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Objective: To compare the pharmacokinetics and efficacy of oral versus intravenous mixed micellar vitamin K prophylaxis in infants with cholestatic liver disease, a known risk factor for vitamin K deficiency bleeding.Design: Prospective randomised controlled study.Setting: Paediatric Liver Unit.Patients: Forty four infants less than 6 months of age with conjugated hyperbilirubinaemia.Main Outcome Measures: Serum concentrations of vitamin K(1) and undercarboxylated prothrombin (PIVKA-II; a sensitive functional indicator of vitamin K status) before and for up to four days after a single dose of mixed micellar K(1) 1 mg intravenously or 2 mg orally. Comparison of K(1) levels 24 hours after oral K(1) with those from 14 healthy newborns given the same dose.Results: At admission, 18 infants (41%) had elevated levels of serum PIVKA-II and eight (18%) had low K(1) concentrations, indicative of subclinical vitamin K deficiency. Median serum K(1) concentrations were similar in the oral and intravenous groups at baseline (0.92 v 1.15 ng/ml), rising to 139 ng/ml six hours after intravenous K(1) but to only 1.4 ng/ml after oral administration. In the latter group, the low median value (0.95 ng/ml) and wide range (< 0.15-111 ng/ml) of serum K(1) compared unfavourably with the much higher levels (median 77, range 11-263 ng/ml) observed in healthy infants given the same oral dose, and suggested impaired and erratic intestinal absorption in cholestatic infants. The severity of malabsorption was such that only 4/24 (17%) achieved an incremental rise in serum K(1) > 10 ng/ml.Conclusions: The intestinal absorption of mixed micellar K(1) is unreliable in infants with conjugated hyperbilirubinaemia. Given the strong association between cholestasis and late vitamin K deficiency bleeding, these data provide an explanation for the failure of some oral vitamin K(1) prophylaxis regimens in infants with latent cholestasis. [ABSTRACT FROM AUTHOR]

Pregnancy may be a challenging period for the maternal systems and has been regarded as a stress test, as imperceptible/mild dysfunctions eventually present may be exacerbated during this period. The cardiovascular system is no exception, and several morphological and functional adaptations accompanying pregnancy have been described. However, long-term pregnancy-induced cardiac molecular alterations remain highly unexplored. The postpartum is marked by reverse remodeling of the pregnancy-induced cardiovascular adaptations, representing a possible critical period for assessing future maternal cardiovascular health. The current study explored the molecular and metabolic alterations in the cardiac tissue eight weeks after a physiological uncomplicated pregnancy. Female Sprague-Dawley rats were fed a chow diet through pregnancy, lactation, and weaning and compared to their non-pregnant counterparts. Eight weeks postpartum, increased levels of the phosphorylated form of AMPKα (Thr172) and its ratio to total AMPKα indicated possible alterations in cardiac metabolic flexibility, accompanied by increased Pparα and Hif1α transcripts levels. Additionally, postpartum hearts exhibited higher mitochondrial ATP and NADH levels without major changes in mitochondrial respiratory function. Elevated Nrf2 levels in the cardiac tissue suggested potential implications for cardiac redox balance, further supported by increased levels or activity of proteins directly regulated by Nrf2. The findings herein reported suggest that at eight weeks postpartum, molecular alterations induced by pregnancy, especially regarding redox balance, are still observed in the mothers' heart. These alterations present at late postpartum may open new avenues to understand the different risk for cardiovascular complications development after normal pregnancies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paulo J. Oliveira reports financial support was provided by European Commission. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Weakly-supervised semantic segmentation (WSSS) methods, reliant on image-level labels indicating object presence, lack explicit correspondence between labels and regions of interest (ROIs), posing a significant challenge. Despite this, WSSS methods have attracted attention due to their much lower annotation costs compared to fully-supervised segmentation. Leveraging reinforcement learning (RL) self-play, we propose a novel WSSS method that gamifies image segmentation of a ROI. We formulate segmentation as a competition between two agents that compete to select ROI-containing patches until exhaustion of all such patches. The score at each time-step, used to compute the reward for agent training, represents likelihood of object presence within the selection, determined by an object presence detector pre-trained using only image-level binary classification labels of object presence. Additionally, we propose a game termination condition that can be called by either side upon exhaustion of all ROI-containing patches, followed by the selection of a final patch from each. Upon termination, the agent is incentivised if ROI-containing patches are exhausted or disincentivised if a ROI-containing patch is found by the competitor. This competitive setup ensures minimisation of over- or under-segmentation, a common problem with WSSS methods. Extensive experimentation across four datasets demonstrates significant performance improvements over recent state-of-the-art methods. Code: https://github.com/s-sd/spurl/tree/main/wss.

Background: Therapy adherence is a key factor in the control of type 2 diabetes mellitus (T2DM). Optimal self-care requires skills in health literacy (HL)., Objective: This study aims to analyze the relationship between HL and adherence to therapy and to understand the possible influence of other sociodemographic and disease variables., Methods: A multicenter, cross-sectional study was conducted in Portuguese in 13 different primary health care units in both rural and urban environments. A sociodemographic questionnaire and two validated instruments, "Medical Term Recognition Test" and "Summary of Diabetes Self-Care Activities," were applied. The last value of hemoglobin A1c (HbA1c) and the number of chronic medications were collected from clinical records. Descriptive statistics and bivariate correlations were performed as well as multivariable linear regression to assess the association between HL and adherence to therapy., Key Results: Participants (n = 354) were on average age 63.67 ± 10.39 years, 57.1% male and 42.9% female, 68.4% with inadequate HL and an average HbA1c of 7 ± 1.18%. Better HL was correlated with higher adherence to the total of self-care activities, nonpharmacological therapy, and foot care. In multivariable linear regression analyses, better HL ( β = 0.176, p = .003), less than minimum wage (β = -0.197, p = .001) and insulin therapy ( β = 0.272, p = .001) were independently associated with increased adherence to overall self-care activities., Conclusion: In a representative sample of people with T2DM in Portugal, HL was a key factor for greater adherence to demanding self-care activities. [ HLRP: Health Literacy Research and Practice . 2024;8(4):e194-e203. ].

