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Abstract Formalin-fixed paraffin-embedded (FFPE) samples are valuable but underutilized in single-cell omics research due to their low RNA quality. In this study, leveraging a recent advance in single-cell genomic technology, we introduce snPATHO-seq, a versatile method to derive high-quality single-nucleus transcriptomic data from FFPE samples. We benchmarked the performance of the snPATHO-seq workflow against existing 10x 3’ and Flex assays designed for frozen or fresh samples and highlighted the consistency in snRNA-seq data produced by all workflows. The snPATHO-seq workflow also demonstrated high robustness when tested across a wide range of healthy and diseased FFPE tissue samples. When combined with FFPE spatial transcriptomic technologies such as FFPE Visium, the snPATHO-seq provides a multi-modal sampling approach for FFPE samples, allowing more comprehensive transcriptomic characterization.

[Purpose] The paper analyzes how municipalities, as decentralized entities, can develop public policies on Internet access as part of their social function, taking as a reference the territorial entities that make up the metropolitan area of the Aburrá Valley (Antioquia - Colombia). [Methodology] Research methods such as deduction, content analysis and comparative analysis, together with other documentary techniques, were used to approach the study from a qualitative and comparative law approach. [Findings] The study examines public policies on Internet access in the Aburrá Valley from 2008 to 2023, highlighting Medellín's leadership in this area. Although some municipalities have more modest advances and the lack of a specific regulatory framework, as in Caldas, limits the formulation of effective policies. In addition, the proactive response to the pandemic and the recognition of the digital divide as a social problem reflect a continued commitment to digital inclusion in the region.

Abstract Background We conducted a scoping review of the evidence for the use of the Pediatric Assessment Triangle (PAT) tool in emergency pediatric patients, in hospital and prehospital settings. We focused on the psychometric properties of the PAT, the reported impact, the setting and circumstances for tool implementation in clinical practice, and the evidence on teaching the PAT. Methods We followed the Joanna Briggs Institute methodology for scoping reviews and registered the review protocol. We searched MEDLINE, PubMed Central, the Cochrane Library, Epistemonikos, Scopus, CINAHL, Grey literature report, Lens.org, and the web pages of selected emergency pediatrics organizations in August 2022. Two reviewers independently screened and extracted data from eligible articles. Results Fifty-five publications were included. The evidence suggests that the PAT is a valid tool for prioritizing emergency pediatric patients, guiding the selection of interventions to be undertaken, and determining the level of care needed for the patient in both hospital and prehospital settings. The PAT is reported to be fast, practical, and useful potentially impacting overcrowded and understaff emergency services. Results highlighted the importance of instruction prior using the tool. The PAT is included in several curricula and textbooks about emergency pediatric care. Conclusions This scoping review suggests there is a growing volume of evidence on the use of the PAT to assess pediatric emergency patients, some of which might be amenable to a systematic review. Our review identified research gaps that may guide the planning of future research projects. Further research is warranted on the psychometric properties of the PAT to provide evidence on the tool’s quality and usefulness. The simplicity and accuracy of the tool should be considered in addressing the current healthcare shortages and overcrowding in emergency services. Review registration: Open Science Framework; 2022. https://osf.io/vkd5h/

Abstract Bistability enables adaptive designs with tunable deflections for applications including morphing wings, robotic grippers, and consumer products. Composite laminates may be designed to exhibit bistability due to pre-strains that develop during the processing of the polymer matrix, enabling fast reconfiguration between two stable shapes. Unfortunately, designing bistable laminates is challenging because of their highly nonlinear behavior. Here, we propose the Switching Tunneling Method to address this challenge by alternating between gradient-based local minimization and tunneling search phases, with the enhancement of objective expression switching to improve numerical conditioning. Results demonstrate high effectiveness compared to existing optimizers; the Switching Tunneling Method achieves a 99% success rate in finding all energy minima across general composite layups. Additionally, our method facilitates the inverse design of variable pre-strain fields, enabling bioinspired, positive Gaussian curvatures, which are not possible with conventional pre-strain laminates. Validations through both finite element analysis and 3D printed samples confirm the optimal designs.

Abstract Background and Aims Crimean‐Congo Hemorrhagic Fever (CCHF) is a significant public health concern transmitted by ticks. This study seeks to thoroughly grasp the epidemiology and transmission patterns of CCHF, which is caused by the CCHF virus (CCHFV), a member of the Nairovirus genus in the Bunyaviridae family. Methods The study investigates the global distribution and endemicity of CCHF, its mortality rates, modes of transmission (including tick bites, contact with infected animal blood, and limited person‐to‐person transmission), and factors influencing its prevalence across different regions. Genetic diversity within CCHFV and its impact on transmission dynamics are explored, along with efforts to control the disease through tick prevention, antiviral treatment, and the development of vaccines and diagnostics. Results CCHFV exhibits widespread distribution, particularly in the Middle East, Africa, Asia, and Eastern Europe, with an overall mortality rate of approximately 30% and a case fatality rate ranging from 10% to 40%. Transmission occurs primarily through tick bites and contact with infected animal blood, with limited person‐to‐person transmission. Livestock workers, slaughterhouse employees, and animal herders in endemic areas are most affected by their frequent interaction with sick animals and ticks. Genetic diversity within CCHFV contributes to variations in transmission dynamics, complicating control efforts. Antiviral ribavirin shows efficacy in treating CCHF infection. Conclusion This study underscores the importance of further research to understand the enzootic environment, transmission routes, and genetic diversity of CCHFV for effective control measures, including the development of vaccines, treatment options, and diagnostics.

