Performance and healthcare analysis in elite sports teams using artificial intelligence: a scoping review.

Introduction: In competitive sports, teams are increasingly relying on advanced systems for improved performance and results. This study reviews the literature on the role of artificial intelligence (AI) in managing these complexities and encouraging a system thinking shift. It found various AI applications, including performance enhancement, healthcare, technical and tactical support, talent identification, game prediction, business growth, and AI testing innovations. The main goal of the study was to assess research supporting performance and healthcare. Methods: Systematic searches were conducted on databases such as Pubmed, Web of Sciences, and Scopus to find articles using AI to understand or improve sports team performance. Thirty-two studies were selected for review. Results: The analysis shows that, of the thirty-two articles reviewed, fifteen focused on performance and seventeen on healthcare. Football (Soccer) was the most researched sport, making up 67% of studies. The revised studies comprised 2,823 professional athletes, with a gender split of 65.36% male and 34.64% female. Identified AI and non-AI methods mainly included Tree-based techniques (36%), Ada/XGBoost (19%), Neural Networks (9%), K-Nearest Neighbours (9%), Classical Regression Techniques (9%), and Support Vector Machines (6%). Conclusions: This study highlights the increasing use of AI in managing sports-related healthcare and performance complexities. These findings aim to assist researchers, practitioners, and policymakers in developing practical applications and exploring future complex systems dynamics.

Analyzing ECG signals in professional football players using machine learning techniques.

Background: Football player's health is important, and preventing sudden cardiac arrest may be a critical issue. Professional football players have different ECG signals than the average population, yet there are considerable gaps in study whereas the general population has been extensively studied. Objectives: (a) Generate a reference and innovative resting 12-lead ECG database from 54 UEFA PRO level male football players from La Liga. This is a novel approach to cope the ECG and possible arrythmias in athletes. (b) Manage each XML athlete ECG data and develop a free-use program to visualize, denoise and filter the signal with the capacity to automate the labelling of the waves and save the reports. (c) Study the ECG wave shape and generate models through ML to analyse its utility to automate basic diagnosis. Methods: The dataset collection is based on a prospective observational cohort and includes 10 s, 12-lead ECGs and rhythm and condition labels for each athlete. Physiological sport arrhythmias, T-Wave shape and other findings were studied and labelled. ECG Visualizer was developed and used for 3 machine learning (ML) methods to automate sinus bradycardia arrhythmia diagnosis. Results: A dataset with 163 ECGs in XML format was collected comprising the Pro Football 12-lead Resting Electrocardiogram Database (PF12RED). "ECG Visualizer" software was developed, and ML was shown to be useful in detecting sinus bradycardia. Conclusions: The study demonstrates that AI and machine learning can detect simple arrhythmias with accuracy, also it provides a valuable dataset and a free software application.

A community-based intervention study involving family gardens with aromatic herbs on changes in dietary and urinary sodium.

OBJECTIVE: To measure dietary and urinary changes in sodium (Na) intake and excretion through the implementation of family gardens with aromatic herbs and workshops for cooking, using the herbs as a substitute for salt and seasoning powder. METHODS: Thirty-five participants from a neighborhood of Mexico City were included. A general questionnaire was administered to collect information on sociodemographic factors. At baseline and 3 months later, a dietary evaluation was conducted, and 24-hour urine samples were collected. Food items reported were classified according to the NOVA classification. Visits to participants´ houses were conducted to measure the amount of salt and seasoning powder added to food during the preparation of meals as well as a home food inventory. All participants were given a family garden with 6 aromatic herbs and a recipe book. The intervention included 7 cooking and 3 garden care workshops. Qualitative information on the experience was also collected. Linear regression models were run in order to estimate the contribution of each NOVA group, salt, and seasoning powder to total dietary Na intake. RESULTS: Participants were 44 years old on average and were mainly women (91.4%). The participation compliance in the workshops was 69.5%. After 3 months, there was a Na intake mean reduction of 976 mg. There was also a reduction in the excreted urinary Na of 325 mg per day. CONCLUSION: A positive level of involvement in this program had a direct influence on dietary habits to lower Na consumption.

Could the aroma of spices produce a cross-modal enhancement of food saltiness and contribute to reducing salt intake?

