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Abstract Objective To develop a domain-specific large language model (LLM) for LI-RADS v2018 categorization of hepatic observations based on free-text descriptions extracted from MRI reports. Material and methods This retrospective study included 291 small liver observations, divided into training (n = 141), validation (n = 30), and test (n = 120) datasets. Of these, 120 were fictitious, and 171 were extracted from 175 MRI reports from a single institution. The algorithm’s performance was compared to two independent radiologists and one hepatologist in a human replacement scenario, and considering two combined strategies (double reading with arbitration and triage). Agreement on LI-RADS category and dichotomic malignancy (LR-4, LR-5, and LR-M) were estimated using linear-weighted κ statistics and Cohen’s κ, respectively. Sensitivity and specificity for LR-5 were calculated. The consensus agreement of three other radiologists served as the ground truth. Results The model showed moderate agreement against the ground truth for both LI-RADS categorization (κ = 0.54 [95% CI: 0.42–0.65]) and the dichotomized approach (κ = 0.58 [95% CI: 0.42–0.73]). Sensitivity and specificity for LR-5 were 0.76 (95% CI: 0.69–0.86) and 0.96 (95% CI: 0.91–1.00), respectively. When the chatbot was used as a triage tool, performance improved for LI-RADS categorization (κ = 0.86/0.87 for the two independent radiologists and κ = 0.76 for the hepatologist), dichotomized malignancy (κ = 0.94/0.91 and κ = 0.87) and LR-5 identification (1.00/0.98 and 0.85 sensitivity, 0.96/0.92 and 0.92 specificity), with no statistical significance compared to the human readers’ individual performance. Through this strategy, the workload decreased by 45%. Conclusion LI-RADS v2018 categorization from unlabelled MRI reports is feasible using our LLM, and it enhances the efficiency of data curation. Critical relevance statement Our proof-of-concept study provides novel insights into the potential applications of LLMs, offering a real-world example of how these tools could be integrated into a local workflow to optimize data curation for research purposes. Key Points Automatic LI-RADS categorization from free-text reports would be beneficial to workflow and data mining. LiverAI, a GPT-4-based model, supported various strategies improving data curation efficiency by up to 60%. LLMs can integrate into workflows, significantly reducing radiologists’ workload. Graphical Abstract

Abstract Background Infection prevention and control (IPC) programs are essential to prevent and control the spread of multidrug-resistant organisms in healthcare facilities (HCFs). The current implementation of these programs in Latin America remains largely unknown. Methods We conducted a mixed-methods evaluation of IPC program implementation in HCFs from Guatemala, Panama, Ecuador, and Argentina, March-July 2022. We used the World Health Organization (WHO) IPC Assessment Framework (IPCAF) survey, a previously validated structured questionnaire with an associated scoring system that evaluates the eight core components of IPC (IPC program; IPC guidelines; IPC education and training; healthcare-associated infection [HAI] surveillance; multimodal strategies; monitoring and audit of IPC practices and feedback; workload, staffing, and bed occupancy; and the built environment and materials and equipment for IPC). Each section generates a score 0–100. According to the final score, the HCF IPC program implementation is categorized into four levels: inadequate (0–200), basic (201–400), intermediate (401–600), or advanced (601–800). Additionally, we conducted semi-structured interviews among IPC personnel and microbiologists using the Systems Engineering Initiative for Patient Safety model to evaluate barriers and facilitators for IPC program implementation. We performed directed content analysis of interview transcripts to identify themes that focused on barriers and facilitators of IPC program implementation which are summarized descriptively. Results Thirty-seven HCFs (15 for-profit and 22 non-profit) completed the IPCAF survey. The overall median score was 614 (IQR 569, 693) which corresponded to an “advanced” level of IPC implementation (32% [7/22] non-profit vs. 93% [14/15] for-profit HCFs in this category). The lowest scores were in workload, staffing and bed occupancy followed by IPC training and multimodal strategies. Forty individuals from 16 HCFs were interviewed. They perceived inadequate staffing and technical resources, limited leadership support, and cultural determinants as major barriers to effective IPC guideline implementation, while external accreditation and technical support from public health authorities were perceived as facilitators. Conclusions Efforts to strengthen IPC activities in Latin American HCFs should focus on improving support from hospital leadership and public health authorities to ensure better resource allocation, promoting safety culture, and improving training in quality improvement.

