Using agro-ecological zones to improve the representation of a multi-environment trial of soybean varieties.

This research introduces a novel framework for enhancing soybean cultivation in North America by categorizing growing environments into distinct ecological and maturity-based zones. Using an integrated analysis of long-term climatic data and records of soybean varietal trials, this research generates a zonal environmental characterization which captures major components of the growing environment which affect the range of adaptation of soybean varieties. These findings have immediate applications for optimizing multi-environment soybean trials. This characterization allows breeders to assess the environmental representation of a multi-environmental trial of soybean varieties, and to strategize the distribution of testing and the placement of test sites accordingly. This application is demonstrated with a historical scenario of a soybean multi-environment trial, using two resource allocation models: one targeted towards improving the general adaptation of soybean varieties, which focuses on widely cultivated areas, and one targeted towards specific adaptation, which captures diverse environmental conditions. Ultimately, the study aims to improve the efficiency and impact of soybean breeding programs, leading to the development of cultivars resilient to variable and changing climates.

'It's like being in a tunnel': Understanding the patient journey from tooth loss to life with removable dentures.

INTRODUCTION: The aim of this study was to conceptualise the key stages of the patient journey in the provision of a new denture and examine the factors leading to successful patient-related outcomes. METHODS: Two partially dentate patient samples were included: (i) Denture wearers - patients who had a denture fitted within the previous five years and (ii) New dentures - patients receiving treatment for a new or replacement denture. The methods involved direct targeted participant observations of the denture fitting process, debriefing interviews and a follow-up focus group exploring the patient journey. Data were analysed through the use of phenomenology and grounded theory. RESULTS: Interviews were completed with twenty participants of the denture-wearing sample (11 males and nine females, age range 22 to 86 years). Thirteen participants were included in the treatment journey sample in two primary care settings (six males and seven females, age range 55 to 101 years). Tooth loss and recovery was described as being in an 'emotional tunnel' resulting from 'bodyphonic processes' associated with tooth loss. 'Bodyphonia' subsequently became the context for 'taking control' and 'managing disclosure' when living with a removable denture. Different courses through this process can be readily observed, moderated by different variables (i.e., previous experience, working knowledge, a good fit, the treatment alliance, negotiated compromises and bounded responsibility). CONCLUSIONS: An'integrating framework' that seeks to describe the patient journey from the experience of tooth loss to recovery with a denture is proposed. This framework could be used to aid development of a clinical pathway to guide treatment options. CLINICAL SIGNIFICANCE: This paper conceptualises the patient journey. It stresses the importance of understanding the stages patients go through and highlights that for the dental team, the try-in stage is perhaps the best stage to give information about the denture and plans for continued care.

Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study.

BACKGROUND: Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar. METHODS: The phase 2, double-blind, randomised, placebo-controlled MERIT-1 trial assessed macitentan in 80 patients with CTEPH adjudicated as inoperable. Patients identified as WHO functional class II-IV with a pulmonary vascular resistance (PVR) of at least 400 dyn·s/cm5 and a walk distance of 150-450 m in 6 min were randomly assigned (1:1), via an interactive voice/web response system, to receive oral macitentan (10 mg once a day) or placebo. Treatment with phosphodiesterase type-5 inhibitors and oral or inhaled prostanoids was permitted for WHO functional class III/IV patients. The primary endpoint was resting PVR at week 16, expressed as percentage of PVR measured at baseline. Analyses were done in all patients who were randomly assigned to treatment; safety analyses were done in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02021292. FINDINGS: Between April 3, 2014, and March 17, 2016, we screened 186 patients for eligibility at 48 hospitals across 20 countries. Of these, 80 patients in 36 hospitals were randomly assigned to treatment (40 patients to macitentan, 40 patients to placebo). At week 16, geometric mean PVR decreased to 71·5% of baseline in the macitentan group and to 87·6% in the placebo group (geometric means ratio 0·81, 95% CI 0·70-0·95, p=0·0098). The most common adverse events in the macitentan group were peripheral oedema (9 [23%] of 40 patients) and decreased haemoglobin (6 [15%]). INTERPRETATION: In MERIT-1, macitentan significantly improved PVR in patients with inoperable CTEPH and was well tolerated. FUNDING: Actelion Pharmaceuticals Ltd.

