The Cell Tracking Challenge: 10 years of objective benchmarking.

The Cell Tracking Challenge is an ongoing benchmarking initiative that has become a reference in cell segmentation and tracking algorithm development. Here, we present a significant number of improvements introduced in the challenge since our 2017 report. These include the creation of a new segmentation-only benchmark, the enrichment of the dataset repository with new datasets that increase its diversity and complexity, and the creation of a silver standard reference corpus based on the most competitive results, which will be of particular interest for data-hungry deep learning-based strategies. Furthermore, we present the up-to-date cell segmentation and tracking leaderboards, an in-depth analysis of the relationship between the performance of the state-of-the-art methods and the properties of the datasets and annotations, and two novel, insightful studies about the generalizability and the reusability of top-performing methods. These studies provide critical practical conclusions for both developers and users of traditional and machine learning-based cell segmentation and tracking algorithms.

Optimizing Venous Stenting: Consensus Recommendations for Enhanced Management of Lower Extremity Deep Vein Thrombosis.

INTRODUCTION: Deep vein thrombosis (DVT) poses a complex challenge and often leads to postthrombotic syndrome (PTS), a debilitating complication. The emergence of venous stents offers a potential preventive avenue against this complication. This study aimed to provide consensus recommendations on the use of venous stent for DVT. MATERIALS AND METHODS: From June to July 2023, 20 internal medicine, angiology and vascular surgery, and vascular and interventional radiology experts were involved in the Delphi process. Thirty-one recommendations, categorized into three thematic areas, were rigorously evaluated: indications for stent use, stent selection and placement, and monitoring and prevention of complications. Agreement was evaluated using a Likert scale, with consensus defined as agreement by two-thirds of the participants. RESULTS: Consensus was reached for 23 (74.2%) of 31 recommendations. The agreement was centered on considerations, such as stent placement in specific acute DVT scenarios, emphasizing pivotal stent characteristics. However, there were divergences in the recommended stent length to prevent migration and stent characteristics based on iliocaval bifurcation morphology. Notably, there was no consensus on whether patients with DVT caused by a major transient risk factor need more than 3 months of anticoagulation therapy or whether aspirin should be added to anticoagulant treatment after venous stenting. CONCLUSIONS: These consensus recommendations offer practical insights into optimizing venous stent use to prevent PTS in DVT patients. Addressing the critical aspects of stent selection, placement, and postprocedural care, these recommendations contribute to clinical decision-making. The identified divergences underscore the importance of consensus and thus indicate the need for further investigation.

ArUco-based stylus reliability for reproductible 3D digitalisation of shoulder cartilage contours.

Imaging techniques in anatomy have developed rapidly over the last decades through the emergence of various 3D scanning systems. Depending on the dissection level, non-contact or tactile contact methods can be applied on the targeted structure. The aim of this study was to assess the inter and intra-observer reproducibility of an ArUco-based localisation stylus, that is, a manual technique on a hand-held stylus. Ten fresh-frozen, unembalmed adult arms were used to digitalise the glenoid cartilage related to the glenohumeral joint and the contour of the clavicle cartilage related to the acromioclavicular joint. Three operators performed consecutive digitalisations of each cartilage contour using an ArUco-based localisation stylus recorded by a single monocular camera. The shape of each cartilage was defined by nine shape parameters. Intra-observer repeatability and inter-observer reproducibility were computed using an intra-class correlation (ICC) for each of these parameters. Overall, 35.2 ± 2.4 s and 26.6 ± 10.2 s were required by each examiner to digitalise the contour of a glenoid and acromioclavicular cartilage, respectively. For most parameters, good-to-excellent agreements were observed concerning intra-observer (ICC ranging between 0.81 and 1.00) and inter-observer (ICC ranging between 0.75 and 0.99) reproducibility. To conclude, through a fast and versatile process, the use of an ArUco-based localisation stylus can be a reliable low-cost alternative to conventional imaging methods to digitalise shoulder cartilage contours.

Rate of recurrence after discontinuing anticoagulation in patients with venous thromboembolism within 30 days after COVID-19 vaccine.

This study generated evidence to guide anticoagulation in patients with VTE after vaccination for COVID-19. We provided data on the low recurrence rate after cessation of anticoagulant therapy and the findings for this study offer timely insights into the management of a potentially vaccine-related adverse event.