Abstract Introduction Synovial sarcoma is one of the most common soft tissue sarcomas in children. Guidelines regarding the adequate extent of resection margins and the role of re‐resection are lacking. We sought to evaluate the adequate resection margin and the role of re‐resection in predicting outcomes in children with synovial sarcomas. Methods A cohort of 36 patients less than 18 years of age at diagnosis who were treated for localized synovial sarcoma at three tertiary pediatric hospitals between January 2004 and December 2020 were included in this study. Patient and tumor demographics, treatment information, and margin status after surgical resection were collected from the medical record. Clinical, treatment, and surgical characteristics, as well as outcomes including hazard ratios (HRs), event‐free survival (EFS), and overall survival (OS) were compared by resection margins group and re‐resection status. Results Patients in the R1 resection group were significantly more likely to relapse or die compared to patients in the R0 resection group. However, there was no significant difference in EFS (HR 0.52, p = 0.54) or OS (HR 1.56, p = 0.719) in R0 patients with less than 5 mm margins compared to R0 patients with more than 5 mm margins. Patients with R1 on initial or re‐resection had significantly worse OS than patients who had R0 resection on initial or re‐resection (HR = 10.12, p = 0.005). Conclusion This study re‐affirms that R0 resection is an independent prognostic predictor of better OS/EFS in pediatric synovial sarcoma. Second, our study extends this finding to report negative margins on initial resection or re‐resection is associated with better OS/EFS than positive margins on initial resection or re‐resection. Lastly, we found that there is no difference in outcomes associated with re‐resection or

Summary: Matrix stiffening by lysyl oxidase-like 2 (LOXL2)-mediated collagen cross-linking is proposed as a core feedforward mechanism that promotes fibrogenesis. Failure in clinical trials of simtuzumab (the humanized version of AB0023, a monoclonal antibody against human LOXL2) suggested that targeting LOXL2 may not have disease relevance; however, target engagement was not directly evaluated. We compare the spatial transcriptome of active human lung fibrogenesis sites with different human cell culture models to identify a disease-relevant model. Within the selected model, we then evaluate AB0023, identifying that it does not inhibit collagen cross-linking or reduce tissue stiffness, nor does it inhibit LOXL2 catalytic activity. In contrast, it does potently inhibit angiogenesis consistent with an alternative, non-enzymatic mechanism of action. Thus, AB0023 is anti-angiogenic but does not inhibit LOXL2 catalytic activity, collagen cross-linking, or tissue stiffening. These findings have implications for the interpretation of the lack of efficacy of simtuzumab in clinical trials of fibrotic diseases.

This study addressed the optimization of biomass and C-phycocyanin (C-PC) concentration and its purity in the thermotolerant cyanobacterium Potamosiphon sp by adjusting key light quality parameters. Custom design and Central Composite Design experimental designs were employed, using LEDs light intensity, wavelength, and photoperiod. The results demonstrated that these lighting parameters significantly influence biomass and C-phycocyanin production, achieving up to a 100 % increase in phycocyanin accumulation and biomass production and a 50 % improvement in purity index compared to conventional white light under optimal conditions of Red:Blue light (3:1), Intensity (283 μmol m−2 s−1), and photoperiod (17.8 H light). The findings support the use of specific LEDs wavelengths that optimize the performance of production processes and the quality of products derived from cyanobacteria, such as high-value phycobiliproteins.

Abstract Background Immune-checkpoint inhibitors (ICIs) have showed unprecedent efficacy in the treatment of patients with advanced non-small cell lung cancer (NSCLC). However, not all patients manifest clinical benefit due to the lack of reliable predictive biomarkers. We showed preliminary data on the predictive role of the combination of radiomics and plasma extracellular vesicle (EV) PD-L1 to predict durable response to ICIs. Main body Here, we validated this model in a prospective cohort of patients receiving ICIs plus chemotherapy and compared it with patients undergoing chemotherapy alone. This multiparametric model showed high sensitivity and specificity at identifying non-responders to ICIs and outperformed tissue PD-L1, being directly correlated with tumor change. Short conclusion These findings indicate that the combination of radiomics and EV PD-L1 dynamics is a minimally invasive and promising biomarker for the stratification of patients to receive ICIs.

Engagement in biodiversity citizen science initiatives can confer health and wellbeing benefits to individuals and communities. Yet, few biodiversity citizen science initiatives are explicitly planned to optimize health and wellbeing as a potential co-benefit, leading to missed opportunities for biodiversity conservation and human health. In this perspective, we use a dose-response approach to discuss the components that determine how engagement in biodiversity citizen science initiatives map onto opportunities to foster health and wellbeing benefits. We considered aspects related to the duration and frequency of contact with nature, and the intensity of interactions with nature and between individuals to highlight the different health benefits across the variety of citizen science initiatives. To illustrate these aspects, we use a sample of 95 citizen science initiatives from seven English and non-English-speaking countries and show how careful project design can increase the potential to confer health and wellbeing benefits to participants. We conclude with considerations on how to enhance the health and wellbeing benefits from citizen science initiatives, and propose potential research avenues to assess synergies and trade-offs between benefits to biodiversity and human health from these initiatives.

There is strong interest in sustainable aviation fuels (SAF) to decarbonize aviation; however, local decision-makers will need to consider what additional incentives could stimulate SAF commercialization within their own jurisdictions. This study analyzed SAF production in Virginia, evaluating two biomass-to-energy platforms (gasification Fischer Tropsch [GFT] and pyrolysis) and two regionally abundant feedstocks (woody wastes and municipal solid wastes). A suite of open-access modeling tools were applied to possible SAF supply chains encompassing feedstock collection and transportation, conversion, and fuel upgrading and transport. Key modeling outputs were minimum product selling price (MPSP) ($/gallon) and life-cycle global warming potential (GWP) (g CO2eq/MJ). Results suggest that early SAF production via GFT will require local incentives of approximately $3.61 per gallon compared to $0.75 per gallon for pilot-scale pyrolysis. Location of production facility (by county) influences economic and environmental metrics but is not nearly as important as facility size (tonnes/year). Different formats of financial incentives (i.e., tax credits, loan forgiveness, etc.) offer markedly different reductions in SAF MPSP. Finally, under current federal incentives in the US, it is still more economically efficient to use pyrolysis (with higher GWP) than GFT (with lower GWP). Therefore, regional stakeholders will need to navigate the tradeoff between economic and environmental performances of these platforms. Though Virginia was used as a case study, the methodology is replicable for other jurisdictions, insofar it can be adapted for use in other locations without decision-makers having to completely build their own TEA models.

