[Home CPAP Remote Monitoring as a System to Control Adaptation and Titration in Obstructive Sleep Apnoea and its Impact on the Management of this Pathology (T-CPAP Project)]. / Impacto de la telemonitorización como sistema para una adecuada titulación y adaptación de la CPAP domiciliaria en la apnea obstructiva del sueño (proyecto T-CPAP).

Introduction: Continuous Positive Airway Pressure (CPAP) constitutes the most effective treatment for Obstructive Sleep Apnea (OSA). Automatic titration systems (ATS) are predominantly used to achieve adaptation to the equipment. Home CPAP devices allow telemonitoring (TM) of the same parameters as those provided by ATS but with access to continuous usage data. Under this premise, we conducted a study on the potential validity of TM for home CPAP devices as a titration system, its direct impact on proper adaptation (AD) to the equipment, and secondarily on the healthcare resources employed to achieve it. Material and methods: An observational study involving 318 patients with OSA who were titrated using TM to achieve AD to CPAP. Patients with OSA were consecutively recruited and evaluated at 1, 3, and 6 months after initiating treatment. Results were compared with a historical group of 307 patients with OSA who achieved AD to CPAP using ATS. Additionally, we assessed the impact on required healthcare resources. Results: Patients with OSA who initiated CPAP treatment with TM over the first six months showed a similar AD rate compared to the historical group titrated using ATS, with lower resource usage in the TM group. Conclusion: Data provided by TM of home CPAP devices allow for titration and achieving similar AD as with ATS in non-complex patients.

Sample multiplexing for retinal single-cell RNA-sequencing.

Rare cell populations can be challenging to characterize using microfluidic single-cell RNA sequencing (scRNA-seq) platforms. Typically, the population of interest must be enriched and pooled from multiple biological specimens for efficient collection. However, these practices preclude the resolution of sample origin together with phenotypic data and are problematic in experiments in which biological or technical variation is expected to be high (e.g., disease models, genetic perturbation screens, or human samples). One solution is sample multiplexing whereby each sample is tagged with a unique sequence barcode that is resolved bioinformatically. We have established a scRNA-seq sample multiplexing pipeline for mouse retinal ganglion cells using cholesterol-modified-oligos and utilized the enhanced precision to investigate cell type distribution and transcriptomic variance across retinal samples. As single cell transcriptomics are becoming more widely used to research development and disease, sample multiplexing represents a useful method to enhance the precision of scRNA-seq analysis.

[Home Respiratory Therapies: SEPAR Technical Document for Institutional Decision Support]. / Terapias respiratorias domiciliarias: documento técnico de la Sociedad Española de Neumología y Cirugía Torácica (SEPAR) de apoyo institucional a la toma de decisiones.

Home Respiratory Therapies (HRT) encompass a variety of treatments for patients with chronic respiratory diseases, administered at home over extended periods. The Service Providers of HRT (SPHRT) collaborate with hospital resources to address chronic respiratory diseases, acting as strategic partners. The contracting of HRT in the public health system involves contests where the SPHRT present technical and economic offers. The purpose of this document is to provide a technical basis that can assist professionals, SPHRT, and the administration in making decisions when calling for, evaluating, and deciding on such contests.

Navigating the landscape of RNA delivery systems in cardiovascular disease therapeutics.

Cardiovascular diseases (CVDs) stand as the leading cause of death worldwide, posing a significant global health challenge. Consequently, the development of innovative therapeutic strategies to enhance CVDs treatment is imperative. RNA-based therapies, encompassing non-coding RNAs, mRNA, aptamers, and CRISPR/Cas9 technology, have emerged as promising tools for addressing CVDs. However, inherent challenges associated with RNA, such as poor cellular uptake, susceptibility to RNase degradation, and capture by the reticuloendothelial system, underscore the necessity of combining these therapies with effective drug delivery systems. Various non-viral delivery systems, including extracellular vesicles, lipid-based carriers, polymeric and inorganic nanoparticles, as well as hydrogels, have shown promise in enhancing the efficacy of RNA therapeutics. In this review, we offer an overview of the most relevant RNA-based therapeutic strategies explored for addressing CVDs and emphasize the pivotal role of delivery systems in augmenting their effectiveness. Additionally, we discuss the current status of these therapies and the challenges that hinder their clinical translation.