BACKGROUND: As a result of its correlation with cardiovascular diseases, salt intake must be reduced. According to multi-sensory integration, aroma plays an important role in saltiness enhancement; this could enable a food's salt content to be reduced without losing acceptance. We therefore studied the effect of three spices, Curcuma longa, Laurus nobilis L. and Petroselinum crispum L., on saltiness enhancement through sensory tests on consumers. This was followed by olfactometric analysis with the aim of relating the effect to the spices' aromatic composition. RESULTS: According to the odour-induced salty taste enhancement (OISE) mean values, bay leaf and turmeric had the highest effect on saltiness enhancement, at a similar level to dry-cured ham aroma, wherwas parsley had a significantly lower OISE value. Only one odour-active compound (OAC), eugenol, showed a direct correlation with the spices' OISE values. Turmeric primarily had OACs with sweet aroma, whereas bay leaf had more OACs belonging to the spicy-aroma category. CONCLUSION: The three spices, turmeric, bay leaf and parsley, investigated in the present study appear to enhance the salty taste of mashed potato with a low salt content. The results suggest that an interaction effect among OACs with different aromatic ranges may exist. Therefore, when the global OAC modified frequency value, grouped according to aroma range, was considered, the sweet range appears to counteract the effect of the spicy aroma on saltiness. © 2024 Society of Chemical Industry.

A systematic review and meta-analysis of human population studies on the association between exposure to toxic environmental chemicals and left ventricular dysfunction (LVD).

BACKGROUND: Exposure to environmental chemicals has been associated with an elevated risk of heart failure (HF). However, the impact on early markers of HF, such as left ventricular dysfunction (LVD), remains limited. OBJECTIVE: To establish a foundation of evidence regarding early HF markers and their association with environmental pollutants, a systematic review and meta-analysis was conducted. METHODS: The search, conducted on October 13th, 2023, encompassed PubMed, Embase, and Web of Science without filters, focusing on observational studies reporting myocardial geometrical, structural, or functional alterations in individuals without a history of heart disease. This included the general adult population, workers, young people, and the elderly. The risk of bias was assessed using the ROBINS-I tool at both study and item levels. RESULTS: The systematic review included 17 studies involving 43.358 individuals exposed to air pollution and 2038 exposed to heavy metals. Approximately 41% of the effect measures of associations reported significant abnormalities in myocardial structure or function. The metanalyses by pollutants categories indicated positive associations between LV systolic and diastolic abnormalities and exposure to PM2.5 [-0.069 (-0.104, -0.033); -0.044 (-0.062, -0.025)] and PM10 [-0.055 (-0.087, -0.022); -0.030 (-0.050, -0.010)] and NO2 [-0.042 (-0.071, -0.013); -0.021 (-0.037, -0.004)], as well as positive associations between lead exposure and LV systolic abnormalities [-0.033 (-0.051, -0.016)]. CONCLUSIONS: Existing evidence shows that specific early markers of HF may be associated with exposure to chemical pollutants. It is recommended to include such endpoints in new longitudinal and case-control studies to confirm further risk associations. These studies should consider co-exposures, account for vulnerable groups, and identify cardiotoxic compounds that may require regulation. When examining the link between myocardial abnormalities and environmental exposure, it is also advisable to explore the supportive use of Adverse Outcome Pathway (AOP) approaches to confirm a causal relationship.

Tretinoin improves the anti-cancer response to cyclophosphamide, in a model-selective manner.

BACKGROUND: Chemotherapy is included in treatment regimens for many solid cancers, but when administered as a single agent it is rarely curative. The addition of immune checkpoint therapy to standard chemotherapy regimens has improved response rates and increased survival in some cancers. However, most patients do not respond to treatment and immune checkpoint therapy can cause severe side effects. Therefore, there is a need for alternative immunomodulatory drugs that enhance chemotherapy. METHODS: We used gene expression data from cyclophosphamide (CY) responders and non-responders to identify existing clinically approved drugs that could phenocopy a chemosensitive tumor microenvironment (TME), and tested combination treatments in multiple murine cancer models. RESULTS: The vitamin A derivative tretinoin was the top predicted upstream regulator of response to CY. Tretinoin pre-treatment induced an inflammatory, interferon-associated TME, with increased infiltration of CD8 + T cells, sensitizing the tumor to subsequent chemotherapy. However, while combination treatment significantly improved survival and cure rate in a CD4+ and CD8+ T cell dependent manner in AB1-HA murine mesothelioma, this effect was model-selective, and could not be replicated using other cell lines. CONCLUSIONS: Despite the promising data in one model, the inability to validate the efficacy of combination treatment in multiple cancer models deprioritizes tretinoin/cyclophosphamide combination therapy for clinical translation.

