SR cambium and/or xylem. Using phylogeny and synteny studies, we identified eight C3HDZ proteins in cassava, namely MeCH3DZ1-8. We observed that MeC3HDZ1 is the MeC3HDZ gene displaying the highest expression in SR and that, within that organ, the gene also shows high expression in cambium and xylem. In-silico analyses revealed the existence of a number of potential C3HDZ targets displaying significant preferential expression in the SR. Subsequent Y1H analyses proved that MeC3HDZ1 can bind canonical C3HDZ binding sites, present in the promoters of these targets. Transactivation assays demonstrated that MeC3HDZ1 can regulate the expression of genes downstream of promoters harboring such binding sites, thereby demonstrating that MeC3HDZ1 has C3HDZ transcription factor activity. We conclude that MeC3HDZ1 may be a key factor for the regulation of storage root development in cassava, holding thus great promise for future biotechnology applications., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Despite the success of therapies in lung cancer, more studies of new biomarkers for patient selection are urgently needed. The present study aims to analyze the role of galectin-3 (GAL-3) in the lung tumor microenvironment (TME) using tumorspheres as a model and explore its potential role as a predictive and prognostic biomarker in non-small cell lung cancer patients. For in vitro studies, lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) primary cultures from early-stage patients and commercial cell lines were cultured, using tumorsphere-forming assays and adherent conditions for the control counterparts. We analyzed the pattern of secretion and expression of GAL-3 using reverse transcription-quantitative real-time PCR (RTqPCR), immunoblot, immunofluorescence, flow cytometry, and immunoassay analysis. Our results using three-dimensional (3D) models of lung tumor cells revealed that soluble GAL-3 (sGAL-3) is highly expressed and secreted. To more accurately mimic the TME, a co-culture of tumorspheres and fibroblasts was used, revealing that GAL-3 could be important as an immunomodulatory molecule expressed and secreted in the TME, modulating immunosuppression through regulatory T cells (T REGS ). In the translational phase, we confirmed that patients with high expression levels of GAL-3 had more T REGS , which suggests that tumors may be recruiting this population through GAL-3. Next, we evaluated levels of sGAL-3 before surgery in LUAD and LUSC patients, hypothesizing that sGAL-3 could be used as an independent prognostic biomarker for overall survival and relapse-free survival in early-stage LUAD patients. Additionally, levels of sGAL-3 at pretreatment and first response assessment from plasma to predict clinical outcomes in advanced LUAD and LUSC patients treated with first-line pembrolizumab were evaluated, further supporting that sGAL-3 has a high efficiency in predicting durable clinical response to pembrolizumab with an area under curve of 0.801 (P = 0.011). Moreover, high levels might predict decreased progression-free survival and OS to anti-PD-1 therapy, with sGAL-3 being a prognosis-independent biomarker for advanced LUAD., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