Age is a prominent risk factor for cardiometabolic disease, often leading to heart structural and functional changes. However, precise molecular mechanisms underlying cardiac remodeling and dysfunction exclusively resulting from physiological aging remain elusive. Previous research demonstrated age-related functional alterations in baboons, analogous to humans. The goal of this study is to identify early cardiac molecular alterations preceding functional adaptations, shedding light on the regulation of age-associated changes. Unbiased transcriptomics of left ventricle samples are performed from female baboons aged 7.5-22.1 years (human equivalent ≈30-88 years). Weighted-gene correlation network and pathway enrichment analyses are performed, with histological validation. Modules of transcripts negatively correlated with age implicated declined metabolism-oxidative phosphorylation, tricarboxylic acid cycle, glycolysis, and fatty-acid β-oxidation. Transcripts positively correlated with age suggested a metabolic shift toward glucose-dependent anabolic pathways, including hexosamine biosynthetic pathway (HBP). This shift is associated with increased glycosaminoglycan synthesis, modification, precursor synthesis via HBP, and extracellular matrix accumulation, verified histologically. Upregulated extracellular matrix-induced signaling coincided with glycosaminoglycan accumulation, followed by cardiac hypertrophy-related pathways. Overall, these findings revealed a transcriptional shift in metabolism favoring glycosaminoglycan accumulation through HBP before cardiac hypertrophy. Unveiling this metabolic shift provides potential targets for age-related cardiac diseases, offering novel insights into early age-related mechanisms., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide. Up to now, no specific screening or diagnostic tests are available for early PDAC detection. As a result, most patients are diagnosed with advanced or metastatic disease, which leads to a poor prognosis. In this study, we aimed to evaluate the diagnostic value of urinary CRP (uCRP) alone and in combination with our previously established urine biomarker panel (REG1B, LYVE1 and TFF1) for early detection of PDAC. A total of 534 urine samples from multiple centres were analysed: 93 from healthy individuals, 265 from patients with benign hepatobiliary diseases and 176 from PDAC patients. The uCRP and the urinary biomarker panel were assessed using commercial ELISA assays, while plasma CA19-9 and blood CRP (bCRP) were measured using Roche Cobas platform. Multiple logistic regression and nonparametric Kruskal-Wallis test were used for statistical analysis. An internal validation approach was applied, and the validated AUC estimators were reported to ensure accuracy. A significant difference was observed in the medians of uCRP between healthy and benign controls and PDAC sample groups (p < 0.001). uCRP levels were not dependent on gender and age, as well as cancer stage. When uCRP was combined with the urinary biomarker panel, it achieved AUCs of 0.878 (95% CI: 0.802-0.931), 0.798 (95% CI: 0.738-0.859) and 0.813 (95% CI: 0.758-0.869) in healthy vs PDAC, benign vs PDAC and healthy and benign vs PDAC sample groups, respectively. However, adding plasma CA19-9 to the urinary biomarker panel yielded a better performance, with AUCs of 0.978 (95% CI: 0.959-0.996), 0.911 (95% CI: 0.873-0.949) and 0.919 (95% CI: 0.883-0.955) in the healthy vs PDAC, benign vs PDAC and healthy and benign vs PDAC comparisons, respectively. In conclusion, we show that measuring CRP in urine is a feasible analytical method, and that uCRP could potentially be a promising biomarker in various diseases including other cancer types., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ali, Debernardi, Kurotova, Tajbakhsh, Gupta, Pandol, Wilson, Pereira, Greenhalf, Blyuss and Crnogorac-Jurcevic.)

