Corrosion Induced on Aluminum by Biodiesel Components in Non-Oxygen Environments.

Biodiesel is a mixture of saturated and unsaturated Fatty Acid Methyl Esters (FAMEs) whose composition affects the corrosion behavior of metal containers during storage. This study examines the effect of the C=C bond present in selected FAMEs (Methyl Stearate, Methyl Oleate, and Methyl Linoleate) in aluminum corrosion in the absence of oxygen. First, mass loss assays were carried out at 100, 200, and 280 °C for 1000 h using pure Methyl Stearate (MS), 5% Methyl Oleate in Methyl Stearate (MS-5% MO), and 5% Methyl Linoleate in Methyl Stearate (MS-5% ML). Next, chemical changes in FAMEs were studied using FTIR, TGA, and GC/MS. SEM/EDS analysis allowed us to inspect the aluminum surfaces and their chemical characterization. We estimated higher corrosion rates for MS assays than those of unsaturated methyl ester mixtures. In a separate set of experiments, we used electrochemical techniques (potentiodynamic polarization, linear polarization resistance, and electrochemical impedance spectroscopy) to investigate aluminum corrosion induced by thermal-degraded products from FAMEs at 100, 200, and 280 °C for 300 h able to dissolve in aqueous extracts. These electrochemical experiments revealed that the products in the aqueous extracts from the unsaturated methyl ester mixture form a passive layer on the Al surface thicker than pure MS at the corresponding degradation temperatures.

Parametric analysis of an integrated cardio-respiratory model in preterm newborns during apnea.

The analysis of the complex interactions involved in the acute physiological response to apnea-bradycardia events in preterm newborns remains a challenging task. This paper presents a novel integrated model of cardio-respiratory interactions, adapted to preterm newborns. A sensitivity analysis, based Morris' screening method, was applied to study the effects of physiological parameters on heart rate and desaturation, during the simulation of a 15-seconds apnea-bradycardia episode. The most sensitive parameters are associated with fundamental, integrative physiological mechanisms involving: (i) respiratory mechanics (intermediate airways and lung compliance), (ii) fraction of inspired oxygen, (iii) metabolic rates (oxygen consumption rate), (iv) heart rate regulation and (v) chemoreflex (gain). Results highlight the relevant influence of physiological variables, involved in preterm apnea-bradycardia events.

Age-Dependent Changes in the Occurrence and Segregation of GABA and Acetylcholine in the Rat Superior Cervical Ganglia.

The occurrence, inhibitory modulation, and trophic effects of GABA have been identified in the peripheral sympathetic nervous system. We have demonstrated that GABA and acetylcholine (ACh) may colocalize in the same axonal varicosities or be segregated into separate ones in the rat superior cervical ganglia (SCG). Neurotransmitter segregation varies with age and the presence of neurotrophic factors. Here, we explored age-dependent changes in the occurrence and segregation of GABA and ACh in rats ranging from 2 weeks old (wo) to 12 months old or older. Using immunohistochemistry, we characterized the expression of L-glutamic acid decarboxylase of 67 kDa (GAD67) and vesicular acetylcholine transporter (VAChT) in the rat SCG at 2, 4, 8, 12 wo and 12 months old or older. Our findings revealed that GAD67 was greater at 2 wo compared with the other ages, whereas VAChT levels were greater at 4 wo than at 12 wo and 12 months old or older. The segregation of these neurotransmitters was more pronounced at 2 and 4 wo. We observed a caudo-rostral gradient of segregation degree at 8 and 12 wo. Data point out that the occurrence and segregation of GABA and ACh exhibit developmental adaptative changes throughout the lifetime of rats. We hypothesize that during the early postnatal period, the increase in GABA and GABA-ACh segregation promotes the release of GABA alone which might play a role in trophic actions.

Describing differences among populations of thoracic tumors patients under and over 80 years: Data analysis from the SLCG thoracic tumor registry.