An archetypal anti-inflammatory compound against cytokine storm would inhibit it without suppressing the innate immune response. AG5, an anti-inflammatory compound, has been developed as synthetic derivative of andrographolide, which is highly absorbable and presents low toxicity. We found that the mechanism of action of AG5 is through the inhibition of caspase-1. Interestingly, we show with in vitro generated human monocyte derived dendritic cells that AG5 preserves innate immune response. AG5 minimizes inflammatory response in a mouse model of lipopolysaccharide (LPS)-induced lung injury and exhibits in vivo anti-inflammatory efficacy in the SARS-CoV-2-infected mouse model. AG5 opens up a new class of anti-inflammatories, since contrary to NSAIDs, AG5 is able to inhibit the cytokine storm, like dexamethasone, but, unlike corticosteroids, preserves adequately the innate immunity. This is critical at the early stages of any naïve infection, but particularly in SARS-CoV-2 infections. Furthermore, AG5 showed interesting antiviral activity against SARS-CoV-2 in humanized mice., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: “AG5 andrographolide derivative for use in the treatment of inflammatory diseases associated with a cytokine storm” is a formal Spanish Patent (ES2908500) since March 15th, 2023. PBA, ERB, CVA, BN, AF, CS, GGA, FP, JA, APL and JMB are co-inventors of this patent., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Aberrant vascular architecture and angiogenesis are hallmarks of glioblastoma IDH-wildtype, suggesting that these tumors are suitable for antiangiogenic therapy. Bevacizumab was FDA-approved in 2009 following promising results in two clinical trials. However, its use for recurrent glioblastomas remains a subject of debate, as it does not universally improve patient survival., Purposes: In this study, we aimed to analyze the influence of tumor vascularity on the benefit provided by BVZ and propose preoperative rCBVmax at the high angiogenic tumor habitat as a predictive biomarker to select patients who can benefit the most., Methods: Clinical and MRI data from 106 patients with glioblastoma IDH-wildtype have been analyzed. Thirty-nine of them received BVZ, and the remaining sixty-seven did not receive a second-line treatment. The ONCOhabitats method was used to automatically calculate rCBV., Results: We found a median survival from progression of 305 days longer for patients with moderate vascular tumors who received BVZ than those who did not receive any second-line treatment. This contrasts with patients with high-vascular tumors who only presented a median survival of 173 days longer when receiving BVZ. Furthermore, better responses to BVZ were found for the moderate-vascular group with a higher proportion of patients alive at 6, 12, 18, and 24 months after progression., Conclusions: We propose rCBVmax as a potential biomarker to select patients who can benefit more from BVZ after tumor progression. In addition, we propose a threshold of 7.5 to stratify patients into moderate- and high-vascular groups to select the optimal second-line treatment.

Immunotherapy has been proven a viable treatment option for non-small cell lung cancer (NSCLC) treatment in patients. However, some patients still do not benefit. Finding new predictive biomarkers for immunocheckpoint inhibitor (ICI) response will improve treatment management in the clinical routine. In this regard, liquid biopsy is a useful and noninvasive alternative to surgical biopsies. In the present study, we evaluated the potential diagnostic, prognostic, and predictive value of seven different soluble mediators involved in immunoregulation. Fifty-two plasma samples from advanced NSCLC treated in first-line with pembrolizumab at baseline (PRE) and at first response assessment (FR) were analyzed. In terms of diagnostic value, our results revealed that sFGL1, sGAL-3, and sGAL-1 allowed for optimal diagnostic efficacy for cancer patients. Additionally, the combination of sFGL1 and sGAL-3 significantly improved diagnostic accuracy. Regarding the predictive value to assess patients' immune response, sCD276 levels at PRE were significantly higher in patients without tumor response ( p = 0.035). Moreover, we observed that high levels of sMICB at PRE were associated with absence of clinical benefit (pembrolizumab treatment less than 6 months) ( p = 0.049), and high levels of sMICB and sGAL-3 at FR are also related to a lack of clinical benefit ( p = 0.027 and p = 0.03, respectively). Finally, in relation to prognosis significance, at PRE and FR, sMICB levels above the 75th percentile are related to poor progression-free survival (PFS) ( p = 0.013 and p = 0.023, respectively) and overall survival (OS) ( p = 0.001 and p = 0.011, respectively). An increase in sGAL3 levels at FR was associated with worse PFS ( p = 0.037). Interestingly, high sGAL-3 at PRE was independently associated with PFS and OS with a hazard ratio (HR) of 2.45 (95% CI 1.14-5.25; p = 0.021) and 4.915 (95% CI 1.89-12.73; p = 0.001). In conclusion, plasma levels of sFGL1, sGAL-3, and sGAL-1 could serve as diagnostic indicators and sMICB, sCD276, and sGAL3 were linked to outcomes, suggesting their potential in assessing NSCLC under pembrolizumab treatment. Our results highlight the value of employing soluble immune biomarkers in advanced lung cancer patients treated with pembrolizumab at first-line.