Background: The grim (<10% 5-year) survival rates for pancreatic ductal adenocarcinoma (PDAC) are attributed to its complex intrinsic biology and most often late-stage detection. The overlap of symptoms with benign gastrointestinal conditions in early stage further complicates timely detection. The suboptimal diagnostic performance of carbohydrate antigen (CA) 19-9 and elevation in benign hyperbilirubinaemia undermine its reliability, leaving a notable absence of accurate diagnostic biomarkers. Using a selected patient cohort with benign pancreatic and biliary tract conditions we aimed to develop a data analysis protocol leading to a biomarker signature capable of distinguishing patients with non-specific yet concerning clinical presentations, from those with PDAC., Methods: 539 patient serum samples collected under the Accelerated Diagnosis of neuro Endocrine and Pancreatic TumourS (ADEPTS) study (benign disease controls and PDACs) and the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS, healthy controls) were screened using the Olink Oncology II panel, supplemented with five in-house markers. 16 specialized base-learner classifiers were stacked to select and enhance biomarker performances and robustness in blinded samples. Each base-learner was constructed through cross-validation and recursive feature elimination in a discovery set comprising approximately two thirds of the ADEPTS and UKCTOCS samples and contrasted specific diagnosis with PDAC., Results: The signature which was developed using diagnosis-specific ensemble learning demonstrated predictive capabilities outperforming CA19-9, the only biomarker currently accepted by the FDA and the National Comprehensive Cancer Network guidelines for pancreatic cancer, and other individual biomarkers and combinations in both discovery and held-out validation sets. An AUC of 0.98 (95% CI 0.98-0.99) and sensitivity of 0.99 (95% CI 0.98-1) at 90% specificity was achieved with the ensemble method, which was significantly larger than the AUC of 0.79 (95% CI 0.66-0.91) and sensitivity 0.67 (95% CI 0.50-0.83), also at 90% specificity, for CA19-9, in the discovery set (p = 0.0016 and p = 0.00050, respectively). During ensemble signature validation in the held-out set, an AUC of 0.95 (95% CI 0.91-0.99), sensitivity 0.86 (95% CI 0.68-1), was attained compared to an AUC of 0.80 (95% CI 0.66-0.93), sensitivity 0.65 (95% CI 0.48-0.56) at 90% specificity for CA19-9 alone (p = 0.0082 and p = 0.024, respectively). When validated only on the benign disease controls and PDACs collected from ADEPTS, the diagnostic-specific signature achieved an AUC of 0.96 (95% CI 0.92-0.99), sensitivity 0.82 (95% CI 0.64-0.95) at 90% specificity, which was still significantly higher than the performance for CA19-9 taken as a single predictor, AUC of 0.79 (95% CI 0.64-0.93) and sensitivity of 0.18 (95% CI 0.03-0.69) (p = 0.013 and p = 0.0055, respectively)., Conclusion: Our ensemble modelling technique outperformed CA19-9, individual biomarkers and indices developed with prevailing algorithms in distinguishing patients with non-specific but concerning symptoms from those with PDAC, with implications for improving its early detection in individuals at risk., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: UM reports stock ownership in Abcodia UK between 2011 and 2021; UM has received grants from the Medical Research Council (MRC), Cancer Research UK, the National Institute for Health Research (NIHR), the India Alliance, NIHR Biomedical Research Centre at University College London Hospital, and The Eve Appeal; UM currently has research collaborations with iLOF, RNA Guardian and Micronoma, with funding paid to UCL; UM holds patent number EP10178345.4 for Breast Cancer Diagnostics; AG currently has research collaborations with Micronoma and iLoF, with the research funding awarded to UCL. The other authors have declared that no competing interests exist., (Copyright: © 2024 Ney et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Obesity during pregnancy has been escalating, becoming a huge problem that poses consequences not only for the health of the offspring but also for the maternal well-being. Women's adipose and hepatic tissue metabolism undergoes significant changes during the gestational period. During pregnancy, obesity is a primary instigator of steatosis, increasing the risk of non-alcholic fatty liver disease (NAFLD), now recognized under the updated nomenclature metabolic dysfunction-associated steatotic liver disease (MASLD). Pregnant women with obesity present higher levels of free fatty acids and glucose, reduction in insulin sensitivity, and adipose tissue endocrine dysregulation. Furthermore, obesity-induced modifications in clock genes and lipid-associated gene expression within adipose tissue disrupt crucial metabolic adaptations, potentially culminating in adipose tissue dysfunction. Thus, the liver experiences increased exposure to free fatty acids through the portal vein. Higher uptake of free fatty acids into the liver disrupts hepatic lipid oxidation while enhances lipogenesis, thereby predisposing to ectopic fat deposition within the liver. This review focuses on the obesity-induced changes during pregnancy in both liver and adipose tissue metabolism, elucidating how the metabolic crosstalk between these two organs can be dysregulated in pregnant women living with obesity., (© 2024 The Author(s).)

Guatteria olivacea R.E. Fries is an Amazonian species known as 'envira-bobó' and 'envira-fofa' and is common in the states of Amazonas, Acre, and Pará. Recently, the essential oil from the leaves of this species has shown promising antitumor activity both in vitro and in vivo. The presence of isoquinoline-derived alkaloids, including aporphinoids and tetrahydroprotoberberine alkaloids, has also been previously reported. In our ongoing search for bioactive compounds from Annonaceae Amazonian plants, the bark of G. olivacea was investigated via classical chromatography techniques, which revealed nine compounds, eight isoquinoline-derived alkaloids, a rare alkaloid with a α -gem-dimethyltetradehydrocularine structure known as gouregine, seven known aporphinoid alkaloids: isopiline, O -methylisopiline, melosmine, 9-hydroxyiguattescine, dihydromelosmine, lysicamine, and guattouregidine, and one known pimaradiene diterpene: acanthoic acid. All the isolated compounds were described for the first time in the bark of G. olivacea, and their structures were elucidated by extensive analyses of their 1D and 2D NMR spectra in combination with MS data. The NMR data of the alkaloids isopiline, O -methylisopiline, melosmine, dihydromelosmine, and guattouregidine were revised due to incomplete data in the literature and some ambiguities. The in vitro cytotoxic activities of the isolated compounds were evaluated against human cancer (HepG2, KG-1a, and HCT116) and noncancerous (MRC-5) cell lines via the Alamar blue assay after 72 h of incubation. Among the compounds evaluated against human cancer cell lines, the most active was the oxoaporphine alkaloid lysicamine, which has strong activity against HCT116 cells, with an IC 50 value of 6.64 µg/mL (22.79 µmol/L). Melosmine had a moderate effect on HCT116 cells, with an IC 50 value of 16.77 µg/mL (49.70 µmol/L), whereas acanthoic acid had moderate effects on HepG2 and HCT116 cells, with IC 50 values of 14.63 µg/mL (48.37 µmol/L) and 21.25 µg/mL (70.25 µmol/L), respectively.

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi , is an important public health problem, occurring mainly in Latin America. The disease has a major social and economical effect, negatively impacting the life of the infected individuals, and bringing great costs to public health. An early and accurate diagnosis is essential for administration of early treatment. In addition, prognostic tests may aid disease management, decreasing hospitalization costs. However, the serological diagnostic scenario for CD still faces several challenges, making the development of new diagnostic kits a pressing matter. Facing this scenario, several researchers have expanded efforts in developing and testing new antigens, such as recombinant proteins and recombinant multiepitope proteins, with promising results. These recombinant antigens offer several advantages, such as improved sensitivity and specificity, in addition to facilitated scaling. Also, it has been possible to observe a rising number of studies using ELISA and point-of-care platforms, employing these antigens in the past few years. Among them, recombinant proteins were the most applied antigens, demonstrating great capacity to discriminate between positive and negative samples. Although fewer in number, recombinant multiepitope proteins also demonstrated an improved diagnostic performance. Indeed, a great number of studies employing these antigens showed sensitivity and specificity values above 90%, greatly impacting diagnostic accuracy. Nevertheless, despite the good results found, it is still possible to observe some bottlenecks in the development of new antigens, such as the scarcity of tests with sera from the acute phase and the variability of results in different geographic areas. In this sense, aiming to contribute to control and health programs, the continuous search for a more accurate serological diagnosis is essential, both for the acute and chronic phases of the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Resende, Ribeiro, Gandra, Silva, Lopes, Barcelos, Couto, de Faria, Pereira, Xavier, Machado, da Paz, Chaves, Coelho, Giunchetti, Chávez-Fumagalli, Dutra, Gonçalves and Galdino.)

