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The Phenobot platform is comprised by an autonomous robot, instrumentation, artificial intelligence, and digital twin diagnosis at the molecular level, marking the transition from pure data-driven to knowledge-driven agriculture 4.0, towards a physiology-based approach to precision viticulture. Such is achieved by measuring the plant metabolome ‘in vivo' and 'in situ', using spectroscopy and artificial intelligence for quantifying metabolites, e.g.: i. grapes: chlorophylls a and b, pheophytins a and b, anthocyanins, carotenoids, malic and tartaric acids, glucose and fructose; ii. foliage: chlorophylls a and b, pheophytins a and b, anthocyanins, carotenoids, nitrogen, phosphorous, potassium, sugars, and leaf water potential; and iii. soil nutrients (NPK). The geo-referenced metabolic information of each plant (organs and tissues) is the basis of multi-scaled analysis: i. geo-referenced metabolic maps of vineyards at the macroscopic field level, and ii. genome-scale 'in-silico' digital twin model for inferential physiology (phenotype state) and omics diagnosis at the molecular and cellular levels (transcription, enzyme efficiency, and metabolic fluxes). Genome-scale 'in-silico' Vitis vinifera numerical network relationships and fluxes comprise the scientific knowledge about the plant's physiological response to external stimuli, being the comparable mechanisms between laboratory and field experimentation - providing a causal and interpretable relationship to a complex system subjected to external spurious interactions (e.g., soil, climate, and ecosystem) scrambling pure data-driven approaches. This new approach identifies the molecular and cellular targets for managing plant physiology under different stress conditions, enabling new sustainable agricultural practices and bridging agriculture with plant biotechnology, towards faster innovations (e.g. biostimulants, anti-microbial compounds/mechanisms, nutrition, and water management). Phenobot is a project under the Portuguese emblematic initiative in Agriculture 4.0, part of the Recovery and Resilience Plan (Ref. PRR: 190 Ref. 09/C05-i03/2021 – PRR-C05-i03-I-000134).

Copyright of RPDI - Revista Portuguesa de Doenças Infecciosas is the property of Sociedade Portuguesa de Doencas Infecciosas e Microbiologia Clinica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of RPDI - Revista Portuguesa de Doenças Infecciosas is the property of Sociedade Portuguesa de Doencas Infecciosas e Microbiologia Clinica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: The Blood and Marrow Transplant (BMT) Clinical Trials Network conducted a phase 3 randomized trial comparing gilteritinib with placebo after allogeneic hematopoietic cell transplantation (HCT) for FLT3-ITD+ acute myeloid leukemia (AML). The primary analysis demonstrated no statistically significant difference in relapse-free survival (RFS); however, patients with FLT3-ITD measurable residual disease (MRD) peri-HCT had significantly longer RFS with gilteritinib. This analysis investigates the effect of post-HCT gilteritinib vs placebo on health-related quality of life (HRQOL). HRQOL was measured with Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), FACT-Leukemia (FACT-Leu), and EuroQOL-5 Dimensions (EQ-5D-5L) at post-HCT randomization; day 29; months 3, 6, 12, 18, 24; and/or end of therapy. HRQOL and clinically meaningful differences were summarized using descriptive statistics and compared using mixed model repeated measures to evaluate longitudinal change from baseline and stratified Cox model to evaluate time to improvement. HRQOL completion rate was acceptable (>70%) across all time points and measures. There were no differences in HRQOL scores at any time point between cohorts. Clinically meaningful and time to improvement in HRQOL were similar in both arms. Despite higher treatment-emergent adverse effects with gilteritinib, response to the question of being "bothered by side effects of treatment" did not differ between groups. Subgroup analysis of MRD-positive and negative patients demonstrated no differences in HRQOL between arms. For patients with FLT3-ITD+ AML undergoing HCT, gilteritinib maintenance was not associated with any difference in HRQOL or patient-reported impact of side effects. This trial was registered at www.ClinicalTrials.gov as #NCT02997202., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)