Unveiling the crystal and magnetic texture of iron oxide nanoflowers.

Iron oxide nanoflowers (IONF) are densely packed multi-core aggregates known for their high saturation magnetization and initial susceptibility, as well as low remanence and coercive field. This study reports on how the local magnetic texture originating at the crystalline correlations among the cores determines the special magnetic properties of individual IONF over a wide size range from 40 to 400 nm. Regardless of this significant size variation in the aggregates, all samples exhibit a consistent crystalline correlation that extends well beyond the IONF cores. Furthermore, a nearly zero remnant magnetization, together with the presence of a persistently blocked state, and almost temperature-independent field-cooled magnetization, support the existence of a 3D magnetic texture throughout the IONF. This is confirmed by magnetic transmission X-ray microscopy images of tens of individual IONF, showing, in all cases, a nearly demagnetized state caused by the vorticity of the magnetic texture. Micromagnetic simulations agree well with these experimental findings, showing that the interplay between the inter-core direct exchange coupling and the demagnetizing field is responsible for the highly vortex-like spin configuration that stabilizes at low magnetic fields and appears to have partial topological protection. Overall, this comprehensive study provides valuable insights into the impact of crystalline texture on the magnetic properties of IONF over a wide size range, offering a deeper understanding of their potential applications in fields such as biomedicine and water remediation.

Fertility in seasonal-calving pasture-based lactating dairy cows following timed artificial insemination or timed embryo transfer with fresh or frozen in vitro-produced embryos.

The objective was to compare pregnancy per service event (P/S) in lactating dairy cows following timed artificial insemination (AI) or timed embryo transfer (ET) using either fresh or frozen in vitro-produced embryos. Oocytes were collected once per week for up to 9 wk using transvaginal ovum pick-up from elite dairy donors (ET-DAIRY; n = 40; Holstein-Friesian and Jersey) and elite beef donors (ET-ELITE-BEEF; n = 21; Angus). Both ET-DAIRY and ET-ELITE-BEEF donors consisted of heifers and cows. In addition, oocytes were collected from the ovaries of beef heifers of known pedigree following slaughter at a commercial abattoir (ET-COMM-BEEF; n = 119). Following in vitro maturation and fertilization, presumptive zygotes were cultured in vitro to the blastocyst stage. Grade 1 blastocysts were either transferred fresh or frozen for on-farm thawing and direct transfer. A total of 1,106 recipient cows (all lactating, predominantly Holstein-Friesian) located on 16 herdlets were blocked based on parity, calving date, and Economic Breeding Index, and randomly assigned to receive AI (n = 243) or ET (n = 863) after estrous synchronization with a 10-d Progesterone-synch protocol. Cows assigned to ET were further randomized to receive fresh (n = 187) or frozen (n = 178) ET-ELITE-BEEF embryos, fresh (n = 169) or frozen (n = 162) ET-DAIRY embryos, or fresh (n = 80) or frozen (n = 87) ET-COMM-BEEF embryos. Pregnancy was diagnosed using transrectal ultrasound on d 32 to 35 after synchronized ovulation and confirmed on d 62 to 65, at which time fetal sex was determined. Pregnancy per service event at d 32 was not different between AI (48.8%) and ET (48.9%) and did not differ between dairy and beef embryos (50.3% vs. 48.1%, respectively). However, P/S was less on d 32 following transfer of frozen embryos (41.6%) compared with fresh embryos (56.1%). Pregnancy loss between d 32 and 62 was greater for ET (15.1%) compared with AI (4.7%), with greater losses observed for frozen beef (18.5%), fresh beef (17.3%), and frozen dairy (19.2%) compared with fresh dairy (6.0%) embryos. Serum progesterone (P4) concentration on d 7 was associated with P/S at d 32 and 62. Cows in the quartile with the least serum P4 concentrations (quartile 1) had less probability of being pregnant on d 32 (33.4%) compared with cows in the 3 upper quartiles for serum P4 (45.7%, 55.6%, and 61.2% for quartile 2, quartile 3, and quartile 4, respectively). Sex ratio (male:female) at d 62 was skewed toward more male fetuses following ET (61.1:38.9) compared with AI (43.2:56.8) and was consistent with the sex ratio among in vitro blastocysts (61.2:38.8). In conclusion, P/S was similar for AI and ET, although pregnancy loss between d 32 and 62 was greater for ET than for AI.