Rocky Mountain or Brazilian spotted fever, caused by Rickettsia rickettsii , is a fulminant, seasonal, and neglected disease that occurs in focal points of North America and South America. Its rapid detection is essential for the better prognosis and survival rate of infected individuals. However, disease diagnosis still faces challenges as the accuracy of many of the available laboratory tests fluctuates. This review aimed to analyze methods for antibody or antigen detection, their gaps, and their evolution over time. A search was conducted to find all studies in the Pubmed database that described the antibody or antigen detection of R. rickettsii infections. Initially, a total of 403 articles were screened. Of these articles, only 17 fulfilled the pre-established inclusion criteria and were selected. Among the different methods applied, the IFA technique was the one most frequently found in the studies. However, it presented varied results such as a low specificity when using the indirect method. Other techniques, such as ELISA and immunohistochemistry, were also found, although in smaller numbers and with their own limitations. Although some studies showed promising results, there is a pressing need to find new techniques to develop a rapid and effective diagnosis of R. rickettssi infection.

Supervised machine learning-based medical image computing applications necessitate expert label curation, while unlabelled image data might be relatively abundant. Active learning methods aim to prioritise a subset of available image data for expert annotation, for label-efficient model training. We develop a controller neural network that measures priority of images in a sequence of batches, as in batch-mode active learning, for multi-class segmentation tasks. The controller is optimised by rewarding positive task-specific performance gain, within a Markov decision process (MDP) environment that also optimises the task predictor. In this work, the task predictor is a segmentation network. A meta-reinforcement learning algorithm is proposed with multiple MDPs, such that the pre-trained controller can be adapted to a new MDP that contains data from different institutes and/or requires segmentation of different organs or structures within the abdomen. We present experimental results using multiple CT datasets from more than one thousand patients, with segmentation tasks of nine different abdominal organs, to demonstrate the efficacy of the learnt prioritisation controller function and its cross-institute and cross-organ adaptability. We show that the proposed adaptable prioritisation metric yields converging segmentation accuracy for a new kidney segmentation task, unseen in training, using between approximately 40% to 60% of labels otherwise required with other heuristic or random prioritisation metrics. For clinical datasets of limited size, the proposed adaptable prioritisation offers a performance improvement of 22.6% and 10.2% in Dice score, for tasks of kidney and liver vessel segmentation, respectively, compared to random prioritisation and alternative active sampling strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective  To investigate the epidemiology of injury types among jiu-jitsu practitioners, as well as the incidence regarding different skill and experience levels, through the question: "What are the characteristics and prevalence of musculoskeletal injuries in Jiu-Jitsu practitioners?". Methods  Since the beginning of the study, in August 2020, we conducted a search on the MEDLINE, LILACS, and SciELO electronic databases. We included cross-sectional studies published between 2018 and 2023 on the epidemiology of the types of injuries among jiu-jitsu practitioners that compared their incidence regarding different levels of ability and experience. Two independent researchers performed the data extraction and assessed the risk of bias. Results  Seven studies were included. The common outcomes involved 2,847 jiu-jitsu practitioners. A high prevalence in the knee joint and chest and rib areas was reported. Considering the difference in experience level among the practitioners, we could observe that most of the individuals included were beginners. Among the age groups observed, male practitioners older than 30 years of age were the ones who presented the highest rate of musculoskeletal injury, especially during training sessions. Conclusion  There is a high prevalence of musculoskeletal injuries among jiu-jitsu practitioners. The most affected anatomical segments are the knee joint, the chest, and the rib region, followed by the shoulder joint. The related factors change according to certain variables, being more common during training in male individuals over 30 years of age and beginners in the sport., Competing Interests: Conflitos de Interesses Os autores não têm conflito de interesses a declarar., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

Introduction: Lung cancer is the most commonly diagnosed and the main cause of cancer death, usually related to cigarette smoking. Furthermore, the microbiota of people exposed to cigarette smoke can be modified, making it difficult to eliminate opportunistic microorganisms. The leaves of Eugenia pyriformis are a by-product of fruit production and, to date, there have been no studies addressing the antiproliferative, anti-inflammatory, and antimicrobial activities., Objective: Investigate the antimicrobial, Nitric Oxide (NO)-production inhibition, and antiproliferative activities of the essential oil from E. pyriformis leaves and its possible effect on the treatment and prevention of damage caused by tobacco., Methods: The essential oil (EO) was obtained by hydrodistillation (3 h). Its chemical composition was investigated by GC-MS. It was proposed to investigate antiproliferative activity against human tumor cell lines, namely, breast adenocarcinoma (MCF-7), lung (NCI-H460), cervical (HeLa), and hepatocellular (HepG2) carcinomas. A non-tumor primary culture from pig liver (PLP2) was also tested. The EO capacity to inhibit nitric oxide (NO) production was evaluated by a lipopolysaccharide stimulated murine macrophage cell line. Antibacterial and antifungal activities against opportunistic pathogens were investigated against seven strains of bacteria and eight fungi., Results: The results indicated the presence of 23 compounds in the essential oil, the majority were spathulenol (45.63%) and β-caryophyllene oxide (12.72%). Leaf EO provided 50% inhibition of nitric oxide production at a concentration of 92.04 µg mL -1 . The EO also demonstrated antiproliferative activity against all human tumor cell lines studied, with GI50 values comprised between 270.86 and 337.25 µg mL -1 . The essential oil showed antimicrobial potential against the bacteria Listeria monocytogenes (Murray et al.) Pirie (NCTC 7973) and Salmonella Typhimurium ATCC 13311 (MIC 1870 µg mL -1 ) and fungi Aspergillus versicolor ATCC 11730, Aspergillus ochraceus ATCC 12066, Penicillium ochrochloron ATCC 90288, Penicillium verrucosum var. cyclopium (Westling) Samson, Stolk & Hadlok (food isolate) (MIC 1870 µg mL -1 ) and Trichoderma viride Pers. IAM 5061 (1,400 µg mL -1 )., Conclusion: The demonstrated anti-inflammatory, antiproliferative, and antimicrobial activities in the leaves of E. pyriformis can add value to the production chain of this plant, being a possible option for preventing and combating cancer, including lung cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 de Medeiros, Rodrigues, Sakumoto, Ruiz, Faria, Gonçalves, Piau Junior, Glamočlija, Soković, Gonçalves, Mandim, Barros and Gazim.)

