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Antecedentes: el estudio abordó la temática de los sistemas de gestión de información y conocimiento agropecuarios. Entre ellos se enfocó en las características de la comunidad virtual de extensionistas Linkata, que integra las plataformas de gestión del conocimiento que soportan al Sistema nacional de innovación agropecuaria (SNIA) de Colombia. Pese al potencial de Linkata como plataforma de gestión de información y conocimiento agropecuario y de estar conformada por un alto número de miembros; existen carencias de uso y apropiación de esta herramienta, que requieren del establecimiento de los aspectos propios de la plataforma asociados a la situación. Objetivos: caracterizar la plataforma desde su sitio web, en sus servicios, contenidos y equipo de trabajo, y evaluar su funcionamiento a partir de referentes, con el fin de identificar los puntos críticos a priorizar en la implementación de mejoras para el aprovechamiento de la herramienta digital. Métodos: se exploró de forma sistemática la página web, sus contenidos y servicios, se sistematizó la información mediante matriz de análisis, se implementó el análisis estratégico de debilidades, oportunidades, fortalezas y amenazas (DOFA) a la plataforma con su equipo desarrollador, se realizó evaluación de la usabilidad del sitio web por referentes en el tema y por medio de la herramienta Lighthouse se auditaron características asociadas a la funcionalidad. Resultados: con el equipo desarrollador se identificaron aspectos tanto administrativos como operativos que ameritan intervención, se establecieron factores limitantes para el funcionamiento y optimización del sitio web de Linkata, como los relacionados con la sencillez, accesibilidad, y rendimiento de este. Al triangular la información se encontró coincidencias en los factores limitantes y la relación de estos con dificultades expresadas tanto por el equipo desarrollador como por los evaluadores. Conclusiones: se analizaron los hallazgos desde el aporte y articulación de Linkata como sistema de gestión de información y conocimiento agropecuario con el sistema de innovación agropecuaria de Colombia. [ABSTRACT FROM AUTHOR]

The use of genetic data for timber species and population assignment is a powerful tool for combating the illegal timber trade, but the challenges of extracting DNA from timber have prevented the routine use of genetics as a supply chain management tool. To overcome these challenges, we explored the feasibility of focused ultrasound extraction (FUSE) for rapid DNA release from timber. Using high-pressure ultrasound pulses, FUSE generates a cavitation bubble cloud that disintegrates samples into acellular debris, resulting in the mechanical release of DNA. In this work, FUSE was applied to white oak (Quercus alba) timber shavings to test the feasibility of using FUSE for timber DNA extraction for the first time. Results showed that FUSE processing disintegrated the tissue samples and released significant quantities of DNA. After five minutes of tissue processing DNA quantities of 0.21 ± 0.02 ng/mg, 0.99 ± 0.32 ng/mg, and 0.14 ± 0.01 ng/mg, were released from medium, coarse, and combination shaving groups, respectively. Amplification and sequencing of regions within the matK and rbcL chloroplast genes confirmed that the quality of DNA prepared with FUSE was suitable for PCR and short-read sequencing applications. Overall, these results show that FUSE can serve as a DNA sample preparation method capable of releasing high-quality DNA from timber in a fraction of the time required by conventional extraction methods. Based on the improved efficiency of DNA release with FUSE, ongoing work aims to develop this technology into portable systems that can be used to rapidly prepare timber samples for genetic species identification., 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., (Published by Elsevier B.V.)