Ferruginol is a promising abietane-type antitumor diterpene able to induce apoptosis in SK-Mel-28 human malignant melanoma. We aim to increase this activity by testing the effect of a small library of ferruginol analogues. After a screening of their antiproliferative activity (SRB staining, 48 h) on SK-Mel-28 cells the analogue 18-aminoferruginol (GI50 ≈ 10 µM) was further selected for mechanistic studies including induction of apoptosis (DAPI staining, p < 0.001), changes in cell morphology associated with the treatment (cell shrinkage and membrane blebbing), induction of caspase-3/7 activity (2.5 at 48 h, 6.5 at 72 h; p < 0.0001), changes in the mitochondrial membrane potential (not significant) and in vitro effects on cell migration and cell invasion (Transwell assays, not significant). The results were compared to those of the parent molecule (ferruginol, GI50 ≈ 50 µM, depolarisation of mitochondrial membrane p < 0.01 at 72 h; no caspases 3/7 activation) and paclitaxel (GI50 ≈ 10 nM; caspases 3/7 activation p < 0.0001) as a reference drug. Computational studies of the antiproliferative activity of 18-aminoferruginol show a consistent improvement in the activity over ferruginol across a vast majority of cancer cells in the NCI60 panel. In conclusion, we demonstrate here that the derivatisation of ferruginol into 18-aminoferruginol increases its antiproliferative activity five times in SK-MEL-28 cells and changes the apoptotic mechanism of its parent molecule, ferruginol.

The use of wearable devices has promoted new ways of integrating these devices, one of which is through the development of smart textiles. Smart textiles must possess the mechanical and electrical properties necessary for their functionality. This study explores the impact of polymer-felt microstructure variations on their morphology, electrical, and mechanical properties. The application of thermal treatment, along with an electric field, leads to a substantial structural reorganization of the molecular chains within pristine felt. This results in a system of nanofibrils coated with MWCNT-PEDOT, characterized by highly ordered counterions that facilitate the flow of charge carriers. Both temperature and an electric field induce reversible microstructural changes in pristine felt and irreversible changes in coated felt samples. Furthermore, electropolymerization of PEDOT significantly enhances electrical conductivity, with PEDOT:BTFMSI-coated fabric exhibiting the highest conductivity.

Background: The creation of computer-supported collaborative clinical cases is an area of educational research that has been widely studied. However, the reuse of cases and their sharing with other platforms is a problem, as it encapsulates knowledge in isolated platforms without interoperability. This paper proposed a workflow ecosystem for the collaborative design and distribution of clinical cases through web-based computing platforms that (1) allow medical students to create clinical cases collaboratively in a dedicated environment; (2) make it possible to export these clinical cases in terms of the Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) interoperability standard; (3) provide support to transform imported cases into learning object repositories; and (4) use e-learning standards (eg, Instructional Management Systems Content Packaging [IMS-CP] or Sharable Content Object Reference Model [SCORM]) to incorporate this content into widely-used learning management systems (LMSs), letting medical students democratize a valuable knowledge that would otherwise be confined within proprietary platforms., Objective: This study aimed to demonstrate the feasibility of developing a workflow ecosystem based on IT platforms to enable the collaborative creation, export, and deployment of clinical cases., Methods: The ecosystem infrastructure for computer-supported collaborative design of standardized clinical cases consists of three platforms: (1) Mosaico, a platform used in the design of clinical cases; (2) Clavy, a tool for the flexible management of learning object repositories, which is used to orchestrate the transformation and processing of these clinical cases; and (3) Moodle, an LMS that is geared toward publishing the processed clinical cases and delivering their course deployment stages in IMS-CP or SCORM format. The generation of cases in Mosaico is exported in the HL7 FHIR interoperability standard to Clavy, which is then responsible for creating and deploying a learning object in Moodle., Results: The main result was an interoperable ecosystem that demonstrates the feasibility of automating the stages of collaborative clinical case creation, export through HL7 FHIR standards, and deployment in an LMS. This ecosystem enables the generation of IMS-CPs associated with the original Mosaico clinical cases that can be deployed in conventional third-party LMSs, thus allowing the democratization and sharing of clinical cases to different platforms in standard and interoperable formats., Conclusions: In this paper, we proposed, implemented, and demonstrated the feasibility of developing a standards-based workflow that interoperates multiple platforms with heterogeneous technologies to create, transform, and deploy clinical cases on the web. This achieves the objective of transforming the created cases into a platform for web-based deployment in an LMS., (© Sergio Guinez-Molinos, Félix Buendía-García, José-Luis Sierra-Rodríguez, Joaquín Gayoso-Cabada, Jaime González-Díaz. Originally published in JMIR Medical Informatics (https://medinform.jmir.org).)