OBJECTIVES: Cancer is a disease of old age; however, most studies usually included minority of patients fit elderly. The purpose is to investigate the clinical characteristics and genetic information of patients with thoracic tumors who are 80 years old or older compared to those under 80 years old. STUDY DESIGN AND METHODS: The Thoracic Tumor Registry (TTR) is a Spanish observational, prospective cohort study that included patients diagnosed with thoracic tumors. Data were collected from medical records related to sociodemographic, epidemiological, clinical, molecular/genetic, and treatment outcome variables. RESULTS: The total number of patients, recruited from August 2016 to April 2023, was 26.193 (93,1 % were younger than 80 years and 6,9 % were 80 years or older). In the group of older patients: the male ratio increased (72,9 % vs. 80 %); the number of elderly people who had never smoked or were ex-smokers increased (9,9 % vs. 21,1 % and 44,8 % vs. 61,3 %, respectively) and the number of current smokers decreased (43,3 % vs. 17,5 %); had higher ECOG performance status at diagnosis (for ECOG ≥ 2, 15 % vs. 32,9 %), and there were more patients with previous cancer (17,3 % vs. 28 %). The proportion of men is higher than that of women (73 % vs. 27 % in <80 years and 80 % vs. 20 % in ≥80 years). For all biomarkers, the proportion of patients who had a molecular determination was lower in older patients. There were no differences in terms of alterations in the biomarkers tested; except for EGFR, for which the positivity rate was higher in patients aged 80 years and older (25 % vs. 15,3 %). CONCLUSION: The proportion of older patients with targeted mutations is higher. So, at least at diagnosis, it should be proceeded in a standard way. Then, when it comes to treatment, comorbidities and patient's baseline situation should be considered. CLINICAL TRIAL REGISTRATION: NCT02941458.

Pathogenic CANVAS (AAGGG)n repeats stall DNA replication due to the formation of alternative DNA structures.

CANVAS is a recently characterized repeat expansion disease, most commonly caused by homozygous expansions of an intronic (A2G3)n repeat in the RFC1 gene. There are a multitude of repeat motifs found in the human population at this locus, some of which are pathogenic and others benign. In this study, we conducted structure-functional analyses of the pathogenic (A2G3)n and nonpathogenic (A4G)n repeats. We found that the pathogenic, but not the nonpathogenic, repeat presents a potent, orientation-dependent impediment to DNA polymerization in vitro. The pattern of the polymerization blockage is consistent with triplex or quadruplex formation in the presence of magnesium or potassium ions, respectively. Chemical probing of both repeats in vitro reveals triplex H-DNA formation by only the pathogenic repeat. Consistently, bioinformatic analysis of S1-END-seq data from human cell lines shows preferential H-DNA formation genome-wide by (A2G3)n motifs over (A4G)n motifs. Finally, the pathogenic, but not the nonpathogenic, repeat stalls replication fork progression in yeast and human cells. We hypothesize that the CANVAS-causing (A2G3)n repeat represents a challenge to genome stability by folding into alternative DNA structures that stall DNA replication.

Comparison of Clinical and Genetic Characteristics Between Younger and Older Lung Cancer Patients.