Diisopentyl phthalate (DiPeP) is primarily used as a plasticizer or additive within the production of polyvinyl chloride (PVC), and has many additional industrial applications. Its metabolites were recently found in urinary samples of pregnant women; thus, this substance is of concern as relates to human exposure. Depending upon the nature of the alcohol used in its synthesis, DiPeP may exist either as a mixture consisting of several branched positional isomers, or as a single defined structure. This article investigates the skin sensitization potential and immunomodulatory effects of DiPeP CAS No. 84777-06-0, which is currently marketed and classified as a UVCB substance, by in silico and in vitro methods. Our findings showed an immunomodulatory effect for DiPeP in LPS-induced THP-1 activation assay (increased CD54 expression). In silico predictions using QSAR TOOLBOX 4.5, ToxTree, and VEGA did not identify DiPeP, in the form of a discrete compound, as a skin sensitizer. The keratinocyte activation (Key Event 2 (KE2) of the adverse outcome pathway (AOP) for skin sensitization) was evaluated by two different test methods (HaCaT assay and RHE assay), and results were discordant. While the HaCaT assay showed that DiPeP can activate keratinocytes (increased levels of IL-6, IL-8, IL-1α, and ILA gene expression), in the RHE assay, DiPeP slightly increased IL-6 release. Although inconclusive for KE2, the role of DiPeP in KE3 (dendritic cell activation) was demonstrated by the increased levels of CD54 and IL-8 and TNF-α in THP-1 cells (THP-1 activation assay). Altogether, findings were inconclusive regarding the skin sensitization potential of the UVCB DiPeP-disagreeing with the results of DiPeP in the form of discrete compound (skin sensitizer by the LLNA assay). Additional studies are needed to elucidate the differences between DiPeP isomer forms, and to better understand the applicability domains of non-animal methods in identifying skin sensitization hazards of UVCB substances., (© 2024. The Author(s).)

Background: NCCN Guidelines recommend screening young women with an increased breast cancer risk (>20 ​% lifetime risk). We sought to evaluate our institutional rates of high-risk screening in young breast cancer patients prior to their diagnoses.", Methods: A single-institution retrospective review (2013-2018) was performed investigating risk scores (Tyrer-Cuzick model) and characteristics of breast cancer patients (age <40 ​y) prior to diagnosis., Results: 92 breast cancer patients age <40 ​y were identified (average age 34.5). Only 3.3 ​% (n ​= ​3) underwent appropriate screening, despite 35.8 ​% meeting high-risk criteria. Nearly all patients underwent genetic testing (98.9 ​%) with pathogenic mutations identified in 36.5 ​%, including 15.3 ​% with BRCA1/2 mutations., Conclusions: This analysis highlights a significant discrepancy between those meeting criteria for high-risk screening and those who underwent appropriate screening. We identified that this cohort carries significant genetic burden. Future analysis should investigate these findings on a broader scale and strategies to improve screening., Competing Interests: Declaration of competing interest The contents of this manuscript are not copyrighted, published previously or under consideration for publication elsewhere., (Copyright © 2023. Published by Elsevier Inc.)

The evaluation of water quality improvement brought about by in situ treatment of eutrophic water bodies, especially those used for human supply is a challenging task since each water system responds differently. To overcome this challenge, we applied exploratory factor analysis (EFA) to understand the effects of using hydrogen peroxide (H 2 O 2 ) on eutrophic water used as a drinking water supply. This analysis was used to identify the main factors that described the water treatability after exposing blue-green algae (cyanobacteria) contaminated raw water to H 2 O 2 at both 5 and 10 mg L -1 . Cyanobacterial chlorophyll-a was undetectable following the application of both concentrations of H 2 O 2 after four days, while not causing relevant changes to green algae and diatoms chlorophyll-a concentrations. EFA demonstrated that the main factors affected by both H 2 O 2 concentrations were turbidity, pH, and cyanobacterial chlorophyll-a concentration, which are important variables for a drinking water treatment plant. The H 2 O 2 caused significant improvement in water treatability by decreasing those three variables. Finally, the use of EFA was demonstrated to be a promising tool in identifying which limnological variables are most relevant concerning the efficacy of water treatment, which in turn can make water quality monitoring more efficient and less costly., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