Evaluation of soluble P-selectin as a predictive biomarker in acute symptomatic pulmonary embolism: Insights from a prospective observational study.

BACKGROUND: Soluble P-selectin (sP-selectin) has been proposed as a potential biomarker for venous thromboembolism (VTE) diagnosis with interesting results. However, its role in predicting early mortality in pulmonary embolism (PE) remains unexplored. METHODS: This observational, prospective, single-center study enrolled consecutive patients aged 18 or older with confirmed acute symptomatic PE and no prior anticoagulation. The study aims to assess the prognostic capacity of sP-selectin measured at the time of PE diagnosis for short-term mortality and major bleeding. RESULTS: A total of 196 patients, with a mean age of 69.1 years (SD 17), were included, of whom 52.6% were male. Within 30 days, 9.7% of patients (n = 19) died, and 5.1% (n = 10) suffered major bleeding. PE risk stratification revealed 4.6% (n = 9) with high-risk PE, 34.7% (n = 68) with intermediate-high-risk PE, 38.3% (n = 75) with intermediate-low-risk PE, and 22.5% (n = 44) with low-risk PE according to the European Society of Cardiology score. Mean plasma sP-selectin levels were comparable between survivors and non-survivors (489.7 ng/mL ±63 vs. 497.3 ng/mL ±51; p = .9). The ROC curve for 30-day all-cause mortality and major bleeding yielded an AUC of 0.49 (95% CI 0.36-0.63) and 0.46 (95% CI 0.24-0.68), respectively. Multivariate and survival analyses were precluded due to lack of significance. CONCLUSIONS: sP-selectin was not useful for predicting short-term mortality or major bleeding in patients with acute symptomatic pulmonary embolism. Further studies are required to clarify the role of sP-selectin in VTE, particularly in prognosticating PE outcomes.

Evaluating gender bias in ML-based clinical risk prediction models: A study on multiple use cases at different hospitals.

BACKGROUND: An inherent difference exists between male and female bodies, the historical under-representation of females in clinical trials widened this gap in existing healthcare data. The fairness of clinical decision-support tools is at risk when developed based on biased data. This paper aims to quantitatively assess the gender bias in risk prediction models. We aim to generalize our findings by performing this investigation on multiple use cases at different hospitals. METHODS: First, we conduct a thorough analysis of the source data to find gender-based disparities. Secondly, we assess the model performance on different gender groups at different hospitals and on different use cases. Performance evaluation is quantified using the area under the receiver-operating characteristic curve (AUROC). Lastly, we investigate the clinical implications of these biases by analyzing the underdiagnosis and overdiagnosis rate, and the decision curve analysis (DCA). We also investigate the influence of model calibration on mitigating gender-related disparities in decision-making processes. RESULTS: Our data analysis reveals notable variations in incidence rates, AUROC, and over-diagnosis rates across different genders, hospitals and clinical use cases. However, it is also observed the underdiagnosis rate is consistently higher in the female population. In general, the female population exhibits lower incidence rates and the models perform worse when applied to this group. Furthermore, the decision curve analysis demonstrates there is no statistically significant difference between the model's clinical utility across gender groups within the interested range of thresholds. CONCLUSION: The presence of gender bias within risk prediction models varies across different clinical use cases and healthcare institutions. Although inherent difference is observed between male and female populations at the data source level, this variance does not affect the parity of clinical utility. In conclusion, the evaluations conducted in this study highlight the significance of continuous monitoring of gender-based disparities in various perspectives for clinical risk prediction models.

Comparative analysis of COVID-19-associated venous thromboembolism outcomes: evolution from 2020 to 2021-2022.