INTRODUCTION: The aim of this study was to analyze the clinical and genetic characteristics of young lung cancer cases, and to compare them with those of older cases. METHODS: We used the Thoracic Tumors Registry (TTR) as a data source representative of lung cancer cases diagnosed in Spain, and included all cases registered until 9/01/2023 which had information on age at diagnosis or the data needed to calculate it. We performed a descriptive statistical analysis and fitted logistic regressions to analyze how different characteristics influenced being a younger lung cancer patient. RESULTS: A total of 26,336 subjects were included. Lung cancer cases <50 years old had a higher probability of being women (OR: 1.38; 95% CI: 1.21-1.57), being in stage III or IV (OR: 1.32; 95% CI: 1.08-1.62), not having comorbidities (OR: 5.21; 95% CI: 4.59-5.91), presenting with symptoms at diagnosis (OR: 1.53; 95% CI: 1.29-1.81), and having ALK translocation (OR: 7.61; 95% CI: 1.25-46.32) and HER2 mutation (OR: 5.71; 95% CI: 1.34-24.33), compared with subjects ≥50 years. Among subjects <35 years old (n=61), our study observed a higher proportion of women (59.0% vs. 26.6%; p<0.001), never smokers (45.8% vs. 10.3%; p<0.001), no comorbidities (21.3% vs. 74.0%; p<0.001); ALK translocation (33.3% vs. 4.4%; p<0.001) and ROS1 mutation (14.3% vs. 2.3%; p=0.01), compared with subjects ≥35 years. CONCLUSIONS: Lung cancer displays differences by age at diagnosis which may have important implications for its clinical management.

Addressing lung cancer screening eligibility in Spain using 2013 and 2021 US Preventive Service Task Force criteria: cross-sectional study.

Objectives: The aim of the study was to ascertain the percentage of Spanish lung cancer cases that would fulfil the lung cancer screening inclusion criteria recommended by the United States Preventive Service Task Force (USPSTF) in 2013 and 2021. Methods: A cross-sectional study was carried out. All lung cancer cases registered in the Thoracic Tumor Registry with data on date of birth, date of diagnosis, smoking habit, number of pack-years and time elapsed since smoking cessation were included. Results: The study included 15 006 patients diagnosed with lung cancer in Spain between 2016 and 2022. Eligibility to participate in screening increased from 53.7% to 63.5% (an increase of 9.8%) according to the 2013 and 2021 recommendations, respectively. The percentage of eligible men rose by 9.2 percentage points with the 2021 versus 2013 recommendations, whereas this rise was 11.5 percentage points in women. Under the 2021 recommendations, 36.6% of women and 5.3% of men would not have fulfilled the screening inclusion criteria due to being never-smokers; 14.9% of women and 11.0% of men would not have fulfilled the age criterion; and 27.0% of ex-smokers among women compared to 35.6% among men would not have been eligible due to >15 years having elapsed since smoking cessation. Conclusions: In Spain, over one-third of lung cancer cases could not be detected through screening, by virtue of not meeting the most recent inclusion criteria stated by the USPSTF. The degree of fulfilment in a potential nationwide screening programme should be analysed, with the aim of establishing inclusion criteria in line with each country's context.

Fracture Resistance of Chairside CAD/CAM Molar Crowns Fabricated with Different Lithium Disilicate Ceramic Materials

PURPOSE: To compare the fracture resistance of five different groups of chairside CAD/CAM molar crowns fabricated from various lithium disilicate ceramic materials (LDC): one conventional precrystallized CAD/CAM LDC, two novel precrystallized LDCs, and one fully crystallized LDC tested both with and without optional sintering. MATERIALS AND METHODS: A total of 60 chairside CAD/CAM lithium disilicate molar crowns (n = 12 per group) with 1.5-mm occlusal thickness and a 1.0-mm chamfer finish were designed and fabricated with a chairside CAD/CAM system (CEREC, Dentsply Sirona). The restorations were divided into five groups: (1) IPS e.max CAD; (2) Amber Mill; (3) Straumann n!ce; (4) Straumann n!ce with optional sintering; and (5) Supreme CAD. Restorations were cemented using conventional resin luting cement and primer system to 3D-printed resin dies. Bonded restorations were loaded for 100,000 cycles with 275-N force, and the load at break (LB) and peak load (PL) until fracture were measured. SEM images of fracture surfaces on the printed dies were obtained. RESULTS: Fracture resistance was significantly different depending on the material. Supreme CAD showed the highest fracture resistance (LB: 1,557.2 N; PL: 1,785.8 N), followed by Amber Mill (LB: 1,393.0 N; PL: 1,604.2 N) and IPS e.max CAD (LB: 1,315.7 N; PL: 1,461.9 N). Straumann n!ce without (LB: 862.4 N; PL: 942.9 N) and with the optional sintering (LB: 490.4 N; PL: 541.0 N) showed significantly lower fracture resistance than the others. CONCLUSION: The fracture resistance of chairside CAD/CAM lithium disilicate molar crowns varied depending on the material, and the novel materials did not perform as well as the conventional equivalents. Fully crystallized lithium disilicate ceramic block materials showed lower fracture resistance than precrystallized counterparts and should be used with caution in the clinic, especially with optional sintering.

