Feasibility of Indirect Treatment Comparisons Between Niraparib Plus Abiraterone Acetate and Other First-Line Poly ADP-Ribose Polymerase Inhibitor Treatment Regimens for Patients with BRCA1/2 Mutation-Positive Metastatic Castration-Resistant Prostate Cancer.

INTRODUCTION: Poly(ADP-ribose) polymerase inhibitors (PARPi) are a novel option to treat patients with metastatic castration-resistant prostate cancer (mCRPC). Niraparib plus abiraterone acetate and prednisone (AAP) is indicated for BRCA1/2 mutation-positive mCRPC. Niraparib plus AAP demonstrated safety and efficacy in the phase 3 MAGNITUDE trial (NCT03748641). In the absence of head-to-head studies comparing PARPi regimens, the feasibility of conducting indirect treatment comparisons (ITC) to inform decisions for patients with first-line BRCA1/2 mutation-positive mCRPC has been explored. METHODS: A systematic literature review was conducted to identify evidence from randomized controlled trials on relevant comparators to inform the feasibility of conducting ITCs via network meta-analysis (NMA) or population-adjusted indirect comparisons (PAIC). Feasibility was assessed based on network connectivity, data availability in the BRCA1/2 mutation-positive population, and degree of within- and between-study heterogeneity or bias. RESULTS: NMAs between niraparib plus AAP and other PARPi regimens (olaparib monotherapy, olaparib plus AAP, and talazoparib plus enzalutamide) were inappropriate due to the disconnected network, differences in trial populations related to effect modifiers, or imbalances within BRCA1/2 mutation-positive subgroups. The latter issue, coupled with the lack of a common comparator (except for olaparib plus AAP), also rendered anchored PAICs infeasible. Unanchored PAICs were either inappropriate due to lack of population overlap (vs. olaparib monotherapy) or were restricted by unmeasured confounders and small sample size (vs. olaparib plus AAP). PAIC versus talazoparib plus enzalutamide was not possible due to lack of published arm-level baseline characteristics and sufficient efficacy outcome data in the relevant population. CONCLUSION: The current randomized controlled trial evidence network does not permit robust comparisons between niraparib plus AAP and other PARPi regimens for patients with 1L BRCA-positive mCRPC. Decision-makers should scrutinize any ITC results in light of their limitations. Real-world evidence combined with clinical experience should inform treatment recommendations in this indication.

Climate Change and Photochemical Ozone Creation Potential Impact Indicators of Cow Milk: A Comparison of Different Scenarios for a Diet Assessment.

An estimate of the environmental impact of dairy farms in Northern Italy producing milk for hard cheese (protected designation of origin) has been obtained through a comprehensive life cycle assessment. The estimate focused on climate change (CC) and photochemical ozone creation potential (POCP) indicators, which were evaluated according to the Intergovernmental Panel on Climate Change (IPCC) guidelines and interpreted with the aid of the feeds' composition evaluated using near-infrared reflectance spectroscopy (Foss NIR-System 5000) as well as with a diet evaluation according to the NRC (National Research Council) or the CNCPS (Cornell Net Carbohydrate and Protein System) nutrient requirement modeling. Herds were classified into high-, mid-, and low-performing based on the daily milk yield per cow. A lower impact on indicators was observed as herd performance increased. The high-performing herds had a lower contribution from enteric fermentation (6.30 × 10-1 kgCO2-eq), and the more milk that they produced allowed for a differentiation of CC from land use and transformation (2.39 × 10-1 kgCO2-eq), compared to low-performing herds (3.66 × 10-1 kgCO2-eq). Compared to the IPCC approach, the CC and POCP indicator estimates were reduced when addressing the feed's quality, particularly in mid- and high-performing herds. The results could be helpful in the dairy sector as they provide an insight into how diet quality affects the environmental impact of milk.

The short-term effect of microplastics in lettuce involves size- and dose-dependent coordinate shaping of root metabolome, exudation profile and rhizomicrobiome.