Environmental sustainability: the attitudes and experiences of UK students in the oral health care profession.

Objective This study aims to provide insight into the attitudes and perspectives of undergraduate dental students from UK dental schools regarding environmental sustainability in dentistry (ESD) and the manner and extent in which ESD is included in the current undergraduate oral health care curricula.Methods This study is a multi-centre, nationally representive study involving a cross-sectional online survey of undergraduate Bachelor of Dental Surgery and dental hygiene and therapy students in UK-based dental schools. Data analysis was conducted through descriptive statistics and thematic analysis.Results In total, 263 students from 13 UK schools completed the survey, resulting in a national school response rate of 68.4%. Key findings are: 97.3% of students believe that the dental profession should be more actively engaged in environmental sustainability but students currently have very little exposure to ESD at an undergraduate level; and 76.8% of students expressed that they are concerned about the impact that oral health care provision has on the environment, but only 23% of students have independently researched ESD.Conclusions Students identify that oral health care professionals should become more engaged in efforts to mitigate the negative impacts from our activities on the environment, principally via education at all levels. The data from this study provide insight into the current level of awareness and concerns for the environmental impacts of oral health care provision, and are a powerful driver for the inclusion of ESD into the undergraduate curriculum in UK based dental schools.

Prognostic Value of a New Right Ventricular-to-Pulmonary Artery Coupling Parameter Using Right Ventricular Longitudinal Shortening Fraction in Patients Undergoing Transcatheter Aortic Valve Replacement: A Prospective Echocardiography Study.

Introduction: Right-ventricular-to-pulmonary artery (RV-PA) coupling, measured as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP), has emerged as a predictor factor in patients undergoing transcatheter aortic valvular replacement (TAVR). Right ventricular longitudinal shortening fraction (RV-LSF) outperformed TAPSE as a prognostic parameter in several diseases. We aimed to compare the prognostic ability of two RV-PA coupling parameters (TAPSE/PASP and the RV-LSF/PASP ratio) in identifying MACE occurrences. Method: A prospective and single-center study involving 197 patients who underwent TAVR was conducted. MACE (heart failure, myocardial infarction, stroke, and death within six months) constituted the primary outcome. ROC curve analysis determined cutoff values for RV-PA ratios. Multivariable Cox regression analysis explored the association between RV-PA ratios and MACE. Results: Forty-six patients (23%) experienced the primary outcome. No significant difference in ROC curve analysis was found (RV-LSF/PASP with AUC = 0.67, 95%CI = [0.58-0.77] vs. TAPSE/PASP with AUC = 0.62, 95%CI = [0.49-0.69]; p = 0.16). RV-LSF/PASP < 0.30%.mmHg-1 was independently associated with the primary outcome. The 6-month cumulative risk of MACE was 59% (95%CI = [38-74]) for patients with RV-LSF/PASP < 0.30%.mmHg-1 and 17% (95%CI = [12-23]) for those with RV-LSF/PASP ≥ 0.30%.mmHg-1; (p < 0.0001). Conclusions: In a contemporary cohort of patients undergoing TAVR, RV-PA uncoupling defined by an RV-LSF/PASP < 0.30%.mmHg-1 was associated with MACE at 6 months.

The environmental consequences of oral healthcare provision by the dental team.