Patients with COVID-19 are at an increased risk for venous thromboembolism (VTE). With the advent of vaccinations and novel treatments from 2020 through 2022, the landscape of COVID-19 has evolved. Notably, the effects of such interventions on the outcomes of COVID-19-associated VTE have not been thoroughly examined. Data from the RIETE registry were analyzed to evaluate 90-day VTE-related outcomes (all-cause mortality, major bleeding, and VTE recurrences) in patients with COVID-19-associated VTE. We compared the periods before and after the widespread introduction of COVID-19 vaccines: March to December 2020 (pre-vaccine period) and March 2021 to December 2022 (post-vaccine period). Statistical analysis included mixed-effects parametric survival-time models. Among 1,620 patients with COVID-19-associated VTE, most (74.1%) were identified during 2020 period. The analysis revealed a more than two-fold increase in the risk of death within 90 days (adjusted hazard ratio [HR]: 2.27; 95% confidence interval, CI: 1.18-4.38) and major bleeding (adjusted HR: 2.91; 95%CI: 1.08-7.84) for patients from the 2020 period compared to those from the 2021-2022 period. Inpatient subgroup analysis confirmed the observed mortality differences. The frequency of recurrent VTE was low (1.1 vs. 0.7%, respectively), and did not show significant variation between the two periods. Our research provides a comparative perspective on the clinical outcomes of COVID-19-associated VTE before and after the introduction of vaccines. Our findings reveal a significant decrease in the incidence of 90-day mortality and major bleeding in patients with COVID-19-associated VTE in the 2021-2022 period.

Transitional discharge interventions for people with schizophrenia.

BACKGROUND: Schizophrenia is a chronic mental illness characterized by delusions, hallucinations, and important functional and social disability. Interventions labeled as 'transitional' add to care plans made during the hospital stay in preparation for discharge. They also include interventions developed after discharge to support people with serious mental illness as they make the transition from the hospital to the community. Transitional discharge interventions may anticipate the future needs of the patient after discharge by co-ordinating the different levels of the health system that can effectively guarantee continuity of care in the community. This occurs through the provision of therapeutic relationships which give a safety net throughout the discharge and community reintegration processes to improve the general condition of users, level of functioning, use of health resources, and satisfaction with care. OBJECTIVES: To assess the effects of transitional discharge interventions for people with schizophrenia. SEARCH METHODS: On 7 December 2022, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, PubMed, CINAHL, ClinicalTrials.gov, ISRCTN, PsycINFO, and WHO ICTRP. SELECTION CRITERIA: Randomized controlled trials (RCTs) evaluating the effects of transitional discharge interventions in people with schizophrenia and schizophrenia-related disorders. Eligible interventions included three key elements: predischarge planning, co-ordination of care and follow-up, and postdischarge support. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Outcomes of this review included global state (relapse), service use (hospitalization), general functioning, satisfaction with care, adverse effects/events, quality of life, and direct costs. For binary outcomes, we calculated risk ratios (RRs) and their 95% confidence intervals (CIs). For continuous outcomes, we calculated the mean difference (MD) or standardized mean difference (SMD) and their 95% CIs. We used GRADE to assess certainty of evidence. MAIN RESULTS: We found 12 studies with 1748 participants comparing transitional discharge interventions to usual care. All were parallel-group RCTs. No studies assessed global state (relapse) or reported data about adverse events/effects. All studies had a high risk of bias, mainly due to serious concerns about allocation concealment, deviations from intended interventions, measurement of the outcomes, and missing outcome data. Transitional discharge interventions may make little to no difference in service use (hospitalization) at short- and long-term follow-ups, but the evidence is very uncertain (RR 1.18, 95% CI 0.55 to 2.50; I2 = 54%; 4 studies, 462 participants; very low-certainty evidence). Transitional discharge intervention may increase the levels of functioning after discharge (clinically important change in general functioning) (SMD 0.95, 95% CI -0.06 to 1.97; I² = 95%; 4 studies, 437 participants; very low-certainty evidence) and may increase the proportion of participants who are satisfied with the intervention (clinically important change in satisfaction) (RR 1.96, 95% CI 1.37 to 2.80; 1 study, 76 participants; very low-certainty evidence), but for both outcomes the evidence is very uncertain. Transitional discharge intervention may make little to no difference in quality of life compared to treatment as usual (SMD 0.24, 95% CI -0.30 to 0.78; I² = 90%; 4 studies, 748 participants; very low-certainty evidence), but we are very uncertain. For direct costs, one study with 124 participants did not report full details and thus the results were inconclusive. AUTHORS' CONCLUSIONS: There is currently no clear evidence for or against implementing transitional discharge interventions for people with schizophrenia. Transitional discharge interventions may improve patient satisfaction and functionality, but this evidence is also very uncertain. For future research, it is important to improve the quality of the conduct and reporting of these trials, including using validated tools for measuring their outcomes.