Failures in mechanical power transmission systems can cause serious operating problems in the systems to which they belong. Misalignments in the shafts of gear transmission systems can produce transmission errors, increased bending stress at the base of the teeth, and increased normal wear between the teeth. Because vibration analysis is very useful as a failure detection mechanism in stationary rotating equipment, the effect of shaft misalignment on vibration measurements was investigated in this study. Combined misalignments are studied because different types of misalignments occur simultaneously in real applications. The effect of a combination of axial, radial, and angular misalignments on vibration measurements in a spur gear transmission system was investigated. This study was developed through the design and construction of a test bench that allows different types of misalignment in a single-stage spur gear transmission system and vibration measurement through accelerometers installed in the support bearings. Indicators, such as kurtosis and skewness, were used to validate the results in the time domain. For the frequency domain analysis, an indicator was developed that compares the frequency spectra of misaligned conditions to the base spectrum in the aligned condition. The critical misalignment combinations were also identified. It was found that for the combined cases, the contact area between the teeth and the contact ratio were influencing factors. The quantitative effects of combined misalignments on vibration measurements were determined, which can be used as a preliminary diagnosis of this type of problem and as a basis for developing more robust prediction models.

Dairy cattle excreta are a valuable source of orthophosphate (Ortho-P), an inorganic form of phosphorus (P) that is readily available for microorganisms, plant growth, and development. There is, however, a growing environmental concern about the potential negative environmental impact of excessive amounts of Ortho-P excretion, which can lead to the eutrophication of water bodies. As a result, the development of mathematical equations to quantify and manage Ortho-P excretion on dairy farms could prove valuable for environmental sustainability. This study aimed to use literature data to develop empirical predictions for Ortho-P (g/kg dry matter [DM]) excretion using total P (TP [g/kg DM]) content of dairy cattle feces (Ortho-Pf) and manure (Ortho-Pm). Data sets from studies that evaluated and characterized the different forms of P in feces and manure from dairy cattle were compiled. After outlier exclusion, the final retained database for feces included 37 treatment means from 4 published papers while the manure comprised 23 treatment means from 7 published papers. A linear-mixed model was used to develop the predictive equations, incorporating the random effect of the study. A leave-one-out cross-validation procedure was used to evaluate the predictive ability of the developed models, whereby studies were regarded as folds. The fecal equation was determined as Ortho-Pf (g/kg DM) = −2.447 (0.572) + 0.966 (0.083) × TP (g/kg DM) (R2 = 0.79) and resulted in a root mean square prediction error as a percentage of mean observed value (RMSPE, %) of 32.8% and error due to random sources of 97.6%. Additionally, the manure equation was determined as Ortho-Pm (g/kg) = −0.204 (0.446) + 0.590 (0.065) × TP (g/kg) (R2 = 0.77) and had an RMSPE of 43.3% with a random error of 93.9%. Both models revealed minimal mean and slope biases on feces and manure data. Findings suggest that these sets of equations can be used to estimate excreted Ortho-P from total excreted P, helping nutritionists and farmers to understand the impact of dietary P changes on the environment. Further, these equations can be incorporated into extant models such as the Cornell Net Carbohydrate and Protein System (CNCPS) to aid in understanding and mitigating P and Ortho-P excretion from dairy cattle and to clarify the portion of P that migrates more rapidly into watersheds.

Abstract Objective Hepatoblastoma (HB) is the most common primary hepatic malignancy in childhood. Relapse occurs in more than 50% of high‐risk patients with a high mortality due to ineffective salvage therapies. The purpose of this study is to identify risk factors for relapsed HB and predictors of survival in a single tertiary referral center. Methods A retrospective chart review showed 129 surgically treated HB patients from October 2004 to July 2020. Of the cohort, 22 patients presented with relapsed HB. Relapse was defined as re‐appearance of malignancy after 4 weeks of normalized AFP and disappearance of all tumors on imaging. Results Patients with relapsed HB had a 5‐year overall survival (OS) of 45.4% compared to 93.1% in those without relapse (p = 0.001). When comparing PRETEXT IV, microvascular invasion, metastatic disease, and age on multivariate logistic regression, only PRETEXT IV was an independent risk factor for relapsed HB with an OR of 2.39 (95% CI: 1.16–4.96; p = 0.019). Mixed epithelial and mesenchymal HB (12/19, 63.2%) was the most common histology of primary tumors while pure epithelial HB (13/15, 86.6%) was the most common relapsed histology. Combination of surgical and medical therapy for relapsed disease was predictive of survival with an HR of 16.3 (95% CI: 1.783–149.091; p = 0.013) compared to only chemotherapy. Conclusions This study demonstrates that PRETEXT IV staging is an independent predictor of relapsed disease. The most common relapsed histology was epithelial, suggesting a potential selection or resistance of this component. Surgical resection is a critical component of multimodal therapy for relapsed HB.

Low back pain poses a significant societal burden, with progressive intervertebral disc degeneration (IDD) emerging as a pivotal contributor to chronic pain. Improved animal models of progressive IDD are needed to comprehensively investigate new diagnostic and therapeutic approaches to managing IDD. Recent studies underscore the immune system’s involvement in IDD, particularly with regards to the role of immune privileged tissues such as the nucleus pulposus (NP) becoming an immune targeting following initial disc injury. We therefore hypothesized that generating an active immune response against NP antigens with an NP vaccine could significantly accelerate and refine an IDD animal model triggered by mechanical puncture of the disc. To address this question, rabbits were immunized against NP antigens following disc puncture, and the impact on development of progressive IDD was assessed radiographically, functionally, and histologically compared between vaccinated and non-vaccinated animals over a 12-week period. Immune responses to NP antigens were assessed by ELISA and Western blot. We found that the vaccine elicited strong immune responses against NP antigens, including a dominant ~37 kD antigen. Histologic evaluation revealed increases IDD in animals that received the NP vaccine plus disc puncture, compared to disc puncture and vaccine only animals. Imaging evaluation evidenced a decrease in disc height index and higher scores of disc degeneration in animals after disc punctures and in those animals that received the NP vaccine in addition to disc puncture. These findings therefore indicate that it is possible to elicit immune responses against NP antigens in adult animals, and that these immune responses may contribute to accelerated development of IDD in a novel immune-induced and accelerated IDD model.