A reduced complexity ECG imaging model for regularized inversion optimization.

The resolution of the inverse problem of electrocardiography represents a major interest in the diagnosis and catheter-based therapy of cardiac arrhythmia. In this context, the ability to simulate several cardiac electrical behaviors was crucial for evaluating and comparing the performance of inversion methods. For this application, existing models are either too complex or do not produce realistic cardiac patterns. In this work, a low-resolution heart-torso model generating realistic whole heart cardiac mappings and electrocardiograms in healthy and pathological cases is designed. This model was built upon a simplified heart-torso geometry and implements the monodomain formalism by using the finite element method. In addition, a model reduction step through a sensitivity analysis was proposed where parameters were identified using an evolutionary optimization approach. Finally, the study illustrates the usefulness of the proposed model by comparing the performance of different variants of Tikhonov-based inversion methods for the determination of the regularization parameter in healthy, ischemic and ventricular tachycardia scenarios. First, results of the sensitivity analysis show that among 58 parameters only 25 are influent. Note also that the level of influence of the parameters depends on the heart region. Besides, the synthesized electrocardiograms globally present the same characteristic shape compared to the reference once with a correlation value that reaches 88%. Regarding inverse problem, results highlight that only Robust Generalized Cross Validation and Discrepancy Principle provide best performance, with a quasi-perfect success rate for both, and a respective relative error, between the generated electrocardiograms to the reference one, of 0.75 and 0.62.

Pathogenic CANVAS (AAGGG)n repeats stall DNA replication due to the formation of alternative DNA structures.

CANVAS is a recently characterized repeat expansion disease, most commonly caused by homozygous expansions of an intronic (A2G3)n repeat in the RFC1 gene. There are a multitude of repeat motifs found in the human population at this locus, some of which are pathogenic and others benign. In this study, we conducted structure-functional analyses of the main pathogenic (A2G3)n and the main nonpathogenic (A4G)n repeats. We found that the pathogenic, but not the nonpathogenic, repeat presents a potent, orientation-dependent impediment to DNA polymerization in vitro. The pattern of the polymerization blockage is consistent with triplex or quadruplex formation in the presence of magnesium or potassium ions, respectively. Chemical probing of both repeats in supercoiled DNA reveals triplex H-DNA formation by the pathogenic repeat. Consistently, bioinformatic analysis of the S1-END-seq data from human cell lines shows preferential H-DNA formation genome-wide by (A2G3)n motifs over (A4G)n motifs in vivo. Finally, the pathogenic, but not the non-pathogenic, repeat stalls replication fork progression in yeast and human cells. We hypothesize that CANVAS-causing (A2G3)n repeat represents a challenge to genome stability by folding into alternative DNA structures that stall DNA replication.

Historiographical approaches to biogeography: a critical review.

