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INTRODUCTION: Malnutrition is frequently found in hospitals, where is related to poor outcomes. There are contradictory data about if prevalence of malnutrition is greater in surgical or medical patients. The aim of this study is to know the prevalence of malnutrition in both groups of patients. METHODS: The nutritional status of 189 patients from medical and surgical wards was assessed with Subjective Global Assessment, and data about sex, age, length of hospital stay, mortality, diseases, and wards of admission were collected. Qualitative variables were compared with chi-square test, and independent quantitative variables with Student's t test. P < 0.05 was accepted as significative. RESULTS: The prevalence of malnutrition was 40.2%. Malnourished patients have lost 7.3% of their weight, 67.1% referred a diminished oral intake, and 53.9% anorexia. Malnutrition was significatively associated to male sex, greater length of stay, and cancer. Prevalence and severity of malnutrition were similar in medical and surgical wards, and malnourished patients just differed in diseases (chronic diseases in medical; surgical procedures and cancer in surgery). CONCLUSIONS: Malnutrition is equally prevalent in medical and surgical wards, probably due to different but highly frequent risk factors, and is related to a longer hospital stay. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Home artificial nutrition (HAN) is a technique in increasing use, but the available data about it is limited because record-keeping in most countries is voluntary. Our objective is to describe the characteristics of HAN in our setting and to design a future proposal that improves its coordination. SUBJECTS: Retrospective review of 237 clinical histories of the patients who began with HAN in 2006 in our unit. Variables: epidemiological information, indications, type of HAN, duration, complications and costs. RESULTS: Mean age: 75.4 years. Neurological and neoplasic diseases were the most frequent diagnoses (39.7% and 32.1%, respectively). Main indications were: reduction of ingestion (41.8%) and neurological dysphagia (27.8%). 48.1% presented an important functional impairment and 63.7% needed a caregiver. HAN duration was < 3 months in 43.9% and the principal cause of suspension was the lack of follow-up. Oral nutrition was the preferred route (70.9%), gastrostomy was found in only 3.4%. High-energy formulas were mostly used in patients with supplements (53.3%) and standard formulas in those with complete diets (32.4%). Complications related to this therapy were low, mainly in the oral route. The most frequent were gastrointestinal (19.3%). Mean monthly cost: 159.3 euros/patient and an average travel distance of 26 km to pick up supplies. CONCLUSION: HAN is a safe, short-term therapy, indicated in patients with diminished ingestion due to an acute situation. Our future proposal tries to improve the selection of patients, to facilitate the provision of materials and to customize follow-up to patient needs. [ABSTRACT FROM AUTHOR]

Background: Glaesserella parasuis (G. parasuis) is the primary agent of Glässer's disease, significantly affecting nursery and early fattening piglets. Current prophylactic measures, mainly serovar-specific bacterins administered to sows, are limited by maternal immunity, which can interfere with active immunization in piglets. Subunit vaccines containing G. parasuis-specific antigenic molecules show promise but are not yet commercially available. Transferrin-binding proteins (Tbp), which enable G. parasuis to acquire iron in low-iron environments like mucosal surfaces, have been proposed as potential vaccine antigens. The mucosal administration of a TbpB-based subunit vaccine could provide a promising solution to overcome the limitations posed by maternal immunity, offering an effective approach to control the disease in weaning piglets. This study, conducted in two phases, primarily evaluates (days 0-45) the immunogenicity of a two-dose oral mucosal TbpB-based subunit vaccine (TbpB Y167A ) administered to colostrum-deprived piglets, and subsequently (days 45-52), its heterologous protection by challenging these piglets with four G. parasuis clinical isolates from different TbpB clusters (I, III) and serovars (SV1, SV4, SV5, SV7) recovered from Spanish pig farms., Results: The oral mucosal administration of the two-dose TbpB-based vaccine induced a robust humoral immune response in immunized colostrum-deprived piglets, significantly increasing IgA and IgM concentration 15 days after the second dose (p < 0.01). Upon challenge with four G. parasuis clinical isolates, the vaccine demonstrated heterologous protection, markedly improving survival rates (OR: 8.45; CI 95%: 4.97-14.36) and significantly reducing clinical signs and lesions, regardless of the TbpB cluster and serovar. The vaccine reduced G. parasuis colonization in the respiratory tract (p < 0.0001) and G. parasuis systemic target tissues, like tarsus and carpus joints, liver, and brain (p < 0.05). Immunohistochemical analysis showed a lower macrophage count in different lung locations of immunized piglets (p < 0.0001)., Conclusions: This study demonstrates that oral mucosal administration of the TbpB Y167A subunit vaccine in piglets provides effective heterologous protection against diverse virulent European G. parasuis field isolates, significantly reducing bacterial colonization and dissemination. This vaccine offers a promising alternative to traditional bacterins, overcoming limitations due to maternal immunity, and represents a strong candidate for universal vaccination against Glässer's disease., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures involving animals were approved by the institutional bioethical committee (Reference Number OEBA-ULE-003–2022) and performed according to European regulations regarding animal welfare and protection of animals used for experimental and other scientific purposes. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Canopy shade enhances the activity of PHYTOCHROME INTERACTING FACTORs (PIFs) to boost auxin synthesis in the cotyledons. Auxin, together with local PIFs and their positive regulator CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1), promotes hypocotyl growth to facilitate access to light. Whether shade alters the cellular redox status thereby affecting growth responses, remains unexplored. Here, we show that, under shade, high auxin levels increased reactive oxygen species and nitric oxide accumulation in the hypocotyl of Arabidopsis. This nitroxidative environment favored the promotion of hypocotyl growth by COP1 under shade. We demonstrate that COP1 is S-nitrosylated, particularly under shade. Impairing this redox regulation enhanced COP1 degradation by the proteasome and diminished the capacity of COP1 to interact with target proteins and to promote hypocotyl growth. Disabling this regulation also generated transversal asymmetries in hypocotyl growth, indicating poor coordination among different cells, which resulted in random hypocotyl bending and predictably low ability to compete with neighbors. These findings highlight the significance of redox signaling in the control of diffuse growth during shade avoidance., Competing Interests: Competing interests statement:The authors declare no competing interest.