OBJECTIVES: To undertake a comparative ecological impact (Total lifetime carbon footprint and single use plastics (SUP) waste generation) derived from the provision of professional oral healthcare (Dentists and hygienist) to five different patient categories up to the age of 50 years, representative of different levels of progressive dental disease and treatment experience. METHOD: CO2e and SUP waste generated was calculated for five patient categories with common preventable diseases; that are representative of different levels of progressive dental disease and treatment experience. The assessment is based on the average restorative care levels for 50-year-olds in the UK. The number of appointments for each procedure was calculated using current evidence-based guidelines. The total lifetime carbon and the SUP waste analysis was calculated using published peer-reviewed data. RESULTS: The total carbon footprint follows a progression with low impacts for individual persons with very low disease and treatment experience (285 KgCO2e), escalating to very high impacts (approximately 2,170 KgCO2e) for people with high levels of disease and treatment experience. SUP waste follows a similar linear rise across the different cohorts of dental experience over a lifetime (6-50 years), from 1,382 items and 4.6 Kg for patients in a the very low dental experience, to 12,200 items and 33.8 Kg for patients in the cohort of very high dental experience. CONCLUSIONS: The provision of all oral healthcare carries an environmental impact in the form of carbon footprint and SUP waste. The cumulative lifetime environmental impact of oral healthcare is proportional to the disease and treatment experience of the individual person for these preventable diseases; with a x8 difference between the two extremes of experience. CLINICAL SIGNIFICANCE: All forms of oral healthcare have an environmental impact. The most effective way to mitigate these impacts is through the promotion and provision of effective evidence-based preventive oral healthcare.

Effect of Macitentan in Pulmonary Arterial Hypertension and the Relationship Between Echocardiography and cMRI Variables: REPAIR Echocardiography Sub-study Results.

INTRODUCTION: The aim of this sub-study was to evaluate the relationship between echocardiography (echo) and cardiac magnetic resonance imaging (cMRI) variables and to utilize echo to assess the effect of macitentan on right ventricle (RV) structure and function. METHODS: REPAIR (NCT02310672) was a prospective, multicenter, single-arm, open-label, 52-week, phase 4 study in pulmonary arterial hypertension (PAH) patients, which investigated the effect of macitentan 10 mg as monotherapy, or in combination with a phosphodiesterase 5 inhibitor, on RV structure, function, and hemodynamics using cMRI and right heart catheterization. In this sub-study, patients were also assessed by echo at screening and at weeks 26 and/or 52. Post hoc correlation analyses between echo and cMRI variables were performed using Pearson's correlation coefficient, Spearman's correlation coefficient, and Bland-Altman analyses. RESULTS: The Echo sub-study included 45 patients. Improvements in echo-assessed RV stroke volume (RVSV), left ventricular SV (LVSV), LV end-diastolic volume (LVEDV), RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), and in 2D global longitudinal RV strain (2D GLRVS) were observed at weeks 26 and 52 compared to baseline. There was a strong correlation between echo (LVSV, 2D GLRVS, and LVEDV) and cMRI variables, with a moderate correlation for RVSV. Bland-Altman analyses showed a good agreement for LVSV measured by echo versus cMRI, whereas an overestimation in echo-assessed RVSV was observed compared to cMRI (bias of - 15 mL). Hemodynamic and functional variables, as well as safety, were comparable between the Echo sub-study and REPAIR. CONCLUSIONS: A good relationship between relevant echo and cMRI parameters was shown. Improvements in RV structure and function with macitentan treatment was observed by echo, consistent with results observed by cMRI in the primary analysis of the REPAIR study. Echo is a valuable complementary method to cMRI, with the potential to non-invasively monitor treatment response at follow-up. TRIAL REGISTRATION NUMBER: REPAIR NCT02310672.

Safety of Macitentan for the Treatment of Portopulmonary Hypertension: Real-World Evidence from the Combined OPUS/OrPHeUS Studies.