We performed a critical review of the historiographical studies on biogeography. We began with the pioneering works of Augustin and Alphonse de Candolle. Then, we analyzed the historical accounts of biogeography developed by (1) Martin Fichman and his history on the extensionism-permanentism debate; (2) Gareth Nelson and his critique of the Neo-Darwinian historiography of biogeography; (3) Ernst Mayr, with his dispersalist viewpoint; (4) Alan Richardson, who wrote a microhistory on the biogeographic model constructed by Darwin; (5) Michael Paul Kinch and the ideas discussed in the 19th century about the geographical distribution of living beings; (6) Janet Browne, who highlighted the importance of the pre-Darwinian naturalists; (7) Peter Bowler, who focused mainly on the influence of paleontology on biogeography; (8) James Larson, who looked into the practices of the naturalists of Northern Europe in the late 18th century; and (9) Malte Ebach, who like Larson, was more interested in analysing the practices rather than the ideas of naturalists who studied the geographical distribution of organisms. Finally, these works are compared with each other. There has not been a dominant paradigm in the construction of historical narratives of biogeography; however, they provide a useful context for understanding problems of biogeography that continue to be debated to this day.

Tratamiento de la dermatochalasis con cirugía de ondas de radio

Objetivo: Describir los resultados de la blefaroplastia de los párpados superiores realizada con radiocirugía a pacientes con dermatochalasis del párpado superior. Métodos: Se realizó un estudio descriptivo longitudinal con pacientes del servicio de Oftalmología en el Hospital Clínico Quirúrgico Hermanos Ameijeiras en el período entre enero de 2021 a diciembre de 2022. Después de aplicar los criterios de selección la muestra quedó constituida por los primeros 50 pacientes que asistieron de forma consecutiva. Resultados: Predominaron los pacientes entre los 60 a 79 años de edad, el sexo femenino y los de color de piel blanca (p > 0,05). Se logró una reducción completa de la piel redundante en más de un 50 %. El tiempo quirúrgico promedio con radiofrecuencia fue de 35.9 min. La satisfacción de los pacientes fue buena en un 96 %. Las complicaciones posoperatorias se manifestaron en un 32 % de los pacientes, solo en dos pacientes fueron serias, las cuales no dejaron secuelas. Conclusiones: La cirugía con ondas de radios para el tratamiento de la dermatochalasis permite alcanzar el resultado estético que se desea, con satisfacción tanto para el médico, como para los pacientes quienes logran mejorar su calidad de vida.

Objective: To describe the results of upper eyelid blepharoplasty performed with radiosurgery in patients with upper eyelid dermatochalasis. Methods: A longitudinal descriptive study was carried out with patients from the ophthalmology service at Hospital Clínico Quirúrgico Hermanos Ameijeiras, from January 2021 to December 2022. After applying the selection criteria, the sample was made up of the first 50 patients who attended consecutively. Results: Patients aged 60-79 years predominated, as well as the female sex and the white skin color (p > 0.05). A complete reduction of redundant skin was achieved in more than 50 %. The average surgical time with radiofrequency was 35.9 min. Patient satisfaction was good in 96 %. Postoperative complications were present in 32 % of patients, only in two patients were they serious, but did not leave any sequelae. Conclusions: Radiowave surgery for treating dermatochalasis allows to achieve the desired aesthetic outcome, with satisfaction for both the physician and the patients, who achieve an improvement in their quality of life.

Interaction Networks Help to Infer the Vulnerability of the Saproxylic Beetle Communities That Inhabit Tree Hollows in Mediterranean Forests.

Insect communities are facing contrasting responses due to global change. However, knowledge on impacts of communities' reorganizations is scarce. Network approaches could help to envision community changes in different environmental scenarios. Saproxylic beetles were selected to examine long-term variations in insect interaction/diversity patterns and their vulnerability to global change. We evaluated interannual differences in network patterns in the tree hollow-saproxylic beetle interaction using absolute samplings over an 11-year interval in three Mediterranean woodland types. We explored saproxylic communities' vulnerability to microhabitat loss via simulated extinctions and by recreating threat scenarios based on decreasing microhabitat suitability. Although temporal diversity patterns varied between woodland types, network descriptors showed an interaction decline. The temporal beta-diversity of interactions depended more on interaction than on species turnover. Interaction and diversity temporal shifts promoted less specialized and more vulnerable networks, which is particularly worrisome in the riparian woodland. Network procedures evidenced that saproxylic communities are more vulnerable today than 11 years ago irrespective of whether species richness increased or decreased, and the situation could worsen in the future depending on tree hollow suitability. Network approaches were useful for predicting saproxylic communities' vulnerability across temporal scenarios and, thus, for providing valuable information for management and conservation programs.