PROTEIN ARGININE METHYLTRANSFERASES (PRMTs) catalyze arginine (R) methylation that is critical for transcriptional and post-transcriptional gene regulation. In Arabidopsis, PRMT5 that catalyzes symmetric R dimethylation is best characterized. PRMT5 mutants are late-flowering and show altered responses to environmental stress. Among PRMT5 targets are Arabidopsis thaliana GLYCINE RICH RNA BINDING PROTEIN 7 ( At GRP7) and At GRP8 that promote the transition to flowering. At GRP7 R141 has been shown to be modified by PRMT5. Here, we tested whether this symmetric dimethylation of R141 is important for At GRP7's physiological role in flowering time control. We constructed At GRP7 mutant variants with non-methylable R141 (R141A, R141K). Genomic clones containing these variants complemented the late-flowering phenotype of the grp7-1 mutant to the same extent as wild-type At GRP7. Furthermore, overexpression of At GRP7 R141A or R141K promoted flowering similar to overexpression of the wild-type protein. Thus, flowering time does not depend on R141 and its modification. However, germination experiments showed that R141 contributes to the activity of At GRP7 in response to abiotic stress reactions mediated by abscisic acid during early development. Immunoprecipitation of At GRP7-GFP in the prmt5 background revealed that antibodies against dimethylated arginine still recognized At GRP7, suggesting that additional methyltransferases may be responsible for modification of At GRP7.

Background: The thrombin generation assay (TGA) evaluates the potential of plasma to generate thrombin over time, providing a global picture of an individual's hemostatic balance., Objectives: This study aimed to identify novel biological determinants of thrombin generation using a multiomics approach., Methods: Associations between TGA parameters and plasma levels of 377 antibodies targeting 236 candidate proteins for cardiovascular risk were tested using multiple linear regression analysis in 770 individuals with venous thrombosis from the Marseille Thrombosis Association (MARTHA) study. Proteins associated with at least 3 TGA parameters were selected for validation in an independent population of 536 healthy individuals (Etablissement Français du Sang Alpes-Méditerranée [EFS-AM]). Proteins with strongest associations in both groups underwent additional genetic analyses and in vitro experiments., Results: Eighteen proteins were associated (P < 1.33 × 10⁻ 4 ) with at least 3 TGA parameters in MARTHA, among which 13 demonstrated a similar pattern of associations in EFS-AM. Complement proteins C5 and C9 had the strongest associations in both groups. Ex vivo supplementation of platelet-poor plasma with purified C9 protein had a significant dose-dependent effect on TGA parameters. No effect was observed with purified C5. Several single nucleotide polymorphisms associated with C5 and C9 plasma levels were identified, with the strongest association for the C5 missense variant rs17611, which was associated with a decrease in C5 levels, endogenous thrombin potential, and peak in MARTHA. No association of this variant with TGA parameters was observed in EFS-AM., Conclusion: This study identified complement proteins C5 and C9 as potential determinants of thrombin generation. Further studies are warranted to establish causality and elucidate the underlying mechanisms., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Glaesserella ( Haemophilus ) parasuis , the causative agent of Glässer's disease, is present in most pig farms as an early colonizer of the upper respiratory tract. It exhibits remarkable variability in virulence and antimicrobial resistance (AMR), with virulent strains capable of inducing respiratory or systemic disease. This study aimed to characterize the virulence and the AMR profiles in 65 G. parasuis isolates recovered from Spanish swine farms. Virulence was assessed using multiplex leader sequence (LS)-PCR targeting vtaA genes, with all isolates identified as clinical (presumed virulent). Pathotyping based on ten pangenome genes revealed the virulent HPS&#95;22970 as the most frequent (83.1%). Diverse pathotype profiles were observed, with 29 unique gene combinations and two isolates carrying only potentially non-virulent pangenome genes. AMR phenotyping showed widespread resistance, with 63.3% classified as multidrug resistant, and high resistance to clindamycin (98.3%) and tylosin (93.3%). A very strong association was found between certain pathotype genes and AMR phenotypes, notably between the virulent HPS&#95;22970 and tetracycline resistance ( p < 0.001; Φ = 0.58). This study reveals the wide diversity and complexity of G. parasuis pathogenicity and AMR phenotype, emphasizing the need for the targeted characterization of clinical isolates to ensure appropriate antimicrobial treatments and the implementation of prophylactic measures against virulent strains.