Micro- and nano-plastics (MNPs) in the soil can impact the microbial diversity within rhizospheres and induce modifications in plants' morphological, physiological, and biochemical parameters. However, a significant knowledge gap still needs to be addressed regarding the specific effects of varying particle sizes and concentrations on the comprehensive interplay among soil dynamics, root exudation, and the overall plant system. In this sense, different omics techniques were employed to clarify the mechanisms of the action exerted by four different particle sizes of polyethylene plastics considering four different concentrations on the soil-roots exudates-plant system was studied using lettuce (Lactuca sativa L. var. capitata) as a model plant. The impact of MNPs was investigated using a multi-omics integrated approach, focusing on the tripartite interaction between the root metabolic process, exudation pattern, and rhizosphere microbial modulation. Our results showed that particle size and their concentrations significantly modulated the soil-roots exudates-plant system. Untargeted metabolomics highlighted that fatty acids, amino acids, and hormone biosynthesis pathways were significantly affected by MNPs. Additionally, they were associated with the reduction of rhizosphere bacterial α-diversity, following a size-dependent trend for specific taxa. The omics data integration highlighted a correlation between Pseudomonadata and Actinomycetota phyla and Bacillaceae family (Peribacillus simplex) and the exudation of flavonoids, phenolic acids, and lignans in lettuce exposed to increasing sizes of MNPs. This study provides a novel insight into the potential effects of different particle sizes and concentrations of MNPs on the soil-plant continuum, providing evidence about size- and concentration-dependent effects, suggesting the need for further investigation focused on medium- to long-term exposure.

The dosage- and size-dependent effects of micro- and nanoplastics in lettuce roots and leaves at the growth, photosynthetic, and metabolomics levels.

The occurrence of microplastics (MPs) and nanoplastics (NPs) in soils potentially induce morphological, physiological, and biochemical alterations in plants. The present study investigated the effects of MPs/NPs on lettuce (Lactuca sativa L. var. capitata) plants by focusing on (i) four different particle sizes of polyethylene micro- and nanoplastics, at (ii) four concentrations. Photosynthetic activity, morphological changes in plants, and metabolomic shifts in roots and leaves were investigated. Our findings revealed that particle size plays a pivotal role in influencing various growth traits of lettuce (biomass, color segmentation, greening index, leaf area, and photosynthetic activity), physiological parameters (including maximum quantum yield - Fv/Fmmax, or quantum yield in the steady-state Fv/FmLss, NPQLss, RfdLss, FtLss, FqLss), and metabolomic signatures. Smaller plastic sizes demonstrated a dose-dependent impact on aboveground plant structures, resulting in an overall elicitation of biosynthetic processes. Conversely, larger plastic size had a major impact on root metabolomics, leading to a negative modulation of biosynthetic processes. Specifically, the biosynthesis of secondary metabolites, phytohormone crosstalk, and the metabolism of lipids and fatty acids were among the most affected processes. In addition, nitrogen-containing compounds accumulated following plastic treatments. Our results highlighted a tight correlation between the qPCR analysis of genes associated with the soil nitrogen cycle (such as NifH, NirK, and NosZ), available nitrogen pools in soil (including NO3- and NH4), N-containing metabolites and morpho-physiological parameters of lettuce plants subjected to MPs/NPs. These findings underscore the intricate relationship between specific plastic contaminations, nitrogen dynamics, and plant performance.

A 3-year application of different mycorrhiza-based plant biostimulants distinctively modulates photosynthetic performance, leaf metabolism, and fruit quality in grapes (Vitis vinifera L.).