High Pathogenicity Avian Influenza (HPAI) poses a significant threat to public and animal health. Clade 2.3.4.4b recently emerged from the Eastern hemisphere and disseminated globally, reaching the Latin American (LATAM) region in late 2022 for the first time. HPAI in LATAM has resulted in massive mortalities and culling of poultry and wild birds, causing infection in mammals and humans. Despite its meaningful impact in the region, only occasional evidence about the genetic and epitope characteristics of the introduced HPAI is reported. Hence, this study seeks to phylogenetically characterize the molecular features and the source of HPAI in LATAM by evaluating potential antigenic variations. For such a purpose, we analyzed 302 whole genome sequences. All Latin American viruses are descendants of the 2.3.4.4b clade of the European H5N1 subtype. According to genomic constellations deriving from European and American reassortments, the identification of three major subtypes and eight sub-genotypes was achievable. Based on the variation of antigenic motifs at the HA protein in LATAM, we detected three potential antigenic variants, indicating the HA-C group as the dominant variant. This study decidedly contributes to unraveling the origin of the 2.3.4.4b clade in LATAM, its geographic dissemination, and evolutionary dynamics within Latin American countries. These findings offer useful information for public health interventions and surveillance initiatives planned to prevent and manage the transmission of avian influenza viruses.

Abstract Concurrent chemoradiotherapy (cCRT) is the mainstay of treatment for patients diagnosed with locally advanced non-small cell lung cancer (NSCLC). One significant challenge in the effectiveness of this therapy is the potential development of resistance mechanisms, where autophagy up-regulation has been proposed as a key contributing factor. However, there is a lack of reliable biomarkers to predict outcomes on these patients. Interestingly, for addressing this gap, extracellular vesicles (EVs) and circulating tumor cells (CTCs) have emerged as potential sources of such biomarkers. In this study, we investigated EV-associated miRNAs and presence of autophagic CTCs in prospectively collected serial samples from 38 patients with stage III NSCLC undergoing cCRT. Our findings revealed that non-responders exhibited low levels of baseline EV miR-375, miR-200c, and miR-30c. In particular, EV miR-30c showed high predictive value with an area under the curve of 87.2%. Low EV miR-30c and the presence of autophagic-activated CTCs emerged as independent predictive biomarkers for shorter relapse-free survival and overall survival. Furthermore, in experimental models simulating the effects of chemo- and radiotherapy, the administration of miR-30c, either through direct transfection or encapsulation into human EVs, led to the inhibition of autophagy in these cells. This is the first report demonstrating that EV miR-30c inhibits tumor autophagy and its quantification, together with autophagic-activated CTCs, could be used as biomarkers for the stratification and monitoring of patients with NSCLC undergoing cCRT, and they may hold promising potential for guiding subsequent consolidation treatment with immunotherapy or other novel therapies based on autophagy inhibitors.

Abstract Chiral molecules are instrumental for molecular recognition in living organisms. Distinguishing between two opposite enantiomers, the mirror twins of the same chiral molecule, is both vital and challenging. Geometric magnetism enables a broad class of phenomena in solids including the anomalous electron velocity, the Hall effect, and related topological observables. Here we show that ultrafast electron currents excited in chiral molecules can generate geometric fields which enable a class of anomalous enantio-sensitive observables in photoionization. Next, we introduce the first member of this class: enantio-sensitive orientation of chiral molecules via photoionization. This effect opens unexplored routes to both enantio-separation and imaging of chiral dynamics on ultrafast time scales. Our work suggests that geometric magnetism in photoionization provides the bridge between the two geometrical properties, chirality and topology.

The effects of corticomuscular connectivity during object manipulation tasks with different haptic sensations have not been quantitatively investigated. Connectivity analyses enable the study of cortical effects and muscle responses during movements, revealing communication pathways between the brain and muscles. This study aims to examine the corticomuscular connectivity of three Electroencephalography (EEG) channels and five muscles during object manipulation tasks involving contact surfaces of Sandpaper, Suede, and Silk. The analyses included 12 healthy subjects performing tasks with their right hand. Power-Based Connectivity (PBC) and Mutual Information (MI) measures were utilized to evaluate significant differences in connectivity between contact surfaces, EEG channels, muscles, and frequency bands. The research yielded the following findings: Suede contact surface exhibited higher connectivity; Mu and Gamma frequency bands exerted greater influence; significant connectivity was observed between the three EEG channels (C3, Cz, C4) and the Anterior Deltoid (AD) and Brachioradialis (B) muscles; and connectivity was primarily involved during active movement in the AD muscle compared to the resting state. These findings suggest potential implementation in motor rehabilitation for more complex movements using novel alternative training systems with high effectiveness.

The energy dissipation in collisionless plasmas as the solar wind is not yet fully understood. The intermittent nature of magnetic structures appears to be a fundamental part of the energy cascade. Understanding energy transfer and dissipation in the solar wind requires an accurate description of its intermittency. Upcoming multi-spacecraft missions will provide new insight on this matter. However, the use of multi-point data requires developing new data analysis techniques as well as cross-validating these techniques. In this study, we address the latter and explore the intermittency in a 3D simulation of anisotropic plasma turbulence using two approaches. We implement the standard single-spacecraft partial variance increments technique as well as a multi-point partial variance increments technique. We contrast these two techniques and explore their dependence on the angle between the spacecraft-configuration travel direction and the background magnetic field.

Abstract Regulation of cutaneous immunity is severely compromised in inflammatory skin disease. To investigate the molecular crosstalk underpinning tolerance versus inflammation in atopic dermatitis, we utilise a human in vivo allergen challenge study, exposing atopic dermatitis patients to house dust mite. Here we analyse transcriptional programmes at the population and single cell levels in parallel with immunophenotyping of cutaneous immunocytes revealed a distinct dichotomy in atopic dermatitis patient responsiveness to house dust mite challenge. Our study shows that reactivity to house dust mite was associated with high basal levels of TNF-expressing cutaneous Th17 T cells, and documents the presence of hub structures where Langerhans cells and T cells co-localised. Mechanistically, we identify expression of metallothioneins and transcriptional programmes encoding antioxidant defences across all skin cell types, that appear to protect against allergen-induced inflammation. Furthermore, single nucleotide polymorphisms in the MTIX gene are associated with patients who did not react to house dust mite, opening up possibilities for therapeutic interventions modulating metallothionein expression in atopic dermatitis.