INTRODUCTION: Portopulmonary hypertension (PoPH) carries a worse prognosis than other forms of pulmonary arterial hypertension (PAH). Data regarding use of PAH-specific therapies in patients with PoPH are sparse as they are usually excluded from clinical trials. This analysis describes patient characteristics, treatment patterns, outcomes, and safety profiles in patients with PoPH newly initiating macitentan in the USA using the OPUS/OrPHeUS combined dataset. METHODS: OPUS was a prospective, US, multicenter, observational drug registry (April 2014-June 2020); OrPHeUS was a retrospective, US, multicenter chart review (October 2013-March 2017). Additional information regarding patients' liver disease was retrospectively collected for patients with PoPH in OPUS. RESULTS: The OPUS/OrPHeUS dataset included 206 patients with PoPH (median age 58 years; 52.4% female), with baseline cirrhosis and liver test abnormalities reported in 72.8% and 31.6% of patients respectively. Macitentan was initiated as combination therapy in 74.8% of patients and median (Q1, Q3) exposure to macitentan was 11.9 (3.1, 26.0) months. One-year Kaplan-Meier estimates (95% confidence limit, CL) of patients free from all-cause hospitalization and survival were 48.6% (40.7, 56.0) and 82.2% (75.1, 87.4). Of the 96 patients with PoPH in OPUS, 29.2% were classified as in need of liver transplant due to underlying liver disease during the study; transplant waitlist registration was precluded because of PAH severity for 32.1% and 17.9% were transplanted. Hepatic adverse events (HAE) were experienced by 49.0% of patients; the most common being increased bilirubin (16.0%), ascites (7.3%), and hepatic encephalopathy (5.8%); 1.5% and 21.8% of patients discontinued macitentan as a result of HAE and non-hepatic adverse events. CONCLUSION: There were no unexpected safety findings in patients with PoPH treated with macitentan. These data add to the evidence supporting the safety and tolerability of macitentan in patients with PoPH. A graphical abstract is available with this article. TRIAL REGISTRATION: OPsumit® Users Registry (OPUS): NCT02126943; OPsumit® Historical Users cohort (OrPHeUS): NCT03197688; www. CLINICALTRIALS: gov .

Prognostic Value of Right Ventricular Longitudinal Shortening Fraction in Patients With ST-Elevation Myocardial Infarction: A Prospective Echocardiography Study.

Right ventricular systolic dysfunction (RVsD) frequently occurs in patients with ST-elevation myocardial infarction (STEMI). However, the diagnosis depends on the echocardiographic parameters to define RVsD. The right ventricle longitudinal shortening fraction (RV-LSF) is an accurate and reproducible 2-dimensional speckle-tracking parameter associated with clinical events in various pathologies. This study aimed to evaluate the association between RVsD and major adverse cardiovascular event (MACE) occurrence in a cohort of patients with STEMI. Adult patients with STEMI admitted to Amiens University Hospital's cardiovascular intensive care unit between May 2021 and November 2022 who underwent coronary angiography and transthoracic echocardiography within 48 hours of admission were included. RVsD was defined as RV-LSF <20%. The primary outcome was MACE occurrence, including heart failure, myocardial infarction, stroke, and death within 6 months of admission. A multivariable Cox regression analysis with proportional hazard ratio models assessed the association between RVsD and MACEs. In the 164 included patients, 72 (44%) had RVsD and 92 (56%) did not. The RVsD group had a significantly higher proportion of MACEs during the 6-month follow-up (n = 23 of 72, 33%) than the group without RVsD (n = 8 of 92, 9%, p = 0.001). RVsD showed an independent association with MACEs at 6 months (hazard ratio 3.1, 95% confidence interval [CI] 1.35 to 7.30, p = 0.008). Left ventricular ejection fraction <40% and Thrombolysis in Myocardial Infarction score >4 were independently associated with RVsD (odds ratio 2.80, 95% CI 1.34 to 5.98 and odds ratio 2.15, 95% CI 1.18 to 4.39, respectively, p = 0.015). The cumulative risk of MACEs at 6 months was 33% for RV-LSF <20% and 9% for RV-LSF ≥20% (log-rank test p <0.001). RVsD, defined by RV-LSF <20%, is associated with an increased risk of MACEs after STEMI.

Contrasted Antibiotics and Pesticides Occurrence in Fish Exposed In Situ to Urban Effluents: A 20-Day Caging Experiment.