Nitrogen (N) deficiency is one of the most prevalent nutrient deficiencies in plants, and has a significant impact on crop yields. In this work we aimed to develop and evaluate innovative strategies to mitigate N deficiency. We studied the effect of supplementing tomato plants grown under suboptimal N nutrition with chitosan microparticles (CS-MPs) during short- and long-term periods. We observed that the supplementation with CS-MPs prevented the reduction of aerial biomass and the elongation of lateral roots (LR) triggered by N deficiency in tomato plantlets. In addition, levels of nitrates, amino acids and chlorophyll, which decreased drastically upon N deficiency, were either partial or totally restored upon CS-MPs addition to N deficient media. Finally, we showed that CS-MPs treatments increased nitric oxide (NO) levels in root tips and caused the up-regulation of genes involved in N metabolism. Altogether, we suggest that CS-MPs enhance the growth and development of tomato plants under N deficiency through the induction of biochemical and transcriptional responses that lead to increased N metabolism. We propose treatments with CS-MPs as an efficient practice focused to mitigate the nutritional deficiencies in N impoverished soils., 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 Elsevier Masson SAS. All rights reserved.)

Reports on neoplasms in bears are scarce, especially concerning ovarian tumors. A large primary ovarian neoplasm with multiple metastasis was found during the necropsy of a 14-year-old free-ranging Eurasian brown bear ( Ursus arctos ) from Northwestern Spain. Histopathology and immunohistochemistry allowed for the diagnosis of a sex cord stromal tumor. This is a complex group of neoplasms which differ in the predominant cell morphology and immunohistochemical features. The microscopic examination revealed two types of cells, one with eosinophilic cytoplasm, intermingled with larger vacuolated cells rich in lipids. The evaluation of the immunoreactivity to different markers, frequently used in the characterization of gonadal tumors (INHA, inhibin-alpha; PLAP, placental alkaline phosphatase; Ki-67; α-SMA, actin alpha-smooth muscle) and inflammation patterns (IBA1, ionized calcium-binding adapter molecule for macrophages; CD3 for T lymphocytes; CD20 for B lymphocytes), displayed significant INHA positive immunostaining of neoplastic cells, as well as inflammatory cell infiltration, mainly composed of macrophages and B lymphocytes. These findings were consistent with a malignant ovarian steroid cell tumor, not otherwise specified. The present study characterizes an unusual type of neoplasm, and also represents the first report of an ovarian sex cord stromal tumor in Ursidae .

Background: Rapid diagnostic clinics (RDCs) provide a streamlined holistic pathway for patients presenting with non-site specific (NSS) symptoms concerning of malignancy. The current study aimed to: 1) assess the prevalence of anxiety and depression, and 2) identify a combination of patient characteristics and symptoms associated with severe anxiety and depression at Guy's and St Thomas' Foundation Trust (GSTT) RDC in Southeast London. Additionally, we compared standard statistical methods with machine learning algorithms for predicting severe anxiety and depression., Methods: Patients seen at GSTT RDC between June 2019 and January 2023 completed the General Anxiety Disorder Questionnaire (GAD-7) and Patient Health Questionnaire (PHQ-8) questionnaires, at baseline. We used logistic regression (LR) and 2 machine learning (ML) algorithms (random forest (RF), support vector machine (SVM)) to predict risk of severe anxiety and severe depression. The models were constructed using a set of sociodemographic and clinical variables., Results: A total of 1734 patients completed GAD-7 and PHQ-8 questionnaires. Of these, the mean age was 59 years (Standard Deviation: 15.5), and 61.5% (n:1067) were female. Prevalence of severe anxiety (GAD-7 score ≥15) was 13.8% and severe depression (PHQ-8 score≥20) was 9.3%. LR showed that a combination of previous mental health condition (PMH, Adjusted Odds Rario (AOR) 3.28; 95% confidence interval (CI) 2.36-4.56), symptom duration >6 months (AOR 2.20; 95%CI 1.28-3.77), weight loss (AOR 1.88; 95% CI 1.36-2.61), progressive pain (AOR 1.71; 95%CI 1.26-2.32), and fatigue (AOR 1.36; 95%CI 1.01-1.84), was positively associated with severe anxiety. Likewise, a combination PMH condition (AOR 3.95; 95%CI 2.17-5.75), fatigue (AOR 2.11; 95%CI 1.47-3.01), symptom duration >6 months (AOR 1.98; 95%CI 1.06-3.68), weight loss (AOR 1.66; 95%CI 1.13-2.44), and progressive pain (AOR 1.50; 95%CI 1.04-2.16), was positively associated with severe depression. LR and SVM had highest accuracy levels for severe anxiety (LR: 86%, SVM: 85%) and severe depression (SVM: 89%, LR: 86%)., Conclusion: High prevalence of severe anxiety and severe depression was found. PMH, fatigue, weight loss, progressive pain, and symptoms >6 months emerged as combined risk factors for both these psychological comorbidities. RDCs offer an opportunity to alleviate distress in patients with concerning symptoms by expediting diagnostic evaluations., 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., (Copyright © 2024 Monroy-Iglesias, Russell, Martin, Fox, Moss, Bruno, Millwaters, Steward, Murtagh, Cargaleiro, Bater, Lavelle, Simpson, Onih, Haire, Reeder, Jones, Smith, Santaolalla, Van Hemelrijck and Dolly.)