Cytotoxicity and concentration of silver ions released from dressings in the treatment of infected wounds: a systematic review.

Introduction: Silver-releasing dressings are used in the treatment of infected wounds. Despite their widespread use, neither the amount of silver released nor the potential in vivo toxicity is known. The aim of this study was to evaluate the cytotoxic effects and the amount of silver released from commercially available dressings with infected wounds. Methods: The review was conducted according to the PRISMA statement. The Web of Science, PubMed, Embase, Scopus, and CINAHL databases were searched for studies from 2002 through December 2022. The criteria were as follows: population (human patients with infected wounds); intervention (commercial dressings with clinical silver authorized for use in humans); and outcomes (concentrations of silver ions released into tissues and plasma). Any study based on silver-free dressings, experimental dressings, or dressings not for clinical use in humans should be excluded. According to the type of study, systematic reviews, experimental, quasi-experimental, and observational studies in English, Spanish, or Portuguese were considered. The quality of the selected studies was assessed using the JBI critical appraisal tools. Studies that assessed at least 65% of the included items were included. Data were extracted independently by two reviewers. Results: 740 articles were found and five were finally selected (all of them quasi-experimental). Heterogeneity was found in terms of study design, application of silver dressings, and methods of assessment, which limited the comparability between studies. Conclusion: In vivo comparative studies of clinical dressings for control of infection lack a standardized methodology that allows observation of all the variables of silver performance at local and systemic levels, as well as evaluation of its cytotoxicity. It cannot be concluded whether the assessed concentrations of released silver in commercial dressings for the topical treatment of infected wounds are cytotoxic to skin cells. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351041, PROSPERO [CRD42022351041].

Gypsum lichens: A global data set of lichen species from gypsum ecosystems.

Lichens are significant components of the biological soil crust communities in gypsum ecosystems and are involved in several processes related to ecosystem functioning, such as water and nutrient cycles or protection against soil erosion. Although numerous studies centered on lichen taxonomy and ecology have been performed in these habitats, global information about lichen species from gypsum substrates or their distributional ranges at a global scale is lacking. Thus, we compiled a global data set of recorded lichen species growing on gypsum. This review is based on systematic searches in two bibliographic databases (Web of Science and the more specialized database Mattick's Literature Index) using various keywords related to the substrate or ecology (i.e., gypsum, gypsiferous, semiarid, saxicolous, terricolous). In addition, we revised lichen literature from countries with gypsum soils using Mattick's, Hamburg University's Worldwide checklist, and different national lichen checklists. Ultimately the review includes a total of 321 studies. This data set included 6114 specimen records belonging to 336 recorded lichen species from 26 countries throughout the world. The results showed large differences in the number of species recorded among countries, reflecting differences in the sampling effort. We provide a table with the number of studies and species in relation to gypsum surface in order to account for the bias produced by sampling effort. The number of studies carried out per country was not related to the gypsum surface but probably to other factors, such as accessibility to field sampling, economic or political factors, or the presence of a wider community of lichenologists. Thus, Spain and Germany hosted the highest number of recorded species (160 and 114 species, respectively). Outside the European continent, only a few countries had a large number of species: Morocco (46), United States (42), and Iran (37). Remarkably, countries from the southern hemisphere (i.e., Australia, Chile, Namibia, and South Africa) showed a low number of studies from gypsum lands, supporting the stated biases observed in sampling efforts among countries. Considering the most studied countries, the results show that Teloschistaceae was the most represented family in gypsum ecosystems followed by Verrucariaceae and Cladoniaceae. Regarding particular species, Psora decipiens and Squamarina lentigera were some of the most widespread and abundant species in these habitats. This data set constitutes a basic and first step toward a much more comprehensive database, to be periodically updated in future releases, which also serves to identify countries or territories where future studies should be accomplished. There are no copyright restrictions on the data; please cite this data paper if the data are used in publications and teaching events.