The use of microbial biostimulants in agriculture is recognized as a sustainable approach to promoting crop productivity and quality due to improved nutrient uptake, enhanced stress tolerance, and improved ability to cope with non-optimal environments. The present paper aimed to comparatively investigate the effect of seven different commercial mycorrhizal-based treatments in terms of yield, phytochemical components, and technological traits of Malvasia di Candia Aromatica grape (Vitis vinifera L.) plants. Metabolomic analysis and photosynthetic performance were first investigated in leaves to point out biochemical differences related to plant growth. Higher photosynthetic efficiency and better PSII functioning were found in biostimulant-treated vines, reflecting an overall decrease in photoinhibition compared to untreated plants. Untargeted metabolomics followed by multivariate statistics highlighted a robust reprogramming of primary (lipids) and secondary (alkaloids and terpenoids) metabolites in treated plants. The analysis of berry yield and chemical components exhibited significant differences depending on the biostimulant product. Generally, berries obtained from treated plants displayed improved contents of polyphenols and sugars, while yield remained unchanged. These results elucidated the significant role of microbial biostimulants in determining the quality of grape berries and eliciting biochemical changes in vines.

A Pseudomonas Plant Growth Promoting Rhizobacterium and Arbuscular Mycorrhiza differentially modulate the growth, photosynthetic performance, nutrients allocation, and stress response mechanisms triggered by a mild Zinc and Cadmium stress in tomato.

This study aimed to assess the effectiveness of plant growth-promoting rhizobacteria (PGPR; Pseudomonas strain So_08) and arbuscular mycorrhizal fungi (AMF; Rhizoglomus irregulare BEG72 and Funneliformis mosseae BEG234) in mitigating the detrimental effects of cadmium (Cd) and zinc (Zn) stress in tomato plants. Plant biomass, root morphology, leaf relative water content, membrane stability, photosynthetic performance, chlorophyll content, and heavy metals (HMs) accumulation were determined. Furthermore, an ionomic profile was conducted to investigate whether microbial inoculants affected the uptake and allocation of macro- and micronutrients. Metabolomics with pathway analysis of both roots and leaves was performed to unravel the mechanisms underlying the differential responses to HMs stress. The findings revealed that the levels of HMs did not significantly affect plant growth parameters; however, they affected membrane stability, photosynthetic performance, nutrient allocation, and chlorophyll content. Cadmium was mainly accumulated in roots, whilst Zn exhibited accumulation in various plant organs. Our findings demonstrate the beneficial effects of PGPR and AMF in mitigating Cd and Zn stress in tomato plants. The microbial inoculations improved physiological parameters and induced differential accumulation of macro- and micronutrients, modulating nutrient uptake balance. These results provide insights into the mechanisms underlying the plant-microbe interactions and highlight the differential modulation of the biosynthetic pathways of secondary metabolites related to oxidative stress response, membrane lipids stability, and phytohormone crosstalk.

Mitigation Actions Scenarios Applied to the Dairy Farm Management Systems.

The environmental impacts of the dairy industry, particularly global warming, are heavily influenced by milk production. Thus, there is an urgent need for farm-level actions and opportunities for improvement, implying mitigation strategies. The aim of this paper is to investigate five possible mitigation actions at the dairy farm and which one the farmers were willing to adopt: management and distribution of livestock manure and fertilizers, anaerobic manure treatment, optimization of the herd composition, feed quality, and heat recovery. A life cycle assessment was conducted on 63 farms using the product environmental footprint approach. The latter was divided into four quartiles, from which four representative farms were selected. For each farm, three scenarios have been analyzed considering the reference impact (reference scenario), the application of the mitigation actions (best-case scenario), and what farmers would implement (realistic scenario). Overall, the most effective mitigation actions in the best-case scenario were anaerobic manure treatment and the management and distribution of livestock manure and fertilizers, showing a potential reduction in total environmental impacts of 7-9% and 6-7%, respectively. Farmers' responses indicated a willingness to implement the latter mitigation strategy better. The optimization of the herd composition, feed quality, and heat recovery reported a range impact reduction between 0.01-5%.

The Combination of Untargeted Metabolomics with Response Surface Methodology to Optimize the Functional Potential of Common Duckweed (Lemna minor L.).