In this study, the main agents associated with endometritis in cows in the state of Santa Catarina, Brazil, were identified and the resistance profile and virulence mechanisms of the bacterial isolates were evaluated. Isolates of Escherichia coli and Trueperella pyogenes were tested for their biofilm forming ability and the antimicrobial action of bromhexine hydrochloride in combination with other antimicrobials. A total of 37 uterine lavage samples were collected from cows with endometritis. Of the 55 bacteria isolated, 25.4% were identified as T. pyogenes and 16.3% as E. coli. The bacterial isolates showed greater resistance to sulfamethoxazole + trimethoprim (58.2%) and tetracycline (56.3%). Among the species, E. coli showed the highest resistance rates, with 100% of isolates showing resistance to amoxicillin, streptomycin, and gentamicin. The results of the minimum inhibitory concentration for the T. pyogenes isolates showed that 91.6% of the isolates were resistant to enrofloxacin and tetracycline, and 75% were resistant to ceftiofur and sulfamethoxazole + trimethoprim. All E. coli and T. pyogenes isolates showed biofilm forming ability. The plo, fimA, and nanH genes were identified in 100% of T. pyogenes isolates. In parallel, 100% of E. coli isolates had the fimH gene, and 11.1% had the csgD gene. Bromhexine hydrochloride showed antimicrobial activity against 100% of E. coli isolates and 66.6% of T. pyogenes isolates. Furthermore, when associated with antimicrobials, bromhexine hydrochloride has a synergistic and additive effect, proving to be an option in the treatment of endometritis in cows and an alternative for reducing the use of antimicrobials., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Recombinant multiepitope proteins (RMPs) are a promising alternative for application in diagnostic tests and, given their wide application in the most diverse diseases, this review article aims to survey the use of these antigens for diagnosis, as well as discuss the main points surrounding these antigens. RMPs usually consisting of linear, immunodominant, and phylogenetically conserved epitopes, has been applied in the experimental diagnosis of various human and animal diseases, such as leishmaniasis, brucellosis, cysticercosis, Chagas disease, hepatitis, leptospirosis, leprosy, filariasis, schistosomiasis, dengue, and COVID-19. The synthetic genes for these epitopes are joined to code a single RMP, either with spacers or fused, with different biochemical properties. The epitopes' high density within the RMPs contributes to a high degree of sensitivity and specificity. The RMPs can also sidestep the need for multiple peptide synthesis or multiple recombinant proteins, reducing costs and enhancing the standardization conditions for immunoassays. Methods such as bioinformatics and circular dichroism have been widely applied in the development of new RMPs, helping to guide their construction and better understand their structure. Several RMPs have been expressed, mainly using the Escherichia coli expression system, highlighting the importance of these cells in the biotechnological field. In fact, technological advances in this area, offering a wide range of different strains to be used, make these cells the most widely used expression platform. RMPs have been experimentally used to diagnose a broad range of illnesses in the laboratory, suggesting they could also be useful for accurate diagnoses commercially. On this point, the RMP method offers a tempting substitute for the production of promising antigens used to assemble commercial diagnostic kits., (© 2024. The Author(s).)

Chagas disease, caused by the protozoa Trypanosoma cruzi, continues to be a serious public health problem in Latin America, worsened by the limitations in its detection. Given the importance of developing new diagnostic methods for this disease, the present review aimed to verify the number of publications dedicated to research on peptides that demonstrate their usefulness in serodiagnosis. To this end, a bibliographic survey was conducted on the PubMed platform using the keyword "peptide" or "epitope" combined with "Chagas disease" or "Trypanosoma cruzi"; "diagno*" or "serodiagnosis" or "immunodiagnosis", without period restriction. An increasing number of publications on studies employing peptides in ELISA and rapid tests assays was verified, which confirms the expansion of research in this field. It is possible to observe that many of the peptides tested so far originate from proteins widely used in the diagnosis of Chagas, and many of them are part of commercial tests developed. In this sense, as expected, promising results were obtained for several peptides when tested in ELISA, as many of them exhibited sensitivity and specificity values above 90%. Furthermore, some peptides have been tested in several studies, confirming their diagnostic potential. Despite the promising results observed, it is possible to emphasize the need for extensive testing of peptides, using different serological panels, in order to confirm their potential. The importance of producing an effective assay capable of detecting the clinical stages of the disease, as well as new immunogenic antigens that enable new serological diagnostic tools for Chagas disease, is evident., (© 2024. The Author(s).)