Objectives: Pressured healthcare resources make risk stratification and patient prioritisation fundamental issues for the investigation of colorectal cancer (CRC) in symptomatic patients. The present study uses machine learning algorithms and decision strategies to improve the appropriate use of colonoscopy., Design: All symptomatic patients in a single health board (2018-2021) proceeding to colonoscopy to investigate for CRC were included. Machine learning algorithms (NeuralNetwork, randomForest, Logistic regression, Naïve-Bayes and Adaboost) were used to risk-stratify patients for CRC using demographics, symptoms, quantitative faecal immunochemical test (qFIT) and haematological tests. Decision curve analyses were performed to determine the optimal decision strategies., Results: 3776 patients were included (median age, 65; M:F,0.9:1.0) and CRC was identified in 217 patients (5.7%). qFIT > 400 μg Hb/g was the most important variable (%IncMSE = 78.5). RandomForrest had the highest area under curve (0.91) and accuracy (0.80) for CRC. When utilising decision curve analysis (DCA), 30%, 46% and 54% of colonoscopies were saved at accepted CRC probabilities of 1%, 2% and 3%, respectively. RandomForrest modelling had superior net clinical benefit compared to default colonoscopy strategies., Conclusions: MLA-derived decision strategies that account for patient and referrer risk preference reduce colonoscopy demand and carry net clinical benefit compared to default colonoscopy strategies., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: The association between antibiotic prophylaxis and infective endocarditis after invasive dental procedures is still unclear. Indications for antibiotic prophylaxis were restricted by guidelines beginning in 2007., Objective: To systematically review and analyze existing evidence on the association between antibiotic prophylaxis and infective endocarditis following invasive dental procedures., Data Sources: PubMed, Cochrane-CENTRAL, Scopus, Web of Science, Proquest, Embase, Dentistry and Oral Sciences Source, and ClinicalTrials.gov were systematically searched from inception to May 2023., Study Selection: Studies on the association between antibiotic prophylaxis and infective endocarditis following invasive dental procedures or time-trend analyses of infective endocarditis incidence before and after current antibiotic prophylaxis guidelines were included., Data Extraction and Synthesis: Study quality was evaluated using structured tools. Data were extracted by independent observers. A pooled relative risk (RR) of developing infective endocarditis following invasive dental procedures in individuals who were receiving antibiotic prophylaxis vs those who were not was computed by random-effects meta-analysis., Main Outcomes and Measures: The outcome of interest was the incidence of infective endocarditis following invasive dental procedures in relation to antibiotic prophylaxis., Results: Of 11 217 records identified, 30 were included (1 152 345 infective endocarditis cases). Of them, 8 (including 12 substudies) were either case-control/crossover or cohort studies or self-controlled case series, while 22 were time-trend studies; all were of good quality. Eight of the 12 substudies with case-control/crossover, cohort, or self-controlled case series designs performed a formal statistical analysis; 5 supported a protective role of antibiotic prophylaxis, especially among individuals at high risk, while 3 did not. By meta-analysis, antibiotic prophylaxis was associated with a significantly lower risk of infective endocarditis after invasive dental procedures in individuals at high risk (pooled RR, 0.41; 95% CI, 0.29-0.57; P for heterogeneity = .51; I2, 0%). Nineteen of the 22 time-trend studies performed a formal pre-post statistical analysis; 9 found no significant changes in infective endocarditis incidence, 7 demonstrated a significant increase for the overall population or subpopulations (individuals at high and moderate risk, streptococcus-infective endocarditis, and viridans group streptococci-infective endocarditis), whereas 3 found a significant decrease for the overall population and among oral streptococcus-infective endocarditis., Conclusions and Relevance: While results from time-trend studies were inconsistent, data from case-control/crossover, cohort, and self-controlled case series studies showed that use of antibiotic prophylaxis is associated with reduced risk of infective endocarditis following invasive dental procedures in individuals at high risk, while no association was proven for those at low/unknown risk, thereby supporting current American Heart Association and European Society of Cardiology recommendations. Currently, there is insufficient data to support any benefit of antibiotic prophylaxis in individuals at moderate risk.

Objectives: To characterize and elucidate the spread of amikacin-resistant Enterobacteriaceae isolates from environmental samples on a pig farm in the UK, following the previous identification of index Salmonella isolates harbouring the rmtB gene, a 16S rRNA methylase., Methods: Environmental samples were collected during two visits to a pig farm in the UK. Isolates were recovered using selective media (amikacin 128 mg/L) followed by real-time PCR and WGS to analyse rmtB-carrying Salmonella and Escherichia coli isolates., Results: Salmonella and E. coli isolates harbouring the rmtB gene were detected at both farm visits. All Salmonella isolates were found to be monophasic S. enterica serovar Typhimurium variant Copenhagen of ST34. rmtB-harbouring E. coli isolates were found to be one of three STs: ST4089, ST1684 and ST34. Long-read sequencing identified the rmtB gene to be chromosomally located in Salmonella isolates and on IncFII-type plasmids in E. coli isolates. The results showed the rmtB gene to be flanked by IS26 elements and several resistance genes., Conclusions: We report on the occurrence of rmtB-harbouring Enterobacteriaceae on a pig farm in the UK. rmtB confers resistance to multiple aminoglycosides and this work highlights the need for surveillance to assess dissemination and risk., (© Crown copyright 2024.)