The present study was designed to evaluate the functional potential of common duckweed (Lemna minor L.) as a source of bioactive compounds of nutraceutical interest. The untargeted profiling of the bioactive components of common duckweed was carried out through ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS), in parallel with assessing in vitro antioxidant and enzymatic inhibition properties. The optimization of extraction parameters was determined using the response surface methodology (RSM) through a 3-factor central composite design. The process parameters included extraction temperature, % of ethanol, and ultrasound power, while the response variables were the phenolic content (considering each main phenolic class), total glucosinolates, total carotenoids, the antioxidant potential, and enzyme inhibition activities. The results revealed that common duckweed was a rich source of carotenoids and total flavonoids (mainly flavones and flavonols), followed by phenolic acids, low-molecular-weight phenolics, and glucosinolates. Interestingly, the total flavones, total flavonols and total carotenoid equivalents showed the highest and most positive correlation values with the bioactive properties measured. Finally, the combined RSM approach and unsupervised statistics allowed us to point out the pivotal impact of ethanol percentage in the extraction solvent to recover the highest amounts of bioactive compounds efficiently.

The Functional Profile and Antioxidant Capacity of Tomato Fruits Are Modulated by the Interaction between Microbial Biostimulants, Soil Properties, and Soil Nitrogen Status.

The application of microbial biostimulants to plants has revealed positive effects related to nutrients uptake, stress tolerance, root development and phenological growth. However, little information is available exploiting the potential synergistic biostimulant action of microbes on the functional quality of the yields. The current research elucidated the effect of single or coupled action of biostimulants, associated with either optimal or reduced nitrogen application, on the functional quality of tomato fruits. Chemical assays and untargeted metabolomics were applied to investigate Rhizoglomus irregulare and Funneliformis mosseae administration (both being arbuscular mycorrhiza, AMF), under optimal or low N input conditions, alone or coupled to Trichoderma atroviride application. The coupling of AMF and Trichoderma fungal inoculations resulted in a synergistic biostimulant effect on tomato fruits under sub-optimal fertility, revealing improved concentrations of carotenoid compounds-B-carotene (0.647 ± 0.243 mg/100 g), Z-carotene (0.021 ± 0.021 mg/100 g), 13-z-lycopene (0.145 ± 0.052 mg/100 g) and all-trans-lycopene (12.586 ± 1.511 mg/100 g), and increased values for total phenolic content (12.9 ± 2.9 mgGAE/g), total antioxidant activity (phosphomolybdenum, 0.9 ± 0.2 mmolTE/g), radical scavenging activity (DPPH, 3.4 ± 3.7 mgTE/g), reducing power (FRAP, 23.6 ± 6.3 mgTE/g and CUPRAC, 37.4 ± 7.6 mg TE/g), and enzyme inhibitory activity (AChE, 2.4 ± 0.1 mg GALAE/g), when compared to control. However, evidence of carotenoid and bioactive compounds were exclusively observed under the sub-optimal fertility and no significant differences could be observed between the biostimulant treatment and control under optimal fertility.

Impact of axenic and mixed starter cultures on metabolomic and sensory profiles of ripened Italian salami.

In this work, the synergistic/antagonistic impact of glucose and mixed starter cultures, namely Latilactobacillus sakei, Pediococcus pentosaceus, and Staphylococcus xylosus, was evaluated in Italian salami in terms of metabolomics and sensory profiles. As expected, Salami manufactured with 0.5 % glucose exhibited a substantial pH drop, showing values close to 5 at 12 days of ripening. Metabolomics revealed 1841 metabolites, mainly belonging to amino acids, peptides, glycerolipids, and nucleic acids, showing a greater hierarchical role of glucose addition when compared with inoculated microbial starters. Distinct metabolomic fingerprints could be observed across treatments, mainly concerning glutamyl peptides like gamma-glutamyl-glutamate (related to the kokumi taste), biogenic amines (spermine), and lipid oxidation products (i.e., the oxylipin 13S-hydroperoxylinolenic acid). Such differences may drive the differences in sensory profiles recorded among treatments. These findings indicate the need to select ad-hoc starter cultures to improve the safety, quality, and sensory traits of salami.