Dexamethasone doses in patients with COVID-19 and hypoxia: A systematic review and meta-analysis.

BACKGROUND: The optimal dose of dexamethasone for severe/critical COVID-19 is uncertain. We compared higher versus standard doses of dexamethasone in adults with COVID-19 and hypoxia. METHODS: We searched PubMed and trial registers until 23 June 2023 for randomised clinical trials comparing higher (>6 mg) versus standard doses (6 mg) of dexamethasone in adults with COVID-19 and hypoxia. The primary outcome was mortality at 1 month. Secondary outcomes were mortality closest to 90 days; days alive without life support; and the occurrence of serious adverse events/reactions (SAEs/SARs) closest to 1 month. We assessed the risk of bias using the Cochrane RoB2 tool, risk of random errors using trial sequential analysis, and certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We included eight trials (2478 participants), of which four (1293 participants) had low risk of bias. Higher doses of dexamethasone probably resulted in little to no difference in mortality at 1 month (relative risk [RR] 0.97, 95% CI: 0.79-1.19), mortality closest to Day 90 (RR 1.01, 95% CI: 0.86-1.20), and SAEs/SARs (RR 1.00, 95% CI: 0.97-1.02). Higher doses of dexamethasone probably increased the number of days alive without invasive mechanical ventilation and circulatory support but had no effect on days alive without renal replacement therapy. CONCLUSIONS: Based on low to moderate certainty evidence, higher versus standard doses of dexamethasone probably result in little to no difference in mortality, SAEs/SARs, and days alive without renal replacement therapy, but probably increase the number of days alive without invasive mechanical ventilation and circulatory support.

First report of Fusarium oxysporum f. sp. fragariae race 1 causing Fusarium wilt of strawberry (Fragaria × ananassa) in the Alentejo region of Portugal.

In the summer of 2023, within the Alentejo region (Portugal), a new occurrence of a plant disease of strawberry (Fragaria × ananassa) cv. 'Monterey' was observed in a Spring commercial planting. Symptoms consisted of foliar wilting, drying of older leaves, deformed and highly chlorotic leaflets, crown discoloration, plant stunting, and in some cases death. Several outbreak foci, covering nearly half a hectare, were observed within the affected farm, with almost 80% of the plants showing symptoms. Four samples,of 6 plants, were collected from 4 locations within the field. Petiole sections (1 cm) were rinsed with 0.1% Tween 20, submersed in 70% EtOH for 20 s followed by 60 s in 1% NaOCL, and then placed on Komada's medium (Komada, 1975). After incubation at room temperature in the dark for a week, white-colored fluffy mycelia grew profusely from the petioles of all samples. Colony morphology and non-septate, ellipsoidal microconidia (5.7-12.4×2.5-4.3 µm) borne on monophialides, exhibited a resemblance to Fusarium oxysporum (Leslie and Summerell, 2006). Ten single strains were obtained from different plants by single hyphal tip isolation. For molecular confirmation, a portion of the translation elongation factor 1-alpha (EF1α) was amplified by PCR using EF1/EF2 primers (O'Donnell et al., 1998). Additionally, the RNA polymerase subunit RPB2 was amplified as two contiguous fragments via primers and protocols described by O'Donnell et al., 2021. Amplicons were sequenced (GenBank Accession Nos. PP426617 - 426626, PQ058494 - 058513). Using Fusarium-ID and Fusarioid-ID databases, EF1α and RPB2 sequences were found to be more than 99% identical to published F. oxysporum type isolates and Fusarium sp. isolates in the F. oxysporum species complex (Crous et al., 2021; Wang et al., 2022). A specific F. oxysporum f. sp. fragariae (Fof) qPCR assay (Burkhardt et al., 2019) was used to determine if these isolates could be Fof race 1. A Fof race 1 isolate (MAFF305558), negative controls, and water controls were included. All ten isolates and the Fof race 1 control were positive (Ct < 30), while other Fusarium spp. used as negative controls and the water controls did not amplify. Two isolates (F.200 and F.202) and MAFF305558 (positive control) were included in a pathogenicity test on two strawberry cultivars, 'Monterey' (susceptible to race 1) and 'Fronteras' (resistant to race 1) (Dilla-Ermita et al., 2023). Each isolate was included in two independent trials. In each trial, 5 plants per cultivar were inoculated by dipping roots for 10 min in 5 × 106 conidia/mL of 0.1% water agar (WA) or in sterile 0.1% WA for the negative control plants. Each plant was then planted in a pot filled with peat. Pots were placed randomly in random positions in a growth chamber at 28/20°C and 12h photoperiod. After 8 - 10 weeks, the control plants and 'Fronteras' plants remained healthy, while the inoculated plants cv. 'Monterey' were severely wilted and/or dead. Fusarium oxysporum was re-isolated from all symptomatic plants. Recovered isolates were confirmed to be the same as the inoculated ones using the Fof-qPCR, including the same controls as above. This is the first report of Fof race 1 in the Iberian Peninsula. Given that the land was not previously used for strawberry, it is highly probable that the pathogen was introduced with the planting material originated from a Spanish nursery. In conclusion, it is imperative to implement more severe control measures in nurseries to avoid the spread of this race.