RESUMEN El objetivo de este estudio fue determinar las tasas de sedimentación (Td) de sedimentos eólicos minerales en un parche de bosque del agroecosistema del semiárido pampeano y analizar la variabilidad estacional de dicha sedimentación. La Td media fue 520,15 kg ha-1 año-1 con alta variabilidad interanual. En primavera-verano, Td fue superior que en otoño-invierno. La temperatura del aire y velocidad media máxima del viento influenciaron de forma más significativa a Td. Sin embargo, la cobertura del suelo y el manejo de los campos agrícolas que rodean al bosque determinarían la producción de sedimentos a partir de la erosión eólica y consecuente sedimentación dentro del bosque. Estos resultados muestran la importancia de mantener los parches de bosques dentro de la matriz agrícola en el semiárido, los cuales retienen sedimentos eólicos que finalmente se depositarían en el suelo forestal, minimizando los impactos negativos que los procesos de erosión eólica tienen en estos ecosistemas.

Abstract Culturing and genomic sequencing of Mycobacterium tuberculosis (MTB) from tuberculosis (TB) cases is the basis for many research and clinical applications. The alternative, culture-free sequencing from diagnostic samples, is promising but poses challenges to obtain and analyse the MTB genome. Paradoxically, culture is assumed to impose a diversity bottleneck, which, if true, would entail unexplored consequences. To unravel this paradox we generate high-quality genomes of sputum-culture pairs from two different settings after developing a workflow for sequencing from sputum and a tailored bioinformatics analysis. Careful downstream comparisons reveal sources of sputum-culture incongruences due to false positive/negative variation associated with factors like low input MTB DNA or variable genomic depths. After accounting for these factors, contrary to the bottleneck dogma, we identify a 97% variant agreement within sputum-culture pairs, with a high correlation also in the variants’ frequency (0.98). The combined analysis from five different settings and more than 100 available samples shows that our results can be extrapolated to different TB epidemic scenarios, demonstrating that for the cases tested culture accurately mirrors clinical samples.

Treatment wetlands (TWs) effectively remove target pollutants and enhance urban water circularity and resilience. They constitute a prominent solution for urban wastewater treatment, thanks to their adaptability across various types of wastewater, scales and climatic conditions. However, the disparity in TW designs and the focus on a restricted set of variables applicable to research studies impede any comprehensive evaluation and comparison of TW performance. Our study introduces a methodology for data validation, in concurrently establishing a workflow specific to TW. This approach is aimed at defining the scope and relationships within the data, implementing checks and concatenating them into a quality flag, as an initial step towards building reliable statistical models. We underscore the importance of both mobilising comprehensive knowledge and identifying customary, yet implicit, choices intertwined in data processing. As for the application workflow, we collected and analysed data sourced from peer-reviewed papers on horizontal and vertical flow TW. Deficiencies were noted in key data elements like dimensions, concentrations and operational conditions. For the data analysis, relationships are highlighted between variables introduced for modelling purposes. These methodologies and workflows assess the quality of the data, in paving the way towards more dependable statistical models for TW design and implementation. HIGHLIGHTS We provide a six-step data validation methodology highlighting the key elements to consider, regardless of the field.; We develop data quality checks, in proposing a probabilistic output that can be used in data-driven modelling.; We analyse a worldwide-scale dataset on treatment wetlands that can serve as a ground reference for data-driven modelling.;

Abstract Background North African human populations present a complex demographic scenario due to the presence of an autochthonous genetic component and population substructure, plus extensive gene flow from the Middle East, Europe, and sub-Saharan Africa. Results We conducted a comprehensive analysis of 364 genomes to construct detailed demographic models for the North African region, encompassing its two primary ethnic groups, the Arab and Amazigh populations. This was achieved through an Approximate Bayesian Computation with Deep Learning (ABC-DL) framework and a novel algorithm called Genetic Programming for Population Genetics (GP4PG). This innovative approach enabled us to effectively model intricate demographic scenarios, utilizing a subset of 16 whole genomes at > 30X coverage. The demographic model suggested by GP4PG exhibited a closer alignment with the observed data compared to the ABC-DL model. Both point to a back-to-Africa origin of North African individuals and a close relationship with Eurasian populations. Results support different origins for Amazigh and Arab populations, with Amazigh populations originating back in Epipaleolithic times, while GP4PG supports Arabization as the main source of Middle Eastern ancestry. The GP4PG model includes population substructure in surrounding populations (sub-Saharan Africa and Middle East) with continuous decaying gene flow after population split. Contrary to ABC-DL, the best GP4PG model does not require pulses of admixture from surrounding populations into North Africa pointing to soft splits as drivers of divergence in North Africa. Conclusions We have built a demographic model on North Africa that points to a back-to-Africa expansion and a differential origin between Arab and Amazigh populations.