Purpose Internal carotid artery (ICA) aneurysm treatment with a flow diverter (FD) has shown an adequate efficacy and safety profile, presenting high complete occlusion or near occlusion rates with low complications during follow-up. The purpose of this study was to evaluate the efficacy and safety of FD treatment in non-ruptured internal carotid aneurysms. Materials and Methods This is a retrospective, single-center, observational study evaluating patients diagnosed with unruptured ICA aneurysms treated with an FD between January 1, 2014, and January 1, 2020. We analyzed an anonymized database. The primary effectiveness endpoint was complete occlusion (O’Kelly–Marotta D, OKM-D) of the target aneurysm through 1-year follow-up. The safety endpoint was the evaluation of modified Rankin Scale (mRS) 90 days after treatment, considering a favorable outcome an mRS 0-2. Results A total of 106 patients were treated with an FD, 91.5% were women; the mean follow- up was 427.2±144.8 days. Technical success was achieved in 105 cases (99.1%). All patients included had 1-year follow-up digital subtraction angiography control; 78 patients (73.6%) completed the primary efficacy endpoint by achieving total occlusion (OKM-D). Giant aneurysms had a higher risk of not achieving complete occlusion (risk ratio, 3.07; 95% confidence interval, 1.70 - 5.54]). The safety endpoint of mRS 0-2 at 90 days was accomplished in 103 patients (97.2%). Conclusion Treatment of unruptured ICA aneurysms with an FD showed high 1-year total occlusion results, with very low morbidity and mortality complications.

Cloud-based Radio Access Network (Cloud-RAN) leverages virtualization to enable the coexistence of multiple virtual Base Band Units (vBBUs) with collocated workloads on a single edge computer, aiming for economic and operational efficiency. However, this coexistence can cause performance degradation in vBBUs due to resource contention. In this paper, we conduct an empirical analysis of vBBU performance on a Linux RT-Kernel, highlighting the impact of resource sharing with user-space tasks and Kernel threads. Furthermore, we evaluate CPU management strategies such as CPU affinity and CPU isolation as potential solutions to these performance challenges. Our results highlight that the implementation of CPU affinity can significantly reduce throughput variability by up to 40%, decrease vBBU’s NACK ratios, and reduce vBBU scheduling latency within the Linux RT-Kernel. Collectively, these findings underscore the potential of CPU management strategies to enhance vBBU performance in Cloud-RAN environments, enabling more efficient and stable network operations. The paper concludes with a discussion on the efficient realization of Cloud-RAN, elucidating the benefits of implementing proposed CPU affinity allocations. The demonstrated enhancements, including reduced scheduling latency and improved end-to-end throughput, affirm the practicality and efficacy of the proposed strategies for optimizing Cloud-RAN deployments.

Enzyme–substrate interactions play a fundamental role in elucidating synthesis pathways and synthetic biology, as they allow for the understanding of important aspects of a reaction. Establishing the interaction experimentally is a slow and costly process, which is why this problem has been addressed using computational methods such as molecular dynamics, molecular docking, and Monte Carlo simulations. Nevertheless, this type of method tends to be computationally slow when dealing with a large search space. Therefore, in recent years, methods based on artificial intelligence, such as support vector machines, neural networks, or decision trees, have been implemented, significantly reducing the computing time and covering vast search spaces. These methods significantly reduce the computation time and cover broad search spaces, rapidly reducing the number of interacting candidates, as they allow repetitive processes to be automated and patterns to be extracted, are adaptable, and have the capacity to handle large amounts of data. This article analyzes these artificial intelligence-based approaches, presenting their common structure, advantages, disadvantages, limitations, challenges, and future perspectives.

Abstract We know little about how smoking prevention interventions might leverage social network structures to enhance protective social norms. In this study we combined statistical and network science methods to explore how social networks influence social norms related to adolescent smoking in school-specific settings in Northern Ireland and Colombia. Pupils (12–15 years old) participated in two smoking prevention interventions in both countries (n = 1344). A Latent Transition Analysis identified three groups characterized by descriptive and injunctive norms towards smoking. We employed a Separable Temporal Random Graph Model to analyze homophily in social norms and conducted a descriptive analysis of the changes in the students’ and their friends’ social norms over time to account for social influence. The results showed that students were more likely to be friends with others who had social norms against smoking. However, students with social norms favorable towards smoking had more friends with similar views than the students with perceived norms against smoking, underlining the importance of network thresholds. Our results support the notation that the ASSIST intervention takes advantage of friendship networks to leverage greater change in the students' smoking social norms than the Dead Cool intervention, reiterating that social norms are subject to social influence.

Increasing integration of distributed energy resources (DER) in the electrical network has led distribution network operators to unprecedented challenges. This issue is compounded by the lack of monitoring infrastructure on the low voltage (LV) side of distribution networks at residential and utility sides. Non-intrusive load monitoring (NILM) methods provide an opportunity to add value to conventional electric measurements and to increase the observability of LV networks for the implementation of active management network techniques and intelligent control of DER. This work proposes a novel implementation of NILM methods for the identification of DER electrical signatures from aggregated measurements taken at the LV side of a distribution transformer. The implementation evaluates three machine learning algorithms such as k Nearest Neighbours (kNN), random forest and a multilayer perceptron under 100 scenarios of DER integration. A year of minutely reported values of electric current, voltage, active power, and reactive power are used to train and test the proposed model. The $F_{1}$ scores achieved of 73% and 93% for Electrical Vehicles (EV) and rooftop photovoltaic (PV) respectively and processing times below $314~\mu \text{s}$ on an Intel Core i7-8700 machine. These results confirm the relevance of the NILM method based on low frequency electric measurements from the real-time identification of DER.

Light pollution is a form of environmental degradation present throughout the world that affects the natural environment, flora, fauna, and various aspects of human life. Despite the growing concern about this problem, its study in Colombia is still minimal. Here we present a comprehensive analysis of the expansion of artificial nighttime lighting in the main Colombian cities between 2012 and 2022. According to the analysis, light pollution levels in the urban areas of Bogotá, Barranquilla, and Cartagena increased, while in Medellín, Cali, and Bucaramanga, they decreased. However, all the cities evaluated experienced an expansion in the coverage of illuminated areas revealing an evident spatial increase of the problem. In the case of Bogotá, the phenomenon was studied at the locality level. Additionally, we used external data to analyze the relationship between increased light pollution and the installation of new luminaires, the change to LED technologies, and the growing population density and gross domestic product (GDP) in the city. Our results provide valuable information on the threat of light pollution in Colombia and the need to take measures to help control the associated environmental degradation.