Cortistatin as a Novel Multimodal Therapy for the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is a complex disorder characterized by the impairment of the dopaminergic nigrostriatal system. PD has duplicated its global burden in the last few years, becoming the leading neurological disability worldwide. Therefore, there is an urgent need to develop innovative approaches that target multifactorial underlying causes to potentially prevent or limit disease progression. Accumulating evidence suggests that neuroinflammatory responses may play a pivotal role in the neurodegenerative processes that occur during the development of PD. Cortistatin is a neuropeptide that has shown potent anti-inflammatory and immunoregulatory effects in preclinical models of autoimmune and neuroinflammatory disorders. The goal of this study was to explore the therapeutic potential of cortistatin in a well-established preclinical mouse model of PD induced by acute exposure to the neurotoxin 1-methil-4-phenyl1-1,2,3,6-tetrahydropyridine (MPTP). We observed that treatment with cortistatin mitigated the MPTP-induced loss of dopaminergic neurons in the substantia nigra and their connections to the striatum. Consequently, cortistatin administration improved the locomotor activity of animals intoxicated with MPTP. In addition, cortistatin diminished the presence and activation of glial cells in the affected brain regions of MPTP-treated mice, reduced the production of immune mediators, and promoted the expression of neurotrophic factors in the striatum. In an in vitro model of PD, treatment with cortistatin also demonstrated a reduction in the cell death of dopaminergic neurons that were exposed to the neurotoxin. Taken together, these findings suggest that cortistatin could emerge as a promising new therapeutic agent that combines anti-inflammatory and neuroprotective properties to regulate the progression of PD at multiple levels.

Machine learning to predict major bleeding during anticoagulation for venous thromboembolism: possibilities and limitations.

Predictive tools for major bleeding (MB) using machine learning (ML) might be advantageous over traditional methods. We used data from the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) to develop ML algorithms to identify patients with venous thromboembolism (VTE) at increased risk of MB during the first 3 months of anticoagulation. A total of 55 baseline variables were used as predictors. New data prospectively collected from the RIETE were used for further validation. The RIETE and VTE-BLEED scores were used for comparisons. External validation was performed with the COMMAND-VTE database. Learning was carried out with data from 49 587 patients, of whom 873 (1.8%) had MB. The best performing ML method was XGBoost. In the prospective validation cohort the sensitivity, specificity, positive predictive value and F1 score were: 33.2%, 93%, 10%, and 15.4% respectively. F1 value for the RIETE and VTE-BLEED scores were 8.6% and 6.4% respectively. In the external validation cohort the metrics were 10.3%, 87.6%, 3.5% and 5.2% respectively. In that cohort, the F1 value for the RIETE score was 17.3% and for the VTE-BLEED score 9.75%. The performance of the XGBoost algorithm was better than that from the RIETE and VTE-BLEED scores only in the prospective validation cohort, but not in the external validation cohort.

Species as a Heuristic: Reconciling Theory and Practice.

Species are crucial to most branches of biological research, yet remain controversial in terms of definition, delimitation, and reality. The difficulty of resolving the "species problem" stems from the tension between their theoretical concept as groups of evolving and highly variable organisms and the practical need for a stable and comparable unit of biology. Here, we suggest that treating species as a heuristic can be consistent with a theoretical definition of what species are and with the practical means by which they are identified and delimited. Specifically, we suggest that theoretically species are heuristic since they comprise clusters of closely related individuals responding in a similar manner to comparable sets of evolutionary and ecological forces, whilst they are practically heuristic because they are identifiable by the congruence of contingent properties indicative of those forces. This reconciliation of the theoretical basis of species with their practical applications in biological research allows for a loose but relatively consistent definition of species based on the strategic analysis and integration of genotypic, phenotypic, and ecotypic data. [Cohesion; heuristic; homeostasis; lineage; species problem.].