Purpose: To evaluate the influence of vitamin D (VD) concentrations coupled with metabolic phenotypes preoperatively and 6 months after Roux-en-Y gastric bypass (RYGB) on body variables and weight loss., Materials and Methods: A longitudinal, retrospective, analytical study comprising 30 adult individuals assessed preoperatively (T0) and 6 months (T1) after undergoing Roux-en-Y gastric bypass. The participants were distributed preoperatively into metabolically healthy obese (MHO) and metabolically unhealthy obese individuals (MUHO) according to the HOMA-IR classification, as well as the adequacy and inadequacy of vitamin D concentrations in the form of 25(OH)D. All participants were assessed for weight, height, body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), visceral adiposity index (VAI), body circularity index (BCI), body adiposity index (BAI), weight loss, and assessment of 25(OH)D and 1,25(OH)2D concentrations using high-performance liquid chromatography with an ultraviolet detector (HPLC-UV). The statistical program used was SPSS version 21., Results: VD adequacy and a healthy phenotype in the preoperative period may play an important role concerning body fat distribution, as the body averages for WHtR (0.020*) and BCI (0.020*) were lower in MHO participants. In comparison, those with VD inadequacy and MUHOs had higher BAI averages (0.000*) in the postoperative period. Furthermore, it is possible that VD inadequacy before and after RYGB, even in the presence of an unhealthy phenotype, may contribute to the increase in VAI values (0.029*) after this surgery. Only those with inadequate VD and MUHOs had higher 25(OH)D concentrations. Besides, this unhealthy phenotype had a greater reduction in BMI in the early postoperative period (p < 0.001)., Conclusion: This study suggests that VD adequacy and the presence of a healthy phenotype appear to have a positive impact on the reduction of visceral fat in the context of pre- and postoperative obesity. In addition, there was a greater weight reduction in those with VD inadequacy and in MUHO, which suggests that the volumetric dilution effect of VD and catabolism after bariatric surgery is more pronounced in this specific metabolic phenotype., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The most prominent genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) is a repeat expansion in the gene C9orf72. Importantly, the transcriptomic consequences of the C9orf72 repeat expansion remain largely unclear. Here, we used short-read RNA sequencing (RNAseq) to profile the cerebellar transcriptome, detecting alterations in patients with a C9orf72 repeat expansion. We focused on the cerebellum, since key C9orf72-related pathologies are abundant in this neuroanatomical region, yet TDP-43 pathology and neuronal loss are minimal. Consistent with previous work, we showed a reduction in the expression of the C9orf72 gene and an elevation in homeobox genes, when comparing patients with the expansion to both patients without the C9orf72 repeat expansion and control subjects. Interestingly, we identified more than 1000 alternative splicing events, including 4 in genes previously associated with ALS and/or FTLD. We also found an increase of cryptic splicing in C9orf72 patients compared to patients without the expansion and controls. Furthermore, we demonstrated that the expression level of select RNA-binding proteins is associated with cryptic splice junction inclusion. Overall, this study explores the presence of widespread transcriptomic changes in the cerebellum, a region not confounded by severe neurodegeneration, in post-mortem tissue from C9orf72 patients., (© 2024. The Author(s).)

Objective: To evaluate the need to develop an application with information about the measles vaccine for Warao indigenous people., Methods: This was a quantitative study conducted at the Espaço de Acolhimento Tapanã refugee shelter in the city of Belém, Pará, Brazil. The study sample was selected for convenience. Data were analyzed descriptively using Bioestat 5.0 software., Results: Twenty-one Warao indigenous individuals were interviewed. It was identified that 91% (n=20) had lost their vaccination card; 91% (n=20) stated they had lost their vaccination card more than three times, and 91% expressed interest in an application to store their vaccination information., Conclusions: The research provided important information for the development of a health application named WaraoMedI (Warao Measles Diversity Indigenous), as well as offered nursing professionals evidence about the challenges Warao indigenous refugees face in self-managing their vaccination information.

We generated 238 Zika virus (ZIKV) genomes from 135 persons in Brazil who had samples collected over 1 year to evaluate virus persistence. Phylogenetic inference clustered the genomes together with previously reported ZIKV strains from northern Brazil, showing that ZIKV has been remained relatively stable over time. Temporal phylogenetic analysis revealed limited within-host diversity among most ZIKV-persistent infected associated samples. However, we detected unusual virus temporal diversity from >5 persons, uncovering the existence of divergent genomes within the same patient. All those patients showed an increase in neutralizing antibody levels, followed by a decline at the convalescent phase of ZIKV infection. Of interest, in 3 of those patients, titers of neutralizing antibodies increased again after 6 months of ZIKV infection, concomitantly with real-time reverse transcription PCR re-positivity, supporting ZIKV reinfection events. Altogether, our findings provide evidence for the existence of ZIKV reinfection events.

Endothelial dysfunction is associated with several lifestyle-related diseases, including cardiovascular and neurodegenerative diseases, and it contributes significantly to the global health burden. Recent research indicates a link between cardiovascular risk factors (CVRFs), excessive production of reactive oxygen species (ROS), mitochondrial impairment, and endothelial dysfunction. Circulating endothelial progenitor cells (EPCs) are recruited into the vessel wall to maintain appropriate endothelial function, repair, and angiogenesis. After attachment, EPCs differentiate into mature endothelial cells (ECs). Like ECs, EPCs are also susceptible to CVRFs, including metabolic dysfunction and chronic inflammation. Therefore, mitochondrial dysfunction of EPCs may have long-term effects on the function of the mature ECs into which EPCs differentiate, particularly in the presence of endothelial damage. However, a link between CVRFs and impaired mitochondrial function in EPCs has hardly been investigated. In this review, we aim to consolidate existing knowledge on the development of mitochondrial and endothelial dysfunction in the vascular endothelium, place it in the context of recent studies investigating the consequences of CVRFs on EPCs, and discuss the role of mitochondrial dysfunction. Thus, we aim to gain a comprehensive understanding of mechanisms involved in EPC deterioration in relation to CVRFs and address potential therapeutic interventions targeting mitochondrial health to promote endothelial function.