Predictive toxicological effects of Artemisia absinthium essential oil on hepatic stellate cells.

Medicinal plants are important worldwide, considering their properties for treating diseases; however, few studies have evaluated their toxicological potential. Among them, Artemisia absinthium is frequently used to treat liver diseases, because its essential oil has several popular therapeutic properties. Based on this information, in the present study, we investigated molecular connectors of physiological effects of the Artemisia absinthium essential oil on human hepatic stellate cell line, LX-2, to explore the potential toxicity of the plant on liver cells. LX-2 is a cellular model to investigate mechanisms of liver fibrosis; then, to analyze the essential oil effects LX-2 was cultured under different conditions, treated or not with the essential oil at 0.4 µg/µL for 24 h. Next, fluorescence microscopy analyses, gene expression measurements, and biochemical approaches revealed that the essential oil reduced pro-fibrogenic markers; however, disrupt lipid metabolism, and cause cellular stress, by the activation of cellular detoxification and pro-inflammatory processes. In conclusion, the hepatic stellate cells incubated with the essential oil present an antifibrotic potential, supporting its popular use; however, the combined results suggest that the essential oil of Artemisia absinthium should be used with caution.

Workplace aggressions on hospital workers: A current and prevalent problem with a high demand for training.

BACKGROUND: Workplace aggressions on hospital workers is a very frequent and under-reported problem. OBJECTIVE: The novel objective of our study was to analyze the number of workplace aggressions per hospital worker. Other objectives of the study were to analyze the management knowledge and interest in receiving training on aggressions by hospital workers. METHODS: An anonymous survey was handed out among all professionals in a university hospital. RESULTS: A total of 1118 anonymous surveys were collected. The responders declared that throughout their working life they had suffered some sort of verbal aggression in the hospital in 766 cases (68.5%) and physical aggression in 393 cases (35.2%). Multiple logistic regression analyses found higher risk of receiving physical and verbal aggression in the nursing category and in the Emergency, Critical Care or Psychiatry Units, and a higher risk of receiving physical aggression in women. The score on the level of personal knowledge regarding the legal, physical, and psychological management of aggressions (score 0-10 for each of the 3 aspects) was 2.91±2.68 in legal management, 2.97±2.77 in psychological management and 2.91±2.76 in physical management. The opinion about the interest of receiving training (score from 0 to 10) on the legal management of hospital aggressions was 8.90±1.72, on psychological management was 8.85±1.78 and on physical management was 8.88±1.78. CONCLUSIONS: Workplace aggression on hospital workers mainly affects women, the nursing category and the Emergency, Critical Care or Psychiatry Units. Hospital workers showed little knowledge on the topic but a great interest in receiving training.

Determination of volatile compounds for the differentiation of PDO fortified wines with different ageing methods as a tool for controlling their authenticity.

The aim of this work was to study the differentiating volatile profiles of the Spanish protected designation of origin (PDO) fortified wines obtained by headspace solid phase microextraction in conjunction with gas chromatography-mass spectrometry and powerful chemometric tools, to finally identify the marker volatile compounds most related to fortified wine types. Results revealed a satisfactory discrimination, for the first time, of the different types of PDO fortified wines, involving only a reduced number of volatile compounds selected by chemometrics. Thus, 28 volatile compounds were responsible for the differentiation according to ageing type (biological, oxidative, or mixed) resulting useful markers for the identification of each specific type of fortified wine. Among them, some esters were strongly related to biological ageing, aldehydes and acids to oxidative ageing, and lactones to mixed ageing. These volatile molecules involved in their differentiation could explain the unique organoleptic characteristics or attributes of these PDO fortified wines.

Can Achilles tendinosis be treated effectively with lidocaine and glucose infiltrations, and if so, is the effect lasting? A longitudinal, observational on 27 consecutive patients.