The saga of dyssynchrony imaging: Are we getting to the point.

Cardiac resynchronisation therapy (CRT) has an established role in the management of patients with heart failure, reduced left ventricular ejection fraction (LVEF < 35%) and widened QRS (>130 msec). Despite the complex pathophysiology of left ventricular (LV) dyssynchrony and the increasing evidence supporting the identification of specific electromechanical substrates that are associated with a higher probability of CRT response, the assessment of LVEF is the only imaging-derived parameter used for the selection of CRT candidates. This review aims to (1) provide an overview of the evolution of cardiac imaging for the assessment of LV dyssynchrony and its role in the selection of patients undergoing CRT; (2) highlight the main pitfalls and advantages of the application of cardiac imaging for the assessment of LV dyssynchrony; (3) provide some perspectives for clinical application and future research in this field. Conclusion: the road for a more individualized approach to resynchronization therapy delivery is open and imaging might provide important input beyond the assessment of LVEF.

Effects of the self-perceived sensorimotor demand and immersion during video gaming on visual-attention skills.

Playing specific genres of video games (e.g., action video games) has been linked to improvements in cognitive skills mostly related to attentional phenomena. Nonetheless, do video games have features or dimensions in common that impact cognitive improvements beyond the game genre? Here, we argue that the sensorimotor demand-the amount of demand for precise coordination between movement and perception-is a key element in the improvements associated with playing video games. We conducted a two-part study to test this hypothesis: a self-report online gaming instrument development and validation and an in-lab behavioural and electrophysiological study. In the first study, data from 209 participants were used to devise the sensorimotor demand instrument (SMDI). The SMDI was split into three dimensions of video game playing: sensorimotor contingency, immersion and unfocused gaming. Criterion validity related to video gamers' characteristics supported that the SMDI is sensitive to the input device (e.g., keyboard or touchscreens), and the most recent experience gained during gaming sessions while not being sensitive to the game genre. In the second study, data from 20 participants who performed four visual-attentional tasks previously reported in the literature showed that the SMDI's dimensions were associated with behavioural performance measures and the latency and amplitude of event-related potentials (N1, P2 and P3). Despite the challenge of studying the video gamer population, our study remarks on the relevance of sensorimotor demands in the performance of attentional tasks and its potential use as a dimension to characterize the experience of playing video games beyond the game genre.

Diversity and composition of beetle assemblages attracted to dung in cloud forests under active and passive restoration practices.

Ecosystem loss and degradation has become a worldwide concern. The implementation of ecological restoration plans has been proposed to facilitate the recovery of ecosystems. It is imperative that once restoration strategies have been implemented, the effects of these actions in the medium and long term be evaluated, particularly the structure and functioning of the ecosystem. Diversity (α- and ß-diversity) of beetles attracted to dung was assessed and compared in 3 habitat conditions (conserved forest, passive restoration, and active restoration) at 2 different seasons during the year (dry vs. rainy season) in cloud forest in San Luis Potosí (central Mexico). We found that the dry season was slightly richer than the rainy season, but the latter was significantly more diverse. Species diversity and composition in active restoration were more similar to passive restoration, and both differed greatly from the conserved forest. In contrast, conserved and passive restoration conditions exhibited similar patterns in ß-diversity of insects likely because they maintain more species associated with the original vegetation of the cloud forest. Beetle assemblages could be of more habitat generalists, as they actively distribute across the restoration sites. Beetles attracted to dung provide an overview of the effect of restoration in early faunal recovery, even though we monitored this entomofauna for a short period (31 months after the restoration plots were established). These beetles can be a useful indicator for exploring the main forces driving species diversity for the management and conservation status of cloud forests, a threatened ecosystem.