Background: Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the nigrostriatal pathway. Even with scientific and technological advances, the therapeutic approaches used for the treatment of PD have shown to be largely ineffective in controlling the progression of symptoms in the long term. There is a growing demand for the development of novel therapeutic strategies for PD treatment. Different herbs and supplements have been considered as adjuvant to treat the symptoms of Parkinsonism. The carrot is one of the most consumed vegetable species worldwide, and its root is known for its content of anthocyanins, which possess antioxidant and antiinflammatory properties. This study evaluated the neuroprotective effect of purple carrot extract (CAR) in rats on the reserpine (RES)-induced progressive parkinsonism model., Methods: Male rats (6-month-old) received orally the CAR (400 mg/kg) or vehicle and subcutaneously RES (0.01 mg/kg) or vehicle for 28 days (Preventive Phase). From the 29th day, rats received CAR or vehicle daily and RES (0.1 mg/kg) or vehicle every other day (for 23 days, Protective phase). Behavioral tests were conducted throughout the treatment. Upon completion, the animals' brain were processed for tyrosine hydroxylase (TH) immunohistochemical assessment., Results: Our results showed that the chronic treatment of CAR protected against motor disabilities, reducing the time of catalepsy behavior and decreasing the frequency of oral movements, possibly by preserving TH levels in the Ventral Tegmental Area (VTA) and SNpc., Conclusion: CAR extract is effective to attenuate motor symptoms in rats associated with increased TH+ levels in the Ventral Tegmental Area (VTA) and SNpc, indicating the potential nutraceutical benefits of CAR extract in a progressive parkinsonism model induced by RES., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Improving the diagnostic technology used to detect tegumentary leishmaniasis (TL) is essential in view of it being a widespread, often neglected tropical disease, with cases reported from the Southern United States to Northern Argentina. Recombinant proteins, recombinant multiepitope proteins, and synthetic peptides have been extensively researched and used in disease diagnosis. One of the benefits of applying these antigens is a measurable increase in sensitivity and specificity, which improves test accuracy. The present review aims to describe the use of these antigens and their diagnostic effectiveness. With that in mind, a bibliographic survey was conducted on the PudMed platform using the search terms "tegumentary leishmaniasis" AND "diagno", revealing that recombinant proteins have been described and evaluated for their value in TL diagnosis since the 1990s. However, there was a spike in the number of publications using all of the antigens between 2013 and 2022, confirming an expansion in research efforts to improve diagnosis. Moreover, all of the studies involving different antigens had promising results, including improved sensitivity and specificity. These data recognize the importance of doing research with new technologies focused on developing quick, more effective diagnostic kits as early diagnosis facilitates treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Neuropathic pain (NP) is caused by a lesion that triggers pain chronification and central sensitization and it can develop in a different manner, dependent of age. Recent studies have demonstrated the efficacy of transcranial direct current stimulation (tDCS) for treating NP. Then, we aimed to investigate the effects of tDCS and BDNF levels in neuropathic pain rats in development, with 30 days old in the beginning of experiments. Eight-five male Wistar rats were subjected to chronic constriction injury. After establishment of NP, bimodal tDCS was applied to the rats for eight consecutive days, for 20 minutes each session. Subsequently, nociceptive behavior was assessed at baseline, 14 days after surgery, 1 day and 7 days after the end of tDCS. The rats were sacrificed 8 days after the last session of tDCS. An increase in the nociceptive threshold was observed in rats in development 1 day after the end of tDCS (short-term effect), but this effect was not maintained 7 days after the end of tDCS (long-term effect). Furthermore, brain derived neurotrophic factor (BDNF) levels were analyzed in the frontal cortex, spinal cord and serum using ELISA assays. The neuropathic pain model showed an effect of BDNF in the spinal cord of rats in development. There were no effects of BNDF levels of pain or tDCS in the frontal cortex or serum. In conclusion, tDCS is an effective technique to relieve nociceptive behavior at a short-term effect in neuropathic pain rats in development, and BDNF levels were not altered at long-term effect., Competing Interests: Conflict of interests: The authors declare no competing interests that are relevant to the content of this article., (© 2023 the Author(s), licensee AIMS Press.)

This study aimed to genotype isolates of Toxoplasma gondii obtained from samples of brain, diaphragm and heart of goats and sheep intended for human consumption in the State of Paraíba, Brazil. Tissue samples from 14 animals, goats ( n  = 5) and lambs ( n  = 9), were sourced from public slaughterhouses in seven cities and bio-assayed in mice. The brains of the mice were utilized for DNA extraction. Genotyping was carried out by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) using 10 markers (SAG1, SAG2, SAG3, BTUB, c22-8, PK1, GRA6, L358, c-29-2 and Apico). A total of 10 isolates were fully genotyped (i.e. at all loci), three from goats and seven from sheep, revealing five distinct genotypes: #13 ( n  = 4); #48 ( n  = 3); #57 ( n  = 1); #273 ( n  = 1); and one new genotype that had not been previously described. Genotype #13 is frequently found in the Northeast of Brazil and represents a clonal lineage circulating in this region and was the most prevalent genotype identified ( n  = 4). Moreover, in the present study genotypes #13, #48, #57, and #273 were documented for the first time in sheep from Brazil, and the novel genotype was isolated from a goat. Our findings align with previous studies on T. gondii from Brazil, where new genotypes are continuously being identified, highlighting a high level of genetic diversity of T. gondii isolates in the country., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Given their role as Co-Editor, Frank Katzer had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Professor Aneta Kostadinova (Editor-in-Chief)., (© 2023 The Authors.)

These guidelines for the diagnosis and management of cholangiocarcinoma (CCA) were commissioned by the British Society of Gastroenterology liver section. The guideline writing committee included a multidisciplinary team of experts from various specialties involved in the management of CCA, as well as patient/public representatives from AMMF (the Cholangiocarcinoma Charity) and PSC Support. Quality of evidence is presented using the Appraisal of Guidelines for Research and Evaluation (AGREE II) format. The recommendations arising are to be used as guidance rather than as a strict protocol-based reference, as the management of patients with CCA is often complex and always requires individual patient-centred considerations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study aimed to analyze the detection and duration of the Zika virus (ZIKV) in plasma, urine, saliva, sweat, rectal swabs, vaginal secretions, breast milk, and semen and to explore risk factors associated with prolonged viral persistence. A prospective cohort study of symptomatic patients and their household contacts was conducted in Brazil from July 2017 to June 2019. A total of 260 individuals (184 women and 76 men) with confirmed ZIKV infection were enrolled and followed up for 12 months. ZIKV RNA was present in all body fluid specimens and detectable for extended periods in urine, sweat, rectal swabs, and semen. The longest detection duration was found in semen, with high viral loads in the specimens. ZIKV RNA clearance was associated with several factors, including age, sex, education level, body mass index, non-purulent conjunctivitis, joint pain, and whether the participant had a history of yellow fever vaccination. The influence of each of these factors on the low or fast viral clearance varied according to the specific body fluid under investigation. Recurrent ZIKV detection events after total viral clearance were observed in the cohort. Our findings provide valuable insights into the persistence and potential recurrence of ZIKV infection, highlighting the need for continued monitoring and follow-up of individuals infected with ZIKV and for effective prevention measures to reduce the risk of transmission., (© 2023. The Author(s).)