Improved feed efficiency is an essential goal for the sustainability of pig production in economic and environmental terms. Traits such as feed conversion rate (FCR), residual feed intake (RFI), residual body weight gain (RG) and feeding behaviour, such as duration (TPV) and feeding rate per visit (FR) can now be measured by automatic feeding systems. The aim of this study was to evaluate the benefits of incorporating feeding behaviour traits into a selection index to improve feed efficiency in a nucleus of purebred Pietrain pigs. Data on body weight, feed intake and duration were recorded at each visit in 1608 animals. The information contained in 843,605 visits was grouped by animal ID to obtain a set of feed efficiency and feeding behaviour traits. These traits were obtained in three periods (first, second and total period). Bayesian models were built to estimate the posterior marginal distribution of the variance components. The heritabilities were between 0.44 and 0.59 for feeding behaviour traits and between 0.31 and 0.49 for feed efficiency traits. The FCR and RFI showed a considerable genetic correlation with daily feed intake (~0.65). FCR showed a genetic correlation with feeding behaviour traits, such as feed intake per visit (FPV) (0.44) and FR (0.33). Furthermore, the fast-eating pigs were less efficient. This was due to the positive genetic correlation found between the FR and the FCR (0.33) and the RFI (0.23), and the negative correlation found with the RG (-0.28). On the other hand, the inclusion of the feeding behaviour traits into a selection index slightly increased the selection response for FCR (4%) and RFI (1.8%). However, there was an increase of up to 19% in the selection response for RG and an improvement in accuracy from 0.59 to 0.70. Therefore, we concluded that it would be interesting to include feeding behaviour traits in a selection index to improve the selection response and accuracy of feed efficiency traits., (© 2023 The Authors. Journal of Animal Breeding and Genetics published by John Wiley & Sons Ltd.)

Currently, understanding the dynamics of the interaction between the agents in a process is one of the most important factors regarding its operation and design. Membrane processes for industrial wastewater management are not strangers to this topic. One such example is the concentration of compounds with high added value, such as the phenolic compounds present in olive mill wastewater (OMW). This process is a viable option, thanks to the forward osmosis (FO) process, osmotically driven by a saline stream. In this context, the transport of the solute and the solvent through the FO membranes, although essential to the process, remains problematic. This paper presents a study to predict, by means of a theoretical model, the water flux for two membranes (a cellulose triacetate flat sheet and a polyamide hollow fiber with integrated aquaporin proteins) with different characteristics using a sodium chloride solution as the draw solution (DS). The novelty of this model is the consideration of the contribution of organic compounds (in addition to the inorganic salts) to the osmotic pressure in the feed side. Moreover, the geometry of the modules and the characteristics of the membranes were also considered. The model was developed with the ability to run under different conditions, with or without tyrosol (the compound chosen as representative of OMW phenolic compounds) in the feed solution (FS), and was fitted and evaluated using experimental data. The results presented a variability in the model prediction, which was a function of both the membrane used and the FS and DS, with a greater influence of tyrosol observed on the permeate flux in the flat cellulose triacetate membrane., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

In this paper, a procedure for experimental optimization under safety constraints, to be denoted as constraint-aware Bayesian Optimization, is presented. The basic ingredients are a performance objective function and a constraint function; both of them will be modeled as Gaussian processes. We incorporate a prior model (transfer learning) used for the mean of the Gaussian processes, a semi-parametric Kernel, and acquisition function optimization under chance-constrained requirements. In this way, experimental fine-tuning of a performance objective under experiment-model mismatch can be safely carried out. The methodology is illustrated in a case study on a line-follower application in a CoppeliaSim environment.