Biodose Tools: an R shiny application for biological dosimetry.

INTRODUCTION: In the event of a radiological accident or incident, the aim of biological dosimetry is to convert the yield of a specific biomarker of exposure to ionizing radiation into an absorbed dose. Since the 1980s, various tools have been used to deal with the statistical procedures needed for biological dosimetry, and in general those who made several calculations for different biomarkers were based on closed source software. Here we present a new open source program, Biodose Tools, that has been developed under the umbrella of RENEB (Running the European Network of Biological and retrospective Physical dosimetry). MATERIALS AND METHODS: The application has been developed using the R programming language and the shiny package as a framework to create a user-friendly online solution. Since no unique method exists for the different mathematical processes, several meetings and periodic correspondence were held in order to reach a consensus on the solutions to be implemented. RESULTS: The current version 3.6.1 supports dose-effect fitting for dicentric and translocation assay. For dose estimation Biodose Tools implements those methods indicated in international guidelines and a specific method to assess heterogeneous exposures. The app can include information on the irradiation conditions to generate the calibration curve. Also, in the dose estimate, information about the accident can be included as well as the explanation of the results obtained. Because the app allows generating a report in various formats, it allows traceability of each biological dosimetry study carried out. The app has been used globally in different exercises and training, which has made it possible to find errors and improve the app itself. There are some features that still need consensus, such as curve fitting and dose estimation using micronucleus analysis. It is also planned to include a package dedicated to interlaboratory comparisons and the incorporation of Bayesian methods for dose estimation. CONCLUSION: Biodose Tools provides an open-source solution for biological dosimetry laboratories. The consensus reached helps to harmonize the way in which uncertainties are calculated. In addition, because each laboratory can download and customize the app's source code, it offers a platform to integrate new features.

Synthesis, insecticidal activity, and ensembled docking of nitroguanidines bearing S- and R-proline.

BACKGROUND: The amino acids R- and S-proline were used to synthesize novel neonicotinoid derivatives that, after being characterized by 1 H, DEPTQ 135, and HRMS-QTOF, were evaluated for use as insecticides against Galleria mellonella (caterpillar), Sitophilus zeamais, Xylosandrus morigerus, Xyleborus affinis, and Xyleborus ferrugineus. RESULTS: Comparisons of biological activity and absolute configuration showed that the R enantiomer had excellent and outstanding insecticidal activity against the insects tested, with up to 100% mortality after 12 h compared with dinotefuran at the same concentration. CONCLUSIONS: The results suggest that compound R6 is an excellent lead enantiopure insecticide for future development in the field of crop protection. Furthermore, intermolecular interactions between nicotinic acetylcholine receptors and the R enantiomer displays a lower score which mean a higher affinity to the nAChR receptor and the π-π interactions are more stable than the S derivative. © 2023 Society of Chemical Industry.

Atezolizumab Plus Bevacizumab as First-line Treatment for Patients With Metastatic Nonsquamous Non-Small Cell Lung Cancer With High Tumor Mutation Burden: A Nonrandomized Controlled Trial.