Urban freshwater ecosystems receive a wide array of organic pollutants through wastewater-treatment plant (WWTP) discharges and agricultural runoff. Evaluating the fate and effects of antibiotics and pesticides can be a challenging task, especially the effects on freshwater vertebrates because of their abilities to metabolize and excrete these chemicals and because of their high mobility and escape behavior when exposed to stressful environmental conditions. In the present study, 37 wild gudgeons (Gobio gobio) were caged for a period of up to 20 days, upstream and downstream of a WWTP effluent discharge in the Orge River (a tributary of the Seine River, France). Levels of pesticides and antibiotics in fish muscles were monitored weekly and compared with environmental contamination (water and sediments). Our results highlighted a slight bioaccumulation of pesticides in the gudgeon muscles at the downstream site after 20 days of exposure. Concerning antibiotics, ofloxacin was the most detected compound in fish muscles (85% of occurrence) and ranged from undetectable to 8 ng g-1 dry weight. Antibiotic levels in fish muscle were not higher at the downstream site and did not increase with exposure duration, despite high levels in the water (up to 29 times greater than upstream). Potential ecotoxicological effects were also evaluated: Body condition did not differ between the caging location and exposure time. Three oxidative status markers in the fish livers showed significant shifts after 14 days of caging. Our results suggest a high clearance rate of antibiotics and, to a lesser extent, of pesticides in wild gudgeons, which could be explained by changes in xenobiotic metabolism with pollutant exposure. Environ Toxicol Chem 2024;43:701-711. © 2023 SETAC.

Resultados de la técnica ortoradial vs técnica paralela en la identificación de conductos de primeros premolares superiores y primeros molares inferiores

Fundamento: los avances en la imagenología y su implementación en la Odontología permiten lograr mejores tratamientos. Objetivo: describir los resultados de la técnica ortoradial vs técnica paralela en la identificación de conductos de primeros premolares superiores y primeros molares inferiores. Métodos: estudio observacional, descriptivo y transversal en pacientes con necesidad de tratamiento de conductos de primeros premolares superiores o primeros molares inferiores, que acudieron a la Unidad de Atención Odontológica de la Universidad Regional Autónoma de los Andes en el periodo abril-agosto de 2019. La muestra la constituyeron 62 pacientes, separados en dos grupos: premolares superiores (n=30) o primeros molares inferiores (n=32) y ambos en otros dos grupos según técnica empleada (técnica paralela y técnica ortoradial). Resultados: en los primeros premolares superiores la técnica ortoradial mostró mejores resultados que la paralela para obtener imágenes precisas (100 % vs. 20 %). En los primeros molares inferiores, la técnica ortoradial mostró resultados superiores a la técnica paralela para el conducto mesiolingual (93,75 % vs 31,25 %) y conducto disto lingual (31,25 % vs 12,5 %). La elongación de las raíces predominó en la técnica ortoradial (n=8), al igual que la superposición dental (n=10). Conclusiones: la técnica ortoradial mostró resultados superiores al momento de localizar tanto el conducto vestibular y palatino en los primeros premolares superiores como para el conducto mesiolingual y el conducto distolingual. La elongación de las raíces se observó en mayor cuantía en la técnica ortoradial, al igual que la superposición dental.

Foundation: advances in imaging and its implementation in Dentistry allow for better treatments. Objective: to describe the results of the orthoradial technique vs parallel technique in the identification of upper first premolars canals and lower first molars. Methods: observational, descriptive and cross-sectional study in patients in need of root canal treatment of upper first premolars or lower first molars, who attended the Dental Care Unit of the Andes Regional Autonomous University from April to August 2019. The sample consisted of 62 patients, separated into two upper premolar groups (n=30) or lower first molars (n=32) and both into two other groups according to the technique used (parallel technique and orthoradial technique). Results: in the upper first premolars, the orthoradial technique showed better results than the parallel technique to obtain accurate images (100% vs. 20%). In the lower first molars, the orthoradial technique showed superior results to the parallel technique for the mesiolingual canal (93.75% vs 31.25%) and distolingual canal (31.25% vs 12.5%). Root elongation predominated in the orthoradial technique (n=8), as did dental overlap (n=10). Conclusions: the orthoradial technique showed superior results when locating both the buccal and palatine canal in the upper first premolars and for the mesiolingual canal and the distolingual canal. Root elongation was observed to a greater extent in the orthoradial technique, as was dental overlap.