Despite advances in breast cancer treatment, it remains the leading cause of cancer-related death in women worldwide. In this context, microRNAs have emerged as potential therapeutic targets but still present some limitations for in vivo applications. Particularly, miR-200c-3p is a well-known tumor suppressor microRNA that inhibits tumor progression and metastasis in breast cancer through downregulating ZEB1 and ZEB2 . Based on the above, we describe the design and validation of a nanodevice using mesoporous silica nanoparticles for miR-200c-3p delivery for breast cancer treatment. We demonstrate the biocompatibility of the synthesized nanodevices as well as their ability to escape from endosomes/lysosomes and inhibit tumorigenesis, invasion, migration, and proliferation of tumor cells in vitro . Moreover, tumor targeting and effective delivery of miR-200c-3p from the nanoparticles in vivo are confirmed in an orthotopic breast cancer mouse model, and the therapeutic efficacy is also evidenced by a decrease in tumor size and lung metastasis, while showing no signs of toxicity. Overall, our results provide evidence that miR-200c-3p-loaded nanoparticles are a potential strategy for breast cancer therapy and a safe and effective system for tumor-targeted delivery of microRNAs.

A novel manufacturing process is presented for producing nanopowders and thin films of CuCoO 2 (CCO) material. This process utilizes three cost-effective synthesis methods: hydrothermal, sol-gel, and solid-state reactions. The resulting delafossite CuCoO 2 samples were deposited onto transparent substrates through spray pyrolysis, forming innovative thin films with a nanocrystal powder structure. Prior to the transformation into thin films, CuCoO 2 powder was first produced using a low-cost approach. The precursors for both powders and thin films were deposited onto glass surfaces using a spray pyrolysis process, and their characteristics were examined through X-ray diffraction, scanning electron microscopy, HR-TEM, UV-visible spectrophotometry, and electrochemical impedance spectroscopy (EIS) analyses were conducted to determine the conductivity in the transversal direction of this groundbreaking material for solar cell applications. On the other hand, the sheet resistance of the samples was investigated using the four-probe method to obtain the sheet resistivity and then calculate the in-plane conductivity of the samples. We also investigated the aging characteristics of different precursors with varying durations. The functional properties of CuCoO 2 samples were explored by studying chelating agent and precursor solution aging periods using Density Functional Theory calculations (DFT). A complementary Density Functional Theory study was also performed in order to evaluate the electronic structure of this compound. Resuming, this study thoroughly discusses the synthesis of delafossite powders and their conversion into thin films, which hold potential as hole transport layers in transparent optoelectronic devices.