Gestational diabetes mellitus (GDM) and maternal obesity (MO) increase the risk of adverse fetal outcomes, and the incidence of cardiovascular disease later in life. Extensive research has been conducted to elucidate the underlying mechanisms by which GDM and MO program the offspring to disease. This review focuses on the role of fetoplacental endothelial dysfunction in programming the offspring for cardiovascular disease in GDM and MO pregnancies. We discuss how pre-existing maternal health conditions can lead to vascular dysfunction in the fetoplacental unit and the fetus. We also examine the role of fetoplacental endothelial dysfunction in impairing fetal cardiovascular system development and the involvement of nitric oxide and hydrogen sulfide in mediating fetoplacental vascular dysfunction. Furthermore, we suggest that the L-Arginine-Nitric Oxide and the Adenosine-L-Arginine-Nitric Oxide (ALANO) signaling pathways are pertinent targets for research. Despite significant progress in this area, there are still knowledge gaps that need to be addressed in future research., 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 B.V. All rights reserved.)

The objective was to describe the seroprevalence of anti-Neospora caninum antibodies in goats and sheep slaughtered in the state of Paraíba and to identify possible associated factors with the infections. Two hundred twenty-nine samples from goats and two hundred five from sheep were analyzed by Indirect Immunofluorescence Reaction (IFAT) using a cutoff point of 1:50. The presence of anti-N. caninum antibodies was identified in 28.4% (65/ 229; 95% Confidence Interval: 22.6-34.2) of the goat samples and in 12.7% (26/ 205; 95% CI: 8.2 - 17.2) of the sheep samples. Contact between goats and dogs (Odds ratio 4.81; CI 1.13 - 2.67; p = 0.041) and cattle (OR. 1.87; CI 1.13 - 2.67; p = 0.002) was identified as a risk factor for goats and contact between sheep and dogs (OR 2.32; CI 1.58 - 3.14; p = 0.026) and history of abortion (OR 1.94; CI 1.28 - 2.90; p = 0.001) was considered a risk factor for sheep. The study revealed a high seroprevalence of anti-N. caninum antibodies in slaughtered goats and sheep in Paraíba. Risk factors such as contact with dogs/cattle and abortion history underscore the need for preventive measures to control infection and enhance animal health management.

Tailoring the order in hierarchical structures is a key goal of bioinspired nanocomposite design. Recently, nacre-like materials have been developed by solvent evaporation methods that are scalable and attain advanced functionalities. However, understanding the alignment mechanisms of 2D fillers, nanosheets, or platelets remains challenging. This work explores possible pathways for nanocomposite ordering via orientation distribution functions. We demonstrate how the immobilization of 2D materials via (pseudo)network formation is crucial to alignment based on evaporation. We show a modified affine deformation model that describes such evaporative methods. In this, a gel network develops enough yield stress and uniformly deforms as drying proceeds, along with the immobilized particles, causing an in-plane orientation. Herein, we tested the dominance of this approach by using a thermo-reversible gel for rapid montmorillonite (MMT) particle fixation. We researched gelatin/MMT as a model system to investigate the effects of high loadings, orientational order, and aspect ratio. The nacre-like nanocomposites showed a semiconstant order parameter (⟨ P 2 ⟩ ∼ 0.7) over increasing nanofiller content up to 64 vol % filler. This remarkable alignment resulted in continuously improved mechanical and water vapor barrier properties over unusually large filler fractions. Some variations in stiffness and diffusion properties were observed, possibly correlated to the applied drying conditions of the hybrid hydrogels. The affine deformation strategy holds promise for developing next-generation advanced materials with tailored properties even at (very) high filler loadings. Furthermore, a gelling approach offers the advantages of simplicity and versatility in the formulation of the components, which is useful for large-scale fabrication methods., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Parkinson's disease (PD) is characterized by the progressive dopaminergic neuron degeneration, resulting in striatal dopamine deficiency. Mitochondrial dysfunction and oxidative stress are associated with PD pathogenesis. Physical activity (PA) has been shown to ameliorate neurological impairments and to impede age-related neuronal loss. In addition, skin fibroblasts have been identified as surrogate indicators of pathogenic processes correlating with clinical measures. The PARKEX study aims to compare the effects of two different PA programs, analyzing the impact on mitochondrial function in patients' skin fibroblasts as biomarkers for disease status and metabolic improvement. Early-stage PD patients (n = 24, H&Y stage I to III) will be randomized into three age- and sex-matched groups. Group 1 (n = 8) will undergo basic physical training (BPT) emphasizing strength and resistance. Group 2 (n = 8) will undergo BPT combined with functional exercises (BPTFE), targeting the sensorimotor pathways that are most affected in PD (proprioception-balance-coordination) together with cognitive and motor training (Dual task training). Group 3 (n = 8) will serve as control (sedentary group; Sed). Participants will perform three sessions per week for 12 weeks. Assessment of motor function, quality of life, sleep quality, cognitive aspects and humor will be conducted pre- and post-intervention. Patient skin fibroblasts will be collected before and after the intervention and characterized in terms of metabolic remodeling and mitochondrial bioenergetics. Ethical approval has been given to commence this study. This trial is registered at clinicaltrials.gov (NCT05963425). Trial registration. https://classic.clinicaltrials.gov/ct2/history/NCT05963425., Competing Interests: No potential conflict of interest was reported by the authors., (Copyright: © 2023 Magaña et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)