Pristine Mo2C MXene has been recently highlighted as a highly active and robust catalyst for the reverse water gas shift (RWGS) reaction. Here, first-principles calculations based on density functional theory (DFT) coupled with mean-field microkinetic (MKM) simulations are performed to investigate the effects of the atomic layer stacking and the surface functionalization with oxo groups on the catalyst performance. The calculated data show that ABA stacked MXene has a reactivity higher than the corresponding ABC counterpart. Moreover, a 2/3 surface monolayer oxygen coverage on both stackings (i.e., Mo2CO4/3 MXene) enhances the overall reactivity compared with their pristine Mo2C counterparts. The reactivity enhancement is small for the more stable ABA-stacked model, with a CO gas production aligned with experimental reports. However, the partial O-surface termination in the MXene with ABC stacking offers a more enhanced reactivity, supported by the higher CO gas production for the Mo2C MXene models here considered. Thus, the MXene stacking and its functionalization are key aspects affecting the performance of the Mo2C MXene for the RGWS reaction, which must be considered for realistic catalytic applications of MXenes.

Although an increased effectiveness has been suggested when phages and antibiotics are combined, this approach has not been tested against a mature biofilm on an endotracheal tube (ETT) surface. This study evaluated the effect of short- and long-term combined phage-antibiotic therapy in a control of a mature biofilm on an ETT surface. Pseudomonas aeruginosa strains, including susceptible and resistant clinical samples, were used to develop the ETT biofilm. Biofilm was treated with 108PFU/mL of phage_2, phage_18 or 5 μg/mL of ceftolozane/tazobactam, alone or in combination with phages. The sequential combination of the two different phages and ceftolozane/tazobactam was also tested. Biofilm viability was assessed after short (2, 4, 24 h) and long-(48, 72 h) term treatment exposure using colony forming unit measurement. For long-term exposition, a new treatment shot was added every 24 h. In the sequential combination, the phage type was switched at 24 h of treatment. Regarding the susceptible strains, the treatments had limited antibiofilm effect after 2, 4 and 24 h. After 48 and 72 h, administering phages alone had no effect on biofilm viability, indicating the emergence of phage-resistant phenotypes. Nonetheless, the combined phage-antibiotic treatment reduced the biofilm viability in about 5-log, whilst antibiotic alone reduced in about 3-log. The sequential combination of phages and antibiotic reduced the biofilm viability in about 6-log. With respect to the resistant strains, no antibiofilm activity was observed regarding the treatment arms. The combination of phages and ceftolozane/tazobactam showed a synergism strain-dependent, being more apparent in susceptible strains.

Histamine intolerance is associated with impaired histamine metabolism due to diamine-oxidase (DAO) enzyme deficiency at intestinal level. The recommended strategy to alleviate the symptomatology is a low-histamine diet supplemented with DAO. Different sources of DAO enzyme have been characterized in the literature (animal, vegetal and microbial), although only the porcine kidney protein extract has been approved as food supplement. Despite optimistic clinical results of DAO supplementation, variability in enzymatic activity of this type of active ingredient is reported, potentially linked to manufacturing processes. The aim of this work was to evaluate the impact of the raw material and the technological process of obtaining the porcine kidney protein extract on DAO activity, and its evolution during storage at room temperature (25 °C) and refrigeration (4 °C). Twenty batches of DAO-containing extract were analyzed and found to have a consistent histamine-degrading activity. The powder extract was prepared by mincing and homogenizing porcine kidneys, defatting with acetone, and drying at 40 °C for 6 h. The inclusion of a biocidal step before acetone extraction was evaluated on DAO activity. The use of sodium hypochlorite and irradiation (8kGy) did not have a negative impact on DAO activity. Moreover, the inclusion of an initial freeze-drying step of the raw material yielded an extract with higher DAO activity. On the other hand, the effect of applying higher temperatures (70 °C, 80 °C, and 90 °C) during the extract drying process for 3 and 6 h was evaluated, reporting a significant decrease of the enzymatic activity, with losses of 10–20 % for every 10 °C increase in temperature. Refrigeration was the only storage method capable of preserving enzymatic activity for at least 24 months. The manufacturing and storage of porcine kidney extract are crucial steps in the formulation of DAO supplements suitable for the treatment of histamine intolerance.

Background: Long non-coding RNAs (lncRNAs) can perform tasks of key relevance in fat cells, contributing, when defective, to the burden of obesity and its sequelae. Here, scrutiny of adipose tissue transcriptomes before and after bariatric surgery (GSE53378) granted identification of 496 lncRNAs linked to the obese phenotype. Only expression of linc-GALNTL6-4 displayed an average recovery over 2-fold and FDR-adjusted p-value