Biosafety evaluation of etoposide lipid nanomedicines in C. elegans.

Neuroblastoma is a pediatric tumor that originates during embryonic development and progresses into aggressive tumors, primarily affecting children under two years old. Many patients are diagnosed as high-risk and undergo chemotherapy, often leading to short- and long-term toxicities. Nanomedicine offers a promising solution to enhance drug efficacy and improve physical properties. In this study, lipid-based nanomedicines were developed with an average size of 140 nm, achieving a high encapsulation efficiency of over 90% for the anticancer drug etoposide. Then, cytotoxicity and apoptosis-inducing effects of these etoposide nanomedicines were assessed in vitro using human cell lines, both cancerous and non-cancerous. The results demonstrated that etoposide nanomedicines exhibited high toxicity and selectively induced apoptosis only in cancerous cells.Next, the biosafety of these nanomedicines in C. elegans, a model organism, was evaluated by measuring survival, body size, and the effect on dividing cells. The findings showed that the nanomedicines had a safer profile than the free etoposide in this model. Notably, nanomedicines exerted etoposide's antiproliferative effect only in highly proliferative germline cells. Therefore, the developed nanomedicines hold promise as safe drug delivery systems for etoposide, potentially leading to an improved therapeutic index for neuroblastoma treatment.

Chronic Obstructive Lung Disease: Treatment Guidelines and Recommendations for Referral and Multidisciplinary Continuity of Care.

Chronic Obstructive Pulmonary Disease (COPD) constitutes a major public health problem, and it is anticipated that its prevalence will continue to increase in the future. Its progressive nature requires a continuous and well-coordinated care approach. The follow-up for COPD should primarily focus on disease screening and control, which includes monitoring of pulmonary function, prevention of exacerbations, identification of aggravating factors and comorbidities, as well as ensuring treatment adequacy and adherence. However, existing clinical practice guidelines and consensus documents offer limited recommendations for the follow-up. In this context, we undertake a review of COPD treatment and the continuity of care recommendations endorsed by several scientific societies. Moreover, we underscore the importance of the involvement of nursing and community pharmacy in this process, as well as the utilization of quality indicators in the provision of care for the disease.

Implementación de un programa para mitigar la resistencia a los antimicrobianos en escenarios de bajos recursos / Implementation of a program to face antimicrobial resistance on a low resources hospital

Estudio cuasi-experimental desarrollado para disminuir el impacto de la resistencia a los antimicrobianos a través de un programa de prevención de infecciones y optimización del uso de antimicrobianos construido "a medida" según las posibilidades de la institución. Se implementó: vigilan-cia de colonización e infección por enterobacterias pro-ductoras de carbapenemasas (EPC); vigilancia y medidas preventivas para infecciones urinarias asociadas a sonda vesical (ITU); vigilancia e intervenciones para mejorar la higiene de manos; guías locales de tratamiento de enfer-medades infecciosas con evaluación de adherencia a las mismas y consumo de antibióticos (ATB). Resultados: Comparando periodo pre y postintervención: tasa de EPC en muestras clínicas: 1,1 a 0/días paciente; razón de tasas de incidencia (IRR: 0.00, p: 0.033); tasa de colonización: 3,3 a 0,61/días paciente (IRR: 0.18, p: 0.5). Tasa de ITU 8,9 a 7,2/1000 días catéter urinario (IRR: 0.81, p 0.5). Adherencia a higiene de manos: 77,5% a 70,38% (p 0.0067). Consumo de ATB: 376,24 a 176,82 DDD, (disminu-ción 53%). Adherencia a guías en elección de ATB: 57,1% a 95,4% (p 0.00031); duración de ATB: 92,8% a 98,4% (p 0.16); adecuación según rescate microbiológico: 57,1% a 100% (p <0.01). Conclusión: Un programa con medidas simples, a medida, con supervisión externa, redujo en un tiempo relativamente corto las infecciones por EPC, el consumo y uso apropiado de ATB en un hospital público de medianos/bajos recursos