OBJECTIVE: Our aim was to add to the small but growing body of evidence on the effectiveness of ultrasound-guided Achilles intratendinous hyperosmolar dextrose prolotherapy and introduce a novel, preceding step of paratenon hydrodissection with lidocaine in patients with chronic Achilles tendinosis resistant to rehabilitation therapy. METHODS: We conducted a longitudinal, observational study on 27 consecutive patients diagnosed with Achilles tendinosis, in whom conservative treatment, ie, physiotherapy or shock wave therapy, had failed. A 2% lidocaine paratenon anesthesia and hydrodissection was followed by ultrasound-guided, intratendinous injections of 25% glucose every 5 weeks. Visual analogue scales (VAS) were used for pain assessment at rest, for activities of daily living, and after moderate exercise at the begining and at the end of the treatment. Moreover, tendon thickness and vascularisation were recorded at baseline and final treatment consultation. Effectiveness was estimated from scoring and relative pain reduction using a 95% CI. The non-parametric Wilcoxon test and a general linear model for repeated measures were applied. Statistical significance was established as p < 0.05. RESULTS: A median of 5 (1-11) injection consultations per patient were required. Pain scores decreased significantly in all three conditions (p < 0.001). Relative reductions were 75% in pain at rest (95% CI;61-93%), 69% in pain with daily living activities (95% CI; 55-83%), and 70% in pain after moderate exercise (95% CI; 57-84%). Tendon neo-vascularisation was significantly reduced (p < 0.001). We did not observe significant changes in tendon thickness (p = 0.083). CONCLUSIONS: Achilles tendinosis treatment with paratenon lidocaine hydrodissection and subsequent prolotherapy with hyperosmolar glucose solution is safe, effective, inexpensive, and virtually painless with results maintained over time.

Farmacia hospitalaria ecológica: un enfoque sostenible del proceso de utilización de medicamentos en un hospital de tercer nivel / Green hospital pharmacy: A sustainable approach to the medication use process in a tertiary hospital

Background Sustainable management of healthcare waste has a positive impact on the global environment. In order to reduce it, the sustainable practice of the pharmacotherapeutic process in all its stages is essential. Objective To analyze the sustainability strategies proposed by the pharmacy service to reduce drug waste derived from the pharmacotherapeutic process. Secondary objectives: to analyze the stage of the pharmacotherapeutic process and the number and type of drugs involved. Methods The study was carried out in a tertiary level hospital. To coordinate the proposals, a referent pharmacist from every pharmacy department area was selected. Four stages of the process were evaluated (procurement, validation, dispensing and compounding), patients concerned were classified as outpatients or inpatients, and drugs potentially involved were analyzed by the administration route: into oral or parenteral. Results 28 ideas were proposed, which could affect more than 1200 drugs. 39.3% would affect the validation process, 17.9% the procurement management, 17.9% dispensing and 7.1% the compounding. Implementation feasibility and acceptability of these proposals were evaluated. Those with the greatest potential were: limiting the duration of treatments when possible, favoring the implementation of computer prescription order entry, favoring the use of the oral route over the parenteral route, and implementing computers in the preparation areas to avoid the use of paper guides. Discussion In our study, many ideas have been proposed by hospital pharmacists to improve the sustainability of the medication use process. When assessing these proposals by impact and feasibility, according to our results, shorten as much as possible the duration of treatments, computerization of the medication use process and oral administration over intravenous should be prioritized in order to reduce environmental impact. (AU)

Antecedentes La gestión sostenible de los residuos sanitarios tiene un impacto positivo en el medio ambiente mundial. Para reducirlo, es esencial la práctica sostenible del proceso farmacoterapéutico en todas sus etapas. Objetivo Analizar las estrategias de sostenibilidad propuestas por el servicio de farmacia para reducir los residuos de medicamentos derivados del proceso farmacoterapéutico. Objetivos secundarios: Analizar la etapa del proceso farmacoterapéutico y el número y tipo de medicamentos implicados. Métodos El estudio se realizó en un hospital de tercer nivel. Para coordinar las propuestas se seleccionó un farmacéutico referente de cada área del servicio de farmacia. Se evaluaron cuatro etapas del proceso (Adquisición, validación, dispensación y formulación), se clasificaron los pacientes afectados como ambulatorios u hospitalizados y se analizaron los fármacos potencialmente implicados según la vía de administración: oral o parenteral. Resultados Se propusieron 28 ideas, que podrían afectar a más de 1.200 medicamentos. El 39,3% afectarían al proceso de validación, el 17,9% a la gestión, el 17,9% a la dispensación y el 7,1% a la formulación. Se evaluó la viabilidad de la aplicación y la aceptabilidad de estas propuestas. Las de mayor potencial fueron: limitar la duración de los tratamientos cuando sea posible, favorecer la implantación de la entrada de órdenes de prescripción por ordenador, favorecer el uso de la vía oral frente a la parenteral e implantar ordenadores en las áreas de preparación para evitar el uso de guías en papel. Conclusiones En nuestro estudio, son muchas las ideas propuestas por los farmacéuticos de hospital para mejorar la sostenibilidad del proceso de utilización de medicamentos... (AU)

Green hospital pharmacy: A sustainable approach to the medication use process in a tertiary hospital.