Glyphosate, glufosinate ammonium, and AMPA occurrences and sources in groundwater of hilly vineyards.

Glyphosate [N-(phosphonomethyl) glycine] and glufosinate ammonium [ammonium dl-homoalanin-4-(methyl) phosphinate] are broad-spectrum, nonselective, post-emergence herbicides extensively used in various applications for weed control in both agricultural and non-crop areas. Aminomethylphosphonic acid (AMPA) is the major degradation product of glyphosate found in plants, water, and soil. Due to glyphosate's presumed low mobility, its monitoring in European water was limited. Recently both glyphosate and AMPA have been detected in several groundwater samples in Europe, U.S, Canada, Argentina, and China. Understanding the sources of these substances in water, especially in groundwater used for drinking, becomes a priority. In the present work the occurrences and the main drives of glyphosate, AMPA, and glufosinate ammonium in the groundwater of hilly vineyards located in the North-West of Italy were evaluated. Groundwater monitoring results showed frequent detection and concentrations above EQSGW for glyphosate and AMPA, while glufosinate ammonium was never detected. More frequent occurrences and higher concentrations were detected in the samples collected from wells located in the farmyards, most of them being used for irrigation and/or preparation of PPPs mixtures. Indeed, AMPA was the only compound detected in one groundwater well used for drinking, at values bellow EQSGw/DWQS. Such monitoring results were not expected as the modelling estimations under local pedoclimatic conditions indicated no risk of leaching to groundwater. However, the modelling performance and output may have been influenced by the non-consideration of important specific processes. Integrating monitoring and modelling results with information concerning the agricultural practices adopted and the wells use and location, possible contamination drivers were identified. These include the non-agricultural use of glyphosate in the farmyard, the point source contamination of wells and the possible transport with the subsurface lateral inflow of water from up-hill vineyard. This study strengthens the position of SETAC EMAG-Pest GW group concerning the necessity of spatial and temporal contextualisation of groundwater monitoring for a better understanding of its contamination drivers by PPPs.

Cardiorenal Outcomes Among Patients With Atrial Fibrillation Treated With Oral Anticoagulants.

RATIONALE & OBJECTIVE: Direct oral anticoagulants (DOACs) have progressively replaced vitamin K antagonists (VKAs) for stroke prevention in patients with nonvalvular atrial fibrillation (AF). DOACs cause fewer bleeding complications, but their other advantages, particularly related to kidney outcomes, remain inconclusive. We studied the risks of chronic kidney disease (CKD) progression and acute kidney injury (AKI) after DOAC and VKA administration for nonvalvular AF. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Cohort study of Swedish patients enrolled in the Stockholm Creatinine Measurements (SCREAM) project with a diagnosis of nonvalvular AF during 2011-2018. EXPOSURE: Initiation of DOAC or VKA treatment. OUTCOME: Primary outcomes were CKD progression (composite of >30% estimated glomerular filtration rate [eGFR] decline and kidney failure) and AKI (by diagnosis or KDIGO-defined transient creatinine elevations). Secondary outcomes were death, major bleeding, and the composite of stroke and systemic embolism. ANALYTICAL APPROACH: Propensity score weighted Cox regression was used to balance 50 baseline confounders. Sensitivity analyses included falsification end points, subgroups, and estimation of per-protocol effects. RESULTS: We included 32,699 patients (56% initiated DOAC) who were observed for a median of 3.8 years. Their median age was 75 years, 45% were women, and 27% had an eGFR <60mL/min/1.73m2. The adjusted HRs for DOAC versus VKA were 0.87 (95% CI, 0.78-0.98) for the risk of CKD progression and 0.88 (95% CI, 0.80-0.97) for AKI. HRs were 0.77 (95% CI, 0.67-0.89) for major bleeding, 0.93 (95% CI, 0.78-1.11) for the composite of stroke and systemic embolism, and 1.04 (95% CI, 0.95-1.14) for death. The results were similar across subgroups of age, sex, and baseline eGFR when restricting to patients at high risk for thromboembolic events and when censoring follow up at treatment discontinuation or change in type of anticoagulation. LIMITATIONS: Missing information on time in therapeutic range and treatment dosages. CONCLUSIONS: Among patients with nonvalvular AF treated in routine clinical practice compared with VKA use, DOAC use was associated with a lower risk of CKD progression, AKI, and major bleeding but a similar risk of the composite of stroke, systemic embolism, or death.