PURPOSETo better understand immigration disparities among a Spanish Early-Onset Colorectal Cancer (SECOC) subset, according to the country of origin.PATIENTS AND METHODSWe selected 250 consecutive participants from the SECOC consortium. Data on baseline patient and tumor characteristics, family history of colorectal cancer (CRC), and follow-up were collected. The presence of mismatch repair deficiency was also assessed. Special data regarding country of origin, time of stay in Spain in case of other different country, and a 10-year cutoff that specifies the obtaining of Spanish nationality defined the variables of interest for comparison.RESULTSSeventy-five percent of patients with early-onset CRC (EOCRC) (188) were born in Spain, whereas the other 25% were born outside of Spain. The mean time of living in Spain until the EOCRC diagnosis was 16.5 years. Comparatively, most of the analyzed features showed equivalent proportions between cohorts. Only Spanish patients appeared to have more familial cancer component in first degree in general (32.3%; P = .01), compared with non-Spaniards, which showed a predominant sporadic component (56.4%; P < .001). Among immigrants, those patients living in Spain before CRC diagnosis ≤10 years were younger at diagnosis (39.1 v 42.5), more frequently male (77.8 v 47.7), were in more advanced stages (88.8% diagnosed at stage III and IV [P = .01]), and had a worse prognosis regarding recurrence rates (29.4% v 6.3%).CONCLUSIONAlthough there were few differences between Spanish and non-Spanish EOCRC, the most remarkable difference was that linked with the situation of those immigrants who have recently arrived in Spain, in relation to their lower health coverage, which could be associated with the delay in the diagnosis and their subsequent worse prognosis.

Objetivo: Describir y evaluar los resultados de la angioplastia con stent ductal en un único centro de alta complejidad durante el periodo 2016-2022. Método: Estudio descriptivo retrospectivo de corte transversal en el que se incluyeron pacientes menores de 3 meses a quienes se implantó un stent en el conducto arterioso como tratamiento paliativo inicial. Se recolectaron datos demográficos, clínicos y anatómicos previos a la intervención. Se registraron la mortalidad, las complicaciones intra- y posprocedimiento, la necesidad de reintervención, los requerimientos de cuidados intensivos y la estadía hospitalaria. Se describen las características al momento de la cirugía definitiva. Las variables discretas son presentadas con porcentajes, y las variables continuas con sus medianas y sus respectivos intervalos intercuartílicos. Resultados: Se revisaron 20 pacientes que habían recibido este tratamiento y se evidenció una tasa de éxito del 80%. Las complicaciones por disfunción del stent requirieron resolución quirúrgica. Egresaron de la institución el 95% de los pacientes luego del procedimiento y lograron arribar a un segundo estadio quirúrgico definitivo 17 pacientes. Fallecieron tres pacientes luego del procedimiento, pero sin relación directa con este. Conclusiones: Las indicaciones de angioplastia del conducto con stent como tratamiento alternativo a la realización de una anastomosis sistémico-pulmonar por cirugía todavía no están completamente definidas; la estrategia constituye una alternativa válida en pacientes adecuadamente seleccionados. La experiencia presentada muestra resultados similares a los de otros centros de referencia internacional.

Abstract Genetic studies have identified the voltage‐gated sodium channel 1.7 (Nav1.7) as pain target. Due to the ineffectiveness of small molecules and monoclonal antibodies as therapeutics for pain, single‐domain antibodies (VHHs) are developed against the human Nav1.7 (hNav1.7) using a novel antigen presentation strategy. A 70 amino‐acid peptide from the hNav1.7 protein is identified as a target antigen. A recombinant version of this peptide is grafted into the complementarity determining region 3 (CDR3) loop of an inert VHH in order to maintain the native 3D conformation of the peptide. This antigen is used to isolate one VHH able to i) bind hNav1.7, ii) slow the deactivation of hNav1.7, iii) reduce the ability of eliciting action potentials in nociceptors, and iv) reverse hyperalgesia in in vivo rat and mouse models. This VHH exhibits the potential to be developed as a therapeutic capable of suppressing pain. This novel antigen presentation strategy can be applied to develop biologics against other difficult targets such as ion channels, transporters and GPCRs.

Summary: Background: We studied the poorly-known dynamics of circulating DNA (cir-nDNA), as monitored prospectively over an extended post-surgery period, in patients with cancer. Methods: On patients with stage III colon cancer (N = 120), using personalised molecular tags we carried out the prospective, multicenter, blinded cohort study of the post-surgery serial analysis of cir-nDNA concentration. 74 patients were included and 357 plasma samples tested. Findings: During post-operative follow-up, the patients’ median cir-nDNA concentration was greater (P 18 months post-surgery, the data suggest that the persistence of NETs formation is not due to the adjuvant CT. Interpretation: (1), Given the inter-patient heterogeneity, the post-surgery cir-nDNA level cannot be considered a reliable value, and caution must be exercised when determining mutation allele frequency or the mutation status; and (2), specific studies must be undertaken to investigate the possible clinical impact of the persistent, low-grade inflammation resulting from elevated NETs levels, such as observed in these post-surgery patients, given that such levels are known to potentially induce adverse cardiovascular or thrombotic events. Funding: This work was supported by the H2020 European ERA-NET grant on Translational Cancer Research (TRANSCAN-2).