The production of sodium hypochlorite in situ is useful for the disinfection of water in aqueducts located in areas of difficult access; published studies on the optimum parameters of electrolysis for the production of sodium hypochlorite are carried out at laboratory scale. The paper includes the results of the evaluation of a prototype for the production of 22 liters of hypochlorite solution, the optimum operating parameters were identified through a design of experiments; the electrodes of the equipment are made of graphite with an anodic surface of 1868 cm2, the retention times, current intensities and the initial concentration of chlorides were varied. The iodometry technique was used to quantify the hypochlorite ion, obtaining 4.46 g.l-1 in conditions of 120 min, 80 A and 150 g Cl-.l-1, with an energy efficiency of 42.58 mgCl2.(kJ)-1. According to the results in the statistical analysis of variance correlate the influence of each variable in the hypochlorite production and energy efficiency of the process.

Atrial fibrillation (AF) is a prevalent arrhythmia, while pulmonary vein isolation (PVI) has become a cornerstone in its treatment. The creation of durable lesions is crucial for successful and long-lasting PVI, as inconsistent lesions lead to reconnections and recurrence after ablation. Various approaches have been developed to assess lesion quality and transmurality in vivo, acting as surrogates for improved lesion creation and long-term outcomes utilizing radiofrequency (RF) energy. This review manuscript examines the biophysics of lesion creation and different lesion assessment techniques that can be used daily in the electrophysiology laboratory when utilizing RF energy. These methods provide valuable insights into lesion effectiveness, facilitating optimized ablation procedures and reducing atrial arrhythmia recurrences. However, each approach has its limitations, and a combination of techniques is recommended for comprehensive lesion assessment during AF catheter ablation. Future advancements in imaging techniques, such as magnetic Resonance Imaging (MRI), optical coherence tomography, and photoacoustic imaging, hold promise in further enhancing lesion evaluation and guiding treatment strategies.

Catheter ablation has become a cornerstone in atrial fibrillation (AF) therapy, improving freedom from all-atrial arrhythmias, as well as outperforming antiarrhythmic drugs in alleviating AF-related symptoms, reducing hospitalizations, and enhancing quality of life. Nevertheless, the success rate of traditional radiofrequency ablation (RFA) methods remains less than ideal. To address these issues, refinement in RFA strategies has been developed to improve efficacy and laboratory efficiency during pulmonary vein isolation (PVI). High-power short-duration (HPSD) RFA has emerged as a safe strategy to reduce the time required to produce durable lesions. This article reviews critical aspects of HPSD ablation in the management of both paroxysmal and persistent AF, covering aspects such as effectiveness, safety, procedural intricacies, and the underlying biophysics.

Abstract Background Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and evidenced the need to identify reliable predictive biomarkers. Liquid biopsy is the non-invasive and repeatable analysis of biological material in body fluids and a promising tool for cancer biomarkers discovery. In particular, there is growing evidence that extracellular vesicles (EVs) play an important role in tumor progression and in tumor-immune interactions. Thus, we evaluated whether extracellular vesicle PD-L1 expression could be used as a biomarker for prediction of durable treatment response and survival in patients with non-small cell lung cancer (NSCLC) undergoing treatment with ICIs. Methods Dynamic changes in EV PD-L1 were analyzed in plasma samples collected before and at 9 ± 1 weeks during treatment in a retrospective and a prospective independent cohorts of 33 and 39 patients, respectively. Results As a result, an increase in EV PD-L1 was observed in non-responders in comparison to responders and was an independent biomarker for shorter progression-free survival and overall survival. To the contrary, tissue PD-L1 expression, the commonly used biomarker, was not predictive neither for durable response nor survival. Conclusion These findings indicate that EV PD-L1 dynamics could be used to stratify patients with advanced NSCLC who would experience durable benefit from ICIs.

Introduction Burn wound infection (BWI) is the second most important cause of death in burn patients. There is currently limited data about the incidence and clinical presentation of BWI using quantitative techniques as quantitative biopsy culture (QBC) to prevent progress to burn wound sepsis (BWS). Methods This is a prospective cohort study of patients diagnosed with BWI, confirmed by QBC, from February 2018 to July 2019 at University Hospital of Santander (HUS). The primary outcome was to determine clinical, microbiological, and histopathological characteristics of patients diagnosed with BWI along with a positive QBC and their relationship with early diagnosis and progression to BWS. Results 525 patients were admitted to HUS Burn Center. Of those, 44/525 (8.23%) presented a clinical diagnosis of BWI (median age, 20.5 years [1–67 years]; 25/44 [56.8%] male). QBC was positive in 26/44 (59%), Staphylococcus aureus 14/44 (31.8%), and Pseudomonas aeruginosa 7/44 (15.9%) were the mainly etiological agents isolated. Bacterial resistance to antibiotics was mostly to beta-lactams in 14/44 (31.8%), corresponding to methicillin-resistant Staphylococcus aureus (MRSA). Clinical signs more related to infection were erythema in 33/44 (61.3%). As many as 10/44 (22.7%) progressed to sepsis and 2/44 (6%) died. Conclusion BWI increases hospitalization time and number of surgeries, increasing the risk of sepsis and death. The QBC allows an accurate diagnosis with lesser false-positive cases that impact antibiotic resistance and mortality. Protocols targeting this problem are needed to decrease the impact of this.

Dermatofibrosarcoma Protuberans is an aggressive form of skin cancer in children. It has a slow growth rate and low chance of metastasizing but is notorious for its aggressive invasive and recurrent nature. In pediatric patients, the resections can be quite aggressive but with appropriate surgical planning and approach, can have quite low morbidity and mortality. We report a unique case of a pediatric patient with dermatofibrosarcoma protuberans that was managed with repeated surgical resections, discuss operative management strategies for this aggressive diagnosis, and provide a review of the literature.