Background: "Kooth" is a web-based mental health platform commissioned by the National Health Service (NHS), local authorities, charities, and businesses in the UK. The platform gives children and young people (CYP) access to an online community of peers and a team of counsellors. This study reports an early economic evaluation of the potential benefits of Kooth in the UK., Methods: An early evidence cost calculator was built to estimate the potential costs and savings of implementing Kooth from a UK NHS and crime sector perspective. A decision tree structure was used to track the progress of CYP with emerging mental health needs (EMHN), comparing CYP with access to Kooth to CYP without access to Kooth. The model implemented a 12-month time horizon and followed a typical Kooth contract in relation to costing, engagement, and CYP demographics., Results: The base case results followed a cohort of 2160 CYP. The results of the cost calculator estimated that engagement with Kooth is associated with a cost saving of £469,237 to the NHS across a 12-month time horizon, or £236.15 per CYP with an EMHN. From a combined NHS and UK crime sector perspective, the cost savings increased to £489,897, or £246.54 per CYP with an EMHN. The largest cost savings were provided by an estimated reduction of 5346 GP appointments and 298 antidepressant prescriptions. For this cohort, the model predicted that engagement with Kooth averted 6 hospitalisations due to suicidal ideation and 13 hospitalisations due to self-harm. Furthermore, the number of smokers and binge drinkers was reduced by 20 and 24, respectively. When a crime sector perspective was taken, 3 crimes were averted., Discussion: This early model demonstrates that Kooth has the potential to be a cost-saving intervention from both an NHS and a combined NHS and UK crime sector perspective. Cost savings were provided through aversion in clinical and social outcomes. The model used a conservative approach to balance the uncertainty around assumptions of the intermediate outcomes (GP and medication use). However, it is limited by a paucity of costing data and published evidence relating to the impact of digital mental health platforms., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: There are no competing interests for Laura Coote, Laura Kelly, Luc Curtis-Gretton, Charlotte Graham, Maisie Green, or Hayden Holmes. Louisa Salhi, Santiago de Ossorno Garcia and Aaron Sefi are all employees of Kooth Plc and receive honorarium from the organisation., (© 2024 The Authors. Published by Elsevier B.V.)

The global dairy market has been increasingly diversified with more dairy product offerings of milk products from different animal species. Meanwhile, milk powders remain the main exported dairy product format due to their ease of transportation. In this work, we studied the structural changes, protein hydrolysis and nutrient delivery during dynamic gastric digestion and small intestinal digestion of cow, goat and sheep milk reconstituted from commercial whole milk powders. The results show that the reconstituted milks digest similarly to processed fresh milk. The digestion behaviors of the three reconstituted ruminant milks are broadly similar (gastric coagulation, kinetics of gastric emptying of protein and fat and the high digestibility in the small intestine) with some differences, which are likely contributed by the processing history of the milk powders. The delivery of individual amino acids to the small intestine differed between the early and late stages of gastric digestion, which were primarily affected by the abundance of amino acids in caseins and whey proteins but also by the difference between milk types associated with their gastric coagulation behaviors. This work showed that powdered milk is similar to fresh processed milk in digestion behavior, and the inherent differences between ruminant milks can be modified by processing treatments.

Objectives: This research aimed to develop best-practice recommendations for identifying the "standard of care" (SoC) and integrate it when it is the comparator in diagnostic economic models (SoC comparator)., Methods: A multi-methods approach comprising 2 pragmatic literature reviews and 9 expert interviews was used. Experts rated their agreement with draft recommendations based on the authors' analysis of the reviews. These were refined iteratively to produce final recommendations., Results: Fourteen best-practice recommendations are provided. Care pathway mapping (using quantitative, qualitative, or mixed-methods approaches) should be used for identifying the SoC comparator. Guidelines analysis can be integrated with expert opinion to identify pathway variability and discrepancies from clinical practice. For integrating the SoC comparator into the model, recommendations around structure, input sourcing, data aggregation and reporting, input uncertainty, and model variability are presented. For example, modelers should consider that the reference standard is not synonymous with the SoC, and the SoC may not be the only comparator. The comparator limitations should be discussed with clinical experts, but elicitation of its diagnostic accuracy is not recommended. Probabilistic sensitivity analysis is recommended when evaluating the overall input uncertainty, and deterministic sensitivity analysis is useful when there is high model uncertainty or SoC variability. Consensus