Arabidopsis (Arabidopsis thaliana) PROTEIN ARGININE METHYLTRANSFERASE5 (PRMT5) post-translationally modifies RNA-binding proteins by arginine (R) methylation. However, the impact of this modification on the regulation of RNA processing is largely unknown. We used the spliceosome component, SM-LIKE PROTEIN 4 (LSM4), as a paradigm to study the role of R-methylation in RNA processing. We found that LSM4 regulates alternative splicing (AS) of a suite of its in vivo targets identified here. The lsm4 and prmt5 mutants show a considerable overlap of genes with altered AS raising the possibility that splicing of those genes could be regulated by PRMT5-dependent LSM4 methylation. Indeed, LSM4 methylation impacts AS, particularly of genes linked with stress response. Wild-type LSM4 and an unmethylable version complement the lsm4-1 mutant, suggesting that methylation is not critical for growth in normal environments. However, LSM4 methylation increases with abscisic acid and is necessary for plants to grow under abiotic stress. Conversely, bacterial infection reduces LSM4 methylation, and plants that express unmethylable-LSM4 are more resistant to Pseudomonas than those expressing wild-type LSM4. This tolerance correlates with decreased intron retention of immune-response genes upon infection. Taken together, this provides direct evidence that R-methylation adjusts LSM4 function on pre-mRNA splicing in an antagonistic manner in response to biotic and abiotic stress., 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. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To analyse the effectiveness of rapid diagnostic clinics (RDCs) as an alternative pathway for patients with concerning symptoms and a faecal immunochemical test (FIT) result <10. Our primary endpoint was rate of colorectal cancer (CRC) detection. Second endpoints were rates of other cancers and gastrointestinal (GI) serious benign conditions. Finally, we analysed the specific pathway followed by FIT <10 patients with cancer at Guy's and St Thomas NHS Foundation Trust (GSTT) RDC., Design: A retrospective and prospective cohort study., Setting: GSTT RDC, one of England's largest single-centre RDCs. Sociodemographic and clinical characteristics of FIT <10 patients were analysed descriptively., Participants: Patients with an FIT result <10, seen at GSTT RDC between 1 January 2020 and 5 May 2023., Results: A total of 1299 patients with an FIT<10 were seen at GSTT RDC between January 2020 and May 2023. Of these, 66% (n=861) reported weight loss, 62% (n=805) pain, 37% (n=481) fatigue, 34% (n=444) were anaemic and 23% (n=301) had nausea and vomiting. Among these patients, 7% (n=88) received a cancer diagnosis, 36% (n=462) were identified as having a serious benign condition. Within the patients with cancer, 9% (n=8) were diagnosed with CRC. Among patients with serious benign conditions, 7% (n=31) were referred to colorectal, hepatopancreatobiliary, or upper GI specialists., Conclusion: This study demonstrates the effectiveness of RDCs as an alternate pathway for FIT <10 patients with ongoing clinical concerns. These results contribute to enhancing patient care and optimising resource allocation within the healthcare system., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

While previous reviews found a positive association between pre-existing cancer diagnosis and COVID-19-related death, most early studies did not distinguish long-term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher-quality evidence on risk of COVID-19-related death for people with recent/active cancer (compared to people without) in the pre-COVID-19-vaccination period. We searched the WHO COVID-19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk-of-bias assessment was based on the Newcastle-Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse-variance random-effects models. Random-effects meta-regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID-19-related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36-1.61, I 2  = 0; people with COVID-19: aOR = 1.58, 95% CI: 1.41-1.77, I 2  = 0.58; inpatients with COVID-19: aOR = 1.66, 95% CI: 1.34-2.06, I 2  = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4-4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68-2.68, I 2  = 0.43), and for metastatic cancers. Meta-regression suggested risk of COVID-19-related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37-1.75) at 1 year and aOR = 0.98 (95% CI: 0.80-1.20) at 5 years post-cancer diagnosis/treatment. In conclusion, before COVID-19-vaccination, risk of COVID-19-related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