BACKGROUND: Sustainable management of healthcare waste has a positive impact on the global environment. In order to reduce it, the sustainable practice of the pharmacotherapeutic process in all its stages is essential. OBJECTIVE: To analyze the sustainability strategies proposed by the pharmacy service to reduce drug waste derived from the pharmacotherapeutic process. SECONDARY OBJECTIVES: to analyze the stage of the pharmacotherapeutic process and the number and type of drugs involved. METHODS: The study was carried out in a tertiary level hospital. To coordinate the proposals, a referent pharmacist from every pharmacy department area was selected. Four stages of the process were evaluated (procurement, validation, dispensing and compounding), patients concerned were classified as outpatients or inpatients, and drugs potentially involved were analyzed by the administration route: into oral or parenteral. RESULTS: 28 ideas were proposed, which could affect more than 1200 drugs. 39.3% would affect the validation process, 17.9% the procurement management, 17.9% dispensing and 7.1% the compounding. Implementation feasibility and acceptability of these proposals were evaluated. Those with the greatest potential were: limiting the duration of treatments when possible, favoring the implementation of computer prescription order entry, favoring the use of the oral route over the parenteral route, and implementing computers in the preparation areas to avoid the use of paper guides. DISCUSSION: In our study, many ideas have been proposed by hospital pharmacists to improve the sustainability of the medication use process. When assessing these proposals by impact and feasibility, according to our results, shorten as much as possible the duration of treatments, computerization of the medication use process and oral administration over intravenous should be prioritized in order to reduce environmental impact.

Toxic effects of Arianor Ebony hair dye on human cells.

To evaluate the risks of hair dye exposure, we investigated cellular and molecular effects of Arianor Ebony dye, which is a mixture of azo and anthraquinone dyes, used in the composition of the black color. Cytotoxicity, genotoxicity, and gene expression of relevant molecules of apoptotic and oxidative stress mechanisms were investigated in HepG2 cells exposed to Arianor Ebony. Results showed that the dye did not induce cytotoxicity to exposed cells at a concentration up to 50 µg/mL compared to the negative control. However, genotoxic assays indicated that the dye was able to damage the genetic material at a concentration of 25 µg/mL, with induction factor values of exposed cells two- to five-fold higher than those recorded for the negative control. Moreover, the lowest observed effect concentration was 12.5 µg/mL. For gene expression, relevant changes were observed in cytochrome c and caspase 9, which decreased in cells incubated with the dye in a dose-dependent manner when compared with the negative control. In parallel, the expression of genes for antioxidant enzymes was increased in exposed cells, suggesting the presence of metabolic routes that protect cells against the toxic effect of the dye, avoiding exacerbated cellular death. Results suggested that the dye disrupted cellular homeostasis through mitochondrial dysfunction, which may be hazardous to human health. Thus, further investigations are necessary to deeply understand the mechanisms of action of the dye, considering its toxic potential found in our ex vivo assays.

Operationalising targeted next-generation sequencing for routine diagnosis of drug-resistant TB.

BACKGROUND: Phenotypic drug susceptibility testing (pDST) for Mycobacterium tuberculosis can take up to 8 weeks, while conventional molecular tests identify a limited set of resistance mutations. Targeted next-generation sequencing (tNGS) offers rapid results for predicting comprehensive drug resistance, and this study sought to explore its operational feasibility within a public health laboratory in Mumbai, India. METHODS: Pulmonary samples from consenting patients testing Xpert MTB-positive were tested for drug resistance by conventional methods and using tNGS. Laboratory operational and logistical implementation experiences from study team members are shared below. RESULTS: Of the total number of patients tested, 70% (113/161) had no history of previous TB or treatment; however, 88.2% (n = 142) had rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB). There was a high concordance between resistance predictions of tNGS and pDST for most drugs, with tNGS more accurately identifying resistance overall. tNGS was integrated and adapted into the laboratory workflow; however, batching samples caused significantly longer result turnaround time, fastest at 24 days. Manual DNA extraction caused inefficiencies; thus protocol optimisations were performed. Technical expertise was required for analysis of uncharacterised mutations and interpretation of report templates. tNGS cost per sample was US$230, while for pDST this was US$119. CONCLUSIONS: Implementation of tNGS is feasible in reference laboratories. It can rapidly identify drug resistance and should be considered as a potential alternative to pDST.