could not be reached for some topics (eg, the role of real-world data, model averaging, and alternative model structures), but the reported discussions provide points for consideration., Conclusions: To our knowledge, this is the first guidance to support modelers when identifying and operationalizing the SoC comparator in diagnostic cost-effectiveness models., Competing Interests: Author Disclosures Author disclosure forms can be accessed in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Abstract: Ruxolitinib reduces spleen volume, improves symptoms, and increases survival in patients with intermediate- or high-risk myelofibrosis. However, suboptimal response may occur, potentially because of signaling via the phosphoinositide 3-kinase (PI3K)/protein kinase B pathway. This phase 2 study evaluated dosing, efficacy, and safety of add-on PI3Kδ inhibitor parsaclisib for patients with primary or secondary myelofibrosis with suboptimal response to ruxolitinib. Eligible patients remained on a stable ruxolitinib dose and received add-on parsaclisib 10 or 20 mg, once daily for 8 weeks, and once weekly thereafter (daily-to-weekly dosing; n = 32); or parsaclisib 5 or 20 mg, once daily for 8 weeks, then 5 mg once daily thereafter (all-daily dosing; n = 42). Proportion of patients achieving a ≥10% decrease in spleen volume at 12 weeks was 28% for daily-to-weekly dosing and 59.5% for all-daily dosing. Proportions of patients achieving ≥50% decrease at week 12 in Myelofibrosis Symptom Assessment Form and Myeloproliferative Neoplasms Symptom Assessment Form symptom scores were 14% and 18% for daily-to-weekly dosing, and 28% and 32% for all-daily dosing, respectively. Most common nonhematologic treatment-emergent adverse events were nausea (23%), diarrhea (22%), abdominal pain and fatigue (each 19%), and cough and dyspnea (each 18%). New-onset grade 3 and 4 thrombocytopenia were observed in 19% of patients, each dosed daily-to-weekly, and in 26% and 7% of patients dosed all-daily, respectively, managed with dose interruptions. Hemoglobin levels remained steady. The addition of parsaclisib to stable-dose ruxolitinib can reduce splenomegaly and improve symptoms, with manageable toxicity in patients with myelofibrosis with suboptimal response to ruxolitinib. This trial was registered at www.clinicaltrials.gov as #NCT02718300., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background & Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by excessive circulating toxic lipids, hepatic steatosis, and liver inflammation. Monocyte adhesion to liver sinusoidal endothelial cells (LSECs) and transendothelial migration (TEM) are crucial in the inflammatory process. Under lipotoxic stress, LSECs develop a proinflammatory phenotype known as endotheliopathy. However, mediators of endotheliopathy remain unclear., Methods: Primary mouse LSECs isolated from C57BL/6J mice fed chow or MASH-inducing diets rich in fat, fructose, and cholesterol (FFC) were subjected to multi-omics profiling. Mice with established MASH resulting from a choline-deficient high-fat diet (CDHFD) or FFC diet were also treated with two structurally distinct GSK3 inhibitors (LY2090314 and elraglusib [9-ING-41])., Results: Integrated pathway analysis of the mouse LSEC proteome and transcriptome indicated that leukocyte TEM and focal adhesion were the major pathways altered in MASH. Kinome profiling of the LSEC phosphoproteome identified glycogen synthase kinase (GSK)-3β as the major kinase hub in MASH. GSK3β-activating phosphorylation was increased in primary human LSECs treated with the toxic lipid palmitate and in human MASH. Palmitate upregulated the expression of C-X-C motif chemokine ligand 2, intracellular adhesion molecule 1, and phosphorylated focal adhesion kinase, via a GSK3-dependent mechanism. Congruently, the adhesive and transendothelial migratory capacities of primary human neutrophils and THP-1 monocytes through the LSEC monolayer under lipotoxic stress were reduced by GSK3 inhibition. Treatment with the GSK3 inhibitors LY2090314 and elraglusib ameliorated liver inflammation, injury, and fibrosis in FFC- and CDHFD-fed mice, respectively. Immunophenotyping using cytometry by mass cytometry by time of flight of intrahepatic leukocytes from CDHFD-fed mice treated with elraglusib showed reduced infiltration of proinflammatory monocyte-derived macrophages and monocyte-derived dendritic cells., Conclusion: GSK3 inhibition attenuates lipotoxicity-induced LSEC endotheliopathy and could serve as a potential therapeutic strategy for treating human MASH., Impact and Implications: LSECs under lipotoxic stress in MASH develop a proinflammatory phenotype known as endotheliopathy, with obscure mediators and functional outcomes. The current study identified GSK3 as the major driver of LSEC endotheliopathy, examined its pathogenic role in myeloid cell-associated liver inflammation, and defined the therapeutic efficacy of pharmacological GSK3 inhibitors in murine MASH. This study provides preclinical data for the future investigation of GSK3 pharmacological inhibitors in human MASH. The results of this study are important to hepatologists, vascular biologists, and investigators studying the mechanisms of inflammatory liver disease and MASH, as well as those interested in drug development., Competing Interests: The authors declare no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2024 The Author(s).)