Background:. Targeted muscle reinnervation has been adopted as a strategy for the management and prevention of phantom limb pain and symptomatic neuroma formation for patients undergoing lower extremity amputation. The procedure is often performed by surgeons different from those performing the amputation, creating scheduling dilemmas. The purpose of this study was to analyze historic trends in lower extremity amputation scheduling in a single hospital system to evaluate if offering routine immediate targeted muscle reinnervation is practical. Methods:. De-identified data over a five-year period for all patients undergoing lower extremity amputation were collected. The data gathered included the specialty performing the amputation, weekly distribution of cases, start time, and end time, among others. Results:. A total of 1549 lower extremity amputations were performed. There was no statistically significant difference in average number of below-the-knee amputations (172.8) and above-the-knee amputations (137.4) per year. Top specialties performing amputations were vascular surgery (47.8%), orthopedic surgery (34.5%), and general surgery (13.85%). No significant difference was noted in the average number of amputations across the week, per year. Most cases started between 6 am and 6 pm (96.4%). The average length of stay after surgery was 8.26 days. Conclusions:. In a large, nontrauma hospital system, most lower extremity amputations are performed during typical working hours and are evenly distributed throughout the week. Understanding peak timing of amputations may allow for targeted muscle reinnervation to be performed concurrently with amputation procedure. Data presented will be a first step to optimizing amputation scheduling for patients in a large nontrauma health system.

Abstract International policies and targets to globally reduce carbon dioxide emissions have contributed to increasing penetration of distributed energy resources (DER) in low‐voltage distribution networks. The growth of technologies such as rooftop photovoltaic (PV) systems and electric vehicles (EV) has, to date, not been rigorously monitored and record keeping is deficient. Non‐intrusive load monitoring (NILM) methods contribute to the effective integration of clean technologies within existing distribution networks. In this study, a novel NILM method is developed for the identification of DER electrical signatures from smart meter net‐demand data. Electrical profiles of EV and PV systems are allocated within aggregated measurements including conventional electrical appliances. Data from several households in the United States are used to train and test classification and regression models. The usage of conventional machine learning techniques provides the proposed algorithm with fast processing times and low system complexity, key factors needed to differentiate highly variable DER power profiles from other loads. The results confirm the effectiveness of the proposed methodology to individually classify DER with performance metrics of 96% for EV and 99% for PV. This demonstrates the potential of the proposed method as an embedded function of smart meters to increase observability in distribution networks.

Sulforaphane, a chemical found in broccoli, has known antioxidant and antiinflammatory effects. Here, the authors show that it can inhibit SARS-CoV-2 and other coronavirus infections in mammalian cells and can decrease viral load in mice when treated prior to SARS-CoV-2 infection.

Pulsed-field ablation (PFA) has emerged as a promising nonthermal ablation alternative for treating atrial fibrillation (AF). By delivering ultra-rapid high-energy electrical pulses, PFA induces irreversible electroporation, selectively targeting myocardial tissue while sparing adjacent structures from thermal or other damage. This article provides a comprehensive review of multiple pre-clinical studies, clinical studies, and clinical trials evaluating the safety, efficacy, and long-term outcomes of PFA in various settings and patient populations. Overall, the reviewed evidence highlights PFA’s potential as a revolutionary ablation strategy for AF treatment. Offering comparable procedural efficacy to conventional ablation methods, PFA distinguishes itself with shorter procedure times and reduced risks of complications such as phrenic nerve palsy and potential esophageal injury. While further research is warranted to establish long-term efficacy, PFA’s distinct advantages and evolving clinical evidence suggest a promising future for this novel nonthermal ablation approach. As PFA continues to advance, it has the potential to transform AF ablation procedures, providing a safer alternative for patients with atrial fibrillation.

Virtual fencing systems have emerged as a promising technology for managing the distribution of livestock in extensive grazing environments. This study provides comprehensive documentation of the learning process involving two conditional behavioral mechanisms and the documentation of efficient, effective, and safe animal training for virtual fence applications on nursing Brangus cows. Two hypotheses were examined: (1) animals would learn to avoid restricted zones by increasing their use of containment zones within a virtual fence polygon, and (2) animals would progressively receive fewer audio-electric cues over time and increasingly rely on auditory cues for behavioral modification. Data from GPS coordinates, behavioral metrics derived from the collar data, and cueing events were analyzed to evaluate these hypotheses. The results supported hypothesis 1, revealing that virtual fence activation significantly increased the time spent in containment zones and reduced time in restricted zones compared to when the virtual fence was deactivated. Concurrently, behavioral metrics mirrored these findings, with cows adjusting their daily travel distances, exploration area, and cumulative activity counts in response to the allocation of areas with different virtual fence configurations. Hypothesis 2 was also supported by the results, with a decrease in cueing events over time and increased reliance with animals on audio cueing to avert receiving the mild electric pulse. These outcomes underscore the rapid learning capabilities of groups of nursing cows in responding to virtual fence boundaries.

Acute febrile syndrome is a frequent reason for medical consultations in tropical and subtropical countries where the cause could have an infectious origin. Malaria and dengue are the primary etiologies in Colombia. As such, constant epidemiological surveillance and new diagnostic tools are required to identify the causative agents. A descriptive cross-sectional study was conducted to evaluate the circulation and differential diagnosis of six pathogens in two regions of Colombia. The results obtained via multiplex reverse transcription polymerase chain reaction combined with a microwell hybridization assay (m-RT-PCR-ELISA) were comparable to those obtained using rapid tests conducted at the time of patient enrollment. Of 155 patients evaluated, 25 (16.1%) and 16 (10.3%) were positive for malaria and dengue, respectively; no samples were positive for any of the other infectious agents tested. In most cases, m-RT-PCR-ELISA confirmed the results previously obtained through rapid testing.

Swine influenza is a respiratory disease that affects the pork industry and is a public health threat. It is caused by type A influenza virus (FLUAV), which continuously undergoes genetic and antigenic variations. A large amount of information regarding FLUAV in pigs is available worldwide, but it is limited in Latin America. The HA sequences of H1 subtype FLUAV-positive samples obtained from pigs in Colombia between 2008–2021 were analyzed using sequence-based antigenic cartography and N-Glycosylation analyses. Of the 12 predicted global antigenic groups, Colombia contained five: four corresponding to pandemic strains and one to the classical swine H1N1 clade. Circulation of these clusters was observed in some regions during specific years. Ca2 was the immunodominant epitope among Colombian viruses. The counts of N-Glycosylation motifs were associated with the antigenic cluster ranging from three to five. The results show for the first time the existence of antigenic diversity of FLUAV in Colombia and highlight the impact of spatial and temporal factors on this diversity. This study provides information about FLUAV variability in pigs under natural conditions in the absence of vaccination and emphasizes the need for surveillance of its phylogenetic and antigenic characteristics.