Combining untargeted profiling of phenolics and sterols, supervised multivariate class modelling and artificial neural networks for the origin and authenticity of extra-virgin olive oil: A case study on Taggiasca Ligure.

Extra-virgin olive oil (EVOO) is subjected to different frauds. This work aimed at integrating the untargeted phenolic and sterol signatures with supervised multivariate discriminant analysis (OPLS-DA) and Artificial Neural Networks (ANN) for tracing the authenticity (as a function of variety, origin, and the blending) of Taggiasca Ligure, a renowned Italian EVOO. Overall, 408 samples from three consecutive growing seasons were used. Despite the cultivar, season, growth altitude, and geographical origin were all contributing to phytochemical profile, OPLS-DA models allowed identifying specific markers of authenticity. Cholesterol-derivatives and phenolics (tyrosols and oleuropeins, stilbenes, lignans, phenolic acids, and flavonoids) were the best markers, based on statistics. Thereafter, ANN was used to discriminate authentic Taggiasca, and the sensitivity was 100% (32/32) thus indicating an excellent classification. Our results strengthen the concept of "terroir" for EVOO and indicate that profiling sterols and phenolics can support EVOO integrity if adequate data treatments are adopted.

Different fractions from wheat flour provide distinctive phenolic profiles and different bioaccessibility of polyphenols following in vitro digestion.

Wheat is a prevalent food worldwide, although its production arises several tonnes of industrial by-products that merit valorisation, owing to sustainable demands. In this work, an untargeted metabolomics approach was applied to shed light on the profile of free and bound phenolic compounds in white and wholegrain flours, as well as the major wheat by-products, namely wheat bran, wheat shorts and wheat middlings. By-products and wholegrain flours were found to be rich sources of ferulic acid derivatives, lignans, and alkylresorcinols, mostly bound to wheat fibre components, whereas different flavonoids were found in their free forms. Afterwards, the in vitro gastrointestinal digestion of these matrices showed that flour phenolics, in particular lignans, were more bioaccessible than those from wheat by-products. These results support the carrier effect attributed to dietary fibre and open a wide perspective on the use of underexploited wheat by-products to formulate novel functional foods.

Biochemical Insights into the Ability of Lemna minor L. Extract to Counteract Copper Toxicity in Maize.

Metal trace elements (MTE) can damage crops if present in excessive amounts in the environment. This research investigated the effect of a plant extract of an aquatic species, Lemna minor L. (duckweed) (LE), on the ability of maize to cope with copper (Cu) toxicity. LE reversed the effects of Cu2+ on photosynthetic activity (Pn), evapotranspiration (E), stomatal conductance (gs), sub-stomatal CO2 concentration (Ci) and biomass which did not differ from the untreated controls. LE did not regulate the amount of copper in maize leaves, but compared to Cu-treated samples, the extract decreased the hydrogen peroxide (H2O2; -26% on average) and malondialdehyde (MDA; -47% on average) content, regardless of the dosage applied. Furthermore, the activity of antioxidant enzymes superoxide dismutase (SOD), ascorbate peroxidase (APX) and catalase (CAT) was significantly increased by LE compared to samples treated with Cu alone. Untargeted metabolomic profiling revealed that LE activated maize secondary metabolism, eliciting the content of non-enzymatic antioxidants (flavonoids, glutathione and glutathione-related compounds, tocopherols and tocotrienols) and modulating plant stress-related hormones (brassinosteroids and ABA derivatives). The results of this study are promising and pave the way for using duckweed as a biostimulant to trigger beneficial effects in maize and increase its resistance to MTEs.