Fetal lungs have fewer and smaller arteries with higher pulmonary vascular resistance (PVR) than a newborn. As gestation advances, the pulmonary circulation becomes more sensitive to changes in pulmonary arterial oxygen tension, which prepares them for the dramatic drop in PVR and increase in pulmonary blood flow (PBF) that occur when the baby takes its first few breaths of air, thus driving the transition from fetal to postnatal circulation. Dynamic and intricate regulatory mechanisms control PBF throughout development and are essential in supporting gas exchange after birth. Understanding these concepts is crucial given the role the pulmonary vasculature plays in the development of complications with transition, such as in the setting of persistent pulmonary hypertension of the newborn and congenital heart disease. An improved understanding of pulmonary vascular regulation may reveal opportunities for better clinical management., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Many untrue statements about cancer prevention and risks are circulating. The objective of this study was to assess Canadians' awareness of known cancer risk factors and cancer myths (untruths or statements that are not completely true), and to explore how awareness may vary by sociodemographic and cognitive factors., Methods: Cancer myths were identified by conducting scans of published, grey literature, and social media. Intuitive-analytic thinking disposition scores included were actively open- and close-minded thinking, as well as preference for intuitive and effortful thinking. A survey was administered online to participants aged 18 years and older through Prolific. Results were summarized descriptively and analyzed using chi-square tests, as well as Spearman rank and Pearson correlations., Results: Responses from 734 Canadians were received. Participants were better at identifying known cancer risk factors (70% of known risks) compared to cancer myths (49%). Bivariate analyses showed differential awareness of known cancer risk factors (p < 0.05) by population density and income, cancer myths by province, and for both by ethnicity, age, and all thinking disposition scores. Active open-minded thinking and preference for effortful thinking were associated with greater discernment. Tobacco-related risk factors were well-identified (> 90% correctly identified), but recognition of other known risk factors was poor (as low as 23% for low vegetable and fruit intake). Mythical cancer risk factors with high support were consuming additives (61%), feeling stressed (52%), and consuming artificial sweeteners (49%). High uncertainty of causation was observed for glyphosate (66% neither agreed or disagreed). For factors that reduce cancer risk, reasonable awareness was observed for HPV vaccination (60%), but there was a high prevalence in cancer myths, particularly that consuming antioxidants (65%) and organic foods (45%) are protective, and some uncertainty whether drinking red wine (41%), consuming vitamins (32%), and smoking cannabis (30%) reduces cancer risk., Conclusions: While Canadians were able to identify tobacco-related cancer risk factors, many myths were believed and numerous risk factors were not recognized. Cancer myths can be harmful in themselves and can detract the public's attention from and action on established risk factors., (© 2024. The Author(s).)

Purpose: To identify trends in female pediatric ophthalmologist authorship and representation at the American Academy of Ophthalmology (AAO) Annual Meeting from 2018 to 2022., Methods: Participant data from 2018 to 2022 were collected from the AAO website, organized by conference activity (papers, posters, instruction courses, videos, symposia, subspecialty day, and awards), and analyzed by sex using an online tool. Chi-squared and odds ratio analyses were performed to determine trends in authorship sex and associations between the sex of paper and poster authors in each category., Results: Of 923 pediatric ophthalmology presentations from 2018 to 2022, 46.2% (426 of 923) of presenters and 46.6% (281 of 603) of unique individual participants were women. Overall, 48% (174 of 362) of first and senior authors of papers and posters were women. No significant difference or association between female first and senior authors was observed (52% vs 44%, P = .14; odds ratio 1.59, P = .13). There was no significant change in the proportion of total female presenters from 2018 to 2019 (-3.09%, P = .53), 2019 to 2020 (0.76%, P = .88), 2020 to 2021 (9.09%, P = .09), 2021 to 2022 (-5.68%, P = .30), or 2018 to 2022 (1.08%, P = .84)., Conclusions: Since 2018, female representation at the AAO Annual Meeting has remained consistent and nears 50%. The lack of a significant difference between the proportion of female first and senior authors suggests that junior female pediatric ophthalmologists are climbing the ranks and more broadly engaging in mentorship roles. Considering the increasing proportion of female pediatric ophthalmologists, the absence of corollary, statistically significant increases in female participation may be of concern. [ J Pediatr Ophthalmol Strabismus . 2024;61(1):6-13.] .