The first crystal structure of an ortho-lithium phosphinothioic amide complexed with tetramethylethylenediamine 12 is reported. The complex consists of a spirane in which the spiro-lithium is N,N- and C,S-chelated by the diamine and organophosphorus ligands, respectively. The analogous ortho anion 14 obtained by Sn(IV)/Li transmetallation in THF has also been synthesized. Nuclear magnetic resonance study of both anions showed that they exist as monomers in solution and are involved in dynamic processes including the restricted rotation around the P-N bond. 14 is converted at room temperature by nucleophilic cyclization to the dearomatized anion 15, which evolves after a few hours to the benzophosphindole sulfide 16. Density functional theory calculations supported the aggregation state in solution and were used to explore the conformational space of anion 12, the mechanism of ortho-lithiation directed by P(X)-N (X=O, S) groups, and the mechanism of formation of 15., (© 2023 Wiley‐VCH GmbH.)

Despite the increasingly widespread clinical impact of adenovirus (HAdV) infections in healthy individuals and the associated high morbidity in immunosuppressed patients, particularly among the paediatric population, a specific treatment for this virus has yet to be developed. In this study, we report the anti-HAdV activity of sub-micromolar concentrations of four heteroleptic (C^S)-cycloaurated complexes bearing a single thiophosphinamide [ Au(dpta)Cl 2 , Au(dpta)(mrdtc) , and Au(dpta)(dedtc) ] or thiophosphonamide [ Au(bpta)(dedtc) ] chelating ligand and a dithiocarbamate moiety. In addition to their low cytotoxicity, the findings of mechanistic assays revealed that these molecules have antiviral activity by targeting stages of the viral replication cycle subsequent to DNA replication. Additionally, all four compounds showed a significant inhibition of human cytomegalovirus (HCMV) DNA replication, thereby providing evidence for potential broad-spectrum antiviral activity., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier Ltd.)

Objective: This work explores the advances in conversational agents aimed at the detection of mental health disorders, and specifically the screening of depression. The focus is put on those based on voice interaction, but other approaches are also tackled, such as text-based interaction or embodied avatars., Methods: PRISMA was selected as the systematic methodology for the analysis of existing literature, which was retrieved from Scopus, PubMed, IEEE Xplore, APA PsycINFO, Cochrane, and Web of Science. Relevant research addresses the detection of depression using conversational agents, and the selection criteria utilized include their effectiveness, usability, personalization, and psychometric properties., Results: Of the 993 references initially retrieved, 36 were finally included in our work. The analysis of these studies allowed us to identify 30 conversational agents that claim to detect depression, specifically or in combination with other disorders such as anxiety or stress disorders. As a general approach, screening was implemented in the conversational agents taking as a reference standardized or psychometrically validated clinical tests, which were also utilized as a golden standard for their validation. The implementation of questionnaires such as Patient Health Questionnaire or the Beck Depression Inventory, which are used in 65% of the articles analyzed, stand out., Conclusions: The usefulness of intelligent conversational agents allows screening to be administered to different types of profiles, such as patients (33% of relevant proposals) and caregivers (11%), although in many cases a target profile is not clearly of (66% of solutions analyzed). This study found 30 standalone conversational agents, but some proposals were explored that combine several approaches for a more enriching data acquisition. The interaction implemented in most relevant conversational agents is text-based, although the evolution is clearly towards voice integration, which in turns enhances their psychometric characteristics, as voice interaction is perceived as more natural and less invasive., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ivan Otero reports financial support was provided by AtlantTIC University of Vigo., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The tautomerism of a series of 5-alkyl substituted 3-(2-pyridyl)-1,2,4-triazoles in DMSO- d 6 -containing water has been investigated by 1 H, 13 C and 15 N NMR spectroscopy. The populations of the three possible regioisomers in the tautomeric equilibrium (A [3-alkyl-5-(2-pyridyl)-1 H ], B [5-alkyl-3-(2-pyridyl)-1 H ] and C [5-alkyl-3-(2-pyridyl)-4 H ]) were determined. Isomers A (17-40%) and B (54-79%) are the major components and their ratio is insensitive to the substitution pattern, except for the unsubstituted and the methoxymethyl substituted derivatives. The isomer C (3-5%) has been fully characterised for the first time by NMR spectroscopy. Activation energies of tautomerisation (14.74-16.78 kcal mol -1 ) were determined by EXSY experiments, which also supported the involvement of water in the tautomerisation. Substituent effects on the 15 N chemical shifts are relatively small. The DFT study of the tautomerism in DMSO-water showed that both A/B and B/C interconversions are assisted by the pyridine substituent and catalysed by solvent molecules. The NH-A/NH-B tautomerisation takes place via a relayed quadruple proton transfer mediated by three water molecules in the hydrogen-bonded cyclic substructure of a triazole·4H 2 O complex. The equilibrium B ⇄ C involves three steps: NH-B transfer to the pyridyl nitrogen mediated by a water molecule in a 1 : 1 cyclic complex, rotamerisation to bring the pyridinium NH close to N4 of the triazole catalysed by complexation to a DMSO molecule and transfer of the NH from the pyridinium donor to the N4 acceptor via a 1 : 1 complex with a bridging water molecule. This mechanism of 1,3-prototropic shift in triazoles is unprecedented in the literature.