Nutritional inter-dependencies and a carbazole-dioxygenase are key elements of a bacterial consortium relying on a Sphingomonas for the degradation of the fungicide thiabendazole.

Thiabendazole (TBZ), is a persistent fungicide/anthelminthic and a serious environmental threat. We previously enriched a TBZ-degrading bacterial consortium and provided first evidence for a Sphingomonas involvement in TBZ transformation. Here, using a multi-omic approach combined with DNA-stable isotope probing (SIP) we verified the key degrading role of Sphingomonas and identify potential microbial interactions governing consortium functioning. SIP and amplicon sequencing analysis of the heavy and light DNA fraction of cultures grown on 13 C-labelled versus 12 C-TBZ showed that 66% of the 13 C-labelled TBZ was assimilated by Sphingomonas. Metagenomic analysis retrieved 18 metagenome-assembled genomes with the dominant belonging to Sphingomonas, Sinobacteriaceae, Bradyrhizobium, Filimonas and Hydrogenophaga. Meta-transcriptomics/-proteomics and non-target mass spectrometry suggested TBZ transformation by Sphingomonas via initial cleavage by a carbazole dioxygenase (car) to thiazole-4-carboxamidine (terminal compound) and catechol or a cleaved benzyl ring derivative, further transformed through an ortho-cleavage (cat) pathway. Microbial co-occurrence and gene expression networks suggested strong interactions between Sphingomonas and a Hydrogenophaga. The latter activated its cobalamin biosynthetic pathway and Sphingomonas its cobalamin salvage pathway to satisfy its B12 auxotrophy. Our findings indicate microbial interactions aligning with the 'black queen hypothesis' where Sphingomonas (detoxifier, B12 recipient) and Hydrogenophaga (B12 producer, enjoying detoxification) act as both helpers and beneficiaries.

Comprehensive comparison of stroke risk score performance: a systematic review and meta-analysis among 6 267 728 patients with atrial fibrillation.

AIMS: Multiple risk scores to predict ischaemic stroke (IS) in patients with atrial fibrillation (AF) have been developed. This study aims to systematically review these scores, their validations and updates, assess their methodological quality, and calculate pooled estimates of the predictive performance. METHODS AND RESULTS: We searched PubMed and Web of Science for studies developing, validating, or updating risk scores for IS in AF patients. Methodological quality was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). To assess discrimination, pooled c-statistics were calculated using random-effects meta-analysis. We identified 19 scores, which were validated and updated once or more in 70 and 40 studies, respectively, including 329 validations and 76 updates-nearly all on the CHA2DS2-VASc and CHADS2. Pooled c-statistics were calculated among 6 267 728 patients and 359 373 events of IS. For the CHA2DS2-VASc and CHADS2, pooled c-statistics were 0.644 [95% confidence interval (CI) 0.635-0.653] and 0.658 (0.644-0.672), respectively. Better discriminatory abilities were found in the newer risk scores, with the modified-CHADS2 demonstrating the best discrimination [c-statistic 0.715 (0.674-0.754)]. Updates were found for the CHA2DS2-VASc and CHADS2 only, showing improved discrimination. Calibration was reasonable but available for only 17 studies. The PROBAST indicated a risk of methodological bias in all studies. CONCLUSION: Nineteen risk scores and 76 updates are available to predict IS in patients with AF. The guideline-endorsed CHA2DS2-VASc shows inferior discriminative abilities compared with newer scores. Additional external validations and data on calibration are required before considering the newer scores in clinical practice. CLINICAL TRIAL REGISTRATION: ID CRD4202161247 (PROSPERO).

Plant species-specific impact of polyethylene microspheres on seedling growth and the metabolome.