CONTEXTE: Les tests phénotypiques de sensibilité aux médicaments (pDST) pour Mycobacterium tuberculosis peuvent prendre jusqu'à 8 semaines, tandis que les tests moléculaires conventionnels identifient un ensemble limité de mutations de résistance. Le séquençage ciblé de la prochaine génération (tNGS) offre des résultats rapides pour prédire la résistance globale aux médicaments, et cette étude avait pour objectif d'explorer sa faisabilité opérationnelle au sein d'un laboratoire de santé publique à Mumbai, en Inde. MÉTHODES: Des échantillons pulmonaires de patients consentants testés positifs au Xpert MTB ont été testés pour la résistance aux médicaments par des méthodes conventionnelles et en utilisant le tNGS. Les expériences des membres de l'équipe de l'étude en matière de fonctionnement du laboratoire et de mise en œuvre logistique sont présentées ci-dessous. RÉSULTATS: Sur le nombre total de patients testés, 70% (113/161) n'avaient pas d'antécédents de TB ou de traitement ; cependant, 88,2% (n = 142) présentaient une TB résistante à la rifampicine/multirésistante aux médicaments (RR/MDR-TB). La concordance entre les prédictions de résistance de la tNGS et de la pDST était élevée pour la plupart des médicaments, la tNGS identifiant globalement la résistance avec plus de précision. La tNGS a été intégrée et adaptée au flux de travail du laboratoire ; toutefois, la mise en lots des échantillons a entraîné un délai d'obtention des résultats beaucoup plus long, le plus rapide étant de 24 jours. L'extraction manuelle de l'ADN a été source d'inefficacité ; le protocole a donc été optimisé. L'analyse des mutations non caractérisées et l'interprétation des modèles de rapport ont nécessité une expertise technique. Le coût du tNGS par échantillon s'élevait à US$230, contre US$119 pour le pDST. CONCLUSIONS: La mise en œuvre de la tNGS est possible dans les laboratoires de référence. Elle permet d'identifier rapidement la résistance aux médicaments et devrait être considérée comme une alternative potentielle à la pDST.

Geldanamycin treatment does not result in anti-cancer activity in a preclinical model of orthotopic mesothelioma.

Mesothelioma is characterised by its aggressive invasive behaviour, affecting the surrounding tissues of the pleura or peritoneum. We compared an invasive pleural model with a non-invasive subcutaneous model of mesothelioma and performed transcriptomic analyses on the tumour samples. Invasive pleural tumours were characterised by a transcriptomic signature enriched for genes associated with MEF2C and MYOCD signaling, muscle differentiation and myogenesis. Further analysis using the CMap and LINCS databases identified geldanamycin as a potential antagonist of this signature, so we evaluated its potential in vitro and in vivo. Nanomolar concentrations of geldanamycin significantly reduced cell growth, invasion, and migration in vitro. However, administration of geldanamycin in vivo did not result in significant anti-cancer activity. Our findings show that myogenesis and muscle differentiation pathways are upregulated in pleural mesothelioma which may be related to the invasive behaviour. However, geldanamycin as a single agent does not appear to be a viable treatment for mesothelioma.

Fruit secondary metabolites alter the quantity and quality of a seed dispersal mutualism.