Sustainability as part of a quality framework for the organisation of oral healthcare.

This paper aims to highlight to the reader that the organisation of dentistry at a system level lags behind other healthcare professions in regulation, policy, education and research. It argues that seeing sustainability as being as important as safety in oral healthcare quality would begin to rectify this. For the practitioner, it also identifies existing guidance on practising sustainably and reinforces that it does not require radical change but evidence-based care.

A narrative review of cracks in teeth: Aetiology, microstructure and diagnostic challenges.

OBJECTIVES: To summarize the available evidence of crack formation in teeth and to discuss the limitations of the current clinical diagnostic modalities for crack detection in teeth. BACKGROUND: Cracks are a common clinical finding in teeth and yet clinicians still struggle to identify the full extent and orientation of cracks for their appropriate timely management. The biomechanics of crack development can be due to multiple factors and can differ from an unrestored tooth to a restored or endodontically treated tooth. DATA & SOURCES: This narrative review has been designed following the guidelines published by Green et al. 2006 [1] Published literature in the English language that addresses the objectives of this review up to July 2022 was sourced from online databases and reference lists. The relevance of the papers was assessed and discussed by two reviewers. A total of 101 publications were included in this narrative review. CONCLUSIONS: The initiation and development of cracks in teeth are likely linked to an interplay between the masticatory forces and fracture resistance of the remaining tooth structure. From the identified literature, the quality and quantity of remaining tooth structure in a restored or endodontically-treated tooth affects the biomechanics of crack development compared to an unrestored tooth. The extent, orientation, and size of the cracks do affect a clinician's ability to detect cracks in teeth. There is still a need to develop reliable diagnostic tools that will accurately identify cracks in teeth beneath restorations to enable effective monitoring of their propagation and provide appropriate interventions. CLINICAL SIGNIFICANCE: The development and propagation of cracks in an unrestored tooth differ greatly from a restored and endodontically treated tooth; mainly linked to the quantity and quality of the remaining tooth structure and the forces acting on them. Identifying the extent of cracks in teeth remains challenging for early clinical intervention.

Safety and efficacy of two-drug combination in elderly patients with locally advanced non-small cell lung cancer and validation of the Charlson Index as a predictor of survival.

Background: The best platinum-based chemotherapy regimen remains to be determined in elderly patients treated with definitive chemoradiotherapy for advanced non-small cell lung cancer (NSCLC). Predictive indexes for toxicity and survival are also needed to give the safest and most effective treatment for this population. Methods: This is a retrospective cohort study. Patients with histologically confirmed stage IIIA, IIIB or IIIC NSCLC over 70 years of age, treated with radiotherapy and chemotherapy, were included. Patients from two cancer centers treated between 12/2006 and 08/2019 were included in the data analysis. Results: Fifty-eight patients were enrolled in the study. The median age was 76.6 years [interquartile range (IQR): 71.6-83.4]. Thirty-nine patients were treated with concomitant chemoradiotherapy and 19 with a sequential strategy. The chemotherapy regimen consisted in a combination of platinum and taxanes. At a median follow-up of 52 months (IQR: 7-69), the 2-year progression-free survival (PFS) and overall survival (OS) were 35.5% and 66.9%, respectively. Male sex and a high Charlson index were identified as independent prognostic factors for worse OS. Acute grade 3-5 toxicities occurred in 34.4% of patients, including 1 grade 5 toxicity, and grade 3-4 late toxicities occurred in 17.2% of patients. In the whole cohort a high Charlson index was the only predictive factor for a higher risk of grade 3-5 acute toxicities (statistical trend in the concurrent cohort, P=0.06). Conclusions: The Charlson index correlated with toxicity and survival in elderly patients treated with chemoradiotherapy in locally advanced NSCLC. The addition of taxanes to platinum chemotherapy was safe in the present study and warrants further exploration.

Coacervate Droplets for Synthetic Cells.