An absolutely and relatively large brain has traditionally been viewed as a distinctive characteristic of the Homo genus, with anatomically modern humans presented at the apex of a long line of progressive increases in encephalization. Many studies continue to focus attention on increasing brain size in the Homo genus, while excluding measures of absolute and relative brain size of more geologically recent, smaller brained, hominins such as Homo floresiensis, and Homo naledi and smaller brained Homo erectus specimens. This review discusses the benefits of using phylogenetic comparative methods to trace the diverse changes in hominin brain evolution and the drawbacks of not doing so., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Despite the wide variety of existing therapies, multiple myeloma (MM) remains a disease with dismal prognosis. Choosing the right treatment for each patient remains one of the major challenges. A new approach being explored is the use of ex vivo models for personalized medicine. Two-dimensional culture or animal models often fail to predict clinical outcomes. Three-dimensional ex vivo models using patients' bone marrow (BM) cells may better reproduce the complexity and heterogeneity of the BM microenvironment. Here, we review the strengths and limitations of currently existing patient-derived ex vivo three-dimensional MM models. We analyze their biochemical and biophysical properties, molecular and cellular characteristics, as well as their potential for drug testing and identification of disease biomarkers. Furthermore, we discuss the remaining challenges and give some insight on how to achieve a more biomimetic and accurate MM BM model. Overall, there is still a need for standardized culture methods and refined readout techniques. Including both myeloma and other cells of the BM microenvironment in a simple and reproducible three-dimensional scaffold is the key to faithfully mapping and examining the relationship between these players in MM. This will allow a patient-personalized profile, providing a powerful tool for clinical and research applications.

Multiple myeloma (MM), the third most frequent hematological cancer worldwide, is characterized by the proliferation of neoplastic plasma cells in the bone marrow (BM). One of the hallmarks of MM is a permissive BM microenvironment. Increasing evidence suggests that cell-to-cell communication between myeloma and immune cells via tumor cell-derived extracellular vesicles (EV) plays a key role in the pathogenesis of MM. Hence, we aimed to explore BM immune alterations induced by MM-derived EV. For this, we inoculated immunocompetent BALB/cByJ mice with a myeloma cell line, MOPC315.BM, inducing a MM phenotype. Upon tumor establishment, characterization of the BM microenvironment revealed the expression of both activation and suppressive markers by lymphocytes, such as granzyme B and PD-1, respectively. In addition, conditioning of the animals with MOPC315.BM-derived EV, before transplantation of the MOPC315.BM tumor cells, did not anticipate the disease phenotype. However, it induced features of suppression in the BM milieu, such as an increase in PD-1 expression by CD4+ T cells. Overall, our findings reveal the involvement of MOPC315.BM-derived EV protein content as promoters of immune niche remodeling, strengthening the importance of assessing the mechanisms by which MM may impact the immune microenvironment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lopes, Caetano, Barahona, Pestana, Ferreira, Lourenço, Queirós, Bilreiro, Shemesh, Beck, Carvalho, Matthiesen, Bogen, Costa-Silva, Serre, Carneiro and João.)

Multiple myeloma (MM) is a hematological malignancy of clonal antibody-secreting plasma cells (PCs). MM diagnosis and risk stratification rely on bone marrow (BM) biopsy, an invasive procedure prone to sample bias. Liquid biopsies, such as extracellular vesicles (EV) in peripheral blood (PB), hold promise as new minimally invasive tools. Real-world studies analyzing patient-derived EV proteome are rare. Here, we characterized a small EV protein content from PB and BM samples in a cohort of 102 monoclonal gammopathies patients routinely followed in the clinic and 223 PB and 111 BM samples were included. We investigated whether EV protein and particle concentration could predict an MM patient prognosis. We found that a high EV protein/particle ratio, or EV cargo >0.6 µg/10 8 particles, is related to poorer survival and immune dysfunction. These results were supported at the protein level by mass spectrometry. We report a set of PB EV-proteins ( PDIA3 , C4BPA , BTN1A1 , and TNFSF13 ) with a new biomarker potential for myeloma patient outcomes. The high proteomic similarity between PB and BM matched pairs supports the use of circulating EV as a counterpart of the BM EV proteome. Overall, we found that the EV protein content is related to patient outcomes, such as survival, immune dysfunction, and possibly treatment response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ferreira, Carneiro, Pestana, Barahona, Caetano, Lopes, Lúcio, Neves, Beck, Carvalho, Matthiesen, Costa-Silva and João.)