Importance: Antiangiogenic drug combinations with anti-programmed cell death 1 protein and anti-programmed cell death 1 ligand 1 (PD-L1) agents are a novel treatment option for lung cancer. However, survival remains limited, and the activity of these combinations for tumors with high tumor mutation burden (TMB) is unknown. Objective: To assess the clinical benefits and safety of atezolizumab plus bevacizumab for patients with high-TMB advanced nonsquamous non-small cell lung cancer (NSCLC). Design, Setting, and Participants: This multicenter, single-arm, open-label, phase 2 nonrandomized controlled trial (Atezolizumab Plus Bevacizumab in First-Line NSCLC Patients [TELMA]) included treatment-naive patients aged 18 years or older with confirmed stage IIIB-IV nonsquamous NSCLC with TMB of 10 or more mutations/megabase and no EGFR, ALK, STK11, MDM2, or ROS1 alterations. From May 2019 through January 2021, patients were assessed at 13 sites in Spain, with follow-up until February 28, 2022. Interventions: Participants were given atezolizumab, 1200 mg, plus bevacizumab, 15 mg/kg, on day 1 of each 21-day cycle. Treatment was continued until documented disease progression, unacceptable toxic effects, patient withdrawal, investigator decision, or death. Main Outcomes and Measures: The primary end point was 12-month progression-free survival (PFS) rate (according to Response Evaluation Criteria in Solid Tumours, version 1.1 criteria); PFS was defined as the time from enrollment to disease progression or death. Adverse events were monitored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: A total of 307 patients were assessed for trial eligibility, of whom 266 were ineligible for enrollment. Of the 41 patients enrolled, 3 did not fulfill all inclusion criteria and were excluded. The remaining 38 patients (28 [73.7%] male; mean [SD] age, 63.7 [8.3] years) constituted the per-protocol population. The 12-month PFS rate was 51.3% (95% CI, 34.2%-66.0%), which met the primary end point. The 12-month overall survival (OS) rate was 72.0% (95% CI, 54.1%-83.9%). The median PFS was 13.0 months (95% CI, 7.9-18.0 months), and the median OS was not reached. Of the 38 patients, 16 (42.1%) achieved an objective response and 30 (78.9%) achieved disease control. The median time to response was 2.8 months (IQR, 2.8-3.58 months), with a median duration of response of 11.7 months (range, 3.57-22.4 months; the response was ongoing at cutoff). Of 16 responses, 8 (50.0%) were ongoing. Most adverse events were grade 1 or 2. For atezolizumab, the most common adverse events were fatigue (6 [15.8%]) and pruritus (6 [15.8%]). For bevacizumab, they were hypertension (10 [26.3%]) and proteinuria (4 [10.5%]). Drug discontinuation occurred in 2 patients receiving atezolizumab (5.3%) and 3 patients receiving bevacizumab (7.9%). PD-L1 levels were not associated with response, PFS, or OS. Conclusions and Relevance: These findings suggest that atezolizumab with bevacizumab is a potential treatment for high-TMB nonsquamous NSCLC. Trial Registration: ClinicalTrials.gov Identifier: NCT03836066.

Same-Day Desensitization in Patients Who Experience Their First Reaction to a Platin Agent at the Oncology Day Unit: A Pilot Study to Safely Include This Technique Within the Multidisciplinary Pathways for the Diagnosis & Management of Hypersensitivity to Platin Agents.

One of the main objectives when assessing patients who react to antineoplastics must be to ensure that they receive the required treatments without delay. From January to July 2021, at the Allergy Department at the Provincial University Consortium Hospital a pilot study was performed in which those patients suspected of having suffered a type I hypersensitivity reaction (grade 1 or 2) following Brown's anaphylaxis severity grading to a platin agent at the Provincial University Consortium oncology day unit, and once the reaction was properly treated and completely resolved, were subjected to a new procedure named as Same-Day Desensitization, which consists in the reintroduction and administration of full chemotherapy dose by allergists on the same day of the reaction by following the 1 bag/10 step protocol, looking forwards to systematize same-day reexposure using Same-Day Desensitization, doing it in the safest way possible. In total, 9 oncological patients suspected of having suffered a type I hypersensitivity reaction (grade 1 or 2) to a platin agent received total dose administration the same day of the initial reaction by following Same-Day Desensitization 1 bag/10 step protocol, without presenting further reactions. The manuscript describes a new approach in the use of Rapid Drug Desensitizations in reactive oncologic patients in treatment with platin agents, presenting the first 9 cases of oncologic patients who have been submitted to this procedure.