Aß Amyloid Fibers Drastically Alter the Topography and Mechanical Properties of Lipid Membranes.

Alzheimer's disease (AD) is related to the fibrillation of the Aß peptides at neuronal membranes, a process that depends on the lipid composition and may impart different physical states to the membrane. In the present work, we study the properties of the Aß peptide when mixed with a zwitterionic lipid (DMPC), using the Langmuir monolayer technique as an approach to control membrane physical conditions. First, we build on previous characterizations of pure Aß monolayers and observe that, in addition to high shear, these films present a pronounced compressional hysteresis. When Aß is assembled with DMPC in a binary film, the resulting membranes become heterogeneous, with a peptide-enriched phase distributed in a network-like pattern, and they exhibit a lateral transition that depends on the Aß content. At lower peptide proportions, the films segregate into two well-defined phases: one consisting of lipids and another enriched with peptides. The reflectivity of these phases differs from that obtained for pure Aß films. Thus, the formed fibers effectively cover most of the interface area and remain stable at higher pressures (from 20 to 30 mN m-1 depending on Aß content) compared to pure peptide films (17 mN m-1). Furthermore, such structures induce a compressional hysteresis in the film, similar to that of pure peptide films (which is nonexistent in the pure lipid monolayer), even at low peptide proportions. We claim that the mechanical properties at the interface are governed by the size of the fibril-like structures. Based on the low molar fractions and surface packing at which these phenomena were observed, we postulate that as a consequence of peptide intermolecular interactions, Aß may have drastic effects on the molecular arrangement and mechanical properties of a lipid membrane.

Evidence of natural selection and dominance of SARS-CoV-2 variant Lambda (C.37) over variants of concern in Cusco, Peru.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage C.37 (Lambda) has spread rapidly in Peru and other Latin American countries. However, most studies in Peru have focused on Lima, the capital city, without knowing the dynamics of the spread of the variant in other departments. Cusco, Peru, is one of the most popular departments in the country for tourists, so the introduction of new variants of SARS-CoV-2 might occur despite closure of the borders. Therefore, in this work, we analyzed the variants circulating in Cusco. The aim of this work was to better understand the distribution of SARS-CoV-2 lineages circulating in Cusco and to characterize the genomes of these strains. To this end, 46 SARS-CoV-2 genomes from vaccinated and unvaccinated patients were sequenced in the first half of 2021. The genomes were analyzed using phylogenetic and natural selection methods. Phylogenetic trees from Cusco showed dominance of the Lambda lineage over the variants of concern (VOCs), and there was no clustering of variants by district. Natural selection analysis revealed mutations, mainly in the spike protein, at positions 75, 246, 247, 707, 769, and 1020. In addition, we found that unvaccinated patients accumulated more new mutations than did vaccinated patients, and these included the F101Y mutation in ORF7a, E419A in NSP3, a deletion in S (21,618-22,501), and a deletion in ORF3a (25,437-26,122).

Sustainable recovery of phenolic antioxidants from real olive vegetation water with natural hydrophobic eutectic solvents and terpenoids.