Background: Aging is associated with most neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Determination of peripheral blood biomarkers represents a low invasive approach for tracking early changes in body metabolism during aging., Objective: This study addresses a cross-sectional analysis to identify changes in lipid, minerals, and antioxidant capacity as potential biomarkers to the onset of neurodegenerative diseases during aging., Methods: A retrospective analysis was performed to determine age-related biomarkers from a clinical sample database. Next, one hundred volunteers between 20-59 (adult) and over 60 years (elderly) were selected for the motor and cognitive tests according to Unified Parkinson's Disease Rating Scale (UPDRS) and Mini-Mental State Examination (MMSE), respectively. Peripheral blood samples were also collected to determine circulating lipids, minerals, and antioxidant capacity., Results: Lipid profile revealed an increase in triglycerides, total, and VLDL Cholesterol. Among the elderlies, HDL was lower than the adult group, particularly in volunteers with severe cognitive decline. Minerals involved in antioxidant defense such as iron, selenium, and manganese were lower in elderly people compared to adults. Catalase activity was also reduced among elderlies with mild cognitive impairment., Conclusion: Here, we show changes in key serum biomarkers correlate with aging and clinical cognitive decline among elderly people. These findings may contribute to the understanding of how biomarkers can be useful for early diagnosis and treatment of aging-related diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In the current context of the emergence of certain infectious diseases and discussion of the One Health concept for many of these, the study of leptospirosis - both in domestic and wild hosts - cannot be neglected. The study of animal leptospirosis has evolved in recent years. It has been demonstrated that the human-animal-environment interface is more important than previously thought. In the present study, 35 strains of five pathogenic Leptospira species were isolated from different animal species in Brazil and characterized by rrs, secY, and Multilocus Sequence Typing (MLST) sequencing. Phylogenetic inferences were performed and the molecular diversity of the populations (intra- and inter-population levels) was evaluated. Among the five studied species, 18 different sequence types (STs) were found (22 new alleles and 11 new STs). eBURST analysis revealed two clonal complexes (CCs) and seven singletons. A high genetic diversity was demonstrated (H = 0.954 ± 0.017), mainly for the L. santarosai population (H = 0.942 ± 0.034, n = 20). The same strain was identified in different host species, as well as strains with zoonotic potential circulating in the country. Although the difficulty of culturing Leptospira strains is well known, the high variability of the strains found in Brazil highlights the importance of animals in maintaining the biological cycle of the bacterium in nature. Moreover, the selection of autochthonous strains for the development of vaccines becomes a challenge., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Occupational allergic contact dermatitis (ACD) in healthcare workers (HCWs) is common, but systemic antibiotics are rarely reported as the cause., Objectives: Characterize occupational ACD by handling systemic antibiotics., Method: A retrospective analysis was performed of ACD caused by systemic antibiotics among HCWs patch tested between 2010 and 2016 with a series of systemic antibiotics., Results: We studied 4 female nurses aged 28-47 years who developed ACD while working in surgical departments. They had eczema of the hands, and forearms or face, and 1 patient, who previously had exanthema caused by flucloxacillin, also developed a generalized rash following airborne exposure to systemic antibiotics. Patch tests showed positive reactions to ampicillin and cefazolin in 1 patient, to cefotaxime and ceftriaxone in 2 patients, and to several penicillins in another patient. Three patients also reacted to rubber allergens, fragrances, and/or preservatives. All patients admitted having direct and sporadic exposure to systemic antibiotic solutions. Avoidance resulted in a significant improvement of ACD, but 1 patient had to change job., Conclusions: Occupational ACD caused by β-lactam antibiotics, particularly cephalosporins, is significant in HCWs. Cross-reactions between β-lactams are similar to those described in non-immediate drug eruptions. A relationship between systemic delayed drug hypersensitivity and ACD, as observed in one case, suggests that patients should avoid future use of the antibiotic to which they are sensitized., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)