This quasi-experimental study was developed in a public hospital with the goal of reducing the impact of antimicrobial resistance through an infection prevention and antimicrobial stewardship program. The following measures were implemented: surveillance of colonization and infection by carbapenemase-producing Enterobacteriaceae (CPE); surveillance and preventive measures for urinary catheter-associated infections (UTIs); surveillance and interventions for hand hygiene; local guidelines for treatment of infectious diseases with compliance and antibiotic (ATB) consumption metrics.Results: comparing the pre-intervention and post-intervention period, CPE rate in clinical samples 1.1 to 0/patient days, incidence rate ratio (IRR): 0.00, p: 0.033 and colonization of 3.3 to 0.61/days patient, IRR: 0.18, p-value: 0.5. UTI rate 8.9 to 7.2/1000 days urinary catheter IRR: 0.81, p 0.5. Hand Hygiene compliance: 77.5% to 70.38%, p 0.0067. ATB consumption: 376.24 to 176.82 DDD, 53% decrease. Compliance to guidelines in ATB selection: 57.1% to 95.4% p 0.00031, duration of ATB from 92.8% to 98.4% p 0.16, and adequacy to microbiological rescue of 57.1% at 100%, p <0.01. Conclusion: it is possible to reduce CPE infections, the consumption of antimicrobials and optimize their use in a public hospital in a country with medium/low resources through a program with basic and tailored measures

Leucine Supplementation Improves Diastolic Function in HFpEF by HDAC4 Inhibition.

Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome associated with a high morbidity and mortality rate. Leucine supplementation has been demonstrated to attenuate cardiac dysfunction in animal models of cachexia and heart failure with reduced ejection fraction (HFrEF). So far, no data exist on leucine supplementation on cardiac function in HFpEF. Thus, the current study aimed to investigate the effect of leucine supplementation on myocardial function and key signaling pathways in an established HFpEF rat model. Female ZSF1 rats were randomized into three groups: Control (untreated lean rats), HFpEF (untreated obese rats), and HFpEF_Leu (obese rats receiving standard chow enriched with 3% leucine). Leucine supplementation started at 20 weeks of age after an established HFpEF was confirmed in obese rats. In all animals, cardiac function was assessed by echocardiography at baseline and throughout the experiment. At the age of 32 weeks, hemodynamics were measured invasively, and myocardial tissue was collected for assessment of mitochondrial function and for histological and molecular analyses. Leucine had already improved diastolic function after 4 weeks of treatment. This was accompanied by improved hemodynamics and reduced stiffness, as well as by reduced left ventricular fibrosis and hypertrophy. Cardiac mitochondrial respiratory function was improved by leucine without alteration of the cardiac mitochondrial content. Lastly, leucine supplementation suppressed the expression and nuclear localization of HDAC4 and was associated with Protein kinase A activation. Our data show that leucine supplementation improves diastolic function and decreases remodeling processes in a rat model of HFpEF. Beneficial effects were associated with HDAC4/TGF-ß1/Collagenase downregulation and indicate a potential use in the treatment of HFpEF.

A specific gut microbiota signature is associated with an enhanced GLP-1 and GLP-2 secretion and improved metabolic control in patients with type 2 diabetes after metabolic Roux-en-Y gastric bypass.