The design and construction of synthetic cells - human-made microcompartments that mimic features of living cells - have experienced a real boom in the past decade. While many efforts have been geared toward assembling membrane-bounded compartments, coacervate droplets produced by liquid-liquid phase separation have emerged as an alternative membrane-free compartmentalization paradigm. Here, the dual role of coacervate droplets in synthetic cell research is discussed: encapsulated within membrane-enclosed compartments, coacervates act as surrogates of membraneless organelles ubiquitously found in living cells; alternatively, they can be viewed as crowded cytosol-like chassis for constructing integrated synthetic cells. After introducing key concepts of coacervation and illustrating the chemical diversity of coacervate systems, their physicochemical properties and resulting bioinspired functions are emphasized. Moving from suspensions of free floating coacervates, the two nascent roles of these droplets in synthetic cell research are highlighted: organelle-like modules and cytosol-like templates. Building the discussion on recent studies from the literature, the potential of coacervate droplets to assemble integrated synthetic cells capable of multiple life-inspired functions is showcased. Future challenges that are still to be tackled in the field are finally discussed.

Engineering the Coacervate Microdroplet Interface via Polyelectrolyte and Surfactant Complexation.

Complex coacervate microdroplets, which are formed via spontaneous liquid-liquid phase separation by mixing two oppositely charged polyelectrolytes in water, have emerged as a new paradigm in the fields of origin of life, membraneless subcellular compartmentalization, bioreactors, and drug delivery. However, how to further improve its stability and enhance its selectivity in one particular coacervate system remains a challenge. By generating a membrane-like layer at the surface of coacervate microdroplets via electrostatic interactions between oppositely charged surfactants and polyelectrolytes, we here achieve tunable permeability and enhanced stability of the coacervates at the same time. Depending on the surfactants used, membrane-like layer-coated coacervate microdroplets exhibit different selectivity over solute sequestration and can promote or inhibit DNA hybridization. Our approach provides a practical tool to engineer functional bioinspired microcompartments with potential applications in the fields of controlled drug release and microreactor technology.

Facile Fabrication of High-Performance Thermochromic VO2-Based Films on Si for Application in Phase-Change Devices.

This work reports on an alternative and advantageous procedure to attain VO2-based thermochromic coatings on silicon substrates. It involves the sputtering of vanadium thin films at glancing angles and their subsequent fast annealing in an air atmosphere. By adjusting thickness and porosity of films as well as the thermal treatment parameters, high VO2(M) yields were achieved for 100, 200, and 300 nm thick layers treated at 475 and 550 °C for reaction times below 120 s. Comprehensive structural and compositional characterization by Raman spectroscopy, X-ray diffraction, and scanning-transmission electron microscopies combined with analytical techniques such as electron energy-loss spectroscopy bring to the fore the successful synthesis of VO2(M) + V2O3/V6O13/V2O5 mixtures. Likewise, a 200 nm thick coating consisting exclusively of VO2(M) is also achieved. Conversely, the functional characterization of these samples is addressed by variable temperature spectral reflectance and resistivity measurements. The best results are obtained for the VO2/Si sample with changes in reflectance of 30-65% in the near-infrared at temperatures between 25 and 110 °C. Similarly, it is also proven that the achieved mixtures of vanadium oxides can be advantageous for certain optical applications in specific infrared windows. Finally, the features of the different structural, optical, and electrical hysteresis loops associated with the metal-insulator transition of the VO2/Si sample are disclosed and compared. These remarkable thermochromic performances hereby accomplished highlight the suitability of these VO2-based coatings for applications in a wide range of optical, optoelectronic, and/or electronic smart devices.

Development of HPV16 mouse and dog models for more accurate prediction of human vaccine efficacy.