Microplastics (MPs) are ubiquitous contaminants. In recent decades, the hazardous impacts of MPs on the environment have raised significant concern. However, little attention has been focused on the interaction between MPs and plants in terrestrial agroecosystems. This study aims to investigate the effects of polyethylene microspheres (PE-MS) on the germination, morphology, and metabolism of barley (Hordeum vulgare L.), cucumber (Cucumis sativus L.), and tomato (Solanum lycopersicum L.). Specifically, seeds were soaked in PE-MS solutions at three concentrations (10, 100, and 1000 mg L-1), while control seeds were treated with distilled water. After five days, the morphological parameters of barley (i.e., shoot and root biomass, length, and average diameter) were significantly affected by PE-MS treatment, even at the lowest concentration, without a dose dependency. On the other hand, the effect of PE-MS on the morphological parameters of cucumber and tomato was evident only at the highest concentration (1000 mg L-1). PE-MS also induced metabolomic reprogramming of shoots and roots in all three plant species. There was a downregulation of fatty acids and secondary metabolites (except in tomato shoots). In addition, the response of amino acids and hormones was highly heterogeneous among species and plant parts. In particular, the response of metabolites changed within species among different plant parts. In conclusion, we found a strong influence of MS-PE on the metabolic profile of the three plant species and a positive priming of seedling growth, especially in barley, where all the morphological parameters considered were significantly improved. Further investigations are needed to fully understand the mechanisms underlying MP-plant interactions, especially in the long term.

Nitrogen use efficiency, rhizosphere bacterial community, and root metabolome reprogramming due to maize seed treatment with microbial biostimulants.

Seed inoculation with beneficial microorganisms has gained importance as it has been proven to show biostimulant activity in plants, especially in terms of abiotic/biotic stress tolerance and plant growth promotion, representing a sustainable way to ensure yield stability under low input sustainable agriculture. Nevertheless, limited knowledge is available concerning the molecular and physiological processes underlying the root-inoculant symbiosis or plant response at the root system level. Our work aimed to integrate the interrelationship between agronomic traits, rhizosphere microbial population and metabolic processes in roots, following seed treatment with either arbuscular mycorrhizal fungi (AMF) or Plant Growth-Promoting Rhizobacteria (PGPR). To this aim, maize was grown under open field conditions with either optimal or reduced nitrogen availability. Both seed treatments increased nitrogen uptake efficiency under reduced nitrogen supply revealed some microbial community changes among treatments at root microbiome level and limited yield increases, while significant changes could be observed at metabolome level. Amino acid, lipid, flavone, lignan, and phenylpropanoid concentrations were mostly modulated. Integrative analysis of multi-omics datasets (Multiple Co-Inertia Analysis) highlighted a strong correlation between the metagenomics and the untargeted metabolomics datasets, suggesting a coordinate modulation of root physiological traits.

The Hierarchical Contribution of Organic vs. Conventional Farming, Cultivar, and Terroir on Untargeted Metabolomics Phytochemical Profile and Functional Traits of Tomato Fruits.

In this work, the impact of terroir, cultivar, seasonality, and farming systems on functional traits of tomato was hierarchically investigated. Untargeted metabolomics, antioxidant capacity, colorimetric assays, and enzyme inhibition were determined. The total phenolic and carotenoid contents significantly varied between growing years, whereas an interaction between the farming system and growing year (p < 0.01) was observed for total phenolics, carotenoids, and flavonoids, and for acetylcholinesterase inhibition. Hierarchical clustering showed that geographical origin and growing year were the major contributors to the differences in phytochemical profiles. Nonetheless, supervised modeling allowed highlighting the effect of the farming system. Several antioxidants (L-ascorbic acid, α-tocopherol, and 7,3',4'-trihydroxyflavone) decreased, whereas the alkaloid emetine and phytoalexin phenolics increased under organic farming. Taken together, our findings indicate that cultivar and pedo-climatic conditions are the main determinants for the functional quality of tomato, whereas the farming system plays a detectable but hierarchically lower.