Twenty-five years ago, a seminal paper demonstrated that warm temperatures increase auxin levels to promote hypocotyl growth in Arabidopsis thaliana. Here we highlight recent advances in auxin-mediated thermomorphogenesis and identify unanswered questions. In the warmth, PHYTOCHROME INTERACTING FACTOR 4 (PIF4) and PIF7 bind the YUCCA8 gene promoter and, in concert with histone modifications, enhance its expression to increase auxin synthesis in the cotyledons. Once transported to the hypocotyl, auxin promotes cell elongation. The meta-analysis of expression of auxin-related genes in seedlings exposed to temperatures ranging from cold to hot shows complex patterns of response. Changes in auxin only partially account for these responses. The expression of many SMALL AUXIN UP RNA (SAUR) genes reaches a maximum in the warmth, decreasing towards both temperature extremes in correlation with the rate of hypocotyl growth. Warm temperatures enhance primary root growth, the response requires auxin, and the hormone levels increase in the root tip but the impacts on cell division and cell expansion are not clear. A deeper understanding of auxin-mediated temperature control of plant architecture is necessary to face the challenge of global warming., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

One hundred Actinobacillus pleuropneumoniae (App) and sixty Pasteurella multocida subsp. multocida serogroup A (PmA) isolates were recovered from porcine pneumonic lungs collected from eight central or southern states of Brazil between 2014 and 2018 (App) or between 2017 and 2021 (PmA). A. pleuropneumoniae clinical isolates were typed by multiplex PCR and the most prevalent serovars were 8, 7 and 5 (43, 25% and 18%, respectively). In addition, three virulence genes were assessed in P. multocida isolates, all being positive to capA (PmA) and kmt1 genes, all negative to capD and toxA , and most of them (85%) negative to pfhA gene. The susceptibility of both pathogens to tildipirosin was investigated using a broth microdilution assay. The percentage of isolates susceptible to tildipirosin was 95% for App and 73.3% for PmA. The MIC 50 values were 0.25 and 1 μg/mL and the MIC 90 values were 4 and >64 μg/mL for App and PmA, respectively. Finally, a multiple-dose protocol of tildipirosin was tested in suckling piglets on a farm endemic for both pathogens. Tildipirosin was able to prevent the natural colonization of the tonsils by App and PmA and significantly ( p < 0.0001) reduced the burden of Glaesserella parasuis in this tissue. In summary, our results demonstrate that: (i) tildipirosin can be included in the list of antibiotics to control outbreaks of lung disease caused by App regardless of the capsular type, and (ii) in the case of clinical strains of App and PmA that are sensitive to tildipirosin based on susceptibility testing, the use of this antibiotic in eradication programs for A. pleuropneumoniae and P. multocida can be strongly recommended.

Canine distemper virus (CDV) affects a huge diversity of domestic and wild carnivores, with increasing numbers of mortality events worldwide. The local cell-mediated immune response elicited against a natural infection is an important factor in determining the outcome of CDV infection. Therefore, the purposes of this study were to describe the local immune response within the central nervous systems (CNSs) of seven badgers naturally infected with CDV in Asturias (Atlantic Spain) and to determine the phenotype and distribution of microglial cells, T and B lymphocytes, and astrocytes in the foci of gliosis located in the thalamus and cerebellum using immunohistochemistry. The immunohistochemical assessment demonstrated the presence of Iba1-positive microglia and GFAP-positive astrocytes in the foci of gliosis, whereas T (CD3-negative) or B (CD20-negative) lymphocytes in those same lesions were absent. Our results also revealed that the badgers with natural CDV encephalitis presented lesions mostly located in the white matter of the thalamus and cerebellum, suggesting a CDV-specific tropism for the white matter of badger brains in those locations. The knowledge gained in the field of the immunopathogenesis of distemper disease affecting the CNSs of badgers could help to clarify CDV disease patterns in this species.