BACKGROUND: Animal models are essential to understand the physiopathology of human diseases but also to evaluate new therapies. However, for several diseases there is no appropriate animal model, which complicates the development of effective therapies. HPV infections, responsible for carcinoma cancers, are among these. So far, the lack of relevant animal models has hampered the development of therapeutic vaccines. In this study, we used a candidate therapeutic vaccine named C216, similar to the ProCervix candidate therapeutic vaccine, to validate new mouse and dog HPV preclinical models. ProCervix has shown promising results with classical subcutaneous murine TC-1 cell tumor isografts but has failed in a phase II study. RESULTS: We first generated E7/HPV16 syngeneic transgenic mice in which the expression of the E7 antigen could be switched on through the use of Cre-lox recombination. Non-integrative LentiFlash® viral particles were used to locally deliver Cre mRNA, resulting in E7/HPV16 expression and GFP reporter fluorescence. The expression of E7/HPV16 was monitored by in vivo fluorescence using Cellvizio imaging and by local mRNA expression quantification. In the experimental conditions used, we observed no differences in E7 expression between C216 vaccinated and control groups. To mimic the MHC diversity of humans, E7/HPV16 transgenes were locally delivered by injection of lentiviral particles in the muscle of dogs. Vaccination with C216, tested with two different adjuvants, induced a strong immune response in dogs. However, we detected no relationship between the level of cellular response against E7/HPV16 and the elimination of E7-expressing cells, either by fluorescence or by RT-ddPCR analysis. CONCLUSIONS: In this study, we have developed two animal models, with a genetic design that is easily transposable to different antigens, to validate the efficacy of candidate vaccines. Our results indicate that, despite being immunogenic, the C216 candidate vaccine did not induce a sufficiently strong immune response to eliminate infected cells. Our results are in line with the failure of the ProCervix vaccine that was observed at the end of the phase II clinical trial, reinforcing the relevance of appropriate animal models.

Non-enzymatic oligonucleotide ligation in coacervate protocells sustains compartment-content coupling.

Modern cells are complex chemical compartments tightly regulated by an underlying DNA-encoded program. Achieving a form of coupling between molecular content, chemical reactions, and chassis in synthetic compartments represents a key step to the assembly of evolvable protocells but remains challenging. Here, we design coacervate droplets that promote non-enzymatic oligonucleotide polymerization and that restructure as a result of the reaction dynamics. More specifically, we rationally exploit complexation between end-reactive oligonucleotides able to stack into long physical polymers and a cationic azobenzene photoswitch to produce three different phases-soft solids, liquid crystalline or isotropic coacervates droplets-each of them having a different impact on the reaction efficiency. Dynamical modulation of coacervate assembly and dissolution via trans-cis azobenzene photo-isomerization is used to demonstrate cycles of light-actuated oligonucleotide ligation. Remarkably, changes in the population of polynucleotides during polymerization induce phase transitions due to length-based DNA self-sorting to produce multiphase coacervates. Overall, by combining a tight reaction-structure coupling and environmental responsiveness, our reactive coacervates provide a general route to the non-enzymatic synthesis of polynucleotides and pave the way to the emergence of a primitive compartment-content coupling in membrane-free protocells.

Two-year prognosis of acute coronary syndrome during the first wave of the coronavirus disease 2019 pandemic.

BACKGROUND: The first wave of the coronavirus disease 2019 pandemic significantly changed behaviour in terms of access to healthcare. AIM: To assess the effects of the pandemic and initial lockdown on the incidence of acute coronary syndrome and its long-term prognosis. METHODS: Patients admitted for acute coronary syndrome from 17 March to 6 July 2020 and from 17 March to 6 July 2019 were included. The number of admissions for acute coronary syndrome, acute complication rates and 2-year rates of survival free from major adverse cardiovascular events or death from any cause were compared according to the period of hospitalization. RESULTS: In total, 289 patients were included. We observed a 30±3% drop in acute coronary syndrome admissions during the first lockdown, which did not recover in the 2months after it was lifted. At 2years, there were no significant differences in the combined endpoint of major adverse cardiovascular events or death from any cause between the different periods (P=0.34). Being hospitalized during lockdown was not predictive of adverse events during follow-up (hazard ratio 0.87, 95% confidence interval 0.45-1.66; P=0.67). CONCLUSIONS: We did not observe an increased risk of major cardiovascular events or death at 2years from initial hospitalization for patients hospitalized during the first lockdown, adopted in March 2020 in response to the coronavirus disease 2019 pandemic, potentially as a result of the lack of power of the study.