Olive oil production leads to the generation of olive mill wastewater (OMWW). Due to the presence of phenolic compounds, they are difficult to process, but they represent a source of high-added value chemicals since they have antioxidant and therapeutic properties. This work has studied the extraction of phenolic compounds from a type of OMWW, olive vegetation water, which presents these compounds in a more diluted dosage than in other studied to date, to revalue this waste stream. A real olive vegetation water from a Spanish olive oil producer was used, and liquid-liquid extraction was applied. Terpenoids and terpene-based hydrophobic eutectic solvents were systematically used to extract phenolic compounds following the concentrations of tyrosol, catechol, caffeic acid, and total phenolic content. By molecular simulation with the COSMO-RS method, 4 terpenoids, and 2 eutectic solvents were selected and compared with 2 conventional solvents. The Solvent/Feed ratio in the extraction of phenolic compounds was studied, showing that the solvents with the highest extraction results were geraniol, eucalyptol, and eutectic solvent menthol + camphor, which outperformed conventional solvents methyl isobutyl ketone and diisopropyl ether. Menthol + camphor gave total phenol extraction yields of 88.73% at a Solvent/Feed ratio in volume of 0.50, surpassing all solvents tested. A solvent reuse and regeneration process was applied by back-extraction of the 4 solvents: FTIR results showed the stability of the solvents while maintaining yields in the solvent reuse process. The phenolic compounds could be concentrated in the alkaline phase to factors up to 49.3 to the initial concentration in olive vegetation water. The alkaline phases were neutralized to obtain a precipitate with a caffeic acid content of up to 26 % wt%, and a tyrosol-rich supernatant with a concentration of up to 6.54 g/L. This work proposes a process using natural solvents to extract phenolic compounds from olive vegetation water.

First Report of Colletotrichum graminicola Causing Maize Anthracnose in Galicia, Northwestern Spain.

Maize (Zea mays) is one of the most important crops worldwide, and fungal diseases are responsible for major losses in food production. Anthracnose caused by Colletotrichum graminicola can infect all maize tissues, although stalk rot and seedling blight cause more significant economic damage (Munkvold and White, 2016). Anthracnose stalk rot is characterized by a distinctive external blackening of the lower stalks resulting in large black streaks, while the pith turns dark brown and has a shredded appearance. Like most stalk rots, the most obvious symptom is a sudden death of plants before grain maturity, and plant lodging. Symptoms commonly appear late in the season, suspicious maize stems of cultivar Tuy exhibiting symptoms of anthracnose stalk rot were collected from a field in Pontevedra, Galicia, Spain (Geographical coordinates: 42°23'27.1" N - 8°30'46.3" W) between June and December of 2022. Stem samples, approximately 50 mm2, were dissected and surface-disinfected for 90 seconds in 20% sodium hypochlorite (v/v) and rinsed three times in sterile distilled water. The samples were transferred to one half-strength acidified potato dextrose agar (PDA) supplemented with ampicillin (100 µg/mL) and lactic acid 90% (1.5 mL/L) and incubated for 5 days at 25 ºC (Sukno et al. 2008). Single spores were transferred to fresh PDA plates to obtain pure culture isolates. A total of six isolates were obtained, and among them, two were selected for further characterization (SP-36820-1 and SP-36820-3). Colonies grown on PDA have dark gray aerial mycelium with orange-colored spore masses. Conidia are falcate, slightly curved, tapered toward the tips, and are produced in acervuli with setae, measuring 37.65 to 24.84 x 8.02 to 4.67 µm, respectively (n = 100). These morphological characteristics are in agreement with C. graminicola previously described by Bergstrom and Nicholson (1999). Isolates were grown in potato dextrose broth (PDB) for 3 days at 25 ºC and total genomic DNA was extracted using a DNeasy Plant Mini Kit (Qiagen Inc., Valencia, CA, USA). The internal transcribed spacer region of rDNA and the manganese-type superoxide dismutase gene (SOD2) were amplified using primers ITS4/ITS5 (White et al. 1990) and SOD625/SOD507 (Fang et al. 2002) and consequently sequenced. GenBank BLAST analysis revealed that the sequences were 100% identical to strains of C. graminicola. All sequences were deposited in GenBank (see e-Xtra 1 for accession numbers). To confirm Koch's postulates, plants of a derivative of maize inbred line Mo940 (developmental stage V3) were placed horizontally in a tray for inoculation and 20 droplets (7.5 µL) of a suspension of 3 x 105 conidia per milliliter were placed on the surface of the third leaf. The trays were closed to retain moisture and incubated overnight at 23ºC. The next day, the plants were returned to a vertical position and incubated in a growth chamber at 25ºC with 80% humidity and a light cycle of 16 h of light and 8 h of dark (Vargas et al. 2012). After four days inoculated leaves presented brown elongated lesions with necrotic centers consistent with C. graminicola infection, whereas control plants remained asymptomatic. The strains reisolated from infected leaves were morphologically identical to the original isolates. To our knowledge, this is the first report of Colletotrichum graminicola causing maize anthracnose in Spain. Recently, maize anthracnose was also reported in Bosnia and Herzegovina and China (Duan et al. 2019; Cuevas-Fernández et al. 2019), suggesting the pathogen's geographic range is increasing, which may be a threat to maize cultivation in locations with optimal humid conditions for disease development.