Atypical teratoid rhabdoid tumors (ATRT) are divided into MYC, TYR and SHH subgroups, suggesting diverse lineages of origin. Here, we investigate the imaging of human ATRT at diagnosis and the precise anatomic origin of brain tumors in the Rosa26-Cre ERT2 ::Smarcb1 flox/flox model. This cross-species analysis points to an extra-cerebral origin for MYC tumors. Additionally, we clearly distinguish SHH ATRT emerging from the cerebellar anterior lobe (CAL) from those emerging from the basal ganglia (BG) and intra-ventricular (IV) regions. Molecular characteristics point to the midbrain-hindbrain boundary as the origin of CAL SHH ATRT, and to the ganglionic eminence as the origin of BG/IV SHH ATRT. Single-cell RNA sequencing on SHH ATRT supports these hypotheses. Trajectory analyses suggest that SMARCB1 loss induces a de-differentiation process mediated by repressors of the neuronal program such as REST, ID and the NOTCH pathway., (© 2023. Springer Nature Limited.)

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease that, due to dyspnea, decreases patients' physical function and quality of life. The aim of the research was to evaluate the effectiveness of water-based exercise (WE) in improving functional capacity and respiratory muscle strength in patients with COPD. It consisted of a systematic review and meta-analysis of eight randomized clinical trials (RCTs) from the last 10 years, found in PubMed, PEDro, Scopus and Web of Science databases. Methodological quality was analyzed using the PEDro scale and the Cochrane Collaboration Risk of Bias Tool. Regarding the evaluation of functional capacity, mainly assessed were lung function, respiratory muscle strength, and maximal or aerobic exercise. The results showed that WE improves functional capacity compared to a non-exercising control group (SMD: 73.42; IC 95%: 40.40 to 106.45; I 2 : 0%). There are no statistically significant differences between a WE treatment and a land exercise (LE) treatment ( p = 0.24) in functional capacity, nor with respect to respiratory muscle strength ( p = 0.97). These data should be interpreted with caution, as more RCTs with aquatic intervention in COPD patients are needed to elucidate whether there are differences between WE or LE according to patient characteristics and comorbidities.

Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker., (© 2023. The Author(s).)

Introduction: Antimicrobial resistance is a pressing global concern that has led to the search for new antibacterial agents with novel targets or non-traditional approaches. Recently, organogold compounds have emerged as a promising class of antibacterial agents. In this study, we present and characterize a (C^S)-cyclometallated Au(III) dithiocarbamate complex as a potential drug candidate., Methods and Results: The Au(III) complex was found to be stable in the presence of effective biological reductants, and showed potent antibacterial and antibiofilm activity against a wide range of multidrug-resistant strains, particularly gram-positive strains, and gram-negative strains when used in combination with a permeabilizing antibiotic. No resistant mutants were detected after exposing bacterial cultures to strong selective pressure, indicating that the complex may have a low propensity for resistance development. Mechanistic studies indicate that the Au(III) complex exerts its antibacterial activity through a multimodal mechanism of action. Ultrastructural membrane damage and rapid bacterial uptake suggest direct interactions with the bacterial membrane, while transcriptomic analysis identified altered pathways related to energy metabolism and membrane stability including enzymes of the TCA cycle and fatty acid biosynthesis. Enzymatic studies further revealed a strong reversible inhibition of the bacterial thioredoxin reductase. Importantly, the Au(III) complex demonstrated low cytotoxicity at therapeutic concentrations in mammalian cell lines, and showed no acute in vivo toxicity in mice at the doses tested, with no signs of organ toxicity., Discussion: Overall, these findings highlight the potential of the Au(III)-dithiocarbamate scaffold as a basis for developing novel antimicrobial agents, given its potent antibacterial activity, synergy, redox stability, inability to produce resistant mutants, low toxicity to mammalian cells both in vitro and in vivo , and non-conventional mechanism of action., Competing Interests: SS, CR, RS, MI, and FL-O have patents on complex 1 and 2. QC and EA are shareholders of Selenozyme AB selling recombinant selenoproteins, including human TrxR. EA is a shareholder of Thioredoxin Systems AB, developing antibiotics targeting the bacterial thioredoxin system. The remaining 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., (Copyright © 2023 Ratia, Ballén, Gabasa, Soengas, Velasco-de Andrés, Iglesias, Cheng, Lozano, Arnér, López-Ortiz and Soto.)

Background: Mycobacterium tuberculosis is a slow-growing bacterium, which could delay its diagnosis and, therefore, promote the spread of the disease. Whole-genome sequencing allows us to obtain the complete drug-resistance profile of the strain; however, bacterial cultivation of clinical samples, along with complex processing, is required., Methods: In this work, we explore AmpliSeq, an amplicon-based enrichment method for preparing libraries for targeted next-generation sequencing, to identify lineage and drug resistance directly from clinical samples., Results: In our study, 111 clinical samples were tested. The lineage was identified in 100% of the culture-derived samples (52/52), in 95% of the smear (BK)-positive clinical samples (38/40) and in 42.1% of the BK-negative clinical samples (8/19). The drug-resistance profile was accurately identified in all but 11 samples, in which some phenotypic and genotypic discrepancies were found. In this respect, our panels were not exact in the detection of streptomycin resistance for isolates derived from clinical samples, as an extremely high number of SNPs in the rrs and rrl genes were detected due to cross-contamination., Conclusion: This technique has demonstrated high sensitivity in obtaining the drug-resistance profile of the isolates, as even those samples with DNA concentrations below the detection limit of Qubit produced a result. AmpliSeq technology is cheaper than whole-genome sequencing, easy to perform by laboratory technicians and applicable to any microorganism using the Ion Torrent platform.