Objective: To develop a spatiotemporal model for de prediction of euploid and aneuploid embryos using time-lapse videos from 10-115 hours after insemination (hpi)., Design: Retrospective study., Main Outcome Measures: The research used an end-to-end approach to develop an automated artificial intelligence system capable of extracting features from images and classifying them, considering spatiotemporal dependencies. A convolutional neural network extracted the most relevant features from each video frame. A bidirectional long short-term memory layer received this information and analyzed the temporal dependencies, obtaining a low-dimensional feature vector that characterized each video. A multilayer perceptron classified them into 2 groups, euploid and noneuploid., Results: The model performance in accuracy fell between 0.6170 and 0.7308. A multi-input model with a gate recurrent unit module performed better than others; the precision (or positive predictive value) is 0.8205 for predicting euploidy. Sensitivity, specificity, F1-Score and accuracy are 0.6957, 0.7813, 0.7042, and 0.7308, respectively., Conclusions: This article proposes an artificial intelligence solution for prioritizing euploid embryo transfer. We can highlight the identification of a noninvasive method for chromosomal status diagnosis using a deep learning approach that analyzes raw data provided by time-lapse incubators. This method demonstrated potential automation of the evaluation process, allowing spatial and temporal information to encode., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Lung oncogenesis relies on intracellular cysteine to overcome oxidative stress. Several tumor types, including non-small cell lung cancer (NSCLC), upregulate the system x c - cystine/glutamate antiporter (xCT) through overexpression of the cystine transporter SLC7A11, thus sustaining intracellular cysteine levels to support glutathione synthesis. Nuclear factor erythroid 2-related factor 2 (NRF2) serves as a master regulator of oxidative stress resistance by regulating SLC7A11, whereas Kelch-like ECH-associated protein (KEAP1) acts as a cytoplasmic repressor of the oxidative responsive transcription factor NRF2. Mutations in KEAP1/NRF2 and p53 induce SLC7A11 activation in NSCLC. Extracellular cystine is crucial in supplying the intracellular cysteine levels necessary to combat oxidative stress. Disruptions in cystine availability lead to iron-dependent lipid peroxidation, thus resulting in a type of cell death called ferroptosis. Pharmacologic inhibitors of xCT (either SLC7A11 or GPX4) induce ferroptosis of NSCLC cells and other tumor types. When cystine uptake is impaired, the intracellular cysteine pool can be sustained by the transsulfuration pathway, which is catalyzed by cystathionine-B-synthase (CBS) and cystathionine g-lyase (CSE). The involvement of exogenous cysteine/cystine and the transsulfuration pathway in the cysteine pool and downstream metabolites results in compromised CD8 + T cell function and evasion of immunotherapy, diminishing immune response and potentially reducing the effectiveness of immunotherapeutic interventions. Pyroptosis is a previously unrecognized form of regulated cell death. In NSCLCs driven by EGFR, ALK, or KRAS, selective inhibitors induce pyroptotic cell death as well as apoptosis. After targeted therapy, the mitochondrial intrinsic apoptotic pathway is activated, thus leading to the cleavage and activation of caspase-3. Consequently, gasdermin E is activated, thus leading to permeabilization of the cytoplasmic membrane and cell-lytic pyroptosis (indicated by characteristic cell membrane ballooning). Breakthroughs in KRAS G12C allele-specific inhibitors and potential mechanisms of resistance are also discussed herein., Competing Interests: No potential conflicts of interest are disclosed., (Copyright © 2023 Cancer Biology & Medicine.)

The abietane diterpene (+)-ferruginol ( 1 ), like other natural and semisynthetic abietanes, is distinguished for its interesting pharmacological properties such as antimicrobial activity, including antiviral. In this study, selected C18-functionalized semisynthetic abietanes prepared from the commercially available (+)-dehydroabietylamine or methyl dehydroabietate were tested in vitro against human coronavirus 229E (HCoV-229E). As a result, a new ferruginol analogue caused a relevant reduction in virus titer as well as the inhibition of a cytopathic effect. A toxicity prediction based on in silico analysis was also performed as well as an estimation of bioavailability. This work demonstrates the antimicrobial and specifically antiviral activity of two tested compounds, making these molecules interesting for the development of new antivirals.

A general methodology to prepare MXene quantum dots (MxQDs) with yields over 20% by liquid-phase laser ablation of the MAX phase is reported. Mechanical and thermal shock by 532 nm laser pulses (7 ns fwhp, 50 mJ × pulse -1 , 1 Hz pulse frequency) produces MAX etching and exfoliation to form MXene QDs, avoiding the use of HF. The process can be followed by absorption and emission spectroscopy and by dynamic laser scattering and it appears to be general, being applied to Ti 3 AlC 2 , Ti 2 AlC, Nb 2 AlC, and V 2 AlC MAX phases. Density functional theory calculations indicate that, depending on the surface terminal groups, the diminution of the MXene size to the nanometric scale makes it possible to control the band gap of the MXene. The photocatalytic activity of these MXene QDs for hydrogen evolution has been observed, reaching an H 2 production for the most efficient Ti 3 C 2 QDs as high as 2.02 mmol × g -1 × h -1 ., (© 2023 The Authors. Small Methods published by Wiley-VCH GmbH.)