Novel Therapeutic Opportunities for Neurodegenerative Diseases with Mesenchymal Stem Cells: The Focus on Modulating the Blood-Brain Barrier.

Neurodegenerative disorders encompass a broad spectrum of profoundly disabling situations that impact millions of individuals globally. While their underlying causes and pathophysiology display considerable diversity and remain incompletely understood, a mounting body of evidence indicates that the disruption of blood-brain barrier (BBB) permeability, resulting in brain damage and neuroinflammation, is a common feature among them. Consequently, targeting the BBB has emerged as an innovative therapeutic strategy for addressing neurological disorders. Within this review, we not only explore the neuroprotective, neurotrophic, and immunomodulatory benefits of mesenchymal stem cells (MSCs) in combating neurodegeneration but also delve into their recent role in modulating the BBB. We will investigate the cellular and molecular mechanisms through which MSC treatment impacts primary age-related neurological conditions like Alzheimer's disease, Parkinson's disease, and stroke, as well as immune-mediated diseases such as multiple sclerosis. Our focus will center on how MSCs participate in the modulation of cell transporters, matrix remodeling, stabilization of cell-junction components, and restoration of BBB network integrity in these pathological contexts.

Bioinformatic Approach of B and T Cell Epitopes of PLD and CP40 Proteins of Corynebacterium pseudotuberculosis ovis Mexican Isolate 2J-L towards a Peptide-Based Vaccine.

Mapping B and T cell epitopes constitutes an important action for peptide vaccine design. PLD and CP40 virulence factors of Corynebacterium pseudotuberculosis biovar ovis, a causal agent of Caseous Lymphadenitis, have been evaluated in a murine model as good candidates for vaccine development. Therefore, the goal of this work was to in silico analyze B and T cell epitopes of the PLD and CP40 proteins of a Mexican isolate of Corynebacterium pseudotuberculosis ovis. The Immune Epitope Data Base and Resource website was employed to predict the linear and conformational B-cell, T CD4+, and T CD8+ epitopes of PLD and CP40 proteins of Corynebacterium pseudotuberculosis ovis Mexican strain 2J-L. Fifty B cell epitopes for PLD 2J-L and forty-seven for CP40 2J-L were estimated. In addition, T CD4+ and CD8+ cell epitopes were predicted for PLD 2J-L (MHC I:16 epitopes, MHC II:10 epitopes) and CP40 2J-L (MHC I: 15 epitopes, MHC II: 13 epitopes). This study provides epitopes, paying particular attention to sequences selected by different predictor programs and overlap sequences as B and T cell epitopes. PLD 2J-L and CP40 2J-L protein epitopes may aid in the design of a promising peptide-based vaccine against Caseous Lymphadenitis in Mexico.

Microanalytical Characterization of an Innovative Modern Mural Painting Technique by SEM-EDS, NMR and Micro-ATR-FTIR among Others.

During the 20th century, modern painters experimented with different mediums and painting techniques, one of them was Rafael Coronel in his mural painting, Paisaje Abstracto (Abstract landscape). The painting was created with a peculiar pouring technique and an unknown binding medium; ageing produced fractures and severe conservation problems. Therefore, the characterization of the painting medium became an urgent matter in order to understand the current condition of the painting and to develop a proper treatment. The aim of this research was to characterize the chemical composition and painting technique of Paisaje Abstracto. To approach this goal two microsamples were taken and analyzed by optical microscopy (OM), scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS), nuclear magnetic resonance (NMR) spectroscopy, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), micro attenuated total reflection Fourier transform infrared spectroscopy (micro-ATR-FTIR) and gas chromatography/mass spectrometry (GC/MS). The analysis allowed for the identification of cadmium sulfide (CdS) and titanium dioxide (TiO2) as inorganic pigments; aluminosilicate fillers; poly(methyl methacrylate) (pMMA) as a binder; MMA monomer, red organic pigment PR181; benzoyl peroxide, dibutyl phthalate and 1-octadecanol as organic additives. This study presents an innovative painting technique with pMMA, a medium not commonly used by artists, which was probably polymerized onto the painting support.