Background: Intraplaque hemorrhage (IPH) is a hallmark of atherosclerotic plaque instability. Biliverdin reductase B (BLVRB) is enriched in plasma and plaques from patients with symptomatic carotid atherosclerosis and functionally associated with IPH., Objective: We explored the biomarker potential of plasma BLVRB through (1) its correlation with IPH in carotid plaques assessed by magnetic resonance imaging (MRI), and with recurrent ischemic stroke, and (2) its use for monitoring pharmacotherapy targeting IPH in a preclinical setting., Methods: Plasma BLVRB levels were measured in patients with symptomatic carotid atherosclerosis from the PARISK study ( n = 177, 5 year follow-up) with and without IPH as indicated by MRI. Plasma BLVRB levels were also measured in a mouse vein graft model of IPH at baseline and following antiangiogenic therapy targeting vascular endothelial growth factor receptor 2 (VEGFR-2)., Results: Plasma BLVRB levels were significantly higher in patients with IPH (737.32 ± 693.21 vs. 520.94 ± 499.43 mean fluorescent intensity (MFI), p = 0.033), but had no association with baseline clinical and biological parameters. Plasma BLVRB levels were also significantly higher in patients who developed recurrent ischemic stroke (1099.34 ± 928.49 vs. 582.07 ± 545.34 MFI, HR = 1.600, CI [1.092-2.344]; p = 0.016). Plasma BLVRB levels were significantly reduced following prevention of IPH by anti-VEGFR-2 therapy in mouse vein grafts (1189 ± 258.73 vs. 1752 ± 366.84 MFI; p = 0.004)., Conclusions: Plasma BLVRB was associated with IPH and increased risk of recurrent ischemic stroke in patients with symptomatic low- to moderate-grade carotid stenosis, indicating the capacity to monitor the efficacy of IPH-preventive pharmacotherapy in an animal model. Together, these results suggest the utility of plasma BLVRB as a biomarker for atherosclerotic plaque instability.

Introduction: The Geriatric Depression Scale is an instrument used to identify depression in people of an older age. The original English version of this scale has been translated into Spanish (GDS- VE ); two shorter versions of 5- (GDS-5) and 15-items (GDS-15) have been developed., Aim of the Study: To assess the validity and compare the 5- and 15-item Spanish versions of the GDS among the Spanish population., Materials and Methods: 573 Galicia residents aged >50 years participated in this study. The following instruments were applied: the 19-item Control, Autonomy, Self-Realization and Pleasure scale, the Subjective Memory Complaints Questionnaire, the Mini-Mental State Examination test, the GDS-5, and the GDS-15., Results: We found differences in total score between GDS-5 and GDS-15 regarding the variable sex. Internal reliability for GDS-5 and GDS-15 was 0.495 and 0.715, respectively. Sensitivity and specificity for GDS-5 - with a cut-off value of 1 - was 0.517 and 0.650, respectively; for GDS-15 - with a cut-off value of 3 points - sensitivity was 0.755 and specificity 0.668. GDS-5 has a ROC curve of 0.617 and GDS-15 of 0.764., Conclusion: GDS-15, and to a greater extent GDS-5, should be revised or even reformulated to improve their diagnostic usefulness by choosing higher discriminative ability items or even include new items with greater sensitivity that consider currently prevailing psychosocial factors., 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., (Copyright © 2023 Bugallo-Carrera, Dosil-Díaz, Pereiro, Anido-Rifón, Pacheco-Lorenzo, Fernández-Iglesias and Gandoy-Crego.)

Introduction and Objectives: The experiences and changes that come along with old age may lead to a feeling of loneliness, usually followed by negative physical and mental manifestations. In this systematic review, we evaluated the existing tools to assess loneliness in older adults., Methods: We performed a literature search in the Web of Science, Medline, and PsycINFO, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After, we examined the psychometric properties of the instruments with a focus on reliability, validity, and main conclusions., Results: We included 27 articles published between 1996 and 2021., Conclusion: To date, there are few instruments to assess loneliness in older adults. In general, they present adequate psychometric properties, although it is true that some scales show somewhat low levels of reliability and validity., 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., (Copyright © 2023 Bugallo-Carrera, Dosil-Díaz, Anido-Rifón, Pacheco-Lorenzo, Fernández-Iglesias and Gandoy-Crego.)