Objective: To determine changes in incretins, systemic inflammation, intestinal permeability and microbiome modifications 12 months after metabolic RYGB (mRYGB) in patients with type 2 diabetes (T2D) and their relationship with metabolic improvement. Materials and methods: Prospective single-center non-randomized controlled study, including patients with class II-III obesity and T2D undergoing mRYGB. At baseline and one year after surgery we performed body composition measurements, biochemical analysis, a meal tolerance test (MTT) and lipid test (LT) with determination of the area under the curve (AUC) for insulin, C-peptide, GLP-1, GLP-2, and fasting determinations of succinate, zonulin, IL-6 and study of gut microbiota. Results: Thirteen patients aged 52.6 ± 6.5 years, BMI 39.3 ± 1.4 kg/m2, HbA1c 7.62 ± 1.5% were evaluated. After mRYGB, zonulin decreased and an increase in AUC after MTT was observed for GLP-1 (pre 9371 ± 5973 vs post 15788 ± 8021 pM, P<0.05), GLP-2 (pre 732 ± 182 vs post 1190 ± 447 ng/ml, P<0.001) and C- peptide, as well as after LT. Species belonging to Streptococaceae, Akkermansiacea, Rickenellaceae, Sutterellaceae, Enterobacteriaceae, Oscillospiraceae, Veillonellaceae, Enterobacterales_uc, and Fusobacteriaceae families increased after intervention and correlated positively with AUC of GLP-1 and GLP-2, and negatively with glucose, HbA1c, triglycerides and adiposity markers. Clostridium perfringens and Roseburia sp. 40_7 behaved similarly. In contrast, some species belonging to Lachnospiraceae, Erysipelotricaceae, and Rumnicocaceae families decreased and showed opposite correlations. Higher initial C-peptide was the only predictor for T2D remission, which was achieved in 69% of patients. Conclusions: Patients with obesity and T2D submitted to mRYGB show an enhanced incretin response, a reduced gut permeability and a metabolic improvement, associated with a specific microbiota signature.

Microbiological diagnosis of pulmonary invasive aspergillosis in critically ill patients with severe SARS-CoV-2 pneumonia: a bronchoalveolar study.

BACKGROUND: Diagnosing COVID-19-associated pulmonary aspergillosis (CAPA) can be challenging since radiological and clinical criteria in the critically ill patient are nonspecific. Microbiological diagnostic support is therefore crucial. The aim of this study was to document the incidence of aspergillosis using bronchoalveolar lavage (BAL) as the diagnostic method and to determine the performance of the current mycological diagnostic tests most widely used for the diagnosis of CAPA, together with evaluation of the Asp lateral flow device (LFD). METHODS: Prospective cohort study conducted between March 2020 and June 2022. Inclusion criteria were critically ill patients admitted to the ICU with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation. Diagnostic bronchoscopy and BAL were performed at the beginning of invasive mechanical ventilation. The sensitivity, specificity, positive and negative predictive value (PPV and NPV), positive and negative likelihood ratio (LR + and LR-) of BAL culture, direct examination with calcofluor white stain, ELISA (Platelia) and LFD (AspLFD) for detection of galactomannan (GM) were evaluated. Aspergillus-qPCR was applied when discrepancies between diagnostic tests arose. RESULTS: Of the 244 critically ill patients with SARS-CoV-2 pneumonia admitted to the ICU, the majority (n = 200, 82%) required invasive mechanical ventilation. Diagnostic bronchoscopic procedures were performed in 160 patients (80%), who were enrolled in this study. The incidence of CAPA was 18.7% (n = 30). LFD-GM demonstrated a sensitivity of 84%, specificity of 99%, PPV 94%, NPV 97%, LR(+) of 84, and LR(-) of 0.16. At GM-ELISA indices of ≥ 0.5 and ≥ 1.0, sensitivity was 92% and 79%, specificity was 95% and 99%, PPV 76% and 91%, NPV 99% and 96%, LR(+) 18 and 79, and LR(-) 0.08 and 0.21, respectively. The optimal cut-off index from the ROC curve was 0.48, with sensitivity of 95% and specificity of 95%. CONCLUSIONS: Using a diagnostic strategy based on bronchoscopy and BAL, we documented a high incidence of pulmonary aspergillosis in patients with severe SARS-CoV-2 pneumonia. Asp-LFD showed moderate sensitivity and excellent specificity, with a high PPV, and could be used for rapid diagnosis of patients with suspected CAPA.

Risk Factors for Salmonella Detection in Commercial Layer Flocks in Spain.