BackgroundHepatoblastoma (HB) is the most common primary liver cancer in children with emerging evidence that incidence is increasing globally. While overall survival for low risk hepatoblastoma is >90%, children with metastatic disease have worse survival. As identifying factors associated with high-risk disease is critical for improving outcomes for these children, a need for a further understanding of the epidemiology of hepatoblastoma is warranted. Therefore, we conducted a population-based epidemiologic study of hepatoblastoma in Texas, a large state characterized by ethnic and geographic diversity.MethodsInformation on children diagnosed with hepatoblastoma at 0–19 years of age for the period of 1995–2018 was obtained from the Texas Cancer Registry (TCR). Demographic and clinical variables including sex, race/ethnicity, age at diagnosis, urban-rural status, and residence along the Texas-Mexico border were evaluated. Multivariable Poisson regression was used to calculate adjusted incidence rate ratios (aIRRs) and 95% confidence intervals (CIs) for each variable of interest. Joinpoint regression analysis was used to determine the trend in incidence of hepatoblastoma, overall and by ethnicity.ResultsOverall, 309 children diagnosed with hepatoblastoma in Texas for the period of 1995–2018. Joinpoint regression analysis showed no joinpoints in the overall or the ethnic-specific analyses. Over this period, the incidence increased at 4.59% annually; with the annual percent change higher among Latinos (5.12%) compared to non-Latinos (3.15%). Among these children, 57 (18%) had metastatic disease at diagnosis. Factors associated with hepatoblastoma included male sex (aIRR = 1.5, 95% CI: 1.2–1.8, p = 0.002); infancy (aIRR = 7.6, 95% CI: 6.0–9.7, p < 0.001); and Latino ethnicity (aIRR = 1.3, 95% CI: 1.0–1.7, p = 0.04). Additionally, children living in rural areas were less likely to develop hepatoblastoma (aIRR = 0.6, 95% CI: 0.4–1.0, p = 0.03). While residence on the Texas-Mexico border association with hepatoblastoma approached statistical significance (p = 0.06) in unadjusted models, this finding did not remain significant after adjusting for Latino ethnicity. The two factors associated with being diagnosed with metastatic hepatoblastoma included Latino ethnicity (aIRR = 2.1, 95% CI: 1.1–3.8, p = 0.02) and male sex (aIRR = 2.4, 95% CI: 1.3–4.3, p = 0.003).ConclusionsIn this large population-based study of hepatoblastoma, we found several factors associated with hepatoblastoma and metastatic disease. The reasons for a higher burden of hepatoblastoma among Latino children is unclear but could be due to differences in geographic genetic ancestry, environmental exposures, or other unmeasured factors. Additionally, it is notable that Latino children were also more likely to be diagnosed with metastatic hepatoblastoma compared to non-Latino white children. To our knowledge, this has not been previously reported and warrants further study to delineate the causes of this disparity and identify interventions to improve outcomes.

Abstract Intervertebral disc degeneration is a common cause of low back pain, the leading cause of disability worldwide. Appropriate preclinical models for intervertebral disc research are essential to achieving a better understanding of underlying pathophysiology and for the development, evaluation, and translation of more effective treatments. To this end, in vivo animal and ex vivo organ culture models are both widely used by spine researchers; however, the relative strengths and weaknesses of these two approaches are a source of ongoing controversy. In this article, members from the Spine and Preclinical Models Sections of the Orthopedic Research Society, including experts in both basic and translational spine research, present contrasting arguments in support of in vivo animal models versus ex vivo organ culture models for studies of the disc, supported by a comprehensive review of the relevant literature. The objective is to provide a deeper understanding of the respective advantages and limitations of these approaches, and advance the field toward a consensus with respect to appropriate model selection and implementation. We conclude that complementary use of several model types and leveraging the unique advantages of each is likely to result in the highest impact research in most instances.

Physical systems exhibiting neuromechanical functions promise to enable structures with directly encoded autonomy and intelligence. A neuromorphic metamaterials class embodying bioinspired mechanosensing, memory, and learning functionalities obtained by leveraging mechanical instabilities integrated with memristive materials is reported. The prototype system comprises a multistable metamaterial whose bistable dome‐shaped units collectively filter, amplify, and transduce external mechanical inputs over large areas into simple electrical signals using embedded piezoresistive sensors. Dome deformations in nonvolatile memristors triggered by the transduced signals, providing a means to store loading events in measurable material states are recorded. Sequentially applied mechanical inputs result in accumulated memristance changes that allow us to physically encode a Hopfield network into the neuromorphic metamaterials. This physical network learns the history of spatially distributed input patterns. Crucially, the neuromorphic metamaterials can retrieve the learned patterns from the memristors’ final accumulated state. Therefore, the system exhibits the ability to learn without supervised training and retain spatially distributed inputs with minimal external overhead. The system's embodied mechanosensing, memory, and learning capabilities establish an avenue for synthetic neuromorphic metamaterials that learn via tactile interactions. This capability suggests new types of large‐area smart surfaces for robotics, autonomous systems, wearables, and morphing structures subjected to spatiotemporal mechanical loading.

In this work, a UV/H2O2 system was evaluated using an experimental design 2 level I-optimal response surface design to analyze the effect of temperature, pH, UV lamp power (W), and H2O2 concentration on dye load removal and nitrification from industrial cleaning wastewater. Results showed that the optimum conditions were 80 °C, pH 4, PW-UV 60 W, and H2O2 3.1 Mol*L-1. Removal percentages of 45% for COD, 47.5% color, 87% Fe, 82% Cr and 91% ammonium oxidation to nitrate were achieved. It can be concluded that the effluents treated by this process could be promising for reuse and exploitation in biotechnological tools through microalgae and cyanobacteria.