Plant secondary metabolites are key mechanistic drivers of species interactions. These metabolites have primarily been studied for their role in defense, but they can also have important consequences for mutualisms, including seed dispersal. Although the primary function of fleshy fruits is to attract seed-dispersing animals, fruits often contain complex mixtures of toxic or deterrent secondary metabolites that can reduce the quantity or quality of seed dispersal mutualisms. Furthermore, because seeds are often dispersed across multiple stages by several dispersers, the net consequences of fruit secondary metabolites for the effectiveness of seed dispersal and ultimately plant fitness are poorly understood. Here, we tested the effects of amides, nitrogen-based defensive compounds common in fruits of the neotropical plant genus Piper (Piperaceae), on seed dispersal effectiveness (SDE) by ants, which are common secondary seed dispersers. We experimentally added amide extracts to Piper fruits both in the field and lab, finding that amides reduced the quantity of secondary seed dispersal by reducing ant recruitment (87%) and fruit removal rates (58% and 66% in the field and lab, respectively). Moreover, amides not only reduced dispersal quantity but also altered seed dispersal quality by shifting the community composition of recruiting ants (notably by reducing the recruitment of the most effective disperser by 90% but having no detectable effect on the recruitment of a cheater species that removes fruit pulp without dispersing seeds). Although amides did not affect the distance ants initially carried seeds, they altered the quality of seed dispersal by reducing the likelihood of ants cleaning seeds (67%) and increasing their likelihood of ants redispersing seeds outside of the nest (200%). Overall, these results demonstrate that secondary metabolites can alter the effectiveness of plant mutualisms, by both reducing mutualism quantity and altering mutualism quality through multiple mechanisms. These findings present a critical step in understanding the factors mediating the outcomes of seed dispersal and, more broadly, demonstrate the importance of considering how defensive secondary metabolites influence the outcomes of mutualisms surrounding plants.

Cellular and Molecular Processes Are Differently Influenced in Primary Neural Cells by Slight Changes in the Physicochemical Properties of Multicore Magnetic Nanoparticles.

Herein, we use two exemplary superparamagnetic iron oxide multicore nanoparticles (SPIONs) to illustrate the significant influence of slightly different physicochemical properties on the cellular and molecular processes that define SPION interplay with primary neural cells. Particularly, we have designed two different SPION structures, NFA (i.e., a denser multicore structure accompanied by a slightly less negative surface charge and a higher magnetic response) and NFD (i.e., a larger surface area and more negatively charged), and identified specific biological responses dependent on SPION type, concentration, exposure time, and magnetic actuation. Interestingly, NFA SPIONs display a higher cell uptake, likely driven by their less negative surface and smaller protein corona, more significantly impacting cell viability and complexity. The tight contact of both SPIONs with neural cell membranes results in the significant augmentation of phosphatidylcholine, phosphatidylserine, and sphingomyelin and the reduction of free fatty acids and triacylglycerides for both SPIONs. Nonetheless, NFD induces greater effects on lipids, especially under magnetic actuation, likely indicating a preferential membranal location and/or a tighter interaction with membrane lipids than NFA, in agreement with their lower cell uptake. From a functional perspective, these lipid changes correlate with an increase in plasma membrane fluidity, again larger for more negatively charged nanoparticles (NFD). Finally, the mRNA expression of iron-related genes such as Ireb-2 and Fth-1 remains unaltered, while TfR-1 is only detected in SPION-treated cells. Taken together, these results demonstrate the substantial impact that minor physicochemical differences of nanomaterials may exert in the specific targeting of cellular and molecular processes. A denser multicore structure generated by autoclave-based production is accompanied by a slight difference in surface charge and magnetic properties that become decisive for the biological impact of these SPIONs. Their capacity to markedly modify the lipidic cell content makes them attractive as lipid-targetable nanomedicines.

Clinical utility of target-based next-generation sequencing for drug-resistant TB.

BACKGROUND: In high TB burden countries, access to drug susceptibility testing is a major bottleneck. Targeted next-generation sequencing (tNGS) is a promising technology for rapid resistance detection. This study assessed the role of tNGS for the diagnosis of drug-resistant TB (DR-TB).METHODS: A total of 161 samples from bacteriologically confirmed TB cases were subjected to tNGS using the Deeplex® Myc-TB kit and sequenced using the MiSeq platform. These samples were also processed for conventional phenotypic DST (pDST) using 13 drugs on Mycobacteria Growth Indicator Tube and line-probe assays (MTBDRplus and MTBDRsl).RESULTS: There were 146 DR-TB and 15 drug-susceptible TB (DS-TB) samples. About 70% of patients with DR-TB had no previous TB treatment history. Overall, 88.2% had rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB), 58.5% pre-extensively drug-resistant TB (pre-XDR-TB) and 9.2% had XDR-TB as defined by the WHO (2020). Around 8% (n = 13) of samples were non-culturable; however, identified 8 were resistant to first and second-line drugs using tNGS. Resistance frequency was similar across methods, with discordance in drugs less reliable using pDST or with limited mutational representation within databases. Sensitivities were aligned with literature reports for most drugs. We observed 10% heteroresistance, while 75% of strains were of Lineages 2 and 3.CONCLUSIONS: Programme data supported tNGS in the diagnosis of DR-TB for early treatment using individualised regimens.