Trends in Salmonella human infections are assumed to be related to the distribution of the pathogen in the animal reservoir/food products, and cases in humans are most often linked to poultry and poultry products (eggs, meat). Therefore, ongoing Salmonella national control programs (NCPs) in European Union Member States have the objective of monitoring and reducing its prevalence in commercial poultry flocks. Results from NCPs have shown certain factors (housing systems, season of sampling and if sampling is conducted by food business operators (FBOps) or competent authorities (CAs), among others) can influence detection rates, but associations are often not consistent. Here, we analyzed data from the Spanish NCP on 7216 laying hen flocks subjected to 36,193 sampling events over a six-year period to characterize its performance and identify variables influencing detection rates. Overall, 1205 sampling events were positive for Salmonella spp. (any serovar) and 132 for S. Enteritidis-S. Typhimurium/monophasic. Bayesian multivariable models adjusting for multiple covariates concluded that sampling events later in the year, in caged flocks with older animals and conducted by CAs had increased odds of positivity for Salmonella spp., revealing aspects linked with a differential estimation of Salmonella levels in laying hen flocks.

Prevalence, Knowledge and Perceptions of Smoking and Tobacco Products and Vape Among SEPAR Members.

Introduction: The professional dedicated to respiratory health has an exemplary role in tobacco control, promoting smoking cessation in their patients. However, multiple circumstances cause a low implementation. Therefore, the objective of the study is to identify the consumption, knowledge and perception of tobacco and its emerging products in a representative sample of professionals involved in the treatment of respiratory patients integrated into the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). Methods: Descriptive analysis of a structured online interview addressed to 5340 SEPAR members. Results: In a sample of 802 respondents, more than 33% have smoked at some time and 6.6% continue to smoke. More than 66% consider smoking as a chronic disease. More than 90% consider their role model important and advise their patients to quit smoking, but less than half carry out a smoking intervention. Only 35% of them believe that the ban on smoking in health centers is always complied. More than 75% do not consider nicotine delivery devices an option for smoking cessation or harm reduction. 22% are unaware of water pipes and 29% of heated tobacco. Conclusions: Professionals specialized in respiratory diseases are highly sensitized to smoking. Despite this, there are still weak points such as the insufficient implementation of smoking cessation interventions or the scant training in smoking and in new emerging products.

Introducción: El profesional dedicado a la salud respiratoria tiene un papel ejemplar en el control del tabaquismo, promoviendo el abandono del hábito tabáquico en sus pacientes. Sin embargo, múltiples circunstancias provocan una baja implementación. Por tanto, el objetivo del estudio es identificar el consumo, el conocimiento y la percepción sobre el tabaco y sus productos emergentes en una muestra representativa de profesionales implicados en el tratamiento de pacientes respiratorios integrados en la Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Métodos: Análisis descriptivo de una entrevista estructurada en línea dirigida a 5.340 miembros de la SEPAR. Resultados: En una muestra de 802 encuestados, más del 33% ha fumado alguna vez y el 6.6% sigue fumando. Más del 66% considera el tabaquismo como una enfermedad crónica. Más del 90% considera importante su modelo a seguir y aconseja a sus pacientes que dejen de fumar, pero menos de la mitad realiza una intervención para dejar de fumar. Solo el 35% de ellos cree que la prohibición de fumar en los centros de salud se cumple siempre. Más del 75% no considera que los dispositivos de suministro de nicotina sean una opción para dejar de fumar o reducir los daños. El 22% desconoce las pipas de agua y el 29% el tabaco calentado. Conclusiones: Los profesionales especialistas en enfermedades respiratorias están altamente sensibilizados al tabaquismo. A pesar de ello, aún existen puntos débiles como la insuficiente implantación de intervenciones para dejar de fumar o la escasa formación en tabaquismo y en nuevos productos emergentes.

Cyanobacterial Variability in Lichen Cephalodia.

The ecological success of lichens is related to both myco- and photobionts which condition the physiological limits of the lichen symbioses and thus affect their ecological niches and geographic ranges. A particular type of lichen, called cephalolichen, is characterized by housing both green algal and cyanobacterial symbionts-the latter is restricted to special structures called cephalodia. In this type of lichen, questions related to specialization within species or within individuals are still unsolved as different patterns have previously been observed. In order to study the variability at the intrathalline, intraspecific, and interspecific level, cyanobionts from different cephalodia within the same thalli and from different thalli were genetically analysed in three cephalolichen species at two different forests (18 thalli, 90 cephalodia). The results showed variability in the cephalodial Nostoc OTUs in all the studied species, both at the intrathalline and intraspecific levels. The variability of Nostoc OTUs found in different cephalodia of the same thallus suggests low specialization in this relationship. Additionally, differences in OTU diversity in the three studied species and in the two forests were found. The variability observed may confer an increased ecological plasticity and an advantage to colonize or persist under additional or novel habitats or conditions.

Lipid nanoparticles for siRNA delivery in cancer treatment.

RNA-based therapies, and siRNAs in particular, have attractive therapeutic potential for cancer treatment due to their ability to silence genes that are imperative for tumor progression. To be effective and solve issues related to their poor half-life and poor pharmacokinetic properties, siRNAs require adequate drug delivery systems that protect them from degradation and allow intracellular delivery. Among the various delivery vehicles available, lipid nanoparticles have emerged as the leading choice. These nanoparticles consist of cholesterol, phospholipids, PEG-lipids and most importantly ionizable cationic lipids. These ionizable lipids enable the binding of negatively charged siRNA, resulting in the formation of stable and neutral lipid nanoparticles with exceptionally high encapsulation efficiency. Lipid nanoparticles have demonstrated their effectiveness and versatility in delivering not only siRNAs but also multiple RNA molecules, contributing to their remarkable success. Furthermore, the advancement of efficient manufacturing techniques such as microfluidics, enables the rapid mixing of two miscible solvents without the need for shear forces. This facilitates the reproducible production of lipid nanoparticles and holds enormous potential for scalability. This is shown by the increasing number of preclinical and clinical trials evaluating the potential use of siRNA-LNPs for the treatment of solid and hematological tumors as well as in cancer immunotherapy. In this review, we provide an overview of the progress made on siRNA-LNP development for cancer treatment and outline the current preclinical and clinical landscape in this area. Finally, the translational challenges required to bring siRNA-LNPs further into the clinic are also discussed.

Specialization patterns in symbiotic associations: A community perspective over spatial scales.

Specialization, contextualized in a resource axis of an organism niche, is a core concept in ecology. In biotic interactions, specialization can be determined by the range of interacting partners. Evolutionary and ecological factors, in combination with the surveyed scale (spatial, temporal, biological, and/or taxonomic), influence the conception of specialization. This study aimed to assess the specialization patterns and drivers in the lichen symbiosis, considering the interaction between the principal fungus (mycobiont) and the associated Nostoc (cyanobiont), from a community perspective considering different spatial scales. Thus, we determined Nostoc phylogroup richness and composition of lichen communities in 11 Nothofagus pumilio forests across a wide latitudinal gradient in Chile. To measure specialization, cyanobiont richness, Simpson's and d' indices were estimated for 37 mycobiont species in these communities. Potential drivers that might shape Nostoc composition and specialization measures along the environmental gradient were analysed. Limitations in lichen distributional ranges due to the availability of their cyanobionts were studied. Turnover patterns of cyanobionts were identified at multiple spatial scales. The results showed that environmental factors shaped the Nostoc composition of these communities, thus limiting cyanobiont availability to establish the symbiotic association. Besides, specialization changed with the spatial scale and with the metric considered. Cyanolichens were more specialized than cephalolichens when considering partner richness and Simpson's index, whereas the d' index was mostly explained by mycobiont identity. Little evidence of lichen distributional ranges due to the distribution of their cyanobionts was found. Thus, lichens with broad distributional ranges either associated with several cyanobionts or with widely distributed cyanobionts. Comparisons between local and regional scales showed a decreasing degree of specialization at larger scales due to an increase in cyanobiont richness. The results support the context dependency of specialization and how its consideration changes with the metric and the spatial scale considered. Subsequently, we suggest considering the entire community and widening the spatial scale studied as it is crucial to understand factors determining specialization.